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Vol. 23, No.

1, 2013

EDITORIAL

Romanian Journal of Cardiology status report 2012

ORIGINAL ARTICLES

Highlights on Romanian cardiologists happiness: results of fellow


cardiologists self-rating

A. Petri, G. Tatu-Chioiu, C. Pop

REVIEWS

Almanac 2012: congenital heart disease. The national society journals present
selected research that has driven recent advances in clinical cardiology
12
M. Burch, Nathalie Dedieu

Almanac 2012, cell therapy in cardiovascular disease: the national society


journals present selected research that has driven recent advances in
clinical cardiology
21
D. A. Jones, Fizzah Choudry, A. Mathur

Long QT Syndrome

29

Structural and functional ventriculo-arterial changes in obesity:


mechanisms, implications and reversibility after weight loss

37

Apnoea syndrome to an obese hypertensive patient

44

L. Lucaci

Mdlina Iancu, Marinela erban, C. Copcescu, Carmen Ginghin

CASE REPORTS

F. Mitu, Daniela Boiteanu, Adina M. urcanu

Hypertrophic obstructive cardiomyopathy and mitral valve abnormalities 47


Nelis Asan, E. Apetrei, D. Deleanu, V. A. Iliescu, I. M. Coman

Vascular Doppler: Complex aortic arch pathology

51

Coronary angiography: Simultaneous acute thrombotic occlusion of two


coronary arteries in ST segment elevation myocardial infarction

54

Ecocardiography: Pseudo-pseudoaneurysm: natural evolution of a rare


myocardial infarction mechanical complication

56

UPDATES IN CARDIOLOGY

Updates in Cardiology

58

ESC GUIDELINES

ESC Guidelines on the management of cardiovascular diseases


during pregnancy

63

IMAGES IN CARDIOLOGY

Ileana Arsenescu

A. Negoi, F. Purcarea, M. Croitoru, D. Deleanu

Maria-Magdalena Gurzun, Marinela erban, B. A. Popescu, Carmen Ginghin

AGENDA

National and International cardiological agenda 2013

123

INSTRUCTIONS FOR
AUTHORS

Instructuctions for authors

126

Vol. 23, No. 1, 2013

Vol. XXII, Nr. 1, 2007

EDITORIAL

Romanian Journal of Cardiology raport de activitate 2012

ARTICOLE ORIGINALE

Calitatea vieii medicului cardiolog romn: rezultatele unui chestionar


colegial

A. Petri, G. Tatu-Chioiu, C. Pop

REFERATE GENERALE

Almanac 2012: cardiopatii congenitale

12

Almanac 2012: terapia genic n boala cardiovascular

21

Sindromul de QT lung

29

Modificri morfologice i funcionale ventriculo-arteriale n obezitate:


mecanisme, implicaii i reversibilitatea lor dup scderea ponderal

37

Sindrom de apnee de somn la o pacient obez hipertensiv

44

Cardiopatia hipertrofic obstructiv i anomaliile de valv mitral

47

Doppler vascular: Patologie complex de arc aortic

51

Coronarografie: STEMI prin ocluzie trombotic acut a dou artere


coronare

54

Ecocardiografie: Pseudo-pseudoanevrism: evoluia natural a unei


complicaii mecanice rare ale infarctului miocardic

56

ACTUALITI N
CARDIOLOGIE

Actualiti n cardiologie

58

GHID ESC

Ghidul ESC de management al bolilor cardiovasculare n timpul sarcinii

63

AGENDA

Calendarul manifestrilor tiinifice cardiologice

123

INSTRUCIUNI PENTRU
AUTORI

Instruciuni pentru autori

126

M. Burch, Nathalie Dedieu

D. A. Jones, Fizzah Choudry, A. Mathur


L. Lucaci

Mdlina Iancu, Marinela erban, C. Copcescu, Carmen Ginghin

PREZENTRI DE CAZ

F. Mitu, Daniela Boiteanu, Adina M. urcanu

Nelis Asan, E. Apetrei, D. Deleanu, V. A. Iliescu, I. M. Coman

IMAGINI N CARDIOLOGIE

Ileana Arsenescu

A. Negoi, F. Purcarea, M. Croitoru, D. Deleanu

Maria-Magdalena Gurzun, Marinela erban, B. A. Popescu, Carmen Ginghin

THE ROMANIAN SOCIETY OF CARDIOLOGY BOARD

President:
President elect:
Former president:
Vice-presidents:
Secretary:
Treasurer:
Members:

Ioan M. Coman
Gabriel Tatu-Chioiu
Dan E. Deleanu
Drago Vinereanu
Radu Ciudin
Bogdan A. Popescu
Ovidiu Chioncel
Eduard Apetrei
erban Blnescu
Mircea Cintez
Marian Croitoru
Dan Gai
Daniel Gherasim
Ioana Ghiorghiu
Carmen Ginghin
Adriana Ilieiu
Daniel Lighezan
Florin Mitu
Clin Pop
Radu Vtescu
Drago Vinereanu

COVER IMAGES
1 - Two dimensional transthoracic echocardiography long axis in diastole showed trabeculae 4mm and 5mm thick (C) insert into IVS and free wall of LV. Left atrium dilated. LA
left atrium, LV - left ventricle, AML - anterior mitral leafl et, PML posterior mitral leafl et, IVS interventricular septum, Ao aorta, PM papillary muscle (page 48); [AO
aorta, LV left ventricle, LA left atrium].
2 - Two dimensional transthoracic echocardiography long axis (up) and M-mode (down). Left ventricular outfl ow tract (subaortic stenosis) caused by anterior systolic displacement
of anterior mitral leafl et and subvalvular mitral apparatus (page 48).
3 - Contrast transthoracic echocardiography the LV cavity is completely opacified but there are no bubbles in the pericardial space, demonstrating the lack of communication; an
intact myocardium layer is present at the tip of the defect (page 56); [LV left ventricle].
4 - Transthoracic echocardiography after 7 months, five chamber view hyperechogenic area replacing the discontinuity observed before and a large apical thrombus covering the
previous pseudo-pseudoaneurysm (page 57); [LV left ventricle, LA left atrium, RV right ventricle, RA right atrium, AO aorta].

ISSN: 1583-2996

EDITORIAL STAFF
Editor-in chief
Eduard Apetrei
Deputy Editor
Carmen Ginghin

Associate editors
Mihaela Rugin
Ruxandra Jurcu
Bogdan A. Popescu
Costel Matei

Editors
Radu Cplneanu
Cezar Macarie
Founding editor
Costin Carp

EDITORIAL BOARD
erban Blnescu - Bucureti
Luigi Paolo Badano - Italia
Ion V. Bruckner - Bucureti
Alexandru Cmpeanu - Bucureti
Gheorghe Cerin - Italia
Mircea Cintez - Bucureti
Radu Ciudin - Bucureti
D. V. Cokkinos - Grecia
Ioan Mircea Coman - Bucureti
G. Andrei Dan - Bucureti
Dan Deleanu - Bucureti
Genevieve Derumeaux - Frana
Doina Dimulescu - Bucureti
Maria Dorobanu - Bucureti
tefan Iosif Drgulescu Timioara
Guy Fontaine - Frana
Alan Fraser - Anglia
Ctlina Arsenescu-Georgescu Iai

Mihai Gheorghiade - USA


Leonida Gherasim - Bucureti
Aurel Grosu - Chiinu,
R. Moldova
Assen R. Goudev - Bulgaria
Anthony Heagerty - Marea
Britanie
Alexandru Ioan - Bucureti
Dan Dominic Ionescu Craiova
Gabriel Kamensky - Slovacia
Andre Keren - Israel
Michel Komajda, Frana
Giuseppe Mancia - Italia
Ioan Maniiu - Sibiu
Athanasios Manolis - Grecia
Martin S. Martin - SUA
Gerald A. Maurer - Austria
erban Mihileanu - Frana
Tiberiu Nanea, Bucureti

Gian Luigi Nicolosi - Italia


Peter Nilsson - Suedia
Nour Olinic - Cluj-Napoca
Fausto Pinto - Portugalia
Clin Pop - Baia Mare
Josep Redon - Spania
Willem J. Remme - Olanda
Michal Tendera - Polonia
Ion intoiu - Bucureti
Panagiotis Vardas - Grecia
Margus Viigimaa - Estonia
Drago Vinereanu - Bucureti
Marius Vintil - Bucureti
Dumitru Zdrenghea Cluj-Napoca
Issue editor
Mihaela Rugin
Secretary
Mihaela Slgean

TECHNICAL INFORMATION
Responsibility for the contents of the published articles falls entirely on the authors. Opinions, ideas, results of studies published in the Romanian Journal of Cardiology are those of the authors and do not reflect the position and politics of the Romanian Society of Cardiology. No
part of this publication can be reproduced, registered, transmitted under any form or means (electronic, mechanic, photocopied, recorded)
without the previous written permission of the editor.
All rights reserved to the Romanian Society of Cardiology
Contact:

Societatea Romn de Cardiologie


Str. Avrig nr. 63, Sector 2, Bucureti
Tel./Fax: +40.21.250 01 00, +40.21.250 50 86, +40.21.250 50 87;
E-mail: office@cardioportal.ro

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

EDITORIAL

Romanian Journal of Cardiology


Status report 2012

After each issue is printed, it is imediattely uploaded on the official website, www.romanianjournalcardiology.
ro. Great efforts were done so that all the issues and supplements beginning with 2003 are uploaded.
To increase its level of visibility, Romanian Journal of Cardiology, with the full support of a dedicated team
of medical authors and translators, has been publishing all the articles in English version beginning with last
years second issue.
In August 2012, Romanian Journal of Cardiology, applied for the worlds leading provider of science and health
information, the Elsevier database. All the requirements were complied and the indexing process has started.

Romanian Journal of Cardiology status report 2012

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

In September last year Romanian Journal of Cardiology was chosen to be part of the pilot project of being
indexed in the European Society of Cardiology search engine.
All the articles in English published in Romanian Journal of Cradiology and its Supplements strating from
2010 were processed.
At present, the indexing process has successfully ended.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

ORIGINAL ARTICLES

Highlights on Romanian cardiologists happiness: results of fellow


cardiologists self-rating
Antoniu Petri1, Gabriel Tatu-Chioiu2, Clin Pop3
Article received on the 11th of February 2013. Article accepted on the 6th of March 2013.
Abstract: Background The quality of physicians private lives is responsible for maintaining an optimal quality level of their
professional lives. Objective Evaluating the quality of Romanian cardiologists private lives by self-rating their happiness
degree, health and involvement in managerial/social/volunteer/religious activities, as well as the ways they choose to spend
their free-time in. Method Members of Romanian Society of Cardiology (RSC) were invited to respond to a confidential
on-line questionnaire available over a 30 day period. Results A group of 187 cardiologists participated: age 45.699.78 years,
experience in the field of 13.958.70 years; 75 (40%) male; 109 (58.28%) consultants; 55 (29.41%), specialist registrars and 23
(12.29%) junior doctors; 135 (72.19%) were general cardiologists, while 35 (18.71%) were interventional/ intensivists. Qualityof-live happiness-degree and health self-rating were scaled 1 (most pessimistic evaluation) to 5 (most optimistic evaluation).
The average scores were 3.340.92 and 3.940.74, respectively. As far as the quality-of-life was concerned, men scored higher
than women (3.520.89 vs 3.210.92 p = 0.026), cardiologists performing abroad scored higher than the ones performing
exclusively into Romania (4.000.73 vs 3.900.74 p = 0.033), and married scored higher than single ones (p=0.010). Almost
13% of respondents were smokers, 38% overweight / obese, 76.47% do not spend their free-time doing outdoors activities, and
more than 33% practice no sports whatsoever. The quality-of-life rating score of the happiest cardiologists was directly correlated to their professional level: junior doctors / specialist registrars / consultants (p<0.01) and years of activity in cardiology
(p = 0.035). Conclusions 1. A high percentage of cardiologists are smokers, overweight / obese, do not spend their free-time
doing outdoor activities and do no sports. 2. Cardiologists least happy are young, single, had previously worked abroad, do
not work in the academic environment, have less than 21 paid vacation days a year, do not own personal households, and are
neither interventional cardiologists, nor emergency cardiology physicians. 3. These data can be a milestone for the education of Romanian cardiologists in cardiovascular disease prevention offering an initial reference point for rating their further
outcome. 4. These data can also be used by the RSC among arguments of improving Romanian cardiologists quality-of-life in
front of decision makers of the national health system.
Key words: cardiologist, lifestyle, happiness, questionnaire, quality-of-life

INTRODUCTION
Happiness can be defined as a state of intense and
absolute contentment (approximate translation from
DEX - The Explanatory Dictionary of the Romanian
Language)1. Quality-of-life evaluations measure the
dependency between living conditions and individual perceptions, states of mind, satisfaction or lack of
it, happiness or frustration2,3. Considering the major
impact that private life has over the professional one,
the quality of physicians private lives is more and more
subject to such evaluations. Giving the context, we
asked ourselves how happy / content Romanian cardiologists really are. Using a model recently tested in
the United States of America4 as its parting point, the

1
University of Medicine and Pharmacy Grigore T. Popa, Sf. Spiridon
Emergency Hospital, Cardiology Clinic, Iai
2
Emergency Hospital Floreasca, Department of Cardiology, Bucureti
3
County Emergency Hospital Baia Mare, University Vasile Goldi, Arad,
Romania

present survey aims to provide you with an answer to


the very question, being the first of its kind ever to be
conducted in Romania.
Aims
The aim of present survey was to evaluate the qualityof-life of Romanian cardiologists by means of a questionnaire allowing them to self-rate degrees of private
life happiness and health.
Methods
The survey was initiated and coordinated by the Acute
Cardiac Care Working Group of the Romanian Society
of Cardiology (SRC), and was grounded on an on-line questionnaire (docs.google.com) representing an

Contact address:
Antoniu Petri, MD, University of Medicine and Pharmacy Grigore
T. Popa, Sf. Spiridon Emergency Hospital, Cardiology Clinic, B-dul
Independenei nr. 1 Iai 700111 antoniupetris@yahoo.com

A. Petris et al.
Romanian cardiologist: happiness questionnaire

adaptation of the toll used by US physicians to self-rate their happiness/contentment degree (MEDSCAPE
Physician lifestyle Report)4. The American questionnaire was published in January 2012 and contains
answers provided by 29025 physicians representing 25
medical fields, 762 of the respondents being cardiologists. In spite of our persistent efforts, we were unable
to identify other similar evaluations thus data filled in
by Romanian cardiologists were compared exclusively
to data in the American survey. The list of questions is
available in Table 1. A 5 point score was used in order
for the sample to self-rate the quality of their private
lives, where 1= least happy and 5 = happiest). Same
way, another 5 point score was used for the self-rating
of the physical health, where 1=least healthy and 5
= healthiest). Members of Romanian Society of Cardiology were asked to answer the questionnaire between September 1st and 30th, 2012 and a single recall was

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

performed during this interval. Preliminary data were


communicated at the Cardiovascular prevention: a
national emergency Session of the National Congress
of Cardiology (October 4th-6th, 2012).
Ethical considerations: The questionnaire was confidential; a format enabling respondents to fill in their
answers under protection of anonymity was used (docs.
google.com). Moreover, Romanian Society of Cardiology transmitted an official commitment to confidentiality to all its members. Legal provisions in the field
- Law No. 677/2001 on the Protection of Individuals
with Regard to the Processing of Personal Data and the
Free Movement of Such Data, amended and completed, and Law No. 506/2004 on the processing of personal data and the protection of privacy in the electronic
communications sector - were respected accordingly.
Statistical analysis: Data collected were centralized in
an Excel data base (Microsoft Office Excel 2003) and

Table 1. Questionnaire rating Romanian cardiologists quality-of-life - components


General data
Sex
Age
Professional level: (junior doctors / specialist registrars / consultants
Field of activity (general cardiology / interventional cardiology / cardiologists working in coronary care units / cardiovascular recovery specialists / pediatric cardiology / other)
Years of activity in the field of cardiology
Type of medical practice (hospital / private clinics / both)
Field of activity (academic/non-academic)
Activity abroad (Yes/ No, period of time)
Interest in practicing cardiology abroad in case such opportunity arises
Quality-of-life
Are you happy with your private life? (score 1 least happy to 5 happiest)
Self-rating health (score 1 least healthy to 5 healthiest)
Marital status
Profession of cardiologists life partner (physician, performing activities related to medical care, non-medical profession)
Number of children
Opinion on the importance of quality-of-life versus life-length
Therapeutic option for prolonging lifetime (palliative care / aggressive care)
Risk factors
Size / weight
Chronic tabagism
Ethanol consumption
You were diagnosed with.. high blood pressure, dyslipidemia, obesity, diabetes, ischemic cardiopathy
Physical exercise (Yes/No, duration)
Sports
Participation in sports competition
Data on properties (household, car, debts) - optional
Data on managerial / social / religious / volunteer-type involvement
Data on ways for spending free-time:
Vacation days / year
Favorite vacation destination (Romania; abroad), (mountains; sea-side)
Free-time activities
Outdoors activities (camping; hunting; fishing)
Social networks participant

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

analyzed using a specialized software (SPSS 14.0; SPSS,


Chicago, Illinois). Results are presented as average
standard deviation (SD). Students T-Test was used to
compare the independent continuous variables, while
chi test2 was used to compare proportions. A value of p
<0.05 was considered statistically significant.

RESULTS
General data: One hundred eighty-seven colleagues,
45.699.78 years old (range 27 to 74 years old, median
45), with an activity in cardiology of 13.958.70 years
(1 to 47 years, median 13) answered the questionnaire. Seventy-five (40.11%) were male, and 112 (59.89%)
female. More than half - 109 (58.29%) were consultants (primari) in cardiology, 55 (29.41%) were specialist registrars (specialiti), and 23 (12.28%) were
junior doctors (rezideni) from which 2.12% were
in their 1st to 3rd year of residency, and 10.16% were in
their 4th to 5th year of residency. Most of the respondents, i.e. 135 (72.19%) were general cardiologists, 22
(11.76%) were interventional cardiologists, 13 (6.95%)
were cardiologists working in Coronary Care Units, 6
(3.21%) were cardiovascular rehabilitation specialists,
2 (1.07%) were pediatric cardiologists, and 9 (4.81%)
had a different area of activity. One hundred and five
respondents (56.15%) performed academic activities.
More than two thirds of the respondents (103; 69.52%)
were working both in public hospitals, and in private
clinics; 37 (19.79%) were working only in public hospitals, while 20 (10.70%) were working in the private
sector exclusively. Thirty-eight (20.32%) of the total
number of respondents had worked abroad for certain
time periods, while 110 (58.82%) stated their availability to seizing such opportunity.
One hundred and forty-one respondents (75.40%)
were married, 9 (4.81%) were remarried, 13 (6.95%)
were divorced, 3 (1.60%) were widowers and 21
(11.23%) were single. In 82 cases (43.85%) married
respondents life partners were also physicians, in 13
cases (6.95%) they were involved in activities related to
medical care, and in 71 cases (38.97%) they had nonmedical professions. The average number of children
was 1.210.90 (0 to 4 children, a median of 2). Most
participants (147; 78.61%) declared themselves as being religious individuals although non-practicants, 33
(17.65%) affirmed being religious and practicants, while 7 (3.74%) were atheists.
Financial status: Ninety-eight respondents (52.41%)
live in personal block apartments, 75 (40.11%) own
houses, 14 (7.49%) live in rented households. Most

A. Petris et al.
Romanian cardiologist: happiness questionnaire

respondents (159; 85.03%) own a car. Most of the respondents (116, 64.09%) declared no financial debts,
while 12 (6.63%) reported debts lower than EUR 5000,
36 (19.89%) reported debts between EUR 5000 and 50
000, and 17 (9.39%) reported debt amounts exceeding
EUR 50 000.
Cardiovascular risk factors: Cardiovascular risk factors distribution as reported by respondents is presented in Figure 1:
- Smoking/Non-smoking: Two thirds of the respondents (118; 63.10%) were non-smoking,
47 (25.13%) used to smoke but quit, while 24
(12.83%) were active smokers.
- Hypertension. A number of 29 respondents
(15.51%) were diagnosed with hypertension.
- Dyslipidemia. Almost one third of the respondents reported suffering from lipid disorders (57;
30.48%).
- Diabetes: Three colleagues (1.60%) mentioned
themselves as having diabetes.
- Overweight / Obesity: Only one hundred sixtytwo from the total 187 respondents mentioned
their Body Mass Index (BMI). Five respondents
(3.09%) declared a BMI under 18.4 kg/m2 (underweight), 95 respondents (58.64%) between
18.5 and 24.9 kg/m2 (normal weight), 49 respondents (30.25%) between 25 and 29.9 kg/m2
(overweight), and 13 respondents (8.02%) declared a BMI over 30 kg/m2 (obese).
Physical exercise: One third of the respondents (68;
36.36%) reported they exercise 30 minutes a day.
Twenty-two of our colleagues (11.76%) reported doing
physical exercises for one hour every day, 8 (4.28%)
reported doing physical exercises for two/more hours daily, while 47 (25.13%) admitted exercising only

Figure 1. Cardiovascular risk factors distribution (no. of respondents).

A. Petris et al.
Romanian cardiologist: happiness questionnaire

weekly (Figure 2). Forty-two (22.46%) of the respondents declared no daily exercising at all. One hundred
eighteen (63.10%) of our colleagues reported practicing at least one sport. A top 5 most frequent sports
includes: 1. Gymnastics/Aerobics/Tai Chi (44; 23.53%);
2. Swimming (41; 21.93%); 3. Skiing (29; 15.51%); 4.
Cycling (24; 12.83%); 5. Athletics (17; 9.09%). Other
mentioned sports were: tennis (12; 6.42%), table tennis
(9; 4.81%), basketball (6; 3.21%), football (5; 2.67%),
volleyball (3; 1.60%), climbing (1; 0.53%), martial arts
(1; 0.53%). Twelve respondents (6.42%) participated in
local sports competitions, 3 (1.60%) in national competitions and one colleague (0.53%) was engaged in international competitions. One third of the respondents
(69 colleagues, 36.90%) declared practicing no sports
whatsoever.
Free-time activities: Most of the respondents (101;
54.01%) mentioned having 21 to 29 vacation days a
year, 60 (32.09%) mentioned 14 to 20 days, 18 (19.63%)
mentioned over 30 days, and 8 (4.28%) mentioned only
7 to 13 vacation days yearly. The number of days spent
on vacation was positively correlated to the quality-oflife rating score (r=0.195, p <0.01). The favorite vacation is spent either in Romania, or abroad (118; 63.10%),
and is mentioned clearly most frequently than vacations spend exclusively abroad (60 respondents; 32.09%)
or only in Romania (9; 4.81%). The majority of the respondents (126 respondents, 67.38%) prefer both sea-side and mountains as vacation destinations, 36 respondents (19.25%) choose mountains exclusively, while 25
of them (13.37%) choose only the sea-side. Outdoor
recreation is appreciated by only 49 respondents (hunting: 3, i.e. 1.60%; fishing: 14, i.e. 7.49%; camping 32,
i.e. 17.11%), while for the most of them (143; 76.47%)
spending free-time in the middle of the nature is not a
preferable free-time activity. Main ways for spending
free-time are: 1. traveling (135; 72.19%); 2. reading

Figure 2. Sample distribution according to physical exercise frequency.

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

(127; 67.91%); 3. movie watching (94; 50.27%); 4. visiting friends (93; 49.73%); 5. shopping (70; 37.43%).
Physical exercise barely holds the 7th position amongst
Romanian cardiologists preferences (n=63; 33.69%).
Only 54 respondents (28.9%) admitted owning social networking accounts. The lack of interest (or of available time !) for joining social networking is also characteristic to American cardiologists who hold top position among the 25 medical specialties inquired who
declare a low use of such social connection methods.
Alcohol consumption: Twenty-three respondents
(12.30%) declared no alcohol consumption whatsoever,
139 (74.33%) declared consuming alcohol occasionally,
24 (12.83%) mentioned moderate consumption, and
one respondent (0.53%) mentioned high alcohol consumption. Only 18 respondents (9.63%) prefer beer, 56
(29.95%) have opted for wine, and 8 (4.28%) for spirits
consumption.
Community life involvement: A number of 63 respondents (33.69%) declared managerial involvement (hospital manager, head of department, private managing),
8 (4.28%) declared political involvement, 54 (28.88%)
declared social involvement (sponsorships, arts patronage, donations), and 54 (28.88%) declared volunteertype involvement (pro-bono activity, tutoring, counseling, international/religious missions).
Quality-of-life happiness degree: The evaluation of
the happiness degree concerning the quality-of-private
life was scored 1 to 5 points as described in the methodology of the survey (Figure 3).
The average score was 3.340.92, lower than the value of 3.92 (no standard deviation indications available)
reported in the American questionnaire3 (Figure 4).
Average happiness degree was higher in males (3.520.89, median 4) as opposed to females

Figure 3. Sample distribution considering answers provided to the question:


Are you happy with your private life? (1 to 5 point score).

A. Petris et al.
Romanian cardiologist: happiness questionnaire

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Figure 4. Romanian vs American quality-of-life rating scores distribution


comparison (see reference 3).

(3.210.92, median 3) (p=0.026). Highest quality-of-life average score was registered in respondents age over
65 (3.800.44), followed by the sub-groups ages 35 to
44 (3.440.87) and 27 to 34 (3.031.08), still no sta-

tistically significant differences were identified except


group age 27 to 34 vs group age 55 to 64 (p=0.049).
Consultants were the happiest (3.440.86), followed
by specialist registrars (3.221.24) and junior doctors (3.180.86), but the differences were not statistically significant. Interventional cardiologists and
intensivists registered an insignificant higher score
(4.110.53) than physicians not working in these areas
(3.540.85) (p=0.143). An interesting detail, i.e. average quality-of-life score in cardiologists who previously
worked abroad was lower (3.410.92) than the one of
their colleagues working within national borders exclusively (3.980.76, p =0.033). No statistical differences were registered between the scores of respondents
performing in the academic environment as opposed
to the ones not doing so (3.450.84 and respectively
3.890.77, p=0,063), nor between consultants and specialist registrars (3.440.86 vs 3.180.86, p=0.072) or
between junior doctors and specialist registrars / con-

Table 2. Quality-of-life and health rating scores in different categories of respondents


Question
MeanSD (median)
Sex
Male (n=75)
Female(n=112)
Age
27-34 years (n=29)
35-44 years (n=55)
45-54 years (n=58)
55-64 years (n=40)
Over 65 years (n=5)
Professional level
Junior doctors (n=23)
Specialist registrars (n=55)
Cosultants (n=109)
Field of activity
Emergency (n=35)
Non-emergency (n=152)
Activity abroad
No (n=149)
Yes (n=138)
Type of activity
Academic (n=105)
Non-academic (n=82)
Marital status
Married (n=141)
Remarried (n=9)
Divorced (n=13)
Widow(er) (n=3)
Single (n=21)
Profession of the life partner
Physician or performing activities related
to medical care (n=95)
Non-medical profession (n=71)

Rating of the quality of personal life


(score 1 least happy to 5 happiest)

Rating health
(score 1 least healthy to 5 healthiest)

3.520.89 (4)
3.210.92 (3)

4.000.73 (4)
3.900.74 (4)

3.031.08 (3)
3.440.87 (3)
3.310.88 (3)
3.400.92 (4)
3.800.44 (4)

4.170.60 (4)
3.970.73 (4)
3.840.79 (4)
3.880.79 (4)
4.200.44 (4)

3.221.24 (3)
3.180.86 (3)
3.440.86 (4)

4.170.83 (4)
3.930.66 (4)
3.900.75 (4)

3.540.85 (4)
3.290.93 (3)

4.110.53 (4)
3.900.77 (4)

3.410.92 (4)
3.050.86 (3)

3.980.76 (4)
3.790.62 (4)

3.450.84 (4)
3.200.99 (3)

3.980.72 (4)
3.890.77 (4)

3.410.87 (3)
3.220.97 (3)
3.311.37 (4)
3.330.57 (3)
2.900.83 (3)

3.960.72 (4)
4.000.50 (4)
3.691.03 (4)
4.001.00 (4)
3.900.76 (4)

3.460.84 (4)

4.050.69 (4)

3.260.94 (3)

3.830.69 (4)

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Vol. 23, No. 1, 2013

ces also failed to appear when comparing respondents


performing in the academic environment (3.980.72)
to the ones not doing so (3.890.77) (p=0.063), and
also when comparing respondents whose life-partners
were either physicians or performing activities related to medical care (4.050.69) to respondents whose life-partners were working in non-medical fields
(3.830.69)(p=0.155). Higher health self-rating scores
were reported by young respondents (27 to 34 years old)
(4.170.60) and respondents age over 65 (4.200.44),
yet no statistically significant difference was identified.
Figure 5. Sample distribution considering health self-rating (1 to 5 point
score).

sultants (3.221.24 vs 3.440.86 / 3.180.86, p=0.508);


statistical differences also failed to appear when comparing married to single cardiologists (3.410.87, and
2.900.83, respectively; p = 0.010), and respondents
whose life-partners were either physicians or persons
involved in activities related to medical care to respondents whose life-partners were working in non-medical fields (3.460.84 vs 3.260.94, p = 0.155) (Table 2).
Quality-of-life versus life-length: The majority of
the respondents (146; 78.07%) mentioned qualityof-life and life-length as being equally important; for
37 respondents (19.79%) the quality-of- life is more
important than its duration, while for one colleague
(0.53%) life-length is the most important of the two.
Three respondents (1.60%) checked the I dont know /
I havent yet thought about it box in the questionnaire.
The best way to prolong ones lifetime is considered to
be the aggressive care regime by 47 of the respondents
(25.13%), the palliative care by 27 respondents (14.44%)
or the ceasing of any drug administration by 11 respondents (5.88%); still, the majority (102; 54.55%) checked
the I dont know / I havent yet thought about it box.
Self-rating health: Average health self-rating score was
3.940.74 (Figure 5), lower than the average of 4.17%
reported by American cardiologists4.
Cardiologists who previously worked abroad considered themselves less healthy (average index =
3.050.86) than the ones working exclusively in Romania (3.790.62) (p=0.033). No significant differences
were registered between males vs females (4.000.73,
and 3.900.74, respectively), between junior doctors (4.170.83) and specialist registrars (3.900.75)
(p=0.123), or between interventional cardiologists / intensivists (3.900.77) and respondents not working in
these areas (3.290.93)(p=0.143); significant differen

Happiest versus least happy respondents


comparison:
When comparing data reported by the least happy
cardiologists (quality-of-life rating scores 1+2) to data
reported by the happiest cardiologists (scores 4+5) (see
Table 3), respondents least happy (n=28) are significantly younger (42.2510.28 years vs 46.739.75 years,
p=0.039), single (21.43% vs 5.68% married, p=0.046),
work less frequent in emergency cardiology (10.71%
vs 22.72%, p<0.001) and own in a significantly lower
percentage personal households (25.00% vs 52.27%,
p=0.001), but consider themselves healthier (average index = 4.220.63 versus 3.360.73, p<0.001). The
least happy respondents had worked abroad (25% versus 13.64%) or would prefer to work abroad (82.14%
versus 51.14%). Moreover, the least happy are more,
yet insignificantly, frequently married to life-partners
working in non-medical fields than to life-partners
working in the medical field (46.43% versus 32.95%,
p=0.059), have more frequently (yet no statistically significant) financial debts exceeding EUR 50 000 (14.29%
vs 9.09% cardiologists with lower debts, p=0.082), or
automobiles (71.43% vs 92.05%, p=0.077).
The percentage of the happy ones was higher in case
of colleagues performing in the academic environment
(60.23% versus 42.86%). The difference was not, however, significant, probably due to the relative low number of respondents (p = 0.109).
Respondents having a BMI over 30 kg/m2 (overweight/obese) appeared more frequently as happy with the
quality of their lives (40.3%) as compared to the least
happy ones (28%). Furthermore, happiest respondents
have more vacation days a year (over 21 days) (71.6%
vs 46.4%, p=0.008), are more frequently religious practicants (14.77% vs 7.14%, p=0.005), are less abstinent
when considering alcohol (9.09% vs 28.57%, p=0.009),
prefer in an slightly more frequent consumers of beer
(11.4% vs 3.6%, p=0.224) and wine (34.1% vs 21,4%,
p=0.211) and declare a managerial, political, social or

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Vol. 23, No. 1, 2013

Table 3. Least happy respondents (score 1+2) versus happiest respondents (score 4+5) comparison
Least happy Romanian cardiologists
(score 1+2, n= 28)

Happiest Romanian cardiologists


(score 4+5, n= 88)

7(25%) / 21 (75%)
42.2510.28 (44)
10.848.29 (8)
1.690.47
3.360.73 (3.5)

45 (51.1%) / 43 (48.9%)
46.739.75 (45.50)
16.199.21 (15)
4.140.34
4.220.63 (4)

8 (28.57%)
7 (25.00%)
9 (32.14%)
4 (14.29%)
0
14 (50.00%)
7 (25.00%)
7 (25.00%)
23 (82.14%)
2 (7.14%)
1 (3.57%)
1 (3.57%)
7 (25.00%)
3 (10.71%)
18 (64.29%)
12 (42.86%)
16 (57.14%)
7 (25.00%)
21 (75.00%)

10 (11.36%)
27 (30.68%)
26 (29.55%)
21 (23.86%)
4 (4.55%)
61 (69.32%)
17 (19.32%)
10 (11.36%)
63 (71.6%)
7 (7.95%)
13 (14.77%)
2 (2.27%)
15 (17.05%)
8 (9.09%)
65 (73.86%)
53 (60.23%)
35 (39.77%)
12 (13.64%)
71 (80.68%)

Male vs female (n, %)


Age (average SD, average) (years)
Years of activity in the field of cardiology (average)
Quality-of-life happiness rating score
Self rating health score (average)
Age categories
27-34 years
35-44 years
45-54 years
55-64 years
Over 65 years
Consultants
Specialist registrars
Junior doctors
General cardiology
Intensivist
Interventional cardiologist
Cardiovascular recovery specialists
Activity in hospitals
private clinics
both
Academic environment
Non-academic environment
Activity abroad
No activity abroad

volunteer involvement similar to the one mentioned


by the least or less happy (22.73% vs 21.43%, p=0.119;
5.68% vs 3.57%, p=0.664, 32.95% vs 25%, p=0.432 and
respectively, 29.55% vs 25%, p=0.646).
Apparently the most satisfied with the quality of personal life prefer to spend their vacations abroad (34,1%
vs 17,9%, p=0.650) and in the mountains (28.6% vs
19.3%, p=0.678); exercise more frequent 30 minutes
/ day (42% vs 35.7%, p=0.895) and participate more
frequent in local sports competitions (9.1% vs 3.6%,
p=0.683); still, when it comes to outdoor recreation activities this category scores 75% vs 82.1%, p=0.440 and
also reports lower interest in social networks (23.9%
vs 35.7%, p=0.221). This absolutely differences did not
appear statistically significant due probably to the relatively low number of respondents.
Quality-of-life rating score declared by the happiest
cardiologists was correlated to their professional level
(p<0.01) and the years of activity in the field of cardiology (p=0.035).
The least happy cardiologists see the problem of the
best treatment to be applied for prolonging lifetime the
same way their happiest colleagues do, i.e. aggressive
care: 25% vs 28.41%, p=0.348; palliative care: 14.29%
vs 15.91%, p=0.468, but the option for ceasing all drug
administration is more frequently reported by the

happiest (5.68% vs 3.57%, p=0.001). No significant differences were registered between the two subgroups
from the point of view of the incidence of hypertension, diabetes, dyslipidemia or ischemic heart disease (17.9% vs 14.8%, p=0.698; 7.1% vs 1.1%, p=0.082;
28.6% vs 27.3%, p=0.895; 7.1% vs 3.4%, p=0.401).

DISCUSSIONS
The present questionnaire rating physicians health and
happiness degree concerning their quality-of-life is the
first of its kind ever to be conducted in Romania. For
comparison purposes, we insistently, yet unsuccessfully, tried to identify specific data reported in other European countries. Basically, the one and only source we
could compare our data to was the American questionnaire4 published in January 2012, which was used as
a model for our questionnaire. Our purpose was not
that of creating to a syndicalist questionnaire, although some of our colleagues might have expected it to
be so. Our analysis revealed a series of particularities
of Romanian cardiologists, some of them being really
surprising. Thus, almost 13% of Romanian cardiologists are smokers (and 25% are ex-smokers). By comparison, only 1% of American cardiologists smoke4. Over
38% of respondents were either overweight (30%) or
obese (8%). More than one third of the cardiologists

A. Petris et al.
Romanian cardiologist: happiness questionnaire

do not do sports. Only 19% of them mentioned daily


exercise, 36% report moderate 30 minute daily physical activity, while 25% dedicate only weekends to doing
sports. More than three quarters of respondents do not
spend their free-time outdoors, within nature, preferring traveling, reading, movie watching, visiting friends or shopping as alternatives. By comparison, 70% of
American cardiologists prefer to spend their free-time
in doing physical activities4.
Quality-of-life happiness index of Romanian cardiologists (3.34+0.92) was inferior to the value reported
by American cardiologists (3.92). In fact, considering
all 25 medical specialties participating to the American
questionnaire, the happiest respondents were the rheumatologists (score = 4.09), followed by dermatologists
(score = 4.06) and urologists (score = 4.04), while the
least happy were the internists (score = 3.88), gastroenterologists (score = 3.88) and neurologists (score =
3.88). American cardiologists (762 respondents)4 came
15th. By comparison to these data, the average qualityof-life rating score provided by Romanian cardiologists
places them under the level reported by any of the 25
specialties who responded to the American questionnaire.
Least happy with the quality of their lives are the young cardiologists, cardiologists having less de 21 paid
vacation days a year, colleagues who previously worked
abroad, colleagues not performing in the academic environment, the ones not owning personal households,
those who are single and, interesting, cardiologists
not working in emergency in interventional cardiology. Still, the least happy ones have lower BMIs and
higher health indexes when compared to the group of
the happiest. Cardiologists age over 65, consultants in
cardiology, intensivists and the ones who never worked
abroad are the happiest ones. The overall health index
of Romanian cardiologists is relatively high (3.94) but
lower than the one reported by American cardiologists
(4.17)4.
An aspect we find important to be highlighted is
that a number of 141 respondents to our questionnaire (75.40%) were married, a percentage lower than the
one reported by American cardiologists (81.2%). The
rate of divorced (and not remarried) cardiologists was
higher in case of Romanian cardiologists (6.95% vs
5.5%). This aspect is significantly important, as divorce rate reported by American cardiologists was found
by MEDSCAPE to be higher than the average of 3.3%
registered at the level of all analyzed specialties4. Family life is an extremely important reference point also
highlighted by our survey; the difference between ave

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Vol. 23, No. 1, 2013

rage quality-of-life rating scores was statistically significant when comparing single cardiologists to married
ones (p=0.010).
Over 95% of the respondents consider themselves religious individuals. By comparison, 85% of MEDSCAPE 2012 respondents declared themselves as such4.
Moreover, WIN-Gallup Internationals recent poll, i.e.
The Global Index of Religiosity and Atheism placed
Romanians on 6th position in the international top of
most religious peoples worldwide (89%)6.
One could ask themselves why such data about professional groups, Romanian cardiologists in our case,
are relevant to be collected and reported. We believe
quantifiable data are needed considering the relation
of interdependency between the quality of ones private
life and their professional performances7. Such data are
the only means for evaluating the Work Life Balance
concept and help ourselves, in a context in which contemporary organizations became greedy for employees time8, especially for the time of the highly specialized ones, amongst who cardiologists are to be found.
These series of introspections become even more relevant in the context of Romania belonging together with
Latvia and Lithuania to the group of countries where
the overall average of life-happiness decreased on the
background of severe recession9. According to some
sources, lowest happiness levels are registered by Romania and Hungary - EU member states, followed by
Armenia and Georgia - two Caucasian countries9.
As a consequence, we believe this first Romanian
cardiologist quality-of-life rating to be valuable from
at least three points of view: 1. The survey highlights
a set of particularities that should alarm part of the
cardiologists (the relatively high number of smokers,
overweight/obese colleagues, as well as that of cardiologists not doing constant physical exercise). Mentioned particularities must become as many targets
hunted down by Romanian Society of Cardiology in
its efforts to prevent cardiovascular diseases; 2. Data
collected lay the perfect grounds for comparison as far
as evaluating immediate future evolutions in our specialty is concerned; 3. Present data can be included in the
set of arguments we present to health policy decision
makers in support of our efforts to improve Romanian
cardiologists quality-of-life. Such efforts should represent a constant concern for all our fellow cardiologists.

STUDY LIMITATIONS
The apparent main limitation of the present survey is
the low number of respondents, only 187 (approximately 19% of the total number of Romanian cardiolo-

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Vol. 23, No. 1, 2013

gists). Nevertheless, we believe this group to represent


a significant sample as far as our specialty is concerned, considering the proportional distribution revealed
(58% consultants, 24% specialist registrars, 12% junior
doctors) which corresponds to the national proportional distribution of mentioned professional categories. By comparison, the American questionnaire was
answered by a little over 700 cardiologists, such total
being most probably inferior to the percentage of Romanian respondents if taking into account that the entire US population is 14 times grater than the one of
Romania10.

CONCLUSIONS
1. The scores of the cardiologists happiness degree
concerning their quality-of-life and the health self
rating one were 3.940.74 and 3.340.92, respectively. Both scores were lower compared with the
ones reported in the American questionnaire.
2. A high percentage of cardiologists are smokers
(12.83%), overweight /obese (38%), do not enjoy
outdoor activities as a way of spending their freetime (76.47%), and practice no sports whatsoever
(over 33%).
3. Least happy with the quality of their lives are the
young cardiologists, cardiologists having less than
21 paid vacation days a year, those who previously worked abroad, those not performing in the
academic environment, single ones, those not
owning households, and those not working in
the emergency cardiology field or in that of interventional cardiology. The least happy cardiologists have a lower BMI and consider themselves
healthier than the ones happy or happiest with the
quality of their lives.
4. Data revealed by our analysis lay the grounds for
the development of educational activities in the
field of cardiovascular disease prevention con-

ducted by Romanian Society of Cardiology; such


concern should evidently extend more and more
among its members. Information collected are
useful for evaluating future evolution of the efforts
made in the field of educating prevention and can
easily be included in the set of valid arguments
used by Romanian Society of Cardiology in front
of sanitary policy decision makers in support of
our plea for improving the quality-of-life of the
Romanian cardiologists.
Acknowledgements
The authors are grateful to Daniela Petri for her skillful assistance and continued support and to Anca TatuChioiu for the English translation of this text.
Conflict of interest: none declared.
References
1.

Academia Romn. Institutul de Lingvistica Iorgu Iordan. Dictionarul explicativ al limbii romne DEX. Ed. Univers Enciclopedic Gold,
Bucureti, 2012.
2. Mrginean I. Calitatea vieii n Romnia: prezent i perspective. Calitatea Vieii 2010; 34: 231237.
3. West CP, Shanafelt TD. Physician well-being and professionalism.
Minn Med. 2007; 90: 44-46.
4. Peckham C. Profiles in happiness: which physicians enjoy life most?
http://www.medscape.com/features/slideshow/lifestyle/2012/cardiology
5. Wood S. Cardiologists Are Happy(ish), Married Non-Tweeters, Survey Reveals. Medscape. Mar 22, 2012. http://www.medscape.com/
viewarticle/760775
6. WIN-Gallup International. The Global Index of Religiosity and Atheism 2012. Win Gallup International, Washington DC, 2012.
7. West CP, Shanafelt TD, Kolars JC. Quality of Life, Burnout, Educational Debt, and Medical Knowledge Among Internal Medicine Residents. JAMA. 2011; 306: 952-960.
8. Ivan GA. Echilibrul dintre munc i viaa personal n Romnia.
Cauze, efecte i tendine. Teza de doctorat 2011 http://www.unibuc.
ro/studies/Doctorate2011Noiembrie/Ivan%20Georgiana%20Aurelia%20-%20Echilibrul%20dintre%20munca%20si%20viata%20personala%20in%20Romania/rezumat.pdf
9. European Bank for Reconstruction and Development. The Life in
Transition. After the crisis. 2011. www.ebrd.com/lifeintransition
10. Institutul Naional de Statistic. Romania n cifre 2012. Ed. Revista
Romn de Statistic, Bucureti, 2012.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

REVIEWS

Almanac 2012: congenital heart disease. The national society


journals present selected research that has driven recent advances
in clinical cardiology*
M. Burch1, Nathalie Dedieu2
Article received on the 25th of September 2012. Article accepted on the 29th of September 2012.
Abstract:

This Almanac highlights recent papers on congenital heart disease in the major cardiac journals. Over 100 articles
are cited. Subheadings are used to group relevant papers and allow readers to focus on their areas of interest, but are not meant
to be comprehensive for all aspects of congenital cardiac disease.

EPIDEMIOLOGY
The prevalence of congenital heart disease in Europe
was recently reported in two major papers. Data from
a central database for 29 population based registries in
16 countries showed a total prevalence of 8 per 10001.
The overall detection rate of non-chromosomal congenital heart disease prenatally was only 20%, although
40% of severe cases were diagnosed before birth. It was
estimated that each year in the European Union 36 000
children are live born with congenital heart disease
and another 3000 are diagnosed with congenital heart
disease but die as a termination of pregnancy for fetal
abnormality. In a systematic review2 of 114 papers and
24 091 867 live births the prevalence of congenital heart
disease increased over time from 0.6/1000 in 1930 to
9.1/1000 after 1995. The rate stabilised in the past 15
years but equates to 1.35 million children born each
year with congenital heart disease. The prevalence was
higher in Europe than in North America.
An increased risk of congenital heart disease was
seen with assisted reproductive techniques using data
from the Paris Registry of Congenital Malformations3.
The higher risk varied with the method of assisted reproductive technique and the type of cardiac abnormality. The authors speculate that this may be due to the
reproductive technology or to the underlying reason
for infertility of the couple.

GENETICS
Three-quarters of patients with 22q11.2 deletion syndrome (22q11.2DS) have congenital heart disease and
* As previously published in Heart (2012). doi:10.1136/
heartjnl-2011-301538
1
Great Ormond Street Hospital, London, UK
2
Department of Paediatric Cardiology, Royal Brompton Hospital, London,
UK

although it is common practice to test all children with


typical cardiac lesions for 22q11.2DS, many adult patients have not been investigated. An adult population
of 479 patients with typical lesions (tetralogy of Fallot
and pulmonary atresia and ventricular septal defect)
was reviewed4. Twenty patients were already known
to have 22q11.2DS but a microdeletion was detected
in a further 24 patients. The authors consider that as
the syndrome has important clinical and reproductive
implications, genetic testing should be considered in all
adult patients with tetralogy of Fallot and pulmonary
atresia with ventricular septal defect.
Tetralogy of Fallot is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1. TBX1 exons
were sequenced in 93 patients with non-syndromic tetralogy5. Single nucleotide polymorphism analysis was
performed in 356 patients with tetralogy, their parents
and healthy controls.
Three new variants not present in 1000 chromosomes from healthy ethnically matched controls were
identified. This study demonstrated that rare TBX1
variants with functional consequences are present in a
small proportion of patients with nonsyndromic tetralogy. The thorny issue of the use and interpretation of
genetic tests was reviewed by Caleshu et al.6.
Familial transposition of the great arteries was
shown to be caused by multiple mutations in the laterality genes7 in a study of seven families. This provides
evidence that some cases of familial transposition are
caused by mutations in laterality genes and therefore
are part of the same disease spectrum of heterotaxy
Contact address:
Dr Michael Burch, Great Ormond, Street Hospital, London WC1N3JH,
UK; burchm@gosh.nhs.uk

Michael Burch, Nathalie Dedieu


Almanac 2012: congenital heart disease

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

syndrome, and argues for an oligogenic or complex


mode of inheritance in these pedigrees. The editorial
by Keavney8 considered this a useful step forward in
understanding transposition. Homocysteine is known
to be an independent risk factor for congenital heart
disease and genetic abnormalities which affect homocysteine may be expected to influence the incidence of
congenital heart problems.
This was demonstrated when a functional variant in
methionine synthase reductase intron-1 significantly
increased the risk of congenital heart disease in the
Han Chinese population9.

FETAL CARDIOLOGY
Fetal cardiology remains a cornerstone of congenital heart practice. The paper by Marek et al.10 offered
a unique overview of prenatal diagnosis in the Czech
republic, which by virtue of the strict organisation of
the health service enabled a comprehensive national
registry to develop over two decades. There were some
particular successes and in recent years antenatal diagnosis of hypoplastic left heart reached 95.8%, whereas
transposition was diagnosed in only 25.6% of cases.
Whether the antenatal development of the cardiac
chambers is dependent on flow is debated, but an elegant paper by Stressig et al from Bonn11 demonstrated
that preferential flow to the right heart in the setting of
a diaphragmatic hernia does impair left heart development.
Isolated fetal atrioventricular block was reviewed
in a retrospective European study of 175 cases12. Risk
factors for poor outcome were gestation <20 weeks,
ventricular rate <50/min., hydrops and impaired ventricular function. No significant effect of treatment
with corticosteroids was seen. In a multicentre French
study13, 141 patients with non-immune atrioventricular block, diagnosed in utero or up to age 15 years, were
followed up long term and showed surprisingly good
outcomes, with no deaths or dilated cardiomyopathy at
a mean follow-up of 11.66.7 years.
Atrioventricular block can reflect prenatal exposure
to maternal anti-SSA/Ro antibodies and the high mortality associated with cardiac neonatal lupus has been
shown14. In a nonrandomised multicentre study of 20
fetuses exposed to maternal lupus antibodies15 it was
found that treatment with intravenous gamma globulin
and steroids potentially improved the outcome for these children, with better than expected survival. However, a prospective study of 165 fetuses with exposure
to anti-Ro/La antibody found that fetal atrioventricular

prolongation did not predict progression to heart block


so management based on the strategy of identifying
and treating fetal atrioventricular prolongation was questioned16.
Transplacental drug treatment for fetal tachyarrhythmias was reviewed in a multicentre study17, which
showed the superiority of flecainide and digoxin; however, the study was weakened by being non-randomised.

CARDIOMYOPATHY, HEART FAILURE AND


TRANSPLANTATION
Pre-participation screening for cardiomyopathy is gaining more attention in the media. An Italian study on
the value of preparticipationscreening of children with
ECGs demonstrated that postpubertal persistence of
Twave inversion was associated with an increased risk
of cardiomyopathy18.
When to propose transplantation remains difficult
in ambulatory patients. The risk of death and transplantation in paediatric dilated cardiomyopathy was
reviewed in a multicentre database, and the authors
showed that an increased left ventricular enddiastolic
dimension was associated with increased risk of transplantation but not death19. Work by Giardini et al.20
has shown that metabolic exercise testing is useful in
predicting prognosis, but the percentages of predicted
values are better than absolute numbers. Transplantation for congenital heart disease is generally considered
higher risk, although encouraging results were shown
in a small adult congenital transplant series from the
UK21. An American database review of over a thousand
transplants for adult congenital heart disease confirmed the high 30-day mortality, but better late survival
after transplantation. Although heart transplants remain a precious resource, at present the results justify the
continued expansion of adult congenital heart transplant programmes22.
An international database showed that extracorporeal membrane oxygenation does not appear to be
a reliable long-term circulatory support for children
awaiting heart transplantation23. Fortunately, other options of support exist, and Stiller et al.24 provide a useful overview of mechanical cardiovascular support in
infants and children.

THE SINGLE VENTRICLE


Patients with a single ventricle remain a great focus for
congenital heart disease resources. Many controversies
exist about the management of these patients. ACE inhibitors are often used in this complex circulation, but

Michael Burch, Nathalie Dedieu


Almanac 2012: congenital heart disease

the effects of their vasodilatation are unclear. Work in


children with bidirectional cavopulmonary shunts demonstrated that enalaprilat did not increase total cardiac output but redistributed flow to the lower body, with
a concomitant decrease in arterial oxygen saturation25.
The authors concluded that it is difficult to increase cardiac output in these patients and ACE inhibitors should be used with caution in those with borderline aortic
saturations. This work fits rather well with the results
of a randomised multicentre trial, which found administration of enalapril to infants with single-ventricle
physiology in the first year of life did not improve somatic growth, ventricular function or heart failure severity26. In a further analysis of their study population,
the authors have also shown that the renin aldosterone
genotype influences ventricular remodelling in infants
with a single ventricle27.
The late outcomes after the Fontan operation remain
a concern.In some patients there is a progressive failure
of the circulationover time, the underlying pathophysiology of which is not fully understood. In a review of
the current evidence for alterations in the pulmonary
vasculature in Fontan patients, the potential of treatments approved for pulmonary arterial hypertension
which may provide benefits was discussed28. Liver disease is now recognised as a serious problem late after
a Fontan operation. Hepatic dysfunction and cirrhotic
change were often seen in a series of Fontan patients29.
Hepatic complications were correlated with the duration of Fontan circulation. The authors concluded that
these patients need regular evaluation of hepatic function, although some non-invasive hepatic fibrosis markers can be used effectively.
At a recent consensus meeting on this problem the
group recommended a prospective study protocol on
the assessment of hepatic function 10 years after a Fontan operation30.
The use of anticoagulation after a Fontan operation
remains controversial. A multicentre randomised study
of warfarin or heparin after a Fontan procedure was
reported31. A total of 111 patients were randomised.
There was a similar, but very, incidence of thrombosis
in both groups: 12/57 with aspirin and 13/ 54 in the
warfarin group. Although there were no differences,
the authors concluded that as the thrombosis rate was
so high, alternative approaches should be considered.
Another Fontan controversy involves the use of fenestrations as although they may improve early surgical results, there is concern about late complications.
The late results for fenestration of the systemic venous

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Vol. 23, No. 1, 2013

pathway at the time of the Fontan operation were reported in a multicentre retrospective nonrandomised
study32. Of the 361 fenestrations, there were few deleterious later outcomes a mean of 863 years after surgery.
Saturations were 89% versus 95% in the fenestrated
group.

IMAGING
Three-dimensional echocardiography is developing
rapidly and its application to congenital heart disease may be one of its key uses in future years33. Other
emerging imaging methods include a new high-resolution ultrasound technique34. The authors described
the technique in adolescents after coarctation repair in
early childhood and demonstrated increased preductal
arterial intima media thickness, left ventricular mass
and ascending aortic stiffness in adolescents. The more
pronounced cardiovascular abnormalities after coarctation stent implantation were felt to be related to older
patient age at the time of intervention.

SURGERY
The Dutch Congenital Corvitia (CONCOR) registry
for adults with congenital heart disease was reviewed
for the results of surgery in predominantly young
adults with congenital heart disease35. One-fifth required cardiovascular surgery during a 15-year period
and in 40% the surgery was a reoperation. Men with
congenital heart disease had a higher chance of undergoing surgery in adulthood and had a consistently worse long-term survival after reoperations in adulthood
than women.
Detailed functional outcomes 8.1 years (range 2.014.0) after the Ross operation were reported in 45 subjects (aged 24.6 years, range 16.9-52.2 years) who underwent the Ross procedure between 1994 and 2006.
Cardiovascular magnetic resonance imaging, echocardiography and cardiopulmonary exercise testing were
used36. The authors demonstrated minor autograft and
homograft dysfunction in the majority of patients after
the Ross procedure, associated with good ventricular
function and exercise capacity. Late survival was compared in a study of 918 Ross patients and 406 mechanical valve patients 18-60 years of age who survived an
elective procedure (1994-2008). With the use of propensity score matching, late survival was compared
between the two groups37. In comparable patients, there was no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoa-

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Vol. 23, No. 1, 2013

gulation self-management. The authors demonstrated


that survival in these selected young adult patients was
excellent, perhaps as a result of highly specialised anticoagulation self-management, better timing of surgery
and improved patient selection in recent years. Despite
the advent of the Ross operation, aortic valve surgery
in children remains a complex and difficult area and a
useful overview was provided by dUdekem38.
In a report of neurodevelopmental risk from surgery39, neuropsychological and structural brain imaging assessments in children 16 years of age with transposition of the great arteries who underwent the arterial switch operation as infants were reviewed. Children
were randomly assigned to total circulatory arrest or
continuous low-flow cardiopulmonary bypass but few
significant differences between the treatment group
were found. However, adolescents with transposition
of the great arteries who have undergone the arterial
switch operation are at increased neurodevelopmental
risk. The authors consider that children with congenital
heart disease may benefit from ongoing surveillance to
identify emerging difficulties.

TETRALOGY OF FALLOT
A study using speckle tracking data in patients with
corrected tetralogy of Fallot demonstrated that right
ventricular outlet deformation is delayed, causing a reduction in right ventricular time delay which is significantly related to impairment in right ventricular performance40. Late right heart failure is a serious problem
in tetralogy and congenitally corrected transposition.
In a study of 40 of these patients, with myocardial
contrast echocardiography it was found that right ventricular myocardial microvascular density of the septal
wall in patients with hypertrophy due to pressure and/
or volume overload is reduced.
The authors considered that this may be related to
a reduced myocardial perfusion reserve and impaired
right ventricular systolic function41. A report on the
impact of restrictive physiology on right ventricular
function after repair of tetralogy found that diastolic
right ventricular stiffness was increased42. However, the
lusitropic response to b adrenergic agents was abnormal regardless of restrictive physiology. In an investigation of 29 asymptomatic children with repaired tetralogy43, despite moderate right ventricular dilatation
and right bundle branch block compared with controls, the authors demonstrated neither right ventricular
nor left ventricular dyssynchrony at rest but exercise
induced mechanical dyssynchrony. This was unrelated

Michael Burch, Nathalie Dedieu


Almanac 2012: congenital heart disease

to QRS duration, ventricular volumes and function, or


peak oxygen consumption. In a study of repaired adult
tetralogy, left ventricular longitudinal dysfunction was
associated with greater risk of sudden cardiac death or
life-threatening arrhythmias44. The authors conclude
that in combination with echocardiographic right heart
variables, these measures provided important outcome
information for estimating prognosis.

PULMONARY HYPERTENSION
Further evidence of the benefits of pulmonary vasodilators in Eisenmenger syndrome was provided in a prospective open-label study of sildenafil in 84 patients45.
Twelve months of oral sildenafil treatment was well
tolerated and appeared to improve exercise capacity,
systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome. The importance of pulmonary vasoreactivity as an
independent predictor of outcome in 38 patients with
Eisenmenger receiving bosentan was reported46.
A unique national patient cohort of childhood pulmonary hypertension was reported from the UK47. The
authors showed, for the first time, that the incidence
of pulmonary hypertension is lower in children than
adults and that the clinical features can be different.
Most children present with clinical evidence of advanced disease, and clinical status at presentation is predictive of outcome. This 7-year experience confirmed
the significant improvement in survival over historical controls. The same group also reported a new CT
approach to prognosis48. They found that fractal branching quantifies vascular changes and predicts survival
in pulmonary hypertension. The need for paediatric
drug development for pulmonary hypertension was
emphasised by Barst49. A study of patients with Eisenmenger syndrome (n=181, age 36.912.1 years, 31%
with Downs syndrome), in whom B-type natriuretic
peptide (BNP) concentrations were measured as part of
routine clinical care, found they predicted outcome50.
In addition, the authors speculated that disease-targeting treatments may help to reduce BNP concentrations in this population, while treatment-naive patients
have static or rising BNP concentrations. This topic was
discussed in more detail in an editorial by DAlto51.

ARTERIAL ABNORMALITIES IN CONGENITAL HEART


DISEASE
While aortic wall abnormalities have been described in
inherited connective tissue disorders such as Marfan
syndrome and bicuspid aortic valve disease52,53, recent

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Almanac 2012: congenital heart disease

reports indicate similar aortic involvement in classical


congenital heart disease entities such as coarctation of
the aorta, tetralogy of Fallot and transposition of the
great arteries; MRI is central in defining the problem54.
Pulmonary artery dilatation is seen with pulmonary
valve abnormalities and connective tissue disease, but
also occurs in association with bicuspid aortic valve, in
the absence of a pulmonary valve abnormality, suggesting a primary vessel wall pathology predisposing to
arterial dilatation55.

CATHETER INTERVENTION
With the increased use of interventional cardiological procedures in the young it is clearly important to
consider radiation exposure. Data from Italy raised a
concern that children with congenital heart disease are
exposed to a significant cumulative dose of radiation56.
Indirect cancer risk estimations and direct DNA studies
showed that children with congenital heart disease are
exposed to a significant radiation dose and emphasised
the need for strict radiation dose optimisation in children. The accompanying editorial from Hoffmann and
Bremerich expanded on the risks57.
New developments in catheterisation techniques
continue. A prospective, randomised, multicentre, investigational device exemption trial in America compared the use of cutting balloons with high-pressure
balloons in treating pulmonary artery stenosis. The
authors found a greater efficacy for cutting balloons
and a similar safety profile58. Data from the UK on
over 100 stent procedures for coarctation from a single
centre59, demonstrated that stenting for aortic coarctation and re-coarctation is effective with loweimmediate complication rates. Postprocedural aneurysm was
rare and stent fractures were not seen with the newergeneration stents. The optimal method of follow-up of
these patients is unclear with both CTand MRI considered useful60. A multicentre observational study from
the USA reported data from 350 children with native
coarctation >10 kg61. There were 217 stents, 61 balloon
angioplasties and 72 surgical procedures.
Stenting and surgery were better than balloon angioplasties in reducing upper limb to lower limb blood pressure gradient at short-term follow-up and had better
integrated aortic arch imaging outcomes. Stent patients
had the shortest stay and the lowest complication rate,
although they were more likely to require a planned intervention. The authors cautioned over interpretation
of the results as the study was not randomised. Balloon
angioplasty for aortic arch obstruction is commonly

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Vol. 23, No. 1, 2013

needed after the Norwood procedure, and results from


a retrospective review62 reported that only 58% of those having an initial balloon angioplasty were free from
arch reintervention at 5 years, with the greatest risk of
reintervention in those < 3 months at initial intervention and those with less successful initial results.
Roberts et al.63 report multicentre experience of successful percutaneous tricuspid valve replacement using
the Melody valve in 15 patients. All patients had a prior
bioprosthetic valve or conduit in place and had developed significant stenosis or regurgitation. Encouraging
results were reported with the Edwards SAPIEN transcatheter valve for conduit failure in the pulmonary position in 36 patients from four centres.64 Helpful images of this device were published by Lauten et al.65. The
outcomes of pre-stenting 1 year after using the Melody
valve in the pulmonary position66 were reported in 65
patients. The early haemodynamic results were sustained at 1 year, but there was no evidence of further positive functional remodelling after the immediate acute
effects.
The strategies surrounding cardiac pacing in infants
and children are often debated. A recent multicentre
study showed that left ventricular pacing was associated with better systolic function than right ventricular pacing67, and a useful review put the problems of
pacing in children into context68.

ADULT CONGENITAL HEART DISEASE


The expanding population of adults with congenital
heart disease is reflected in the increasing numbers
of publications in this field. The emerging burden of
hospital admissions of adults with congenital heart disease was described using a Dutch national registry69.
During 28 990 patient-years, 2908 patients (50%) were
admitted to hospital. Median age at admission was 39
years (range 18e86). Admission rates were at least two
times higher than in the general population, and most
marked in the older-age groups. With the ageing of this
population, the authors advocate timely preparation of
healthcare resources.
A paper from Toronto described the respiratory
and skeletal muscle weakness in adults with congenital
heart disease which resembles that seen in older adults
with advanced heart failure70. The importance of this
shift in focus in the mechanisms of reduced exercise tolerance in congenital heart disease is further discussed
in the editorial by Giardini71. Biomarkers may also
have an important role in assessment of these patients.
The relationship of systemic right ventricular function

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Vol. 23, No. 1, 2013

to ECG and NT-proBNP levels in adults late after the


Senning or Mustard procedure was investigated72. Circulating NT-proBNP levels and several surface ECG
parameters were shown to constitute surrogate markers
of systemic right ventricular function and provide additional information on heart failure status. Although paediatricians are well aware of the association of Downs
syndrome and congenital heart disease, information
from the Netherlands documented that 17% of patients
with Downs syndrome living in residential centres had
undiagnosed congenital heart disease. Thirty-one centres and 1158 patients were included in the first stage of
the study73. The authors recommend cardiac screening
in older patients with Downs syndrome, for whom new
therapeutic options are available, and for prevention of
cardiac complications in old age.
Stroke was a major cause of morbidity in adult
congenital heart disease in a retrospective analysis of
aggregated European and Canadian databases74 with a
total of 23 153 patients aged 16-91 years (mean 36.4).
Among them, 458 patients (2.0%) had one or more cerebrovascular accident. The highest prevalence was in
cyanotic lesions 50/215 (23.3%).
A meta-analysis and systematic review of atrial septal defect closure identified 26 studies including 1841
patients who underwent surgical closure and 945 who
underwent percutaneous closure75. Meta-analysis using
a random effects model demonstrated a reduction in
the prevalence of atrial tachyarrhythmias after atrial
septal defect closure (OR=0.66 (95% CI 0.57 to 0.77)).
This effect was demonstrated after both percutaneous and surgical closure. Immediate (< 30 days) and
mid-term (30 days5 years) follow-up also showed a
reduction in the prevalence of atrial tachyarrhythmias.
Inuzuka et al reviewed data of 1375 consecutive
adult patients with congenital heart disease (age 3313
years) who underwent cardiopulmonary exercise testing at a single centre over a period of 10 years76. They
showed that cardiopulmonary exercise testing provides
strong prognostic information in adult patients with
congenital heart disease. However, they considered
prognostication should be approached differently, depending on the presence of cyanosis, use of rate-lowering drugs and achieved level of exercise.

PREGNANCY AND CONGENITAL HEART DISEASE


Heart disease has become the major factor in maternal mortality during pregnancy in developed countries. The increasing number of women with congenital
heart disease surviving to adult life has made care in

Michael Burch, Nathalie Dedieu


Almanac 2012: congenital heart disease

pregnancy for this group an important area of obstetric


cardiology. The care needed for this vulnerable group
has been highlighted77. The outcomes of 405 pregnancies of women with congenital heart disease were investigated and late cardiac events investigated78. While
adverse events during pregnancy are well known, the
problem of late cardiac events after pregnancy is less
well known. The authors found pre-pregnancy maternal characteristics can help to identify women at increased risk for late cardiac events. Adverse cardiac events
during pregnancy were also important and are associated with an increased risk of late cardiac events. Opotowsky et al used the US nationalregistry of hospital
admissions to assess annual deliveries for women with
congenital heart disease79. These increased 34.9% from
1998 to 2007 compared with an increase of 21.3% in the
general population. Women with congenital heart disease were more likely to sustain a cardiovascular event
(4042/100 000 vs 278/100 000 deliveries); arrhythmia
was the most common cardiovascular event. Death
occurred in 150/100 000 patients with congenital heart
disease compared with 8.2/100 000 patients without.
Complex disease was associated with greater odds of
having an adverse cardiovascular event than simple
congenital heart disease (8158/100 000 vs 3166/100
000, multivariable OR=2.0, 95% CI 1.4 to 3.0).
Lui et al. investigated heart rate response during
exercise and pregnancy outcome in women with congenital heart disease80. Peak heart rate, percentage of
maximum age predicted heart rate and chronotropic
index were associated with a cardiac event. Neonatal
events occurred in 20%. Peak oxygen consumption was
not associated with an adverse pregnancy outcome.
The authors concluded that an abnormal chronotropic
response correlates with adverse pregnancy outcomes
in women with congenital heart disease and should be
considered in refining risk stratification schemes.

GLOBAL BURDEN OF CARDIOVASCULAR DISEASE


Congenital heart disease in developing countries is
clearly important as the great majority of patients are
born there. A concerning finding from New Delhi81
is that female gender is an important determinant of
non-compliance with paediatric cardiac surgery. Their
prospective study of 405 cases included indepth interviews. They concluded that deep-seated social factors
underlie this gender bias. An interesting overview of
this problem is given by Daljit Singh and colleagues82.
In a developed country (Taiwan) an investigation of
289 patients with adult congenital heart disease found

Michael Burch, Nathalie Dedieu


Almanac 2012: congenital heart disease

that female gender was associated with poor physical


and psychological quality of life83. The common denominators for quality of life were primarily personality
trait, psychological distress and family support, but interestingly, not disease severity.
A patent ductus is an easily treatable lesion but, if
untreated, large ducts can lead to pulmonary vascular disease. Late presentation in developing countries
means that many patients have a level of pulmonary
hypertension that could make intervention dangerous.
The results from a study in Mexico84 are important and
encouraging. They reported 168 patients with isolated
patent ductus arteriosus (PDA) and pulmonary artery
systolic pressure $50 mm Hg. Mean age was 10.314.3
years (median 3.9), PDA diameter was 6.42.9 mm
(median 5.9), pulmonary artery systolic pressure was
63.516.2 mm Hg (median 60), The overall success
rate was 98.2%. Follow-up in 145 (86.3%) cases for
37.1+/24 months (median 34.1) showed further decrease of the pulmonary pressure to 30.17.7 mm Hg
(p <0.0001). The authors have shown that in selected
cases percutaneous treatment of hypertensive ductus is
safe and effective and that pulmonary pressures decrease immediately and continue to fall with time.

IMAGES OF CONGENITAL HEART DISEASE


Perhaps one of the most alluring aspects of congenital
heart disease is the aesthetics of the abnormalities. This
lends itself to imaging, and congenital heart images
brighten up the pages of many major cardiac journals.
Therefore it seems appropriate to end this Almanac
with reference to some of the more stunning images
that reflect the key areas in congenital heart disease
that were discussed above, including intervention85-91,
fetal and neonatal92-95, heart failure and mechanical
support96, adolescent and adult congenital heart disease97,98, advanced imaging with MRI and CT99,100 and
unusual morphology101-107. All of which are well worth
a look to brighten up a night catching up on the cardiac
journals.
Contributors MB and ND carried out the literature
review; MB wrote the first draft of the manuscript, which was revised and approved by both authors.
Competing interests: None.
Provenance and peer review: Commissioned; internally peer reviewed.
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Almanac 2012: congenital heart disease
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67. van Geldorp IE, Delhaas T, Gebauer RA, et al. Impact of the permanent ventricular pacing site on left ventricular function in children:
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68. McLeod KA. Cardiac pacing in infants and children. Heart 2010;96:
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69. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. The emerging
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Heart 2010;96:872-8.
70. Greutmann M, Le TL, Tobler D, et al. Generalised muscle weakness in
young adults with congenital heart disease. Heart 2011;97:1164-8.
71. Giardini A. Generalised myopathy in young adults with congenital
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72. Plymen CM, Hughes ML, Picaut N, et al. The relationship of systemic
right ventricular function to ECG parameters and NT-proBNP levels
in adults with transposition of the great arteries late after Senning or
Mustard surgery. Heart 2010;96:1569-73.
73. Vis JC, de Bruin-Bon RH, Bouma BJ, et al. Congenital heart defects
are underrecognised in adult patients with Downs syndrome. Heart
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74. Hoffmann A, Chockalingam P, Balint OH, et al. Cerebrovascular accidents in adult patients with congenital heart disease. Heart 2010;
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75. Vecht JA, Saso S, Rao C, et al. Atrial septal defect closure is associated with a reduced prevalence of atrial tachyarrhythmia in the short
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76. Inuzuka R, Diller GP, Borgia F, et al. Comprehensive use of cardiopulmonary exercise testing identifies adults with congenital heart disease at increased mortality risk in the medium term. Circulation 2012;
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77. Kaleschke G, Baumgartner H. Pregnancy in congenital and valvular
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78. Balint OH, Siu SC, Mason J, et al. Cardiac outcomes after pregnancy
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79. Opotowsky AR, Siddiqi OK, DSouza B, et al. Maternal cardiovascular
events during childbirth among women with congenital heart disease.
Heart 2012;98:145-51.
80. Lui GK, Silversides CK, Khairy P, et al. Heart rate response during
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81. Ramakrishnan S, Khera R, Jain S, et al. Gender differences in the utilisation of surgery for congenital heart disease in India. Heart 2011;97:
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82. Singh D, Wander GS, Singh RJ. Gender equality in India for children
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83. Chen CA, Liao SC, Wang JK, et al. Quality of life in adults with congenital heart disease: biopsychosocial determinants and sex-related
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85. Mullens W, Dubois C, De Keyser J. Images in cardiology: coronary
fistula: a rare case of right heart failure. Heart 2005;91:1329.
86. Tzifa A, Razavi R. Test occlusion of Fontan fenestration: unique contribution of interventional MRI. Heart 2011;97:89.
87. MacDonald ST, Arcidiacono C, Butera G. Fenestrated Amplatzer
atrial septal defect occluder in an elderly patient with restrictive left
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88. De Vlieger G, Budts W, Dubois CL. Images in cardiology: Horner
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89. Mitchell G, Loo B, Morgan-Hughes G. Atrial septal defect closure device, a threedimensional volume render. Heart 2010;96:1222.
90. Bartel T, Bonaros N, Mller S. Device failure weeks to months after
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91. Deo SV, Burkhart HM, Ammash N, et al. Successful hybrid rescue of
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92. Padalino MA, Vida VL, Bhattarai A, et al. Giant intramural left ventricular rhabdomyoma in a newborn. Circulation 2011;124:2275-7.
93. Battista Danzi G, Salice P, Mosca F. Double aortic arch in neonates:
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95. Sridharan S, Dedieu N, Marek J. Images in cardiology: power doppler
threedimensional visualisation of aortic arch interruption in fetal life.
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96. Arendt K, Doll S, Mohr FW. Failing mustard circulation with secondary pulmonary hypertension: mechanical assist device to achieve
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97. Farahmand P, Redheuil A, Chauvaud S, et al. Images in cardiovascular medicine: septic pulmonary thromboemboli in an adolescent with
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98. Radojevic J, Redheuil A, Iserin L. Pulmonary atresia with intact ventricular septum and diastolic liver expansion. Heart 2011;97:1813-14.
99. Gulati A, Gheta R, Chan CF, et al. Longitudinal follow-up of a right
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100. Fukui D, Kai H, Takeuchi T, et al. Longest survivor of pulmonary
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101. Defaye P, Kane A, Jacon P. An unusual connection of the right and
left inferior pulmonary veins in the left atrium via a common ostium.
Heart 2010;96:1951.
102. Lee MS, Pande RL, Rao B, et al. Cerebral abscess due to persistent
left superior vena cava draining into the left atrium. Circulation 2011;
124:2362-4.
103. Chaowu Y, Xin S, Shihua Z, et al. Complete transposition of the atrioventricular valves associated with left ventricular apical hypoplasia.
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104. Cheng ST, Lan CC. Obstructive sleep apnoea syndrome related to
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105. Jayan JP, Vijayalakshmi IB, Narasimhan C. Images in cardiology: a
rare anomaly: hemitruncus. Heart 2011;97:12.
106. Jang SW, Rho TH, Kim JH. Membranous interventricular septal aneurysm resulted in complete atrioventricular block. Heart 2010;96:244.
107. Salahuddin S, Ramakrishnan S, Bhargava B. Classic supravalvular
aortic stenosis. Heart 2010;96:1808.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

REVIEWS

Almanac 2012, cell therapy in cardiovascular disease: the national


society journals present selected research that has driven recent
advances in clinical cardiology*
D. A. Jones1,2,3, Fizzah Choudry1,3, A. Mathur1,2,3
Article received on the 25th of September 2012. Article accepted on the 29th of September 2012.
Abstract: The rapid translation from bench to bedside that has been seen in the application of regenerative medicine to
cardiology has led to exciting new advances in our understanding of some of the fundamental mechanisms related to human
biology. The first generation of cells used in phase I-II trials (mainly bone marrow mononuclear cells) are now entering phase III clinical trials with the goal of producing a cell based therapeutic that can change the outcome of cardiac disease. First
generation cell therapy appears to have addressed safety concerns as well as showing activity in numerous published metaanalyses. With the knowledge gained to date, the field is moving towards the next generation of cells-the engineered cell-that
have been developed to display a phenotype that will further enhance the myocardial repair/salvage process. This almanac
review covers the latest basic research that may soon have application to humans as well as the results of the latest clinical trials.

UPDATE ON CELL THERAPY FOR THE TREATMENT OF


CARDIOVASCULAR DISEASE
Cell therapy is one of the most important new horizons in cardiovascular disease. It offers new opportunities to develop therapeutics that could revolutionise
the way we treat patients and a field of research that
combines an increased understanding of the pathophysiology of the cardiovascular disease with some of the
most basic biological concepts involved in embryology.
The resultant growth of preclinical research in the cardiovascular system and the rapid translation into humans have led to benefits for human biology as a whole. The field is rapidly advancing; here, we present key
developments in the last 2 years. In order to reflect the
synergy between basic and translational research, this
review is therefore divided into two sections.

BASIC SCIENCE UPDATE ON CELL THERAPY


INCARDIOVASCULAR DISEASE
New models enhancing our understanding of
regeneration
Zebrafish
There is a long history of research on amphibian heart
regeneration with the most adopted model the zebra* As previously published in Heart (2012). doi:10.1136/
heartjnl-2011-301540
1
Department of Cardiology, London Chest Hospital, London, UK
2
Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University, London, UK
3
NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital,
London, UK

fish given its substantial regenerative capacity and amenability to genetic manipulation.
The zebrafish heart fully regenerates after the surgical amputation of the cardiac apex: an injury that
corresponds to a loss of approximately 20% of the total
ventricular mass1. Initial experiments suggested that
undifferentiated progenitor cells were the principal
source of regenerating cardiomyocytes in zebrafish;
however, two recent gene mapping studies clearly demonstrate that preexisting committed cardiomyocytes
are instead the main source2,3. These two groups independently generated transgenic zebrafish in which the
cardiomyocyte-specific cmlc2 (also known as myl7)
promoter drives the expression of tamoxifen-inducible
Cre recombinase. These animals were crossed with a
reporter line in which Cre-mediated excision of a loxPflanked stop sequence induces constitutive expression
of green fluorescent protein (GFP). In the offspring of
this cross, all pre-existing cardiomyocytes and their
progeny were induced to express GFP by tamoxifen
treatment. Therefore, if the regenerated myocardium
was derived from undifferentiated progenitor cells, the
new ventricular apex should be GFP. Instead, both
groups found that the vast majority of the newly regenerated cardiomyocytes were GFP+, suggesting that the
Contact address:
Professor Anthony Mathur, Department of Cardiology, London Chest
Hospital, Bonner Road, Bethnal Green, London E2 9JX, UK; E-mail:
a.mathur@qmul.ac.uk

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

heart regeneration in zebrafish is principally mediated


by the proliferation of pre-existing cardiomyocytes.
This is contrary to the previously held belief that the
generation of new cardiomyocytes from stem cells was
the underlying aetiology.
Mice versus zebrafish
Although they lack the regenerative capacity of the
zebrafish heart, postnatal mammalian hearts also undergo a degree of cardiomyocyte renewal during normal ageing and disease. Recently, a study4 showed that
the differences between mammalian and fish hearts
may not necessarily apply early in development. Using
approaches from the zebrafish model, the authors resected the left ventricular (LV) apex of 1-day-old neonatal mice and observed a brisk regenerative response
similar to that in the adult zebrafish. By 3 weeks after
injury, the defect had been replaced by normal myocardial tissue, which showed normal contractile function
by 8 weeks. Genetic fate mapping studies indicated that
this regeneration was mediated by the proliferation of
pre-existing cardiomyocytes, again as in the zebrafish.
Notably, this regenerative capacity was not observed in
7-day-old mice, suggesting that its loss may coincide
with cardiomyocyte binucleation and reduced cell-cycle activity. Nonetheless, this study indicates that zebrafish-likeprovides a genetically tractable model for
dissecting the blocks to these mechanisms in the mammalian adult.
Alternative sources of cardiomyocytes: new
concepts and advanced understanding
Fibroblasts as source of cardiomyocytes
It has recently been demonstrated that fibroblasts in
infarcts could potentially be reprogrammed directly to
cardiomyocytes. Fifteen years ago, researchers showed that fibroblasts could be differentiated into skeletal
muscle in vitro or in the injured heart by overexpressing the gene encoding the myogenic transcription factor, MyoD. However, despite extensive work, no comparable master gene for cardiac muscle was found, and
interest in reprogramming waned. Spurred by the discovery of induced pluripotent stem cells (iPSCs), scientists have now returned to this field, using combinations of transcription factors to reactivate core transcriptional networks of desired cell types. In the last 2 years,
two groups have made progress to this goal. The first
group5 screened a total of 14 cardiac transcription factors finding that a specific combination of three transcription factors, Gata4, Mef2c and Tbx5, was sufficient
to generate functional beating cardiomyocytes directly

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Vol. 23, No. 1, 2013

from mouse postnatal cardiac or dermal fibroblasts and


that the induced cardiomyocytes were globally reprogrammed to adopt a cardiomyocyte-like gene expression profile. These factors activated the transgene in 20%
of fibroblasts of which approximately 4% of the cells
expressed endogenous sarcomeric proteins such as
cardiac troponin T, with ~1% showing functional properties such as spontaneous beating. Thus, most of the
cells were only partially reprogrammed, although their
global gene expression patterns had shifted markedly
from fibroblast to cardiomyocyte.
The second group6 used a different method of reprogramming mouse embryonic fibroblasts to cardiomyocytes. They used the Yamanaka factors OCT4 (also
known as POU5F1), SOX2, KLF4 and c-MYC to
initiate reprogramming, but then blocked signalling
through the JAK-STAT pathway, which is required for
pluripotency in the mouse, and added the cardiogenic
factor BMP4. These modifications yielded minimal
generation of iPSCs, but instead activated the cardiac
progenitor programme and, within 2 weeks, generated
substantial numbers of beating colonies. By 18 days after induction, approximately 40% of the cells expressed
cardiac troponin T. It should be noted that this study
used mouse embryonic fibroblasts, whereas Leda et al.5
principally used postnatal mouse cardiac fibroblasts.
Reprogramming the scar-forming fibroblast to a cardiomyocyte is appealing, particularly if it can be done
directly in the infarct. To succeed clinically, we need
to know how normal these reprogrammed cardiomyocytes are, and the process will have to be much more
efficient and transgene-free.
Induced pluripotent stem cells
A recent report in this journal drew attention to the
great promise of iPSC (reprogrammed somatic cells) as
a renewable source of autologous cells7. These cells were
first discovered only 5 years ago by Takahashi and Yamanaka8 following the introduction of genes into adult
mouse cells reprogramming them to resemble embryonic stem (ES) cells. Given that the DNA of such cells
is identical to that of the patient, it has been assumed
that they would not be attacked by the immune system
although their immunogenicity has not been vigorously examined. However, a study9 published in Nature in
2011 showed that in a mouse transplantation model,
some iPS cells are indeed immunogenic, raising concerns about their therapeutic use. This study examined
the immunogenicity of mouse iPS cells, using a teratoma-formation assay. They injected iPS cells into mice

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that were either immune-compromised or genetically


matched with the donor cells. This normally results
in the formation of benign tumours called teratomas,
which consist of many types of differentiated cells. The
approach was validated using a line of genetically matched (autologous) ES cells which gave rise to teratomas,
whereas a line of unmatched ES cells was rejected before teratomas were produced. The transplantation of
autologous iPS cells derived from fetal fibroblasts into
matched mice resulted in the rejection of teratomas,
irrespective of the approach used to generate the IPS
cells, indicating that, in this assay, matched iPS cells are
more immunogenic than matched ES cells.
The study also identified the antigens that may have
caused immune rejection of the iPS cells, discovering a
group of nine genes that were expressed at abnormally
high levels. Inducing the expression of three of these
genes (Hormad1, Zg16 and Cyp3a11) in the non-immunogenic ES cells significantly impaired the cells
ability to form teratomas on transplantation into genetically matched mice. This study provides more questions than answers with many limitations in relation
in clinical studies; however, it highlights that a great
deal needs to be understood about the mechanisms
underlying cellular reprogramming and the inherent
similarities and differences between ES cells and iPS
cells.
Adjunctive therapies to improve stem cell
differentiation
As a related spin-off to cell therapy, two new approaches to cardiac repair have been reported.
Thymosin 4
One of the most exciting developments in regenerative
medicine over the past 2 years has been the identification of bona fide source of myocardial progenitors
(epicardial derived cells)10 which can be induced by
thymosin 4 to differentiate into cardiomyocytes. This
landmark study by Smart et al.11 provides a major step
forward in identifying a viable source of stem/progenitor cells that could contribute to new muscle after
ischaemic heart disease and acute myocardial infarction (AMI). They demonstrated that in a mouse model the adult heart contains a resident progenitor cell
population, which has the potential to become terminally differentiated cardiomyocytes after MI. Progenitor cells were primed with a peptide called thymosin
4 which induced embryonic reprogramming resulting
in the mobilisation of this population and subsequent
differentiation to give rise to de novo cardiomyocytes.

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

Following experimentally induced MI, these cells were


shown to migrate to the site of injury and then differentiate without any evidence of cellular fusion into structurally and functionally active cardiomyocytes.
These cardiomyocytes showed evidence of gap junction formation with adjacent cells, synchronous calcium transients and the formation of operational contractile apparatus.
Despite a low overall fraction of these cells being
present at the site of injury and a relatively poor overall
efficiency of differentiation, serial MRI scans revealed
significant improvements in ejection fraction, cardiac
volumes and scar size in comparison with sham treated
animals. The pretreatment with thymosin 4 was crucial to these effects and may suggest a new strategy for
promoting myocardial repair in humans.
MicroRNAs
MicroRNAs (small non-coding RNAs) play a critical
role in differentiation and self-renewal of pluripotent
stem cells, as well as in the differentiation of cardiovascular lineage cells. As a result, microRNAs have emerged as potential modulators of stem cell differentiation;
specifically, miR-1 has been reported to play an integral role in the regulation of cardiac muscle progenitor
cell differentiation. A study published in 201112 looked
to take this one step further and assessed whether the
overexpression of miR-1 in ES cells (miR-1-ES cells)
enhances cardiac myocyte differentiation following
transplantation into the infarcted myocardium. In this
study, mice models of MI had miR-1-ES cells, ES cells or
culture medium (control) transplanted into the border
zone of the infarcted heart. Overexpression of miR-1 in
transplanted ES cells protected host myocardium from
MI-induced apoptosis through activation of -AKTand
inhibition of caspase-3, phosphatase and tensin homologue, and superoxide production. A significant reduction in interstitial and vascular fibrosis was quantified
in miR-1-ES cells compared with control MI. Finally,
mice receiving miR-1-ES cells had significantly improved heart function compared with respective controls.
This would suggest that miR-1 drives cardiac myocyte
differentiation from transplanted ES cells and inhibits
apoptosis post-MI; however, importantly with respect
to fibrosis no statistical significance between miR-1-ES
cell and ES cell groups was observed suggesting further
study in this area is needed. A review13 of the current
evidence for the role of microRNAs in stem/progenitor
cells and cardiovascular repair has recently been published.

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

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Vol. 23, No. 1, 2013

CLINICAL UPDATE ON CELL THERAPY IN


CARDIOVASCULAR DISEASE

lled trial in stem cell therapy for cardiac repair to date.


The original study that enrolled 204 patients with AMI
demonstrated a significantly greater improvement in
absolute LVEF in patients treated with BMMNCs compared with control at 4 months. As seen in BOOST, the
patients with larger infarcts derived the most benefit.
Although not sufficiently powered for the purpose, this
was the first large scale clinical endpoint data showing
mortality and morbidity benefit conferred by intracoronary administration of stem cells20. This was borne
out at 2 years with significant reductions in combined
clinical end point and increases in LV wall motion
when assessed on MRI in the patients who received
BMMNCs21. The 5-year follow-up data, presented at the
American Heart Association (AHA) Scientific Sessions
201122, included 100 patients in each treatment arm.
While there was only a trend towards improvement in
mortality, there was a significant reduction of the combined end point of death, recurrence of MI and revascularisation conferred by a single intracoronary infusion of cells.
Long-term follow-up data from 100 patients enrolled in the Autologous Stem-cell Transplantation in
Acute Myocardial Infarction (ASTAMI) trial showed
a significant improvement in exercise capacity in the
treated cohort at 3 years, although there was no significant difference in LVEF between treatment and placebo
arms.23 The 5-year follow-up for the BALANCE study
(Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction)
showed significant and sustained improvement in LV
function and reduction in mortality in 62 treated patients compared with 62 control patients. Although this
suggests a significant mortality benefit, it is noted that
this study was non-randomised24. Another large trial
(HEBE) consisting of 200 patients has also been published recently25 showing no significant improvement
in LV function in BMMNC treated patients compared
with placebo up to 4 months; however, the long-term
effects of cell therapy in this study are yet to be reported.
The majority of these studies are in the context of cell
administration 5-8 days following AMI. There is still a
need to define the optimal time point for cell transfer
relative to ischaemic insult. It is conceivable that the
improvement in LV function and outcome seen inconsistently between trials may be dependent on the
timing of cell transfer as the postinfarct myocardium
will have a changing inflammatory milieu. The later
time point of 2-3 weeks post-AMI is addressed by the

The translational path from preclinical observation to


new treatment development can take many years, even
decades. Ten years after the first clinical application
of stem cells in cardiac disease14, many questions regarding cell types and their administration have been
addressed and researchers are better understanding
this area of research and the challenges of translational
medicine.
Although many candidate cell types for myocardial repair exist, a pragmatic approach has been used in
clinical trials which have utilised autologous bone marrow mononuclear cells (BMMNCs) and some of the
component cell types found therein (haematopoeitic
stem cells, mesenchymal stem cells (MSCs) and endothelial progenitor cells) in the first steps into the clinical setting15. Recent years have seen several phase I-II
clinical trials of BMMNC transplantation in cardiac
disease which have demonstrated safety and feasibility
while reports of efficacy, although less consistent, have
provided grounds for further investigation.

RECENT DEVELOPMENTS IN THE USE OF


AUTOLOGOUSBMMNCS
The last 2 years has seen the some of the larger trials
examining BMMNCs in the setting of AMI report
long-term results confirming safety to 3-5 years. Reassuringly, recent meta-analyses to look at these studies
have again confirmed a small but important activity
of cell therapy in improving various surrogate parameters of cardiac function16,17.
The first randomised controlled trial of stem cell
therapy in AMI was the BOOST trial (BOne marrOw
transfer to enhance ST-elevation infarct regeneration)
reporting a 6.7% increase in global left ventricular ejection fraction (LVEF) in the treatment group compared
with a 0.7% increase in the control group at 6 months;
this was attributed to improved regional systolic wall
motion in the infarct zone18. The 5-year follow-up
data19 showed a decline in LVEF and increase in LV
volumes in both groups with no significant difference
in mortality or clinical end points between the groups.
Interestingly, subgroup analyses suggested that in more
severe infarction, defined as greater transmurality, cell
therapy conferred a significant benefit in LVEF and LV
dimension compared with control.
The Reinfusion of Enriched Progenitor cells And
Infarct Remodeling in Acute Myocardial Infarction
(REPAIR-AMI) trial is the largest randomised contro

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recent LateTIME study26. Here, the authors found that


in 87 patients randomised to either BMMNCs or control, BMMNC treatment at the given time point did not
improve either global LVEF or regional wall motion at
6 months. Although the likelihoodis that day 5-7 is the
optimal time for delivery of cell therapy post-AMI, not
all time points have been investigated.
The ongoing trials TIME27 and SWISS-AMI28 aim
to evaluate the timing of injection further. As yet, the
only time point that has not been considered is the very
early phase (<12 h postrevascularisation). The REGENERATE-AMI clinical trial (EUDRACT 2007-00214416) in which BMMNCs are transferred approximately
6h post-PCI is over halfway through recruitment and
will report in 2013.
There is now a need to better define those patients
who will benefit from cell therapy. The results of the
5-year follow-up from the BOOST and REPAIR-AMI
trials suggest that if ejection fraction is used as a surrogate end point, while the overall effect may be modest
for all-comers, subgroups with a large functional deficit at baseline do experience clinically meaningful increments in LVEF. This is further substantiated by the
FINCELL substudy29 in which 78 patients received either BMMNCs or placebo post-thrombolysis and PCI
for AMI. Here, a significantly greater BMMNC associated improvement in LV function was observed in
patients with baseline LVEF below the median for the
group.
Despite the heterogeneity of trial results described,
the largest meta-analysis to date comprising 1765 patients and 33 randomised controlled trials demonstrates a modest but significant improvement in LVEF of
2.87% in short-term follow-up, with sustained LVEF
improvement of 3.75% after follow-up over 1 year16
suggesting that adjunctive stem cell treatment in AMI
offers an improvement over conventional therapy. These effects while modest are comparable with those seen
in landmark studies of primary angioplasty, ACE inhibitors and b-blockers30 and suggest that a similar additional mortality benefit may be achieved. The majority
of trials in this field to date use LVEF as a surrogate
clinical end point with little understanding of how this
parameter relates to outcome.
Recently, two trials of BMMNCs in AMI have been
published attempting to explore alternative surrogate end points. The aim of the Bone Marrow in Acute
Myocardial Infarction (BONAMI) was to assess the
effect on myocardial variability at 3 months recruiting
101 patients with poor LV function post- AMI to recei-

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

ve BMMNCs or placebo. Myocardial viability was significantly improved in the treated group compared with
control.31 In another trial,32 LVEF was assessed alongside myocardial perfusion in a similar patient cohort up
to 12 months. A small improvement in myocardial perfusion was observed in the BMMNC group compared
with control; there was however a significantly lower
incidence of combined major adverse cardiac events in
the treatment group, highlighting again an ill-defined
relationship between potential surrogate markers and
hard clinical outcome measures.
One of the most important developments to date
is the move from phase II to phase III clinical trials.
The majority of the current clinical trials have been designed to assess safety and feasibility only, and being
underpowered to assess efficacy of the technology use
surrogate markers such as LVEF to assess activity. In
order to address this issue, the EU funding programme
recently awarded a consortium composed of 17 clinical
centres across Europe 6 million to design and conduct the definitive outcome study of BMMNC in AMI
(BAMI; http://www.bami-fp7.eu). BAMI will enrol
3000 patients with the primary end point as all-cause
mortality making it one of the most exciting developments in the field for several years. The study will be
reported in 5 years.
Cell therapy for chronic LV disease
The STAR-heart study is the largest reported experience of BMMNCs in ischaemic heart failure and reported
its 5-year follow-up data in 201033. The non-randomised study originally recruited 391 patients with an
LVEF of 35% or less who were offered intracoronary
administration of autologous BMMNCs. In all, 191 patients received cell therapy and 200 patients received
best medical treatment alone. At 5-year follow-up, there were significant improvements in LVEF, contractility, oxygen uptake and exercise tolerance in patients
treated with BMMNCs associated with perhaps more
interestingly a significantly lower death rate than the
control group. This requires confirmation in a doubleblinded randomised study. The FOCUS-HF trial34 is
a randomised controlled trial of 30 patients designed
to evaluate the effects of transendocardial delivery of
BMMNCs in patients with chronic ischaemic heart failure with no option for further revascularisation. At
6 months, although there was no difference in LVEF
between the treated and placebo groups, cell therapy
was found to significantly improve symptoms and quality of life scores and in subgroup analysis oxygen uptake in patients who were 60 years and younger. Another

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

recent study35 assessed the effect of cell therapy as an


adjunct to bypass surgery (coronary artery bypass graft
(CABG)) in patients with ischaemic heart failure undergoing CABG. An impressive increase in LVEF and
reduction in LV dimensions in the BMMNC group
were reported at 6-month follow-up.
Long-term data from the first randomised controlled trial of BMMNCs in dilated cardiomyopathy (Autologous Bone marrow Cells in Dilated cardiomyopathy
(ABCD) trial) were reported in 201036. In the 41 patients followed to 3 years, there was a significant improvement in LVEF in the treatment group, greater in
patients with the New York Heart Association (NYHA)
class 3 symptoms compared with NYHA class 4 suggesting improvement in patients was greater in those with
less severely damaged myocardium. There was also an
associated symptomatic improvement but no mortality
benefit was shown. Trials of BMMNCs in non-ischaemic cardiomyopathy are ongoing.
Translation of other cell types into the clinical
setting
Another major development in the last 2 years has been
the move towards clinical translation of different cell
populations and a search for the optimal cell type for
cardiac repair with a number of first-in-human trials.
Circulating/mobilised haemopoietic stem cells identified most commonly by markers CD34 and CD133
have been investigated as potential candidate populations in cardiac repair. These cell populations can either be fractionated from BMMNC or mobilised into
the circulation using pharmacological agents such as
Granulocyte colony stimulating factor (G-CSF). CD34
cells contain more endothelial lineage determined cells
and have been previously evaluated in both AMI and
refractory angina. The Autologous Cellular Therapy
CD34 in Chronic Myocardial Ischemia (ACT-CMI)
investigators have recently reported on a large phase
II trial evaluating intramyocardial injection of low and
high dose autologous peripherally mobilised CD34 cell
therapy against placebo in 167 patients with refractory angina. There was found to be a significant improvement in angina frequency and exercise tolerance in
the low dose group compared with placebo at 6 and 12
months. There was also an increased mortality in the
placebo arm37. In contrast, Chih et al report that despite mobilisation of CD34 and CD34/CD133 cells using
G-CSF, no improvement in angina or myocardial perfusion was observed in patients with chronic Ischaemic
heart disease (IHD)38. Again, this discrepancy in the
findings from these studies suggests that careful consi

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

deration to the method of delivery should be given and


that intramyocardial delivery may be more effective in
this type of patients.
MSCs are able to release a large range of cardioprotective paracrine factors and transdifferentiate into a
number of cell types that are involved in cardiac repair
and are therefore increasingly being used in clinical
trials which have shown promising results. Another
advantage of MSCs is their logistical ease of access via
bone marrow and adipose tissue.
The 6 month results of the first-in-human randomised controlled 14 patient trial of autologous adipose
tissue derived stem and regenerative cells (ADRCs) for
AMI (the Adiposederived stem cells in the treatment
of patients with ST-elevation myocardial Infarction
(APOLLO) trial) have recently been reported39. All patients received either cell therapy or placebo within 24h
of primary PCI. These were first MI patients with an
LVEF between 35% and 50%. At 6 months, there was
a significant improvement in myocardial scar formation and perfusion defect, near significant reduction
in infarct size and improvement in estimated ejection
fraction with cell therapy compared with control, and
the treatment proved safe. The 18 month data were presented at the 2011 International Symposium on Stem
Cell Therapy & Cardiovascular Innovation and showed
sustained benefits. The next step, a larger study called
ADVANCE, enrolling 375 patients will give greater statistical power. 18 month results for a similar first-inhuman trial of ARDCs for ischaemic heart failure, PRECISE, although not yet published, have been presented
at the AHA Scientific Sessions 201040. Here, 27 patients
were randomised to receive transendocardial ADRCs
or placebo. Results at 6 months showed a significant reduction in infarct size in the treatment group relative to
the controls but with no difference in LVEF. Out to 18
months, cell therapy was found to be safe with no difference in adverse outcomes between the two groups and
found to significantly improve both NYHA and Canadian cardiovascular society (CCS) class symptoms, metabolic equivalents and peak oxygen consumption, in
the treatment group.
Allogeneic as opposed to autologous MSCs have also
recently been evaluated as a potential novel therapeutic strategy allowing for off-the-shelf logistical ease.
MSCs are able to evade immune detection meaning
immunosuppression is not required for these patients.
The first-in-human phase I randomised controlled
study comparing allogeneic MSCs with placebo in the
setting of first AMI and LV dysfunction enrolled 53 patients41. Importantly, the study demonstrated no diffe-

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

rence in adverse events, rehospitalisation or arrhythmia


between the groups. At 18 months, the treatment group
conferred significant improvement in LVEF relative to
controls. The preliminary results of a phase II randomised controlled trial assessing allogeneic MSCs in the
setting of ischaemic heart failure were presented at the
AHA Scientific Sessions 201122. The study consisted
of 60 patients with a 12 month follow-up period and
confirmed safety of the technology. While there was no
difference in LVEF between the two groups, there was
a significantly lower incidence of major adverse cardiac
events, mortality and symptoms in the treated group
supporting the concept of LVEF not being a useful
surrogate marker for outcome.
The attractive opportunity to exploit cardiac stem
cells (CSC) which are capable of regrowing healthy
heart tissue was realised with the discovery that the
adult heart contains its own reservoir of progenitor
cells. There are two main CSC populations that have
been described, the c-kit+ population and cardiosphere- derived cells, which are a natural mix of heart derived cell subpopulations including c-kit+/CD90- and
cardiac MSCs c-kit-/CD90. Although it is uncertain as
to whether these will prove advantageous over other
stem cell types, particularly if they act in a paracrine
manner, both populations have been studied in the clinical setting.
The recently published SCIPIO trial (Cardiac stem
cells in patients with ischaemic cardiomyopathy) is a
first-in-human phase I trial assessing the value of ckit+ CSCs in ischaemic heart failure post-CABG.42
Here, autologous atrial appendage c-kit+ cells are isolated and expanded at the time of CABG and re-infused 3-4 months after surgery. Importantly, there was
no difference in adverse event rate between treatment
and control arms. At 8 months, there was a significant
improvement in infarct size and LVEF in treated patients. The CADUCEUS trial (cardiosphere-derived
autologous stem cells to reverse ventricular dysfunction) assessed the impact of intracoronary infusion of
autologous cardiosphere-derived cells harvested from
endomyocardial biopsies in patients 2-3 months postAMI in a phase I clinical trial43. Here, LVEF was significantly improved at 12 months compared with controls
and there was a major reduction in scar mass on Cardiac magnetic resonance imaging (CMR) in the treated
but not the control group. There was no difference in
adverse outcome between the groups. Importantly, this
is one of the first trials of cell therapy to suggest that the
benefits seen in relation to myocardial repair are expla-

ined by a regenerative process. The results of a phase II


trial will be eagerly awaited.
Although the ultimate goal of cell therapy is to restore cardiac function and thereby improve quality of life
and survival, the mechanism by which this is achieved
using cell therapy continues to remain a topic of debate depending on the cell type used. This area of research has nonetheless led to a better understanding of
how cells can in vitro be made to differentiate into a
phenotype that may improve cardiac repair. The first
results of this approach in humans have recently been
published. In the C-Cure trial, the investigators have
driven the differentiation of BMMNCs into lineagespecific cardiac progenitor cells using cardiogenesis
proteins before cell transfer via the transendocardial
route44 to 45 patients with ischaemic heart failure. At
6 month follow-up, there was significant improvement
in LVEF and reduction of LV volumes as well as significant symptomatic improvement evidenced by the 6
min. walk test in the treated group compared with the
control group. There were no significant differences in
adverse outcome. The second phase of this trial is ongoing.

SUMMARY
Cell therapy research offers the prospect of a completely new therapeutic approach in cardiology. The last 2
years has seen a systematic move from phase I to phase II clinical trials using established cell types together
with the emergence of new cell types in phase I studies
that have only become feasible due to the research that
has been driven by the early translation into humans.
For the pragmatic approach of bone marrow derived
cell therapy, recent meta-analysis again confirms the
potential for benefit and this will now be addressed in
a phase III outcomestudy that will also standardise the
technique of cell processing and administration. Other
cell types will need to follow a similar path of investigation and no doubt the trials of bone marrow derived
cells will set the standards by which different cell types
and techniques will be judged.
Acknowledgements: NIHR cardiovascular biomedical research unit based at Bartshealth NHS trust.
Contributors: DJ and FC contributed equally to the
writing of this manuscript. The concept and idea as well
as editing was undertaken by AM.
Competing interests: None.
Provenance and peer review: Commissioned; internally peer reviewed.

Daniel A Jones et al.


Almanac 2012: cell therapy in cardiovascular disease

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

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Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

REVIEWS

Long QT Syndrome
L. Lucaci
Article received on the 1st of October 2012. Article accepted on the 15th of February 2013.
Abstract: The long QT syndrome is a potentially lethal electric disorder of the heart, characterized by a transient or permanent prolongation of the QT interval, carrying a risk for syncope, due to torsade de pointes and / or for sudden cardiac death,
secondary to ventricular fibrillation. It comprises a congenital form and an acquired one. The congenital form has a genetic
background, representing one of the several channelopathies, as an inherited dysfunction of a ion channel or of a regulatory
protein is their common denominator.The acquired form has an extrinsic cause, usually a QT prolonging drug, an electrolyte
imbalance or a bradyarrhythmia, possibly occuring in individuals with low penetrance of the congenital type. The genetic
classification, the mechanisms for arrhythmogenesis, as well as the principles of management, tailored to the categories at risk,
are presented.
Keywords: long QT, congenital, acquired, syncope, sudden death
Rezumat:

Sindromul QT lung se caracterizeaz prin alungirea temporar sau permanent a intervalului electrocardiografic
QT, asociind risc de sincop, secundar torsadei vrfurilor i / sau de moarte cardiac subit, secundar fibrilaiei ventriculare.
Exist o form congenital i una dobndit a sindromului. Forma congenital reprezint una dintre aritmiile de origine genetic, datorate disfunciei nnscute a unui canal ionic din membrana celulei miocardice, mai rar a unei proteine reglatoare i
numite astfel canalopatii. Forma dobndit are o mulime de cauze extrinseci, de obicei un medicament cu potenial alungitor
al QT, o diselectrolitemie sau o bradiaritmie. Sunt prezentate clasificarea genetic actual a sindromului congenital, mecanismele aritmogenezei, precum i principiile de tratament, adaptate stratificrii riscului.
Cuvinte-cheie: QT lung, congenital, dobndit, sincop, moarte subit

INTRODUCTION
The long QT syndrome (LQTS) consists of a transient
or a permanent prolongation of the QT interval above
the upper limit of normal, corrected for the heart rate,
age and gender, predisposing to syncope due to torsade
de pointes (TdP) type of ventricular tachycardia (VT)
and / or to sudden cardiac death, secondary to ventricular fibrillation (VF)1-3. The LQTS has two forms:
a congenital and an acquired one. The prevalence of
the congenital form is estimated between 1/2000 and
1/3000 live births4,5. The acquired form is more common than the inherited one.
LQTS as a cause of sudden cardiac death
Most sudden deaths arise in connection with a structural defect of the heart, be it an ischaemic (80% of cases),
a non-ischaemic or an acute mechanical one (aortic
dissection, acute massive pulmonary embolism, interventricular septum rupture, blunt chest trauma). In a
minority of cases (5-15%), including most of the cases
Prof. Dr. George Georgescu Institute of Cardiovascular Diseases, Iai

of LQTS6-9 no morphologic abnormality of the heart


can be found (Table 1).
Congenital LQTS inside the genetic anomalies of the
ion channels
So far, there is a spectrum of inherited arrhythmia syndromes arising from genetic defects in structures involved in the genesis of action potentials (AP), including congenital LQTS, Brugada syndrome, short QT
syndrome (SQTS), catecholaminergic polymorphic
ventricular tachycardia (CPVT), idiopathic VF, familial atrial fibrillation (AF) and at least some cases of the
sick sinus sindrome (SSS) and of the progressive cardiac conduction defect (PCCD)3,11. Because a ion channel
is usually the affected target, these diseases represent
the so-called channelopathies11,12, as a group (Figure 1).
Either the increased efflux or the decreased influx of
positive ions across the cell membrane, through defective channels within at least one myocardial wall layer,
bring about short AP syndromes, as for example SQTS
Contact address:
Laureniu Lucaci MD, Prof. Dr. George Georgescu Institute of Cardiovascular Diseases, Iai, Bulevardul 50 Carol I Boulevard, Postal code:
700503, Iai, Tel./fax 0232 219 270, 0232 267 602. E-mail: laurentiulucaci@
yahoo.com.

L. Lucaci
Long QT Syndrome

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Figure 1. Congenital LQTS as a genetic channelopathy. LQTS = long QT syndrome; SQTS = short syndrome; IK1 = inward rectifier potassium channel; INa+
= sodium channel; ICa+2 L = L-type calcium channel; IKr = rapid component of the delayed outward rectifier channel; IKs = slow component of the delayed
outward rectifier channel.

and Brugada syndrome. On the other hand, either the


increased influx, or the decreased efflux of positive
ion, again through defective channels, within at least
one myocardial layer, give rise to long AP syndromes,
including most of the types of LQTS13. A relationship
between the traditional description and the current genetic classification of LQTS has been revealed. Accordingly, the autosomal dominant forms of the genetic
types 1, 2, 3, 5 and 6 represent altogether the Romano-Ward syndrome, whereas the autosomal recessive
forms of the failing subunits in the slow outward rectifier potassium channel IKs merge into the Jervell and
Lange-Nielsen syndrome3,12,14,15.
The genetic classification of congenital LQTS and the
relationship to the risk profile
As yet, a number of 13 types of congenital LQTS have
been characterized (Table 2). Together, they stand for
Table 1. Etiology of sudden death in an apparently normal heart
(7-10)
Genetic alterations of the action potential, including:
a) repolarization: long QT syndrome, Brugada syndrome, short QT
syndrome, familial atrial fibrillation;
b) automaticity: sick sinus syndrome (some cases);
c) conduction: progressive cardiac conduction defect (Lenegres disease)
Genetic anomalies of the intracellular calcium handling:
catecholaminergic polymorphic ventricular tachycardia
Accesory pathways: Wolff-Parkinson-White syndrome
Ventricular tachycardia due to electrolyte disturbances:
loop/thiazide diuretics, endocrine disorders: primary hyperaldosteronism, Addisons disease, hyper and hypoparathyroidism
Alcohol-induced ventricular tachycardia

75-80% of all patients diagnosed with congenital LQTS.


However, the first three ones discovered and therefore
allocated as LQTS 1, LQTS 2 and LQTS 3 still remain the
most common ones, comprising as a whole 95% of those with a genetic label and at least 70% of all congenital
LQTS patients5,16. Most of the cases are the outcome of
a direct change of the function (either a loss of function
of the repolarizing channels, or a gain of function of the
depolarizing ones), secondary to a mutation inside the
gene coding for the synthesis of the channel subunit.
The remaining cases usually derive from an indirect
change of the ion channel function, due to a genetic
alteration of a regulatory protein5. There is not just one,
but several possible mutations for each type of congenital LQTS (over 700 mutations for all types of LQTS
are described by now)5. Every one of them encodes for
a region of the ion channel subunit or of the regulatory protein, resulting in different levels of infringement
upon channel function and thus various degrees of clinical severity, even inside each type of LQTS, whatever
it may be. The degree of the QT prolongation and its
temporal variability, the shape of the T wave, the severity of the symptoms, along with some scarce anatomic
features inside or outside the heart eventually result
from the type of malfunctioning channel / protein and
its mutation, as well as from the pattern of inheritance.
For instance, among the most three common types of
LQTS, IKs (LQTS 1) mutation has the least likely lethal
cardiac event (when occurring) and INa+ (LQTS 3)
mutation the most likely lethal one3,17,18. ICa+2L (LQTS
8) mutations are presumably lethal in early life, where-

L. Lucaci
Long QT Syndrome

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013
Table 2. The genetic classification of the types of congenital long QT syndrome (4,5,13,54)
Genetic type of
LQTS
1
2
3
4
5
6
7
8
9
10
11
12
13

Prevalence
>90% of all genetically
proved cases

Uncommon types:
each_1%
of all genetically
proved

Type of dysfunction
loss/gain
loss
loss
gain
loss
loss
loss
loss
gain
gain

loss

Channel/
protein affected
IKs
IKr
INa+
*Ankyrin B
IKs
IKr
IK1
ICa+2 L
Caveolin 3
INa+
**Yotiao
_1syntrophin
IKAch

Affected
subunit

Encoding
gene

(MinK)
(MiRP)

INa+ gain

INa+ loss
INa+ gain

KCNQ1
KCNH2
SCN5A
ANK2
KCNE1
KCNE2
KCNJ2
CACNA1C
CAV3
SCN4B
AKAP9
SNTA1
KCNJ5

Equivalence with
traditional classification
Romano Ward JLN 1

Romano Ward JLN 2

IKs = slow part of delayed outward rectifier potassium channel; IKr = rapid part of delayed outward rectifier potassium channel; INa+ = sodium channel; IK1 = inward rectifier potassium channel; ICa+2L
= L-type calcium channel; JLN = Jervell-Lange-Nielsen; Alpha subunits of the channels contain the pore forming regions. * Ankyrin B anchors sarcolemmal proteins to the cytoskeleton; **Yotiao = protein
within the adrenergetic dependent chain of activating IKr; alpha1syntrophin = cytoskeleton protein.

The acquired LQTS


The same IKr channel involved in the pathogenesis of
congenital LQTS can be affected by a manifold of drugs
or non-pharmacological factors, producing the acquired LQTS13,28,29 (Table 3). Hence, the sinus rhythm electrocardiogram of the acquired syndrome is usually alike
to that of the congenital LQTS 2. Unlike the congenital

CAUSES

Table 3. Causes and risk factors for LQTS (10,28,29,31)

RISK FACTORS

as IK1 (LQTS 7) has usually a lenient course5,13,19. Males bear higher risk than females in childhood whatever
LQTS type might be20, and throughout life in LQTS 310,
while the opposite is true in all other instances for the
first three types of congenital LQTS21,22, as well as in
the acquired form, a suppressive effect of the estrogens
upon IKr channel being hypothesized23. However, the
womans risk does not lessen at menopause24. Channel
conducting pathway (pore) region mutations in LQTS
2 harm more than non-pore coding ones10,25, especially
in men26 and the homozygously affected individuals
(e.g. Jervell-Lange-Nielsen) evolve worse than their heterozygous counterparts15. Moreover, in the so-called
concealed cases (genotype-positive, but with normal
corrected QT (QTc) at rest), transmembrane (non-pore) region mutations and the genetic type (LQTS 1 and
LQTS 3) still carry a higher risk than that of non-affected persons, even if lower than in case of prolonged
QTc27. Compared with baseline prolonged QTc individuals, in concealed cases the mutation itself and the genetic type of the syndrome are more powerful risk factors than the clinical descriptors (for example, female
gender)27. The greater the number of distinct mutations
in the same patients, the earlier the onset of the clinical
picture may be.

LQTS
CONGENITAL
ACQUIRED
GENETIC DYSFUNCTION OF QT PROLONGING DRUGS
ION CHANNELS
HYPOKALAEMIA
MYOCARDIAL ISCHAEMIA
MYOCARDITIS
MITRAL VALVE PROLAPSE
BRADYARRHYTHMIA
SUBARACHNOID HEMORRAGE
HYPOTHYROIDISM
Ikr MINOR GENETIC DEFECT
LQTS 1: PHYSICAL EXERCISE FEMALE GENDER
(especially swimming)
LQTS 2: EMOTIONAL STRESS RECENT ATRIAL FIBRILLATI(especially NOISE)
ON CARDIOVERSION USING
LQTS 3: SLEEP
INTRAVENOUS IA/ III CLASS
ANTIARRHYTHMIC AGENT
ANY LQTS: QT PROLONGING DRUGS,
HIGH MAINTENANCE DOSE
HYPOKALAEMIA
(except QUINIDINE)

form, a noticeable cause for the acquired syndrome comes into sight. It can be one of the following: a structural cardiac abnormality, bradyarrhythmia, central
sympathetic storm (secondary to subarachnoid hemorrhage), electrolyte imbalance (especially hypokalaemia and hypomagnesemia), hypothyroidism, or, more
commonly, a QT prolonging drug7,29,30, falling into one
of several distinct therapeutic classes, all pertaining to
an extensive and currently updating list (www.azcert.
org) and blended together because of their ability to
block the IKr current29,31, or to inhibit the hepatic metabolism of IKr blockers30. Class IA or III antiarrhythmic
drugs are often the culprit agents. Their propensity to

L. Lucaci
Long QT Syndrome

prolong QT interval and to increase the TDR is dosedependent for almost all, except quinidine32. However,
the amiodarone is perceived as a relatively safe drug.
Its ability to perform a relatively homogenous prolongation of the APs and the attendant Na+ and Ca+2L
channels blocking quality result in a lower risk for developing early afterdepolarizations (EADs) and thus for
TdP, compared with other antiarrhythmics31,33,34. While
safe in most instances, clustering of causes and of risk
factors increases dramatically the risk for TdP, and this
holds true for amiodarone, too10,28,29,31 (Table 3). As a
corollary to the acquired form of LQTS, the discrimination between causes and risk factors is sometimes
elusive.
Issues regarding the measurement and the
correction of QT interval
Both the measurement of the QT interval and its adjustment can be done either manually, or by dedicated
software built in many present day electrocardiographic
machines. Some cautions regarding the manual measurement must be observed, however. A stable isoelectric
line and a fairly constant heart rate tracing should be
looked for. Choosing the lead with the most clearly defined end of the T wave, from those leads where QT is
expected to be the longest (V2 or V3) is recommended35,36. When a TU complex is present, the end of the
T wave should be defined by the crossing point between the isoelectric line TP and the tangent line at the
steepest downslope of the T wave final portion35. The
RR interval used for correction is the RR interval just
before the measured QT. The lead chosen as above is
kept for subsequent comparisons. Still, one of the most
widely used formula to adjust the QT for heart rate is
Bazett s formula: QTc = QT / RR, where QT and RR
are measured in seconds1,35,36, so it follows that Bazett
QTc is measured in seconds1/2. The fact that QTc is the
slope of graph of the square root of RR interval explains the two big shortcomings of the formula, namely
the underestimation of QTc (= QT overcorrection) in
bradycardia (where the slope of the graph is gentle) and
the overestimation of QTc (= QT undercorrection) in
tachycardia (where the slope of graph is steep)36,37. Therefore, linear regression formulas are recommended to
adjust for rate: QTc = QT + 1.75 (HR - 60), where QT
is measured in miliseconds and HR is the heart rate35,36.
Moreover, age and gender must be taken into account,
as well. The upper limits of normal for QTc values, as
recommended by American Heart Association in 2009
are 0.45 sec for men and 0.46 sec for women, while the
lower limit of normal is 0.39 sec for both genders35. To

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Vol. 23, No. 1, 2013

allow for age influence in children, the upper limit of


normal of QTc for those younger than 6 months is 0.49
s and 0.44 s for other age groups, these last values
being derived using Bazett formula38. Rate correction
becomes useless in case of large RR variability (as for
example AF), where the longest observed uncorrected
QT should be reported accordingly.
The mechanism of arrhythmogenesis. The ECG
diagnosis. Concealed cases
Different distributions of potassium channels within
ventricular layers (particularly a minimal density of IKs
in M-cells)39 contribute to the normal transmural dispersion of AP durations and of the refractory periods
(TDR). The M-cell has the longest AP and the subepicardial cell the shortest40,41. The intrinsic failure (seen
in congenital LQTS) or the extrinsic impairment of an
ion channel in the acquired form prolong the AP of the
M-cell and exert variable influences upon the AP durations in the subendocardial and subepicardial layers13.
On the one side, one can see the prolongation of QT
interval, often associated, but not always, with an increased TDR. On the other side, the long AP of the Mcell allows the Ca+2L channels to be reactivated during
the same AP39, promoting excessive Ca+2 storing in the
sarcoplasmic reticulum. The ensuing release of intracellular Ca+2 further depolarizes the membrane (by activating Ca+2 dependent chloride current and Na+/ Ca+2
exchange mechanism), giving rise to EADs. Besides
further increasing the TDR, an EAD can manifest itself
as the ventricular premature beat (VPB) triggering the
TdP, if a certain voltage threshold is reached. Thereafter, the augmented TDR favors the perpetuation of the
tachycardia by the reentry mechanism30,33,42,43. On the
electrocardiogram (Figure 2), the TdP associated with

Figure 2. The onset of the pause-dependent torsade de pointes. VPB = ventricular premature beat. Data in references 30,32.

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the acquired LQTS and with the congenital LQTS 3 is


labeled pause-dependent TdP. Herein it is initiated by a
typical sequence, called short-long-short cycle32. The
first short cycle is represented by the coupling interval of a VPB. The long cycle is the compensatory pause
following that VPB, whereas the second short cycle is
the coupling interval of the first beat of the tachycardia. In sinus rhythm, QT interval is already long and
after the pause it becomes longer32. The twisting pattern
of the spikes of QRS complexes around the baseline is
explained by a periodic rotation in space of the spiral
wave of the tachycardia33. Depending on the amplitude
of the EAD and on the value of the TDR, several electrocardiographic scenarios may follow: T wave / TU
complex alternance, VPB bigeminism and the TdP. A
bidirectional type of VT may also be seen in LQTS 7
(Andersen)11,44. Usually, the TdP is recurrent and self
limited, but sometimes (less then 10% of cases) degenerates into VF11,32. TdP in congenital LQTS 1 and 2 may
begin without the typical short-long-short sequence45. It appears and persists during the sympathetic
stimulation in LQTS 1, but only at the beginning of
sympathetic release in LQTS 246. Forms of the LQTS
where the AP prolongation is quite homogenous have a
relatively benign history, with a low prevalence of TdP
(LQTS 7 Andersen13, or cases with mild prolongation
of QTc under amiodarone as sole risk factor). There has
been depicted a characteristic pattern in sinus rhythm
for each of the main three types of congenital LQTS,
as follows: LQTS 1 has a broad based T wave, LQTS 2
has a low amplitude T wave (sometimes notched, too),
whereas LQTS 3 has a narrow based T wave1,2,3,11. The
acquired LQTS shows often a pattern similar to that of
congenital type 2. Unlike in other types of congenital
LQTS, an exaggerated U wave has been described in
LQTS 7 (Andersen)10,11,47. Narrow-based T waves (alike those in LQTS 3) and sometimes giant negative T
waves in precordial leads are seen in Timothy syndrome48. Aside from the QT prolongation itself and its
dispersion in surface leads, the Tpeak-Tend interval in
precordial leads (or, more generally, the interval from
the peak/nadir of the first component of the T wave
to its end) is considered to be a non-invasive indicator of TDR33, while a fragmented QRS is suggested to
be a risk indicator for torsade in acquired LQTS, too49.
The electrocardiogram of certain cases of congenital
LQTS behaves somehow alike to that of the acquired
form, as both show a significant variability of QTc over
time. It happens especially in heterozygous carriers of
IKs mutations in LQTS 1 and LQTS 54. The temporal
variability of QTc in congenital LQTS can reach 47

L. Lucaci
Long QT Syndrome

40 ms, including an incidental normal QTc and still


carrying a small risk for TdP50. The term concealed
was coined to label these cases, which may account for
36% of all cases of LQTS 1, 19% of all cases of LQTS
2 and 10% of cases of LQTS 346. The concealed cases
fall under the heading of a more general phenomenon
of incomplete penetrance of all genetic disorders of the
ion channels, while standing for a difficult diagnosis.
Persons with the acquired form of LQTS may well be
recruited from the bulk of concealed cases. The electrocardiographic diagnosis of concealed LQTS relies upon
time (ambulatory Holter recordings) and space followup (multiple lead body surface ecg), but provocative
tests (exercise stress testing, epinephrine stress) may
be needed, as some cases of Brugada syndrome need
provocative diagnostic testing (Na+ channel blockers in
this case), too4,46. Roughly speaking, the concealed cases of channelopathies are endowed with a risk falling
between the risk of spontaneously manifest cases and
that of non-carriers, and LQTS does not break this foregoing record6,51.
The diagnostic criteria for congenital LQTS presented elsewhere, have been released in 1993, building
up a probability diagnosis, founded upon electrocardiographic, personal history and family history elements1,52. Albeit stated before the genetic knowledge
breakthrough, they still hold useful, either when genetic diagnosis is out of reach, or as a complementary diagnosis to the genetic work-up done for concealed cases.
Structural abnormalities associated with LQTS
Most cases of congenital LQTS have a normal morphological heart and no extracardiac abnormality. The first
historically known abnormality was the sensorineural
deafness in Jervell and Lange-Nielsen syndrome14,15,53.
Since the beginning of the genetic Odyssey, two other
types of LQTS joined the puzzle. One of them is the
Andersen-Tawil syndrome (LQTS 7), whose array of
features includes a potassium-sensitive periodic paralysis (triggered by exercise or by glucose ingestion),
hypertelorism, widened nose base, low-set ears, highly
convex palate, small lower jaw, small hands and feet,
with syndactyly of the toes5,11,13,47,54,55. The other one is
Timothy syndrome (LQTS 8), featuring autism, baldness, low-set ears, small upper jaw, dysmorphic teeth,
syndactyly both in fingers and in toes, along with congenital heart defects, such as patent ductus arteriosus,
patent foramen ovale, ventricular septal defect, tetralogy of Fallot. Timothy syndrome may include a functional 2/1 atrioventricular block, due to an exceedingly
long QT interval5,19,48. Even if the acquired LQTS is fun

L. Lucaci
Long QT Syndrome

Figure 3. The risk stratification for a first cardiac event in life, before age of
40 and without treatment in congenital LQTS types 1, 2 and 3, depending
upon QTc value and gender. High-risk is superior to 50%, medium-risk lies
between 30 and 49%, whereas low-risk is inferior to 30%. Data in reference
21.

damentally an electric disorder, a particular anatomic


substrate can occasionally be found (myocardial infarction, myocarditis, or a mitral valve prolapse).
Risk stratification
Congenital LQTS: 1) High risk for relapse: patients
with personal (not family)10,56 history of aborted cardiac arrest22,57,58, or recent and / or repetitive syncope
(especially when first event early in life59,60 and / or on
treatment61); 2) Categories at risk for a first cardiac
event in life, in the next 5 years (syncope / cardiac arrest / sudden cardiac death) before the age of 40 and without being treated1,21 (Figure 3): 2a) high risk 50%:
LQTS 1, 2 and 3 with QTc 500 ms 1/2, apart from the
woman with LQTS 3; 2b) low risk <30%: LQTS 1 and 2
with QTc <500 ms1/2, apart from the woman with LQTS
2; 2c) medium risk 30-49%: the LQTS 3 woman with
QTc 500 ms1/2, the LQTS 2 woman with QTc <500 ms
1/2
and all LQTS 3 patients with QTc <500 ms1/2; 3) risk
increased for the woman with LQTS 2 in the first few
months after a childbirth, whereas pregnancy is relatively safe62. While being well above the upper limits of
normal for both genders, the 500 ms1/2 QTc is a cut-off
value for high risk individuals37,50. Acquired LQTS: any
clustering of causes and risk factors, especially if symptomatic before.
Principles of management of the LQTS
As not all syncopes in a patient having LQTS are automatically due to TdP, the treatment of any form of
LQTS is essentially the prevention and termination of
TdP and consequently the prevention of sudden cardiac death. Shortening of QT interval is neither the main
goal, nor is always possible. The long-term prevention
of TdP in congenital LQTS is attempted by a) avoiding

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Vol. 23, No. 1, 2013

Figure 4. Management of LQTS.

the known risk factors (Table 3), b) safeguard against


sympathetic stimulation (betablockers, the mainstay of
the treatment1, are mandatory and highly efficient in all
cases of LQTS13,20,63, moderately efficient in LQTS 2, including the pregnancy62 and asthma patients64, but are
questionable in LQTS 311,65 and in JLN patients15) and
c) the possible reduction of the dispersion of refractoriness (by left superior cervico-thoracic sympathectomy,
in selected cases66). The long-term prevention of TdP in
acquired LQTS is obtained by in-hospital monitoring
of the first days of IA / III antiarrhythmic drugs32 and
by removal and / or treatment of any identified cause28,32 (Table 3). The prevention of a TdP dependent on
a bradyarrhythmia benefits from the bradyarrhythmia
treatment10 for any causal LQTS, be it acquired or congenital type 3. Potassium allows the short-term prevention of TdP10, not only in hypokalaemia-induced case,
but also in congenital LQTS (here even if no hypokalaemia documented). Stopping TdP in any congenital
or acquired case is achieved with intravenous magnesium sulphate and delivery of external electric shock (if
TdP episode prolonged or degenerating into VF)32. Moreover, tachyarrhythmia episodes can also be terminated by the implantable cardioverter-defibrillator (ICD)
a patient with congenital LQTS has already received67.
Some of the aforementioned methods shorten the QTc
in sinus rhythm, while others do not (without meaning
being less efficient). A synthesis of the available management methods is presented in Figure 4.
Recommendations for prophylactic management of
the congenital LQTS, according to the categories at
risk10
All patients must avoid known risk factors (strenuous exercise in LQTS 1, emotional stress and noise in

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Vol. 23, No. 1, 2013

LQTS 2, and any reversible risk factor for the acquired


cases) (class I recommendation). Betablockers are recommended (class I) for any patient with electrocardiographic diagnosis and QTc 500 ms1/2 (including the
pregnant woman) and they are useful (class IIa recommendation) for the patient with QTc <500 ms1/2. The
ICD is recommended (class I) for the secondary prevention of sudden cardiac death after an aborted cardiac arrest, it is useful (IIa) in the secondary prevention
of both syncope and TdP and it is suggested (IIb) for
the asymptomatic patient carrying a high or medium
risk (30%)68. The ICD must be associated with the
betablocker. The left superior cervico-thoracic sympathectomy is suggested (IIb) for unabating symptoms
while on betablocker plus ICD.
Conflict of interests: The author declare that no
conflict of interest exists.
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Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

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Structural and functional ventriculo-arterial changes in obesity:


mechanisms, implications and reversibility after weight loss
Mdlina Iancu1, Marinela erban2, C. Copescu1, Carmen Ginghin2,3
Article received on the 19th of February 2013. Article accepted on the 5th of March 2013.
Abstract: Obesity is a public health problem, being the fifth cause of death worldwide. Adverse cardiovascular prognosis of
obesity is linked to: endothelial dysfunction, abnormal left ventricular geometry, systolic and diastolic left ventricular dysfunction, heart failure, increased arterial stiffness, coronary artery disease, dilated left atrium and atrial fibrillation. Pathophysiologic mechanisms of structural and functional cardiovascular changes of obesity are complex: cardiac metabolism disturbances,
mitochondrial dysfunction, impaired insulin signalling, inflammation, neuro-hormonal activation, impaired production of
adipokines, fibrosis, changes in the extracellular matrix and cardiomyocytes apoptosis. Obesity is characterized by a mixed
left ventricular overload, with predominance of one component (pressure or volume), depending on which a certain type of
cardiac remodelling appears (eccentric or concentric hypertrophy, concentric remodelling), with specific prognostic implications. The main modalities of obesity treatment are diet, physical activity, behaviour modification, pharmacological therapy
and bariatric surgery. Favorable metabolic and blood pressure changes were demonstrated after losing weight by any means,
but reversibility of cardiac morphological changes (mainly regression of left ventricular hypertrophy) and of left ventricular
diastolic and systolic dysfunction were demonstrated only after bariatric surgery. Described effects are probably due to a large
and sustained weight loss.
Keywords: obesity, left ventricular remodeling, vascular dysfunction, weight loss, reversibility
Rezumat: Obezitatea reprezint o problem de sntate public, fiind a cincea cauz de mortalitate n lume. Prognosticul cardiovascular nefavorabil al obezitii este legat de: disfuncie endotelial, geometrie anormal a ventriculului stng, disfuncie
sistolic i diastolic ventricular stng, insuficien cardiac, rigiditate arterial crescut, boala coronarian ischemic, dilatarea atriului stng, fibrilaie atrial. Mecanismele fiziopatologice ale modificrilor structurale i funcionale cardiovasculare
din obezitate sunt foarte complexe: perturbri ale metabolismului cardiac, disfuncie mitocondrial, alterri ale semnalului
insulinei, inflamaie, activare neuro-hormonal, dereglarea produciei de adipokine, modificri ale matricei extracelulare,
fibroza i apoptoza cardiomiocitelor. Obezitatea este caracterizat de un mecanism mixt de suprasarcin ventricular stng:
de presiune i de volum, cu predominana uneia dintre componente, n funcie de care apare un anumit tip de remodelare
ventricular stng (hipertrofie excentric sau concentric, remodelare concentric), cu implicaii prognostice specifice. Principalele modaliti de tratament ale obezitii sunt: dieta, activitatea fizic, modificrile comportamentale, terapia farmacologic i chirurgia bariatric. Modificri metabolice favorabile i scderea tensiunii arteriale au fost demonstrate prin scderea
ponderal prin orice metod, ns numai dup chirurgia bariatric au fost descrise reversibilitatea modificrilor morfologice
cardiace (n principal regresia hipertrofiei ventriculare stngi) i a disfunciei ventriculare stngi diastolice i sistolice. Efectele
descrise sun cauzate probabil de scderea ponderal ampl i susinut.
Cuvinte-cheie: obezitate, remodelare ventricular stng, disfuncie vascular, scdere ponderal, reversibilitate

THE MAGNITUDE OF THE PROBLEM


Obesity is now considered a major clinical and epidemiological problem, a worldwide epidemy with a rapid
increase of its incidence.
Obesity epidemiology
The global prevalence of excessive weight has doubled in the last 30 years and is at a level of approximately
33% for obesity and 50% for overweight and obesity.
1

Delta Hospital Bariatric Centre of Excellence, Bucharest


Prof. Dr. C. C. Iliescu Emergency Institute for Cardiovascular Diseases,
Bucharest
3
Carol Davila University of Medicine and Pharmacy, Bucharest
2

In the world there are currently registered 200 million


obese men, 300 million obese women and 1.4 billion
overweight subjects, there are regions (from U.S.A.)
where overweight and obese individuals account for
over 65% of the population. Equally worrying is the
current number of obese adults and high prevalence of
obesity among children in 2010 more than 40 million
of children younger than 5 years were overweight1,2.

Contact address:
Dr. Iancu Mdlina, Delta Hospital, 6A Racari Street, District no. 3,
Postal code: 031828, Bucharest, Romania. E-mail: madalina.iancu@gmail.
com

Madalina Iancu et al.


Structural and functional ventriculo-arterial changes in obesity

In Romania, epidemiological studies conducted between 2000-2005 have shown a obesity prevalence in
the general population of 28%, with a distribution of
26.3% in males and 35.1% in females; in patients with
coronary heart disease, obesity had a higher prevalence:
31% of which 29% in men and 34% in women; in the
study Urziceni body mass index (BMI) in adults with
average age of 25 years was 27.4 kg/m2 (corresponding
to overweight), and 30.6% of them had high cholesterol
level and excess weight (overweight or obesity)3,4.
Obesity is a major public health problem, which is
reflected in the constant concern of the medical world
to develop comprehensive guidelines for the identification, evaluation and treatment of obesity. In Europe,
obesity applies directly for 6% of the funds allocated to
health; health expenditure in individuals with obesity is
twice higher than in normal weight subjects5.
Definition and classification of obesity
There are many definitions of obesity. The most used
is based on body mass index (BMI = weight / height2);
a BMI between 18.5 to 24.9 kg/m2 is normal, 25 to 29.9
kg/m2 defines overweight and BMI > 30 kg/m2 defines
obesity6.
There are five classes of obesity: class 1 - BMI 30 to
34.9 kg/m2, class 2 BMI 35 to 39.9 kg/m2, class 3
BMI 40 to 49.9 kg/m2, class 4 BMI 50 to 59.9 kg/m2,
class 5 BMI 60 kg/m2 6.
The excess weight prognosis is extremely unfavourable: obesity is the fifth cause of death worldwide,
giving 2.8 million deaths/year, with a mortality that increases by 30% at every BMI augmentation of 5 kg/m2 7.
In the most recent version of European Guidelines on Cardiovascular Disease Prevention in Clinical
Practice it is shown that obesity and overweight are
both associated with an increased risk of cardiovascular death, with a direct and linear relationship between
BMI and all causes mortality. It emphasizes that optimal body mass index with the lowest mortality is 20-25
kg/m2, it points out that greater weight reduction does
not confer additional cardiovascular protection6.
Although its the first guide that mentions obesity paradox8 in patients with coronary artery disease (possibly better prognosis in patients with obesity
undergoing coronary revascularization procedures),
it shows that existing data in this respect are contradictory and do not provide other recommendations in
addition to those described above6.
Obesity prognosis
Obesity potential adverse effects are related to:
insulin resistance, high blood pressure, systemic pro

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inflammatory and prothrombotic status, albuminuria


and dyslipidemia (increased serum levels of total cholesterol, LDL-cholesterol, other forms of non-HDL
cholesterol, triglycerides, apolipoprotein B, small dense LDL particles and decreased concentrations of HDL
cholesterol and apolipoprotein AI)6.

METABOLIC AND CARDIOVASCULAR OBESITY


DISORDERS
Major cardiovascular and cerebrovascular abnormalities seen in obesity are: endothelial dysfunction, increased sympathetic nervous system activity, abnormal
left ventricular (LV) geometry, systolic and diastolic LV
dysfunction, heart failure, coronary artery disease, dilated left atrium, atrial fibrillation, stroke6.

Pathophysiological mechanisms of
cardiovascular changes in obesity
Pathophysiologic mechanisms of structural and
functional cardiovascular changes of obesity are complex9:
Changes in cardiac metabolism.
Mitochondrial dysfunction and increased oxidative stress.
Impaired insulin signalling: insulin resistance,
hyperglycaemia and diabetes mellitus.
Inflammation the association between obesity
and inflammation is considered one of the main
links of increased incidence of myocardial infarction and heart failure in obese subjects. In patients
with obesity and heart failure it has been demonstrated increased serum levels of proinflammatory cytokines: interleukin 6, interleukin-1, atrial
natriuretic peptide and tumor necrosis factor, without a compensatory increase of antiinflammatory cytokines: interleukin-10 or transforming
growth factor 10.
Neuro-hormonal activation in obesity there is
an overactive sympathetic nervous system.
Hypersympathetic state leads to left ventricular
hypertrophy by increasing myocardial contractility, by
increasing blood pressure, but also through direct hypertrophic effects of catecholamines; in addition, obesity has been demonstrated hyperactivity of the reninangiotensin-aldosterone secretion mechanism, incriminated mechanism being angiotensionogen secretion
from adipocytes of visceral fat.
Production of adipokines disorder with decreased
levels of protective adipokines (adiponectin)
and increase of and proinflammatory and proate-

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rogene adipokines (leptin, insulin, angiotensinogen)10.


Changes of extracellular matrix and fibrosis: in
experimental models of obesity induced in laboratory animals, there was an increase in fibrosis
in the wall of the coronary arteries and increased
accumulation of collagen in the cardiac interstitium9,11.
Apoptosis: experimental studies in obese animals
showed an increase in cardiomyocyte apoptosis
associated with increased ceramide and triglyceride levels in these cells9.
Sleep-apnea syndrome is very common in obese patients and most studies have been shown to
be associated with the presence of left ventricular
hypertrophy by the following mechanisms: increased sympathetic tone, chronic hypoxia, diurnal
and nocturnal exacerbation of hypertension and
excessive changes of intrathoracic pressure during
obstructive periods13.
Overload types and LV geometry changes in obesity
Volume overload was initially considered the primary pathophysiologic mechanism leading to cardiac
remodeling in obesity. Thus increased metabolic needs
of obesity is accompanied by circulating blood volume
expansion, increased stroke volume and cardiac output,
then by the appearance of eccentric LV hypertrophy9,12.
It was subsequently reported an increased predominance of concentric LV hypertrophy in patients with
obesity, a remodeling pattern typical of left heart pressure overload. Pressure overload mechanisms of obesity are related to the coexistence of systemic hypertension, to the nondipper profile (no nocturnal decrease
in blood pressure) and to increased arterial stiffness
reported in obese patients9,13.
Obesity is therefore characterized by a mixed LV
overload with predominance of one component (pressure or volume), depending on which (as well as on
other factors: ethnicity, age, gender, comorbidity, hormonal status, genetic factors) a certain type of cardiac
remodeling appears, with specific prognostic implications12.
Left ventricular geometry evaluation and prognosis
Parameters defining the geometry of the LV are relative wall thickness and LV mass14.
The most accurate determination of LV mass is by
magnetic resonance imaging, followed by three-dimensional echocardiography14.
LV mass can be calculated from two-dimensional
echocardiography parameters by Devereux formula, a

Madalina Iancu et al.


Structural and functional ventriculo-arterial changes in obesity

necropsy validated equation15 and indexed to height in


meters to the power of 2.7 as previously described14.
LV Mass (g) = 0,8*(1,04*[(IVS+LVEDD+PW)3 LVEDD3]+0,6
IVS = interventricular septum thickness, PW = LV
posterior wall thickness, LVEDD = LV end-diastolic
diameter.
The LV mass has to be indexed to the power of 2.7
to minimise the interference of obesity in the estimate
of ventricular mass (LV mass indexed to body surface
area is known to underestimate the prevalence of LV
hypertrophy in overweight and obese patients)16.
LV mass index = LV mass/height2,7.
To evaluate the concentricity of LV geometry, LV
wall thickness (LV posterior wall + interventricular
septum) was divided by LV end-diastolic dimension to
generate relative wall thickness.
Based on LV Mass index and relative wall thickness,
LV geometry can be divided into14:
normal geometry: normal LV mass index, normal
relative wall thickness.
concentric remodelling: normal LV mass index,
increased relative wall thickness.
eccentric hypertrophy: increased LV mass index,
normal relative wall thickness.
concentric hypertrophy: increased LV mass index, increased relative wall thickness.
Prognostic implications of LV geometry changes
Type of LV remodeling is very important in practice,
since each left ventricular geometric pattern was found
to have symptoms, evolution and special prognostic implications in general population. Thus, subjects
with concentric left ventricular hypertrophy showed
the greatest limitation of exercise capacity by reduced systolic and chronotropic reserve. Also concentric
hypertrophy, in the Framingham study, had the worst
cardiovascular prognosis, followed by eccentric hypertrophy, eccentric remodeling and normal LV geometry17. Despite normal LV mass, concentric remodeling
was, in another study, an independent predictor of cardiovascular risk in hypertensive patients18. The LIFE
study has shown an increased risk of ischemic stroke associated with concentric remodeling, increased
risk of cardiovascular death associated with eccentric
hypertrophy and concentric remodeling and an increased risk of myocardial infarction in both concentric
and eccentric hypertrophy19.
It is very likely that in obese patients, electrocardiogram present a low sensitivity in detecting LV hypertrophy, since obesity is known as one of the situations
that are associated with low QRS voltage on ECG20.

Madalina Iancu et al.


Structural and functional ventriculo-arterial changes in obesity

LV geometry changes in obesity are asymptomatic


in the early stages but may later develop into heart failure with LV systolic dysfunction or, more commonly,
to diastolic dysfunction and preserved ejection fraction; the latter is also associated with a poor long term
prognosis21.
LV systolic function in obesity
Studies on LV systolic function in obese patients
provide conflicting information: some authors reported predominantly systolic dysfunction, most normal
ejection fraction and others supernormal systolic function9. Perhaps the results depend on other features of
the different lots of obese patients; it is always very difficult to separate the pure cardiac effects of obesity
from the cardiac effects of its comorbidities (diabetes,
hypertension, etc.), the latter being known to be associated more frequently with coronary artery disease,
which often evolves in LV systolic dysfunction9.
A previous study showed that inducing obesity in
hypertensive mice with concentric LV hypertrophy
leads to a rapid progression to left ventricular systolic
dysfunction, independent of BP or glycosylated hemoglobin values. Several mechanisms have been incriminated: cardiomyocyte apoptosis, activation of mitochondrial collagenases and leptino-resistance22.
Diastolic function in obesity
Diastolic dysfunction is often described in obesity.
Increased LV filling pressures lead to left atrial dilation,
increased risk of atrial fibrillation and secondary embolic stroke9.
Vascular function in obesity
Extensive studies demonstrating that obesity is an
independent predictor of cardiovascular disease, correlated to research results showing the important role of
arterial stiffness in cardiovascular morbidity-mortality
led to hypothesis of vascular dysfunction in obesity.
Numerous works then confirmed increased levels
of arterial stiffness in obese subjects (measured locally,
in the ascending aorta or common carotid artery or by
pulse wave velocity measuring), independent of age,
sex, race or blood pressure levels, but the results are divergent over the role of general adiposity or abdominal
adiposity in the induction of increased arterial stiffness.
Thus, the study by Orr et al. demonstrated that moderate weight gain in normal weight patients is followed
by increased arterial stiffness and reduced arterial compliance in interrelation with abdominal adiposity level
without correlation with overall adiposity level23.

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Wildman et al. demonstrated increased pulse wave


velocity in direct relation to the degree of overall obesity (BMI) independent of ethnicity (both Caucasian
subjects and in Afro-Americans) and showed that vascular dysfunction is present in all age groups adults, including obese youth (20-30 years)24.
Children with obesity are also characterized by increased arterial stiffness and endothelial dysfunction,
as demonstrated Tounian et al., long term effects becoming increasingly important, given that 77% of children
overweight children become obese into adulthood25.
Endothelial dysfunction, arterial stiffening and other
micro- and macrovascular changes described in obesity result in an increased incidence of atherosclerotic
events in this group of patients and in cardiac structural and functional abnormalities9.

OBESITY TREATMENT
The main modalities of obesity treatment are diet,
physical activity, behavior modification, pharmacological therapy and bariatric surgery6,26.
Diet, physical activity and behavioral changes
Reducing total calories intake and regular exercise
are essential for weight control. Overweight control
is dependent on achieving a balance between intake
and energy expenditure. Various types of diets differ
in: total calories, macronutrient composition (protein,
carbohydrates and lipids), energy value and glycemic
index27.
Behavioral attitude change (long-term lifestyle changes) leads to a gradual weight loss and represents the
basis of all obesity treatments.
According to a Cochrane review, behavioral and
cognitive-behavioral therapy is very useful for weight
loss when added to diet and exercise programs27.
Medication
Generally, the contribution of drugs is modest and,
in the past, some products had severe side effects27.
Orlistat inhibits intestinal lipases, preventing hydrolysis and absorption of lipids. Weight loss is usually
modest and cause gastrointestinal disorders, but has a
very good lipid-lowering effect. This product should
be used in combination with a complete and balanced
diet28.
Sibutramine increases the feeling of satiety after
food intake through its metabolites that inhibit the uptake of norepinephrine and serotonin. It was however
associated with sinus tachycardia and increased blood

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pressure28. In 2010, the European Medicines Agency


recommended suspension of marketing authorizations
for sibutramine following a six-year study which showed an increased risk of non-fatal but serious cardiovascular events in patients with a known or high risk for
cardiovascular disease29.
Rimonabant is an inhibitor of endocannabinoid
receptors, which seems to be able to induce a modest
but sustained weight loss in combination with a caloric
controlled diet. Rimonabant may improve glucose tolerance, may beneficially affect lipid metabolism and is
associated with a modest reduction in blood pressure,
but it was also associated with significant psychiatric
disorders (anxiety and depression)30.
In July 2012, the U.S. Food and Drug Administration
approved two new drugs for the treatment of obesity:
Lorcaserin (serotonin 2C receptor antagonist) and an
extended release combination between Phentermine
(previously used in short term treatment of obesity)
and Topiramate (formerly known as antiepileptic and
antimigrain). Both drugs are indicated, as an adjunct,
in obese patients that already made exercise and maintain a reduced calorie diet.
Although diet, exercise and behaviour modification
are essential for weight loss success, in many cases, especially in the long term, are difficult to maintain and
are followed by weight regain.
In this situation, bariatric surgery is an extremely
important and is indicated in patients with BMI> 40
kg/m2 or BMI> 35 kg/m2 in the presence of comorbidities6.
Bariatric surgery
Bariatric surgery is practiced around the world for
34 years and the main types of bariatric interventions
are26:
gastric banding mounting laparoscopic adjustable silicone ring.
longitudinal gastrectomy (gastric sleeve) longitudinal cutting of the stomach, with removal of
its dorsal portion (about 80% of its volume) and
hunger centres - is a recently practiced intervention (in the last 5 years), with very good results on
weight loss without being followed by malabsorption.
gastric-folding - performing folds in the gastric
wall, followed by folds surgical suture with absorbable wires.
gastric bypass complete isolation of a small portion of the stomach that connects to the gut - its

Madalina Iancu et al.


Structural and functional ventriculo-arterial changes in obesity

the most often practiced bariatric intervention in


the U.S. for the last 20 years.
bilio-pancreatic diversion - the most severe way
interfere with the absorption of food calories and
nutrients, which consists of almost complete gastric resection and connection to the distal small
intestine, requiring further supplements in the
form of vitamins and minerals, in order to avoid
anemia, osteoporosis and other diseases caused by
malabsorption.
Weight loss is 40-80% of excess weight in the first
year and it is long term maintained.
Most bariatric procedures are performed laparoscopically, thus presenting the advantages of minimal hospitalization and faster postoperative recovery26.
Reversibility of metabolic and ventriculo-vascular
changes after weight loss
Removal of subcutaneous fat by liposuction was not
associated with significant metabolic changes9.
Pharmacotherapy was associated with weight loss,
improved lipid profile and insulin resistance, but none
of the drugs used to date had significant effect on cardiac dimensions or the pulmonary artery pressure9.
A meta-analysis on 16.867 patients with severe obesity treated by bariatric surgery (mainly aggressive interventions, most frequently gastric bypass) has shown,
after a mean follow-up of 34 months, a significant reduction in cardiovascular risk factors (low level blood
pressure, improved lipid and glycemic status) and a
40% decrease in coronary risk assessed by the Framingham score31.
Another recently published meta-analysis, performed on 19.543 subjects with severe obesity undergoing
bariatric surgery, with mean follow up of 57.8 months,
showed an excess weight loss of approximately 54%
(16-87%), relief or cure of hypertension in 63% of subjects, of diabetes mellitus in 73% of cases and of dyslipidemia in 65% of cases. Echocardiographic data was
available in 713 patients and showed improvement of
LV mass and diastolic function32.
Important studies, over a period of 1-2 years followup after gastric bypass, showed reverse cardiac remodeling after weight loss by decreasing LV mass and its
geometry normalization and decreased right ventricular dimensions; morphological changes were accompanied by improved diastolic function and decreased LV
filling pressures, as by biventricular systolic function
improvement33-36.
It was assumed that bariatric interventions per se
would have a positive role in cardiovascular prognosis

Madalina Iancu et al.


Structural and functional ventriculo-arterial changes in obesity

beyond weight loss by bridging of neuro-hormonal gastrointestinal circuits33; however, this hypothesis cannot
be verified because it is impossible to find a group of
patients that have adopted dietary or medical methods
and have achieved weight loss of similar magnitude
and duration to that secondary to bariatric surgery.
The above studies demonstrated favourable cardiovascular changes after gastric bypass; however, limited
data exists regarding the cardiovascular system effects
of less radical interventions, without risk of malabsorption, such as recently practised laparoscopic longitudinal gastrectomy (gastric sleeve).

PERSPECTIVES
Extent and duration of cardiovascular benefits obtained by weight loss by any means are currently poorly
known. Bariatric surgery produces greater and longterm weight loss and cardiovascular benefits are therefore probably more important33.
Given the high and growing prevalence of obesity
in the world as well as increased experience and number of cases treated by bariatric surgery, studies over
the effects of bariatric surgery on cardiac and vascular
structure and function are needed.
Abbreviations: BMI = body mass index, LV = left
ventricle, IVS = interventricular septum thickness, PW
= Left ventricular posterior wall thickness, LVEDD =
Left ventricular end-diastolic diameter.
Conflict of interests: None declared.
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CASE REPORTS

Apnoea syndrome to an obese hypertensive patient


F. Mitu1,2, Daniela Boiteanu1,3, Adina M. urcanu1,3
Article received on the 18th of October 2012. Article accepted on the 7th of February 2013.
Abstract: The severe forms of sleep apnoea often lead to sudden deaths, and the implementation of an efficient treatment
leads to the normalisation of patients lives by using this pathology. We report the case of a patient, aged 60 years, with morbid
obesity and essential hypertension, who came for cardiovascular re-evaluation, and accused sleepiness, dyspnoea degree III
mMRC, excessive diurnal sleepiness, memory and focus problems. Up to the admission, the patient has not benefitted from an
expert opinion for a correct diagnosis. Following the clinical and paraclinical investigations, it is given the diagnosis of highly
severe sleep apnoea, which requires permanent ventilation with positive pressure throughout the sleep periods.
Keywords: apnoea, hypertension, obesity

INTRODUCTION
Sleep apnoea is among the most frequent chronic disorders. Obstructive sleep apnoea is defined as an interruption of the airflow with persistent effort to breathe, while central apnoea represents an interruption
of the airflow with absence of the effort to breathe.
Hypopnoea is defined as a reduction of at least 30%
of the flow, associated with a minimum reduction of
4% of the Oxygen saturation. The apnoea-hypopnoea
index (AHI) represents the total number of apnoeas
and hypopnoea occurred throughout the entire sleep
period. The SAHS severity is classified according to the
number of episodes per hour: slightly 5-10 episodes/
hour, moderate 15-30 episodes/hour, severe more
than 30 episodes/hour1,2.
The risk factors of obstructive sleep apnoea are age,
obesity, male gender, familial and genetic predisposition, smoking and alcohol, medical co-morbidities (high
blood pressure, congestive heart failure)3.
In cardiology, sleep apnoea might influence the incidence and control of the systemic blood pressure. The
action mechanism is not precisely known, but the presence of hypoxia associated to apnoea may determine
an increased sympathetic activity and, therefore, the
occurrence of high blood pressure. Some researchers
proved that sleep apnoea occurs in 30-50% of male
patients suffering from high blood pressure, and more
than 90% of the patients with apnoea included in the
study already had high blood pressure4,5.
In addition, sleep apnoea registers an increased importance among patients with type II diabetes.
1
Gr. T. Popa University of Medicine and Pharmacy, Iai, Faculty of General Medicine, Department of Medical Semiology
2
The Hospital of Clinical Rehabilitation of Iai, Clinic for Cardiovascular
Recovery
3
Clinical Hospital of Pulmonary Diseases of Iai

Case presentation
We present the case of a patient, aged 60 years, who
came to the Clinic for Cardiovascular Recovery of Iasi
for dyspnoea degree III mMRC, vertigo, fatigue, excessive diurnal sleepiness, diurnal asthenia, focus difficulties, memory problems and tinnitus.
From the hereditary and collateral history, it is observed a familial aggregation of the cardiovascular pathology and of type II diabetes.
Six years earlier, the non-smoker patient had received the diagnosis of essential hypertension (maximum
value of the systolic blood pressure of 170 mmHg), type
II diabetes, treated with oral antidiabetic drugs.
Clinical examination on devices and systems reveals
a body weight of 136 kilos and a body mass index of 54
kg/m2, bilateral leg oedema, bilateral knee pain at joint
mobilisation.
Considering the admission reasons and the clinical
examination, it was suspected that the patient suffered
from sleep apnoea syndrome, and additional investigations were recommended.
Thoracic imaging indicated an emphasized pulmonary drawing of bilateral interstitial type, ecstatic thoracic aorta, left inferior arch of the heart sticking out.
The performed spirometry was normal.
The ENT examination identified the papillomatosis
of the palate veil, without any obstructive effect, chronic hypertrophic rhinitis and also aroused the suspicion of sleep apnoea.
Due to the suspicion of this diagnosis, it was recommended to perform a respiratory polygraphy within the
Contact address:
E-mail: adinagheorghita@yahoo.com

F. Mitu et al.
Apnoea syndrome to an obese hypertensive patient

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

sleep laboratory of the Hospital of Pulmonary Diseases.


The result of the polygraphic records indicates the presence of sleep apnoea of obstructive type, very severe,
with an AHI index = 101/sleep hour, a desaturation index of 101/hour, Oxygen nocturnal average saturation
77% (Tables 1 and 2). It was commenced ventilation
with positive pressure via nasal mask. Self-titration of
the positive pressure via the nasal mask led to a pressure of 12.2 mBarr and to the occurrence of only three
remaining apnoeas. Therefore, it was advised to use an
APAP device adjusted between 4 and 16 mBarr, with
humidifier, at least five hours a night, for an unlimited
period. In addition, the patient will come for follow-up
after 1, 3, 6, 12 months, and then annually.
The analyses performed in order to highlight sleep
apnoea complications and associated pathology lad to
the treatments subsequent implementation.
The echocardiography highlighted calcifications of
the anterior aortic ring, atheromatosis of the posterior
aortic ring, mitral deficiency degree I Doppler. Carotid
ultrasound highlighted calcified plaques at the bifurcation of the right carotid, small calcified plaques on the
left carotid bifurcation. The ankle-right arm index was
1,13, and left arm 1,36. The 24-hour monitoring of the
blood pressure revealed high values of the blood pressure, the highest being 171/89 mmHg and the lowest
128/64 mmHg.
The eye exam identified lens transparency disorders,
retinal angiosclerosis stage III, peripheral pigmentation disturbances.
Haematological and biochemical blood tests revealed the presence of an inflammatory syndrome (VSH=
82 mm/hour, fibrinogen= 7.90 mg/dl, CRP= 3.77) and
of hyperuricaemia (uric acid 8, 64).
The advised basic system was ventilation with positive pressure via nasal mask, in accordance with the
established indications, continuation of the treatment
with oral antidiabetic drugs, nebivolol 10 mg per day,
olmesartanum 40mg per day, allopurinol 100 mg three

times a day, colchicine 1 mg per day, hyposodic, hypocaloric diet, kinetic therapy at home.
After a month with nocturnal APAP ventilation at
home and compliance with the indications, the patients condition returned to normal. The clinical and
paraclinical examination reveals an important weight
loss (12 kilos), increase of the effort capacity, an overall
improved condition, AHI index remaining at 3/sleep
hour and the same efficient pressure to continue nocturnal ventilation.

DISCUSSIONS
Sleep apnoea is a pathology, which must not be neglected because it can lead to sudden death. In the said
case, a very severe form was diagnosed (AHI-101/sleep
hour with desaturation index = 101/hour and average
SpO2 = 77%), which could have led to death at any time
during the sleep.
The patients weight status (BMI = 54 kg/m2), as
well as the increased diameter of the neck represents
another severity factor. In this case, weight loss will
lead to an improvement regarding the effort capacity
and the apnoea form. Therefore, there are recommenTable 2. Oximetry distribution
<95% (minutes)
<90% (minutes)
<85% (minutes)
<80% (minutes)
<75% (minutes)
<70% (minutes)
<60% (minutes)
<50% (minutes)
Total Dur\ (min)97
Average (%)
Desat Index (#/hour)
Desat Max\ (%)
Desat Max dur\ (sec)
Lowest SpO2(2 sec)(%)
# Episodes (5 min)88%
Longest dur\ (min) SpO288%

386.5
381
307.5
213
145
74.5
5.5
0
386.5
77
101.8
35
53
51
19
48.8

Table 1. Type of events recorded through poligrafy

Central Apneas
Obstructive Apneas
Mixed Apneas
Hypopneas
Total

Code

Index
(#/hour)

CA
OA
MA
HY

59.8
0
0
41.8
101.6

Total Number of
Events

512
0
0
358
870
Time in position
AHI in position

Mean duration
(sec)

Max duration
(sec)

15.9
0
0
56.5
56.5

44.5
0
0
332

Events by Position
Supine(#) Non-supine(#)
451
0
0
332

61
0
0
26

462.2
101.6

51.8
100.8

F. Mitu et al.
Apnoea syndrome to an obese hypertensive patient

ded a hypocaloric diet, respiratory rehabilitation and


kinetic therapy.
The association of high blood pressure with sleep
apnoea was confirmed over time by several studies.
The systolic pressure increases more than the diastolic one; the variation is 1.4 0.8 mmHg in relation to
the Oxygen saturation change compared to the diastolic pressure (2.4 1.3 mmHg), which determined the
debit-volume increase by increase of the venous return
during the apnoeic episodes1-3. This aspect is associated
to the increase of the negative intrathoracic pressure.
In this case, the patient had long apnoea episodes and
high values of the blood pressure, which were controlled via drugs for a long period. At the same time, it was
also observed the association of the diabetes.
A series of studies proved that SAHS influences cardiovascular risk by sympathetic activation, chronic inflammatory system, dyslipidemia and insulin resistance, oxidative stress, etc.1,2. Therefore, the treatment of a
patient with sleep apnoea who also presents disorders
such as essential hypertension, diabetes, morbid obesity represents a challenge for the team made up of car-

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

diologists, pulmonologists, diabetologists, kinetic therapy physicians.

CONCLUSIONS
Sleep apnoea is associated to cardiovascular and metabolic changes and significantly contributes to patients
mortality. It is recommended to commence treatment
as soon as possible because most of the times this leads
to an improvement of all parameters and of the overall
condition.
Conflict of interests: none declared.
References
1.
2.
3.

4.

5.

Boiteanu D, Simionescu V, Haulica I et al. Medicina Somnului, Editura Medical, Iai, 2008.
Mihai V, Mihescu T, Luca G et al. Apneea de somn, Editura Edit
DAN, Iai, 2011.
Lawati Al, Patel SR, Ayas NT. Epidemiology, risk factors and consequences of obstructive sleep apnea and short sleep duration. Prog
Cardiovasc Dis 2009;51:285-293.
Nieto FJ, Young TB, Lind KB et al. Association of sleep disordered
breathing, sleep apnea, and hypertension in a large community based study. JAMA 2000;283:1829-1836.
Leung TSR, Douglas TB, Sleep apnea and cardiovascular disease. Am
J Respir Crit Care Med 2001;164:2147-2165.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

CASE REPORTS

Hypertrophic obstructive cardiomyopathy and mitral valve


abnormalities
Nelis Asan1, E. Apetrei1,2, D. Deleanu1, V. A. Iliescu1,2, I. M. Coman1,2
Article received on the 6th of February 2013. Article accepted on the 24th of February 2013.

Abstract:

Hypertrophic obstructive cardiomyopathy is a fascinating disease entity and a source of controversy since the first
modern descriptions by Brock in 19572. Recognition and understanding the significance of left ventricle outflow obstruction
has indeed been a winding road, but one that has eventually provided clinically relevant answers directly related to patient
management. We report a case of hypertrophic obstructive cardiomyopathy (resting left ventricular outflow tract gradient of
136 mmHg) and mitral valve abnormalities in a 63 year-old woman.

CASE STUDY
A 63 year-old woman presented with fatigue and progressive shortness of breath on exertion (class III
NYHA). The patient reported remained asymptomatic until age 55, when she was diagnosed with severe
subaortic stenosis. Transthoracic echocardiography, at
that time, showed left ventricle (LV) hypertrophy intraventricular septum (IVS) 13 mm and LV posterior
wall (PP) 13 mm, LV outflow tract gradient of 107/43
mmHg, mitral regurgitation grade I-II and 50% ejection fraction (EF). There is no any data available related with the morphology of aortic or mitral valve. The
patient had several cardiovascular risk factors, such as
6- year history of moderate hypertension, dyslipidemia, 6-year history of diabetes mellitus type II treated
with oral antidiabetic agents and family history of sudden cardiac arrest (father died of sudden cardiac arrest
when he was 65 years). She followed the treatment as
prescribed in 2005 with betablockers and non-dihydropyridine calcium channel blocker and had a favorable clinical evolution. Over a period of 3 months, the
patient readmitted to the hospital because of dyspnea
on minimal-moderate exertion. Clinical examination
revealed stable patient with a blood pressure of 120/70
mmHg, pulse rate of 80 bpm, the first sound is soft at
the apex, the second sound is normal, mydsistolic ejection murmur heard best at third left parasternal space
and at apex, increased in orthostatism; without systemic or pulmonary congestion signs. The electrocardiogram (Figure 1) indicated sinus rhythm 70bpm, QRS
1
Prof. Dr. CC. Iliescu Institute of Emergency for Cardiovascular Diseases, Bucharest
2
Carol Davila University of Medicine and Pharmacy, Bucharest

Figure 1. Electrocardiogram at admission (see text).

axis +20 grade, left ventricle hypertrophy, ST segment


depression 3.5 mm with negative T wave in V4-V6, DI,
DII and aVL. Chest X-ray showed slight enlargement
of the heart silhouette with cardiothoracic ratio of 55%
and mild accentuation of pulmonary arterial vessels.
Transthoracic echocardiography (TTE) showed that
the interventricular septum and LV posterior wall are
thickened (Figure 3), left ventricular outflow tract peak
gradiente (Figures 4 and 7), intrinsic abnormalities of
the mitral valve direct papillary insertion into the anterior mitral leaflet and a particular structure of interventricular septum (Figure 5)
In Figure 3, two dimensional TTE long axis plane
identified left ventricle (LV) with end-diastolic diameter 37mm, end-systolic diameter 20mm, left atrium diameter 43mm, left ventricular hypertrophy IVS 21mm
at base and 17mm at middle, PP 13mm. The thickness
of the anterior wall of the right ventricle is 7mm.
Left ventricular outflow tract obstruction is showed in Figure 4 and Figure 7. Continuous-wave (CW)
Contact address:
Prof. Dr. Eduard Apetrei, Prof. Dr. CC. Iliescu Institute of Emergency for
Cardiovascular Diseases, Bucharest, 258 Fundeni Street, District number 2.
E-mail: eapetrei@gmail.com

N. Asan et al.
Hypertrophic obstructive cardiomyopathy and mitral valve abnormalities

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Figure 2. The posterior anterior view of chest X ray.

Figure 5. Two dimensional transthoracic echocardiography long axis in diastole showed trabeculae 4mm and 5mm thick (C) insert into IVS and free
wall of LV. Left atrium dilated. LA left atrium, LV - left ventricle, AML anterior mitral leaflet, PML posterior mitral leaflet, IVS interventricular
septum, Ao aorta, PM papillary muscle.

Figure 3. Transthoracic echocardiography parasternal long-axis showing


insertion of papillary muscle into the anterior mitral leaflet (see arrow). LA
left atrium. LV- left ventricle. PP - posterior wall. IVS - interventricular
septum. Ao aorta.

Figure 6. Transthoracic echocardiography long axis Color Doppler systolic


turbulent flow in LV outflow tract (red arrow) and posteriorly directed jet of
mitral regurgitation within the left atrium (green arrow).

Figure 4. Two dimensional transthoracic echocardiography long axis (up)


and M-mode (down). Left ventricular outflow tract (subaortic stenosis)
caused by anterior systolic displacement of anterior mitral leaflet and subvalvular mitral apparatus.

Doppler in apical 5 chambers recorded a left ventricular outflow tract peak gradient of 138 mmHg (Figure
7).
The anomalies of mitral subvalvular apparatus include (Figure 3 and Figure 5) nodular calcifications on
anterior mitral valve chordae, thickening chordae, anomalous papillary muscle with direct insertion into the
anterior mitral leaflet. Aortic valve are thickening and

stiffness (calcification), but with normal leaflet mobility. Tricuspid and pulmonary valves are normal. Color
Doppler shows high velocities across the left ventricular outflow tract in mosaic color and mitral regurgitation jet of III-IV grade (Figure 6).
Assessment of LV diastolic function mitral inflow
shows a restrictive inflow pattern. LV systolic function
is normal with a LV ejection fraction of 65%.
Particularly is the structure of interventricular
septum (Figure 5). In long axis plane, we observed 2
thickening trabeculae 4mm-5mm inserting into LV
free wall at apex and into the interventricular septum.

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Vol. 23, No. 1, 2013

Figure 7. Transthoracic echocardiography apical 5 chambers (up) and continuous-wave Doppler (CW) (down) the concave-to-the left contour of
the Doppler CW jet. Peak gradient in LVOT is 138 mmHg.

The trabeculaes are parallel with interventricular septum and can be part of interventricular septum. IVS
measured 17mm without trabeculae.
Following the clinical profile, electrocardiography
and transthoracic echocardiography data and cardiovascular risk factors, coronary angiography was performed. Epicardial coronary arteries were normal. Left
ventricular catheterization and angiography revealed
VS/Ao pressure gradient of 96 mmHg, mitral regurgitation grade III, left ventricle ejection fraction of 70%
and telediastolic LV pressure of 30 mmHg.

DISCUSSIONS
Structural intrinsic and functional mitral valve or
subvalvular abnormalities have been reported in left
ventricular outflow tract obstruction in hypertrophic
cardiomyopathy. The most frequent is an anomalous
papillary muscle insertion directly into the anterior mitral leaflet, an entity that has been well documented by
Klues et al. in 1991. Of 78 mitral valve specimens from
patients with hypertrophic obstructive cardiomyopathy, 10 were identified as havingdirect insertion of
one or both left ventricular papillary musclesinto the
anterior mitral leaflet8. Is a congenital malformation,
consequence of selective failure of chordal development
at about 12 weeks gestation. Normally, at this stage, the
papillary muscles are contiguous with the mitral leaflets. The cephalad portions of the papillary muscles are
first transformed into a thick muscular chordae, which
finally become fibrous chordae positioned between the
mitral leaflets and the papillary muscles. The arrest in
normal embryological development is not pathognomonic of obstructive hypertrophic cardiomyopathy8.

N. Asan et al.
Hypertrophic obstructive cardiomyopathy and mitral valve abnormalities

Other anomalies of mitral subvalvular apparatus include abnormal chordae tendineae that attach to the
ventricular septum or left ventricular free wall and
accessory papillary musclese, all which may tether the
mitral leaflets toward the septum and produce LVOT
obstruction9.
The choice of optime procedure must be individualizad based on age, comorbidities, suitability of coronary
anatomy, intrinsec mitral valve disease, patient preferente and operator experience4.
The conventional septal myectomy (Marrow procedure) is not the optimal procedure.
After the classic septal myectomy, the patients with
HOCM and anomalies of the mitral subvalvular apparatus can lead to intraoperative death, incomplete or
only temporary relief of LVOT obstruction, persistent
of SAM and mitral regurgitation3,8.
Additional procedures are represented by: anterior
mitral leaflet excision or plicating, false chordae excision and papillary muscle realignment2,6,10.
Rankin J at al. described o new surgical concept:
septal myectomy, excision of papillary muscle incriminated in LVOT obstruction, chordae excision and mitral ring anuloplasty; the mitral valve was repaired by
connecting the left aspect of the leaflets to the posterior
papillary muscle, using Gore-Tex artificial chords11.
Mitral valve replacement is possible in mitral regurgitation associated with chordae rupture, mitral valve
prolapse, mitral ring dilatation or in valvular morphological disease like restrictioned, thickened, calcifications or myxomatous valve9,12.
In conclusion, we reported a patient with obstructive
hypertrophic cardiomyopathy (LVOT peak gradient of
138 mmHg on transthoracic echocardiography and 96
mmHg on left ventricular catheterization) and severe
mitral regurgitation of III-IV grade. A spectrum of mitral leaflet abnormalities and systolic displacement of
mitral anterior leaflet and subvalvular apparatus have
been related to the mechanism of mitral regurgitation.
The patient is at increased risk for sudden death
(SCD). We have identified 2 risk factors for SCD: LV
septal hypertrophy and family history of sudden death.
Three members of family (the daughter and 2 nephew)
were evaluated or screened with ecg and ecocardiography, which were normal. In our case report, percutaneous alcohol septal ablation, method we perform
currently in our institute, is constrained by mitral valve
abnormalities1. The myectomy has the advantage of direct visualization of complex LV outflow tract anatomy

N. Asan et al.
Hypertrophic obstructive cardiomyopathy and mitral valve abnormalities

and recognition of all structural abnormalities that


contribuite to mechanical subaortic obstruction.
European Society of Cardiology and American College
of Cardiology12 recommend surgical septal myectomy
as the gold standard treatment for most drug-refractory
and severely symptomatic HOCM patients. However,
in Europe after the introduction of alcohol septal ablation 15-20 years ago, septal myectomy has essentially
disappeared, alcohol septal ablation being promoted as
a superior and easier treatment strategy for decrease or
abolition of the LVOT obstruction1,2,4.
Surgical myectomy is performed in only 5 European
centres (3 in Italy)6.
Recent the Italian Bergamo Center published a
report about 124 patients with obstructive HCM and
heart failure symptoms who underwent myectomy. The
LV outflow gradient decreased from 95 36 mmHg before surgery to 12 6 mmHg post surgery. Periprocedural mortality was 0.8% (1 patient) and 0.8%, 3.3% at
1 and 5 years respectively5. The study of Iacovoni et al.
has important implications for the management of obstructive HCM in Europe and should be a stimulus for
other institutions elsewhere in Europe to initiate HCM
programmes13.

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Vol. 23, No. 1, 2013
2.

3.

4.
5.

6.

7.

8.

9.

10.

11.

12.

Conflict of interests: The authors declare that no


conflict of interest exists.
References
1.

Apetrei E, Seggewiss H, Deleanu D i col. Ablaia miocardic septal


percutan n cardiomiopatia hipertrofic obstructiv. Revista Romn de Cardiologie, Vol IX; nr 3-4;1999.

13.

Maron BJ, Maron MS, Douglas Wigle E, Braunwald E. The 50-year


history, controversy and clinical implications of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: from idiopathic hypertrophic subaortic stenosis to hypertrophic cardimyopathy, J Am Coll Cardiology 2009;54:191-200.
Minakata K, Dearani JA, Nishimura RA et al. Extended septal myectomy for hypertrophic obstructive cardiomyopathy with anomalous
mitral papillary muscles or chordae J Thorac Cardiovasc Surg 2004;
127:481-489.
Carolyn Ho Y. Hypertrophic Cardiomyopathy in 2012 Circulation
2012;125:1432-1438.
Iacovoni A, Spirito P, Simon C, Ferrazzi PA et al. A contemporary
European experience with surgical septal myectomy in hypertrophic
cardiomyopathy Eur Heart J 2012;33:2080-2087.
Maron BJ, Yacoub M, Dearani JA. Benefits of surgery in obstructive
hypertrophic cardimyopathy: bring septal myectomy back for European patients Eur Heart J 2011 32: 1055-1058.
Nagueh SF, Bierig SM, Budoff MJ et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with hypertrophic cardiomyopathy J Am Soc
Ecocardiogr 2011:24:473-98.
Klues GH, Robert WC, Maron BJ. Anomalous insertion of papillary
muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy significance in producing left ventricular outflow obstruction.
Circulation 1991;84:1188-1197.
Imoto Y, Kado H, Yasuda H, et al. Subaortic stenosis caused by anomalous papillary muscle of the mitral valve Ann Thorac Surg 1996; 62:
1858-1860
Bryant R, Smedira NG Papillary muscle realignment for symptomatic
left ventricular outflow tract obstruction J Thorac Cardiovasc Surg
2008;135:223-224.
Rankin JS, Binford RS, Johnston TS, et al. A new mitral valve repair
strategy for hypertrophic obstructive cardiomyopathy. The Journal of
heart valve disease 2008;17:642-647.
Maron BJ, McKeena WJ, Danielson GK et al. American College of
Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A report of the
American College of cardiology Foundation task Force on Clinical
Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;
42:1687-1713.
Dearany J.A. Septal myectomy remains the gold standard. Eur Heart J
2012;33:1999-2000.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

IMAGES IN CARDIOLOGY

Vascular Doppler: Complex aortic arch pathology


Ileana Arsenescu
Article received on the 25th of November 2012. Article accepted on the 8th of February 2013.

56

years old hypertensive, dyslipidemic patient,


with a personal history of smoking, known in
the Cardiology clinic for recurring pectoral angina
episodes. The patient presents bilateral latero-cervical
murmurs and the systolic blood pressure measured on
the left arm is 70 mm Hg higher than on the right arm.

Figure 1. Right carotid axis. The CCA does not present color Doppler signal, except for the terminal portion, just before the bifurcation. The different color of the Doppler signal present in the ICA and ECA shows that the
blood flows in opposite directions.

Figure 2. The proximal and medium portions of the right CCA do not register spectral Doppler signal.

Prof. Dr. C. C. Iliescu Emergency Institute of Cardiovascular Diseases,


Bucharest, Romania

Abreviations:
CCA common carotid artery
ICA
internal carotid artery
ECA external carotid artery
SV
systolic velocity
DV
diastolic velocity
RI
resistance index

Figure 3. Right ICA: SV = 35 cm/s, DV 17 cm/s, RI = 0.50. The Doppler signal is anterograde. Low velocities, normal RI. A notable aspect is the slower
systolic ascension.

Figure 4. Right ECA: SV = - 55 cm/s, DV = - 29 cm/s, RI = 0.48. The Doppler


signal is retrograde. We can notice the increased diastolic component and
the very low resistance index.

Contact address:
Arsenescu Ileana, MD, Prof. Dr. C. C. Iliescu Emergency Institute
of Cardiovascular Diseases, 258 Fundeni Street, District no. 2, 022328,
Bucharest, Romania.

Ileana Arsenescu
Vascular Doppler: Complex aortic arch pathology

Figure 5. Right vertebral artery: SV = 67 cm/s, DV = 29 cm/s, RI = 0.66.


Symmetrical increase of the systolic and diastolic velocities, with normal
resistance index.

Figure 6. Right subclavian artery: SV = 65 cm/s. Without significant signal


anomalies, except for the fading positive wave in the protodiastole, indicating low arterial elasticity.

Figure 7. Left CCA: SV = 135 cm/s, DV = 50 cm/s, RI = 0.62). Slightly increased velocities. Normal resistance index.

Figure 8. Left ICA: SV = 127 cm/s, DV = 54 cm/s, RI = 0.57. Slightly increased velocities. Normal resistance index.

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Vol. 23, No. 1, 2013

Figure 9. Left ECA: SV = 135 cm/s, DV = 36 cm/s, RI = 0.72. Slightly increased velocities. The resistance index is lower than 0.75, relatively low for
an external carotid artery, suggesting a degree of flow internalization.

Figure 10. Left vertebral artery. The Doppler signal is totally reversed (5th
grade arterial blood theft). The absence of the diastolic component suggests that the flow is directed to a high resistance territory.

Figure 11. The left subclavian artery, in the sterno-clavicular region. Increased velocities and the turbulent flow show that the recording is made
immediately after the occurrence of a severe lesion. The presence of a hyperemic monophase wave aspect with a significant diastolic component suggests that it is a severe lesion.

Figure 12. Left subclavian artery, after the emergence of the vertebral artery. The hyperemic monophase wave is maintained, with an increase in the
systolic ascension time, an aspect typical for a poorly compensated, severe
stenosis.

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Vol. 23, No. 1, 2013

COMMENTS
Right side
- The inversed and internalized Doppler signal on
the right ECA (Fig. 1 and Fig. 4) shows that the
incomplete occlusion of the right CCA allows a
blood supply to the ICA from the ECA, at the bifurcation
- The right ECA has an incoming blood flow from
the left ECA, where the Doppler signal has increased velocities and a degree of internalization
suggested by the low resistance index (Fig. 9).
- The moderate increase of velocities on the left
ICA (Fig. 8) show that it also has a role in compensating the occlusion of the right CCA, via the
anterior communicating artery
Left side
- The hyperemic monophase Doppler wave, with a
permanent anterograde diastolic component and

Ileana Arsenescu
Vascular Doppler: Complex aortic arch pathology

the slow systolic ascension recorded in the subclavian artery (Fig. 11 and Fig. 12) is a typical,
indirect sign found below a severe arterial lesion.
- The severity of the proximal subclavian artery
lesion is confirmed by the complete flux inversion present in the vertebral artery (Fig. 10), now
oxygenating the left superior limb. The Doppler
curve lost its anterograde diastolic component,
characteristic for a normal vertebral flux. Now
it has the aspect of an artery supplying blood for
a high resistance territory, like the left superior
limb.
- The Doppler signal was normal on the right vertebral artery, thus eliminating the possibility of its
involvement in compensating the occlusion of the
right CCA, or in the blood theft phenomenon
present in the left vertebral artery.
Conflict of interests: none declared.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

IMAGES IN CARDIOLOGY

Coronary Angiography: Simultaneous acute thrombotic


occlusion of two coronary arteries in ST segment elevation
myocardial infarction
A. Negoi, F. Purcarea, M. Croitoru, D. Deleanu
Article received on the 12th of February 2013. Article accepted on the 28th of February 2013.

e present the case of an 85 year old woman with


a personal history of hypertension and dyslipidemia, brought by the ambulance to the emergency
room two hours after the debut of an intense retrosternal chest pain. During transportation to the emergency
room the patient suffered an episode of conscience loss.
The EKG performed in the ambulance revealed a ventricular tachycardia episode, electro-converted to sinus
rhythm.
The clinical examination performed upon presentation marks a deteriorated state, blood pressure (BP)
70/40 mmHG, heart rate (HR) 35 bpm, EKG shows a
IIIrd degree atrioventricular block, ST elevation in DII,
DIII, aVF, V4 - V6, (a maximum of 5 mm), ST depression in DI, aVL , V1-V3. The echocardiography reveals
a moderate systolic dysfunction (ejection fraction (EF)
40%) and segmentary kinetic abnormalities of the late-

ral and inferior walls, with severe mitral regurgitation.


The patient is immediately brought to the catheterization laboratory, where an emergency angiography
is performed, after the implantation of a temporary
stimulation electrode. The coronarography discovers
an acute thrombotic occlusion both in the second segment of the circumflex artery, as well as in the first segment of the right coronary artery(RCA) with TIMI 0
distal flux in both vessels. Thromboaspiration with the
extraction of thrombotic material is performed on both
occlusions and tight stenosis areas can be observed on
both coronary vessels, requiring stent implantation.
Postoperatory, the patients evolution was favorable,
she was hemodynamically stable, with a significant improvement concerning the degree of mitral regurgitation (IInd degree) and the remission of the atrioventricular block.

Figure 1. Acute thrombotic lesion on the IInd segment of the circumflex


coronaryartery (CxA), TIMI 0 flux (continuous arrow), cardiostimulation
electrode placed in the right ventricle (RV) (dotted arrow).

Figure 2. Acute right coronary artery thrombotic lesion in the Ist segment.
Timi 0 flux (continuous arrow).

Prof. Dr. C. C. Iliescu Emergency Institute of Cardiovascular Diseases,


Bucharest, Romania

Contact address:
Negoita Adrian, MD, Prof. Dr. C. C. Iliescu Emergency Institute
of Cardiovascular Diseases, 258 Fundeni Street, District no. 2, 022328,
Bucharest, Romania.

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

A. Negoita et al.
Acute thrombic occlusion of two coronary arteries in STEMI

Figure 3. Final result after thromboaspiration and stent implantation on the CxA and RCA, with TIMI III distal flux.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

IMAGES IN CARDIOLOGY

Ecocardiography: Pseudo-pseudoaneurysm natural evolution


of a rare myocardial infarction mechanical complication
Maria-Magdalena Gurzun1, Marinela erban1, B. A. Popescu1,2, Carmen Ginghin1,2
Article received on the 5th of February 2013. Article accepted on the 18th of February 2013.

ardiac rupture is a well known and feared mechanical complication of myocardial infarction. It is
diagnosed in approximately 4% of myocardial infarctions and is the second most common cause of in-hospital mortality in this patient population1. Contrary to

Figure 1. Transthoracic echocardiography, four-chamber view discontinuity of the endocardium extending toward the epicardial layer (arrow); [LV
left ventricle, LA left atrium, RV right ventricle, RA right atrium].

widely held medical belief, myocardial rupture is not


always a fatal condition2.
A 59 year old man with a recent history of non-revascularized anterior myocardial infarction was admitted for exertional chest pain.
Transthoracic echocardiography showed extensive
left ventricular (LV) regional wall motion abnormalities, mainly in the left anterior descending artery territory (akinesis of the anterior wall, apex, anterior septum
and apical segments of the lateral and inferior walls)
with severe LV global systolic dysfunction and no pericardial effusion. The apical anterior septum presented a small gap in the endocardium extending toward
the epicardium (Figure 1). The defect appeared to be
contained within the myocardium and did not involve
the whole wall thickness (Figure 2). Contrast echocardiography (SonoVue, Bracco) demonstrated the absence of communication with the pericardial sac or with
the right ventricle (Figure 3), suggesting an incomplete
rupture of the LV myocardial wall.

Figure 2. Transthoracic echocardiography, modified four chamber view


a defect measuring 1cm that communicates with the left ventricle cavity
through a narrow neck. The defect appears to be circumscribed within theventricular wall; [LV left ventricle, AO aorta].

Figure 3. Contrast transthoracic echocardiography the LV cavity is completely opacified but there are no bubbles in the pericardial space, demonstratingthe lack of communication; an intact myocardium layer is present at
the tip of the defect; [LV left ventricle].

1
Prof. Dr. C. C. Iliescu Emergency Institute of Cardiovascular Diseases,
Bucharest, Romania
2
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Contact address:
Maria-Magdalena Gurzun, MD, Prof. Dr. C. C. Iliescu Emergency Institute of Cardiovascular Diseases, 258 Fundeni Street, District no. 2, 022328,
Bucharest, Romania. Tel./Fax +4021 317 52 27. E-mail: magdalenagurzun@
gmail.com.

Maria-Magdalena Gurzun et al.


Ecocardiography: Pseudo-pseudoaneurysm

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Coronary angiography showed occlusion of the left


anterior descending coronary artery and a 90% stenosis
of the right coronary artery in the mid segment.
Serial echocardiograms performed during the first
week showed that the rupture did not progress to an
interventricular communication or a ventricular pseudoaneurysm.
Surgical treatment was denied by the patient.
After seven months the patient was clinically stable,
without angina or heart failure on optimal medical
treatment. Transthoracic echocardiography showed a
hyperechogenic area replacing the discontinuity observed before and a large thrombus covering this area
(Figure 4).
Morphologically, four patterns of myocardial rupture have been described1,3. Type I and type II represent
complete myocardial rupture with either linear or multicanalicular trajectory with devastating haemodynamic consequences; emergent surgical treatment is
mandatory in these cases. In type III (pseudoaneurysm), the orifice of rupture is protected by thrombus on
the ventricular side or pericardial symphysis; surgical
treatment is indicated4. In type IV (pseudo-pseudoaneurysm) the trajectory does not extend through all
layers and is therefore not transparietal; the rupture re-

mains circumscribed within the ventricular wall itself


but in communication with the ventricular cavity; the
natural course and the optimal management is not clear because there are only few cases reported4. Both type
III and type IV ruptures are often grouped together as
incomplete myocardial rupture5.
Lack of communication with the pericardium and
echocardiographic appearence of an intact myocardial layer suggested that pseudo-pseudoaneurym is the
most likely diagnosis in our case. For confirmation a
cardiac magnetic resonance study would have been
useful. Contrast echocardiography seems to be an alternative method for the early diagnosis of myocardial rupture providing quick information regarding the
rupture type: complete (i.e. emergent surgery is mandatory) or incomplete (i.e. surgery may be delayed)6,7.
The take home message of this case is that conservative management of pseudo-pseudoaneurym with
close clinical and echocardiographic follow up may be
considered in asymptomatic patients with high surgical
risk.
Conflict of interests: The authors declare that no
conflict of interest exists.
References
1.

2.

3.

4.

5.

6.
Figure 4. Transthoracic echocardiography after 7 months, five chamber
view hyperechogenic area replacing the discontinuity observed before and
alarge apical thrombus covering the previous pseudo-pseudoaneurysm; [LV
left ventricle, LA left atrium, RV right ventricle, RA right atrium,
AO aorta].

7.

Sutherland FW, Guell FJ, Pathi VL, Naik SK. Postinfarction ventricular free wall rupture: strategies for diagnosis and treatment. Ann
Thorac Surg 1996: Apr;61(4):1281-5.
Mittle S, Makaryus AN, Mangion J. Role of contrast echocardiography in the assessment of myocardial rupture. Echocardiography 2003:
Jan;20(1):77-81.
Perdigao C, Andrade A, Ribeiro C. Cardiac rupture in acute myocardial infarction. Various clinico-anatomical types in 42 recent cases
observed over a period of 30 months. Arch Mal Coeur Vaiss 1987:
Mar;80(3):336-44.
Gollol-Raju N, Olearczyk B, Johnson R. Pseudo-pseudoaneurysm: a
rare and unexplored mechanical complication of myocardial infarction. J Am Soc Echocardiogr 2007: Nov; 20(11):1317.
Helmy TA, Nicholson WJ, Lick S, Uretsky BF. Contained myocardial
rupture: a variant linking complete and incomplete rupture. Heart
2005: Feb;91(2):e13.
Garca-Fernndez MA, Macchioli RO, Moreno PM, Yangela MM,
Thomas JB, Sendn JL, Lopez de Sa E, Abdou YH. Use of contrast
echocardiography in the diagnosis of subacute myocardial rupture
after myocardial infarction. J Am Soc Echocardiogr 2001: Sept;
14(9):945-7.
Ishida T, Yasu T, Arao K, Kawakami M, Saito M. Bedside diagnosis
of cardiac rupture by contrast echocardiography. Circulation 2005:
Dec:13;112(24):e354-5.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

UPDATES IN CARDIOLOGY

Progrese n valvulopatii n 2012


Spre deosebire de alte patologii cardiovasculare, bolile valvulare nu au fost studiate pe larg n numeroase
studii clinice. n 2012 Societatea European de Cardiologie n colaborare cu Asociaia European de Chirurgie Cardiotoracic a elaborat un ghid ce vizeaz bolile
valvulare n care au fost incluse noile progrese fcute n
managementul medical, intervenional i chirurgical.
Terapia medical
Puinele studii clinice efectuate legate de terapia medicamentoas la pacienii cu valvulopatii au avut rezultate negative, astfel nct managementul pacienilor
asimptomatici rmne dificil. Noile metode imagistice
au artat importana calcificrilor i inflamaiei n geneza valvulopatiilor, oferind unele direcii pentru dezvoltarea de noi terapii.
Noul ghid atrage atenia la nevoia de o mai bun caracterizare a pacienilor cu stenoz aortic (SA) sever
asimptomatic n funcie de aria valvular, gradientul
transvalvular i diveri biomarkeri, n vederea unei intervenii mai precoce. n ceea ce privete insuficiena
mitral (IM) sever, s-a artat ntr-un studiu randomizat, placebo controlat, c tratamentul cu metoprolol
ar determina o modest prezervare a fraciei de ejecie
i o tendin ctre reducerea necesitii de intervenie
chirurgical la 2 ani, dar fr un beneficiu notabil pe
remodelare.
Terapia intervenional
Implantarea percutan de valv aortic (TAVI) a fost
introdus ca terapie pentru pacienii cu SA sever inoperabili n ghidul din 2012 n urma publicrii rezultatelor trialului PARTNER. TAVI a determinat o reducere
a mortalitii la 2 ani cu 25%, o mbuntire a simptomatologiei i calitii vieii, o scdere a spitalizrilor
spre deosebire de terapia medical optim asociat sau
nu cu valvuloplastie cu balon. Nu a existat o diferen n mortalitatea la 2 ani i n incidena accidentelor
vasculare cerebrale ntre TAVI i operaia de nlocuire
valvular la pacienii cu risc chirurgical crescut. Totui,
la pacienii cu TAVI s-a nregistrat mai des apariia regurgitrilor paravalvulare. Recomandarea este ca TAVI
s se realizeze n centre nalt specializate ce dispun de
chirurgie cardiovascular, cazurile s fie discutate de
Heart Team i s nu fie realizat la pacienii cu risc operator sczut sau intermediar.

Valvulotomia mitral percutan pentru stenoz mitral este o terapie care i-a dovedit eficiena de-a lungul timpului. Ce aduce nou ghidul sunt criteriile de
selecie a pacienilor pentru valvulotomie mitral percutan, care ar putea justifica o intervenie la pacienii
mai tineri, cu simptomatologie minim dar cu morfologie valvular favorabil.
n ceea ce privete IM sever, terapia percutan este
o intervenie considerat dificil datorit anatomiei
complexe a valvei mitrale. Actual este recomandat
doar valvuloplastia mitral cu MitraClip, cu toate c
trailul EVEREST II nu a artat beneficii convingtoare a acesteia fa de valvuloplastia chirurgical. Astfel,
aceast procedur este indicat n cazul pacienilor cu
IM sever inoperabili care rmn simptomatici n ciuda terapiei medicale maximale.
Terapia chirurgical
Severitatea insuficienei mitrale ischemice afecteaz
supravieuirea dup revascularizarea chirurgical sau
percutan. O subanaliz a trialului STICH a investigat
dac repararea IM ischemice la pacienii cu fracie de
ejecie sczut n momentul efecturii bypass-ului aortocoronarian are un impact asupra supravieuirii. S-a
observat c att mortalitatea intraspitaliceasc ct i
mortalitatea pe termen lung a fost mai mic la cei la
care s-a practicat reparare valvular pentru IM moderat sau sever, dar fr semnificaie statistic.
Endocardita infecioas
n ceea ce privete endocardita infecioas se rentrete faptul c profilaxia ar trebui instituit doar la pacienii cu risc crescut i c intervenia chirurgical ar
trebui efectuat precoce la pacienii cu distrucii valvulare severe sau/i la risc crescut de embolii sistemice (n
special la cei cu vegetaii >10 mm). n urma abordrii
acestor noi recomandri legate de profilaxia endocarditei s-a observat c incidena global a endocarditei,
precum i cea determinat de streptococ s-a meninut
la fel, pe cnd endocardita asociat cu stafilococul auriu a nregistrat o cretere a incidenei. Astfel, se atrage
atenia asupra importanei prevenirii bacteriemiei cu
stafilococ, mai presus dect profilaxia antibiotic la pacienii fr indicaie clar.
(Prendergast BD. The Year in Cardiology 2012: valvular heart disease. Eur Heart J. 2013 Feb;34(6):427-31)
(LP)

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Progrese n insuficiena cardiac n 2012


n anul 2012 s-au nregistrat cteva progrese n ceea
ce privete insuficiena cardiac (IC). Aceste progrese
au fost prezentate n noul ghid de insuficien cardiac
cronic i acut al Societii Europeane de Cardiologie
elaborat sub conducerea lui John McMurray, i au fost
dezbtute pe larg la Congresul European de Cardiologie de la Munich i Sesiunea tiinific a American
Heart Association de la Los Angeles.
Noul ghid european de insuficien cardiac clarific
pentru fiecare medicament utilizat legtura dintre clasa
de recomandare i nivelul de eviden i indicaia clinic a acestuia (de ex. Inhibitorii de enzim de conversie
(IEC) sunt indicai la pacienii cu insuficien cardiac
cu fracie de ejecie (FE) sczut pentru a reduce spitalizrile i mortalitatea). Alte modificri majore sunt
reprezentate de:
Antagonitilor receptorului pentru mineralocorticoizi (MRA) (spironolatona i eplerenona) li se
acord o atenie mai mare i sunt indicai la pacienii care rmn n clas funcional NYHA IIIV i au FE 35% n ciuda tratamentului cu IEC
i betablocant pentru reducerea spitalizrilor i
mortalitii (I-A).
Conform dovezilor din trialul SHIFT, ivabradina
se poate administra pentru scderea spitalizrilor
pacienilor n ritm sinusal, cu FE 35%, frecven cardiac 70/minut i clas funcional II-IV
NYHA n ciuda tratamentului cu beta blocant,
IEC i MRA (IIa-B)
Trialurile RAFT i MADIT-CRT au adus dovezi
pentru recomandarea terapiei de resincronizare cardiac (TRC) la pacienii cu IC n clas II
NYHA, care sunt n ritm sinusal, au o durat a
complexului QRS 130 ms, cu o morfologie de
bloc de ramur stng, FE30% i o speran de
via > 1 an, cu scopul de a reduce spitalizrile i
mortalitatea. De remarcat este c pacienii care au
o morfologie a complexului QRS alta dect blocul
de ramur stng, TRC se poate indica doar dac
durata complexului QRS 150 ms (IIa-A). Ghidul
atrage atenia asupra lipsei de dovezi n ceea ce
privete dou situaii frecvente n practica curent: pacienii n fibrilaie atrial i pacienii cu FE
sczut care necesit implantarea unui stimulator
cardiac dar care nu au criteriile necesare pentru
TRC.
La pacienii n stadiul terminal al IC n ciuda terapiei maximale se pot utiliza n centre nalt specializate aparate de asistare ventricular ca o terapiei
temporar pn la un transplant cardiac.

Updates in cardiology

La pacienii inoperabili cu stenoz aortic sever


sau insuficien mitral sever se poate utiliza implantarea percutan de valv aortic i repararea
percutan a valvei mitrale cu MitraClip.
Bazndu-se pe rezultatele trailului WARCEF (care
nu a evideniat nicio diferen ntre aspirin i
warfarin n endpointul primar compozit de mortalitate, accident vascular cerebral ischemic i hemoragie intracracian) terapia anticoagulant nu
se recomand de rutin la pacienii cu IC.
Nu exist dovezi robuste n ceea ce privete restricia srii n IC.
La congresul european de cardiologie au fost prezentate dou trialuri care vizeaz pacienii cu IC cu FE
pstrat: PARADIGM-HF i ALDO-HF.
n trailul PARAGIGM-HF a fost comparat inhibitorul de receptor de angiotensin neprilysin (LCZ696) cu
valsartanul la pacienii cu FE45% i NT-pro-BNP400
pg/ml. S-a artat c LCZ696 reduce concentraia NTpro-BNP, mbuntete clasa NYHA i parametrii de
remodelare ai atriului stng spre deosebire de valsartan. Sunt rezultate promitoare la o categorie de pacieni la care IEC i sartanii nu i-au dovedit eficiena.
ALDO-HF a studiat spironolactona 25 mg/zi fa de
placebo la pacienii n clas II NYHA, cu FE50% i
disfuncie diastolic de ventricul stng. Spironolactona
a determinat mbuntirea parametrilor de remodelare a ventricului stng (mbuntete raportul E/E, scade masa ventricului stng, concentraia NT-pro-BNP),
dar fr a avea un impact pe simptomatologie, spitalizare, mortalitate i peak VO2. Sunt ateptate rezultatele
unui trial mai mare (TOPCAT) la sfritul anului 2013
pentru elucidarea acestei discrepane.
La sesiunea AHA din 2012 au fost prezentate rezultatele altor dou studii importante: RELAX-HF i
CARRESS-HF.
RELAX-HF a studiat un hormon de sarcin (relaxina-seralaxina) versus placebo la 1160 pacieni cu IC
acut care au tensiunea arterial sistolic >125 mmHg.
Seralaxina a fost administrat n perfuzie timp de 48
ore n primele 16 ore de la prezentare. Aceasta a determinat scderea cu 19% a dispneei, dar nu s-a nregistrat
un efect pe mortalitate i spitalizare la 60 zile. De asemenea, seralaxina a sczut concentraia NT-pro-BNP,
creatininei, troponinei i a sczut durata spitalizrii.
Totui, la 6 luni s-a nregistrat o scdere cu 37% a mortalitii cardiovasculare i mortalitii de orice cauz.
n CARRESS-HF s-au randomizat 188 pacienti cu IC
acut decompensat i disfuncie renal fie ctre tratament medicamentos, fie ctre ultrafiltrare. Nu s-au

Updates in cardiology

nregistrat diferene n scderea n greutate, nivelul creatininei, spitalizri dar ultrafiltrarea a determinat o deteriorare semnificativ a funciei renale i reacii adverse mai importante. Astfel se consider c ultrafiltrarea
rmne o metod de utilizat mai degrab la pacienii
neresponsivi la tratamentul diuretic.
(McDonagh TA, The Year in Cardiology 2012: heart
failure, Eur Heart J. 2013 Feb;34(7):499-502) (LP)
Managementul hemoragiilor acute la pacienii aflai
n tratament cu anticoagulante orale noi
Anticoagulante orale noi care inhib direct trombina
(dabigatran) sau factorul Xa (rivaroxaban, apixaban)
sunt disponibile n prezent pentru prevenirea tromboembolismului venos (TEV), dup intervenii chirurgicale ortopedice, tratamentul TEV acut, i n prevenia
trombo-embolismului arterial n fibrilaia atrial nonvalvular. Aceti ageni ofer avantaje fa de antivitaminele K, inclusiv debut rapid, timp mai scurt de
njumtire, interaciuni mai puine cu medicamente
sau alimente, precum i lipsa monitorizrii de rutin.
Cu toate acestea, n prezent nu exist vreun antidot al
noilor anticoagulante orale. Abordarea managementului pacienilor cu complicaii hemoragice este diferit i
cuprinde mai multe strategii. Pacienii cu sngerare activ trebuie s fie supui unei evaluri rapide cu urmrire atent a stabilitii / instabilitii hemodinamice,
trebuie identificat ct mai rapid sursa de sngerare urmat de stratificarea riscului. Timpul scurs de la ultima
doz i funcia renal (n special pentru dabigatran), ar
trebui s fie stabilite cci acestea pot influena conduita
ulterioar.
Sngerri minore (de exemplu epistaxis, echimoze,
menoragie) ar trebui gestionate prin msuri locale hemostatice. O perioad scurt de ntrerupere a anticoagulantului oral poate fi considerat, dar trebuie s fie
pus n balan cu riscul tromboembolic individual i
urmat de re-iniierea anticoagulantului.
n caz de sngerare moderat (de exemplu, hemoragie gastro-intestinal superioar sau inferioar), anticoagulantele orale trebuiesc ntrerupte. O perioad
lung de ntrerupere poate fi necesar n funcie de fezabilitatea hemostazei locale sau mecanice. Pacienii ar
trebui s fie monitorizai pentru evaluarea hemodinamic i propui pentru intervenii definitive hemostatice.Adugarea unui anticoagulant parenteral n doze
mici poate fi luat n considerare la pacienii cu risc
nalt de evenimente tromboembolice.
Hemoragia sever /amenintoare de via impune
terapii suportive (de exemplu, nlocuirea volum, vasopresoare, ventilaie mecanic), dup cum este necesar.

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

n urgen ar trebui fcut hemostaza procedural sau


chirurgical.
Nu exist date cu privire la utilizarea plasmei proaspete congelate (FFP) la pacienii cu hemoragii asociate
anticoagulantelor orale noi. La oarecii care primesc
doze mari de dabigatran, FFP a redus hemoragia intracerebral, dar nu a avut niciun efect asupra mortalitii.
FFP prezint riscuri de suprancrcare volemic i, rar,
reacii alergice, i infecie. Concentratul de complex
protrombinic (activat) (PCC) conine doze mari de factori de coagulare dependeni de vitamina K i cantiti
variabile de proteine C i S. Transfuzii de trombocite
pot fi administrate la pacienii care au primit tratament
antiagregant plachetar concomitent. Se recomand
concentratuldecomplex protrombinic -complex de 4
factori n doz de 50 UI / kg sau concentratuldecomplex protrombinic activat (aPCC) (80 U / kg) pentru rivaroxaban sau apixaban. Pentru dabigatran, aPCC (80
U / kg) este preferat de peste 4-PCC (50 UI / kg). Exist
ns o lips de date privind utilizarea acestor ageni i
se recomand luarea n considerare a riscului de tromboz crescut nainte de administrare. Terapii adjuvante,
cum ar fi desmopresina sau ageni antifibrinolitici pot
fi adugai. Hemodializa poate fi luat n considerare
n cazul hemoragiilor sub dabigatran, dac este posibil.
Utilizarea de crbune activat poate fi eficient n reducerea absorbiei dabigatranului dup ingestia recent. Nu exist date cu privire la utilizarea de crbune activat pe cale oral, n cazul sngerrii sub rivaroxaban
sau apixaban.
Anticorpi monoclonali ndreptai mpotriva dabigatranului sunt n prezent n curs de dezvoltare. Acetia
inhib puternic i n mod special activitatea anticoagulant a dabigatranului n plasma uman in vitro i in
vivo la obolani. Derivate din plasm uman i Factorul
Xa recombinant care nu dispun de activitate catalitic
i de legare membranar sunt investigate ca antidot
pentru inhibitorii de Factor Xa. Studiile preliminare au
artat c att derivatele din plasm uman ct i Factorul Xa recombinant sunt capabile s neutralizeze coagularea anormal indus de rivaroxaban i apixaban in
vitro i pe modele animale.
(Deborah M. Siegal and Mark A. Crowther. Acute
management of bleeding in patients on novel oral anticoagulants. European Heart Journal (2013) 34, 489500)
(MS)
Patternurile hemodinamice ale diverselor tipuri de
prezentri clinice ale stenozei aortice severe
Principalele simptome ale stenozei aortice severe sunt
reprezentate de sincop, durere toracic i dispnee. S-a

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

demonstrat c supravieuirea este net redus la aceti


pacieni odat cu apariia simptomelor i supravieuirea este influenat de tipul simptomului prezent, dispneea avnd cel mai mare impact asupra supravieuirii.
Plecnd de la aceste date, studiul discutat a evaluat
dac exist vreo corelaie ntre tipul simptomului predominant al pacienilor cu stenoz aortic sever i
parametrii de hemodinamic intracardiac. Studiul a
fost unul prospectiv, i a inclus 498 pacieni cu stenoz aortic sever (aria valvei aortice <1cm2) i fracie
de ejecie >50%. Au fost exclui pacienii cu nlocuire
valvular aortic, alt valvulopatie moderat sau sever
concomitent, boal cardiac ischemic (>50% stenoz pe o arter coronar), istoric de infarct miocardic,
sindrom coronarian acut i boal renal cronic stadiul
V. Pacienii au fost mprii n 4 grupuri n funcie de
simptomul dominant: asimptomatici (68.5%), sincop
(3%), angin (6.4%) i dispnee (22.1%).
n populaia studiat aria valvular medie a fost de
0.74+0.19, iar fracia de ejecie medie de 64.6%+0,6.
S-a observat c pacienii simptomatici au fost mai
vrstnici dect cei asimptomatici i c au avut valori
ale funciei diastolice (E, E) mai mari, dar fr a exista
o diferen n severitatea stenozei valvulare ntre cele
dou grupuri.
Nu s-a nregistrat nicio diferen ntre cele 4 grupuri
ale studiului n ceea ce privete diametrul telesistolic al
ventricului stng (VS), grosimea pereilor VS, masa VS,
fracia de ejecie i severitatea stenozei aortice. Pacienii cu sincop au avut diametre telediastolice VS, volume bataie, debite cardiace i volume de atriu stng indexate semnificativ mai mici dect celelalte grupuri. n
grupul cu dispnee velocitatea undei E a fost mai mare i
velocitatea undei E mai mic dect n celalalte grupuri.
Principala concluzie a acestui studiu este c exist un
pattern al profilului hemodinamic intracardiac diferit
pentru fiecare simptom dominant la prezentarea pacienilor cu stenoz aortic sever n ciuda ariei valvulare
aortice i gradienilor transvalvulari similari. Pacienii cu dispnee au prezentat o funcie diastolic sever
alterat i presiuni de umplere ventricular crescute,
pe cnd pacienii cu sincop au avut un volum bataie
redus i o funcie diastolic mai puin alterat. Acest
lucru este important avnd n vedere faptul c presiunile de umplere crescute la pacienii cu stenoz aortic
sever au fost asociate cu o cretere a mortalitii. Apariia anginei, sincopei sau dispneei s-au corelat cu un
timp mediu de supravieuire de 5, 3 i, respectiv, 2 ani.
Avnd n vedere prognosticul negativ atribuit de apariia dispneii i decelarea presiunilor de umplere crescu-

Updates in cardiology

te, se consider util investigarea ipotezei c nlocuirea


valvular aortic determin o mbuntire simptomatic i a supravieuirii la pacienii cu dispnee i stenoz
aortic mai puin sever.
n final, colectivul studiului ntrete recomandarea
de evaluare de rutin a funciei diastolice i a volumului btaie la toi pacienii cu stenoz aortic avnd n
vedere asocierea acestora cu evenimentele cardiace ulterioare.
(Park S.J et all, Hemodynamic Patterns for Symptomatic Presentations of Severe Aortic Stenosis, JACC:
Cardiovascular Imaging, VOL. 6, NO. 2, 2013)(LP)
Implicarea prognostic a prezenei sau absenei
anginei la pacienii cu diabet zaharat tip 2 i boal
cardiac ischemic
Pacienii cu diabet zaharat tip 2 i boal coronarian
pot prezenta angin tipic, echivalente anginoase precum dispneea sau pot fi asimptomatici (ischemie silenioas). Acest lucru a ridicat ntrebarea dac tipul
simptomului are implicaii prognostice la aceti pacieni, avnd n vedere c pacienii simptomatici sunt
diagnosticai i tratai mai devreme, pe cnd cei cu ischemie silenioas sunt mai rar diagnosticai corespunztor.
Dovezi legate de aceast situaie au venit din o subanaliz a trialului BARI 2D. Acest trial a fost elaborat
pentru a evidenia dac exist o diferen ntre revascularizarea coronarian precoce asociat terapiei medicale optime i terapia medical optim iniial urmat de revascularizare dac aceasta nu e suficient. Au
fost inclui 2368 pacieni cu diabet zaharat tip 2, boal
coronarian (stenoz >50% a unei artere coronare epicardice, exceptnd trunchiul arterei coronare stngi) i
ischemie miocardic evideniat pe eletrocardiogram,
scintigram miocardic sau ecocardiografie de stres.
Durata de urmrire a fost de 5,3 ani. Pacienii au fost
mprii n 3 grupuri: cei cu angin tipic, cei cu echivalente anginoase i cei asimptomatici.
Dintre cei 2364 pacieni nrolai, 1434 (61%) aveau
angin, 506 (21%) aveau echivalente anginoase i 424
(18%) erau asimptomatici. Dintre cei 1434 pacieni cu
angin 1005 erau n clasa canadian I-II i 429 n clasa III-IV. S-a observat c pacienii cu angin erau mai
tineri, erau mai frecvent femei, erau mai frecvent pe
tratament beta blocant i cu nitrai i aveau o fracie de
ejecie usor mai mare comparativ cu celelalte grupuri.
n grupul pacienilor asimptomatici s-a nregistrat o
pondere mai mare a brbailor, o frecven mai mic
a hipertensiunii i o cantitate de miocard la risc mai
mare.

Updates in cardiology

n primii 3 ani de urmrire s-a observat o frecven mai mic a interveniilor percutane coronariene n
grupul pacienilor asimptomatici, lucru nevalabil pentru bypass-ul aortocoronarian. Rata mortalitii la 5
ani a fost de 12% n grupul cu angin, 14% la cei cu
echivalente anginoase i 10% la cei asimptomatici.,
dar fr semnificaie statistic. Nu au existat diferene
semnificativ statistice ntre grupuri n ceea ce privete
mortalitatea de orice cauz, mortalitatea cardiovascular, infarctul miocardic nonfatal i accidentul vascular
cerebral nonfatal. Aceste rezultate au fost similare cnd
au fost studiate cele dou ramuri ale trialului, ramura
cu terapie medical optim i ramura cu revascularizare precoce. Important n interpretarea rezultatelor este
c se menioneaz faptul c aceste metode de prezentare a pacienilor cu diabet nu sunt explicate de diferene
n severitatea angiografic a bolii coronariene sau diferene n funcia ventriculului stng.

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

n concluzie, pacienii asimptomatici cu diabet zaharat tip 2, boal coronarian stabil i ischemie miocardic documentat se afl la risc crescut de mortalitate
i alte evenimente cardiovasculare majore, dar acest
risc este similar cu cel al pacienilor simptomatici, fie
cu angin pectoral tipic, fie echivalente anginoase.
Astfel, aceti pacieni ar trebui abordai similar n ceea
ce privete stratificarea riscului i terapiile de prevenie.
(Dagenais GR, Prognostic Impact of the Presence and
Absence of Angina on Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Stable Coronary Artery Disease: Results from the BARI 2D (Bypass
Angioplasty Revascularization Investigation 2 Diabetes)
Trial, J Am Coll Cardiol. 2013 Feb 19;61(7):702-11)(LP)
Rubric realizat de ctre dr. Lucian Predescu, dr.
Mihaela Slgean sub coordonarea dr. Mihaela Rugin.

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

Ghidul ESC de management al bolilor cardiovasculare n


timpul sarcinii
Grupul de Lucru pentru Managementul Bolilor Cardiovasculare n timpul Sarcinii,
al Societii Europene de Cardiologie (ESC)
nsuit de Societatea European de Ginecologie (ESG), Asociaia de Cardiologie
Pediatric European (AEPC) i Societatea German de Medicin difereniat pe
sexul pacientului (DGesGM)
Autori/Membrii Grupului de Specialitate: Vera Regitz-Zagrosek (Preedinte) (Germania)*, Carina Blomstrom Lundqvist (Suedia), Claudio Borghi (Italia), Renata Cifkova (Republica Ceh), Rafael Ferreira (Portugalia), Jean-Michel Foidart
(Belgia), J. Simon R. Gibbs (Marea Britanie), Christa Gohlke-Baerwolf (Germania), Bulent Gorenek (Turcia), Bernard Iung
(Frana), Mike Kirby (Marea Britanie), Angela H.E.M. Maas (Olanda), Joao Morais (Portugalia), Petros Nihoyannopoulos
(Marea Britanie), Petronella G. Pieper (Olanda), Patrizia Presbitero (Italia), Jolien W. Roos-Hesselink (Olanda), Maria Schaufelberger (Suedia), Ute Seeland (Germania), Lucia Torracca (Italia).
Comitetul ESC pentru Ghiduri Practice (CPG): Jeroen Bax ( Preedinte CPG) (Olanda), Angelo Auricchio (Elveia),
Helmut Baumgartner (Germania), Claudio Ceconi (Italia), Veronica Dean (Frana),Christi Deaton (Marea Britanie), Robert
Fagard (Belgia), Christian Funck-Brentano (Frana), David Hasdai (Israel), Arno Hoes (Olanda), Juhani Knuuti (Finlanda),
Philippe Kolh (Belgia), Theresa McDonagh (Marea Britanie),Cyril Moulin (Frana), Don Poldermans (Olanda), Bogdan A.
Popescu (Romnia), Zeljko Reiner (Croaia), Udo Sechtem (Germania), Per Anton Sirnes (Norvegia), Adam Torbicki (Polonia), Alec Vahanian (Frana), Stephan Windecker (Elveia).
Reprezentnd Societatea European de Ginecologie.
Reprezentnd Asociaia de Cardiologie Pediatric European.
Alte structuri ESC care au participat la redactarea acestui document:
Asociaii: Asociaia European de Intervenii Cardiovasculare Percutane (EAPCI), Asociaia European de Ritmologie (EHRA), Asociaia de Insuficien
Cardiac (HFA).
Grupuri de Lucru: Thromboz, Boli cardiace congenitale, Hipertensiunea i Cordul, Circulaia Pulmonar i Funcia Ventricului Drept, Valvulopatii,
Farmacologie Cardiovascular i Terapie Medicamentoas, Urgen, Chirurgie Cardiovascular.
Consilii: Practic Cardiologic, ngrijire Cardiovascular Primar, Imagistic Cardiovascular.
Coninutul acestor ghiduri ale Societii Europene de Cardiologie (ESC) au fost publicate doar pentru uz personal i educaional. Nu este autorizat
folosirea lor n scop comercial. Nicio parte a acestor Ghiduri ale ESC nu poate fi tradus sau reprodus fr acordul scris din partea ESC. Acordul poate fi
obinut dup depunerea unei solicitri scrise la Oxford University Press, editor al European Heart Journal i parte autorizat s se ocupe cu aceste acorduri
n numele ESC.
Not. Ghidurile ESC reprezint punctul de vedere al ESC i au fost redactate dup o atent analiz a evidenelor disponibile la momentul redactrii lor.
Personalul medical este ncurajat s le foloseasc n practica lor clinic. Cu toate acestea, ghidurile nu se substituie responsabilitii individuale a profesionitilor din domeniul sntii n luarea deciziilor potrivite n ngrijirea pacienilor. Intr, de asemenea, n responsabilitatea cadrelor medicale verificarea
regulilor i reglementrilor privitoare la medicamente i dispozitive medicale, la momentul prescrierii acestora.
Societatea European de Cardiologie 2011. Toate drepturile rezervate. Solicitri de permisiuni se pot adresa pe e-mail la: journals.permissions@oxfordjournals.org.
Recenzori: Helmut Baumgartner (Coordonator Recenzii CPG) (Germania), Christi Deaton (Coordonator Recenzii CPG) (Marea Britanie), Carlos Aguiar
(Portugalia), Nawwar Al-Attar (Frana), Angeles Alonso Garcia (Spania), Anna Antoniou (Grecia), Ioan Coman (Romnia), Uri Elkayam (USA), Miguel
Angel Gomez-Sanchez (Spania), Nina Gotcheva (Bulgaria), Denise Hilfiker-Kleiner (Germania), Robert Gabor Kiss (Ungaria), Anastasia Kitsiou (Grecia),
Karen T. S. Konings (Olanda), Gregory Y. H. Lip (Marea Britanie), Athanasios Manolis (Grecia), Alexandre Mebaaza (Frana), Iveta Mintale (Letonia), Marie-Claude Morice (Frana), Barbara J. Mulder (Olanda), Agnes Pasquet (Belgia), Susanna Price (Marea Britanie), Silvia G. Priori (Italia), Maria J. Salvador
(Spania), Avraham Shotan (Israel), Candice K. Silversides (Canada), Sven O. Skouby (Danemarca), Jrg-Ingolf Stein (Austria), Pilar Tornos (Spania),
Niels Vejlstrup (Danemarca), Fiona Walker (Marea Britanie), Carole Warnes (USA).
Declaraiile autorilor i recenzorilor sunt disponibile pe site-ul ESC: www.escardio.org/guidelines
Traducerea prezentului ghid a fost realizat de Bianca Moise, Irina Spnu, Cornelia Crciunescu, Florin Mitu, Apvloaie Maria-Cristina, Bararu Iris, Grbea
Alexandra i Munteanu Romulus, coordonat i revizuit de Daniel Gherasim.
Cuvinte cheie: Sarcin Boli cardiovasculare Ghiduri Aprecierea riscului Management Boli congenitale Valvulopatii Hipertensiune Insuficien cardiac Aritmii

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

CUPRINS
Abrevieri i acronime ...............................................................65
1. Preambul .............................................................................66
2. Consideraii generale .........................................................67
2.1. Introducere ............................................................67
2.2. Metodologie ..........................................................67
2.3. Epidemiologie .......................................................67
2.4. Modificrile hemodinamice, hemostatice i
metabolice n sarcin ...........................................67
2.5. Testarea genetic i consilierea ...........................68
2.6. Diagnosticul afeciunii cardiovasculare n
sarcin ....................................................................69
2.7. Evaluarea fetal .....................................................71
2.8. Intervenii asupra mamei n timpul sarcinii .....72
2.9. Momentul declanrii i modalitatea de
natere: risc pentru mam i copil......................72
2.10. Endocardita infecioas ........................................74
2.11. Estimarea riscului: contraindicaii pentru
sarcin ....................................................................75
2.12. Metode de contracepie i de ntrerupere a
sarcinii i fertilizarea in vitro ...............................77
2.13. Recomandri generale ..........................................78
3. Bolile cardiace congenitale i hipertensiunea
pulmonar ...........................................................................79
3.1. Afeciunile asociate cu risc matern crescut
(Organizaia Mondial a Sntii III-IV;
vezi i Seciunea 2.11) ..........................................79
3.2. Afeciuni asociate cu risc matern sczut i
moderat (Organizaia Mondial a Sntii
I, II, i III; vezi i Tabelele 6 i 7) ........................82
3.3. Defecte congenitale specifice ..............................82
3.4. Recomandri pentru managementul bolilor
cardiace congenitale .............................................86
4. Bolile aortei .........................................................................86
4.1. Riscul matern i fetal ............................................87
4.2. Sindroame specifice .............................................87
4.3. Management..........................................................88
4.4. Recomandri privind managementul bolii
aortice.....................................................................88
5. Valvulopatiile ......................................................................89
5.1. Leziuni valvulare stenozante ...............................89
5.2. Regurgitrile valvulare .........................................91
5.3. Fibrilaia atrial valvular (valve native) ...........92
5.4. Proteze valvulare ...................................................92
5.5. Protezele mecanice i tratamentul
anticoagulant .........................................................92
5.6. Recomandri pentru managementul
valvulopatiilor .......................................................95
6. Boala arterial coronarian i sindroamele
coronariene acute ...............................................................95
6.1. Riscul matern i fetal ............................................96
6.2. Management..........................................................96
6.3. Recomandri pentru managementul bolii
arteriale coronariene ............................................97

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

7. Cardiomiopatiile i insuficiena cardiac ........................97


7.1. Cadiomiopatia peripartum .................................97
7.2. Cardiomiopatia dilatativ ....................................99
7.3. Cardiomiopatia hipertrofic ...............................99
7.4. Recomandri pentru managementul
insuficienei cardiace ......................................... 100
8. Aritmii .............................................................................. 100
8.1. Aritmii asociate cu boli cardiace structurale
i congenitale ...................................................... 100
8.2. Aritmii specifice................................................ .100
8.3. Terapia intervenional: ablaia pe cateter...... 102
8.4. Defibrilatorul cardiac implantabil ................... 103
8.5. Bradiaritmiile ..................................................... 103
8.6. Recomandri pentru managementul
aritmiilor ............................................................. 103
9. Afeciunile hipertensive ................................................. 104
9.1. Diagnostic i evaluarea riscului ....................... 104
9.2. Definiia i clasificarea hipertensiunii n
sarcin ................................................................. 104
9.3. Managementul hipertensiunii n sarcin........ 105
9.4. Tratamentul non-farmacologic i prevenia
hipertensiunii n sarcinii................................... 105
9.5. Tratamentul farmacologic al hipertensiunii
n sarcin............................................................. 106
9.6. Prognosticul postnatal ...................................... 107
9.7. Recomandri pentru managementul
hipertensiunii ..................................................... 107
10. Tromboembolismul venos n timpul sarcinii i
postpartum ....................................................................... 107
10.1. Epidemiologie i riscul matern ........................ 107
10.2. Factorii de risc pentru tromboembolismul
venos asociat sarcinii i stratificarea riscului . 107
10.3. Prevenia tromboembolismului venos............ 108
10.4. Managementul tromboembolismului venos
acut ...................................................................... 108
10.5. Recomandri pentru prevenia i
managementul tromboembolismului venos
n sarcin i postpartum ................................... 111
11. Terapia medicamentoas n timpul sarcinii i
alptrii ............................................................................. 112
11.1. Principii generale ............................................... 112
11.2. Recomandri pentru utilizarea
medicamentelor ................................................. 112
12. Mulumiri ......................................................................... 112
13. Bibliografie ....................................................................... 114

LISTA TABELELOR
Tabel 1.
Tabel 2.
Tabel 3.

Tabel 4.

Clasele de recomandri
Niveluri de eviden
Dozele efective maternale i fetale estimate
pentru diferite proceduri radiologice de diagnostic i intervenionale
Predictorii evenimentelor cardiovasculare
maternale i scorul de risc din studiul CARPREG

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Tabel 5.

Tabel 6.
Tabel 7.
Tabel 8.
Tabel 9.
Tabel 10.
Tabel 11.
Tabel 12.
Tabel 13.
Tabel 14.
Tabel 15.
Tabel 16.
Tabel 17.
Tabel 18.

Tabel 19.
Tabel 20.

Tabel 21.

Predictorii evenimentelor cardiovasculare


maternale identificabili n bolile cardiace
congenitale n studiile ZAHARA i Khairy
Clasificarea modificat OMS a riscului cardiovascular maternal: principii
Clasificarea modificat OMS a riscului cardiovascular maternal: aplicare
Predictorii maternali ai evenimentelor neonatale la femeile cu boal cardiac
Recomandri generale
Recomandri pentru managementul bolilor
congenitale
Recomandri pentru managementul bolilor
aortei
Recomandri pentru managementul valvulopatiilor
Recomandri pentru managementul bolii
cardiace ischemice
Recomandri pentru managementul cardiomiopatiilor i insuficienei cardiace
Recomandri pentru managementul aritmiilor
Recomandri pentru managementul hipertensiunii
Lista factorilor de risc pentru tromboembolismul venos
Prevalena trombofiliei congenitale i riscul
asociat de tromboembolism venos n timpul
sarcinii
Grupele de risc n concordan cu factorii
de risc: definiie i msuri preventive
Recomandri pentru prevenia i managementul tromboembolismului venos n sarcina i peripartum
Recomandri pentru medicaie

ABREVIERI I ACRONIME
ABPM
ACC
ACE
ACS
FA
AHA
aPTT
AV
BRA
SA
DSA

monitorizarea ambulatorie a tensiunii


arteriale
American College of Cardiology
enzima de conversie a angiotensinei
sindrom coronarian acut
fibrilaie atrial
American Heart Association
timpul de tromboplastin parial
activat
atrioventricular
blocant de receptor de angiotensin
stenoz aortic
defect septal atrial

DSV
DSAV
IMC
BNP
TA
CDC
CHADS

IC
DC
CoA
CT
BCV
TAD
CMD
TVP
ECG
FE
ESC
ESH
ESICM
FDA
CMH
ICD
INR
i.v.
HGMM
VS
FEVS
LVOTO
IRM
SM
NT-proBNP
NYHA
ACO
HTP
PAP
PCI
CMPP
SP
VD
TAS
TSV
TGA
RT
HNF

defect septal ventricular


defect septal atrioventricular
indice de mas corporal
peptidul natriuretic tip B
tensiune arterial
Centers for Disease Control
insuficien cardiac congestiv,
hipertensiune, vrst ( > 75 ani),
diabet, AVC
interval de confiden
debit cardiac
coarctaie de aort
tomografie computerizat
boal cardiovascular
tensiune arterial diastolic
cardiomiopatie dilatativ
tromboz venoas profund
electrocardiogram
fracie de ejecie
Societatea European de Cardiologie
Societatea European de
Hipertensiune
Societatea European de Terapie
Intensiv
Food and Drug Administration
cardiomiopatia hipetrofic
defibrilator cardiac implantabil
international normalized ratio
intravenos
heparin cu greutate molecular mic
ventricul stng
fracia de ejecie a ventriculului stng
obstrucie n tractul de ejecie a VS
imagistic prin rezonan magnetic
stenoz mitral
segmentul N-terminal al peptidului
natriuretic tip B
New York Heart Association
anticoagulare oral
hipertensiune arterial pulmonar
presiunea n artera pulmonar
intervenie coronarian percutan
cardiomiopatia peripartum
stenoz valvular pulmonar
ventricul drept
tensiune arterial sistolic
tahicardie supraventricular
transpoziie complet de vase mari
regurgitare tricuspidian
heparin nefracionat

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

1. PREAMBUL
Ghidurile prezint n mod sintetizat i evalueaz toate evidenele disponibile la momentul redactrii pe un
anumit domeniu, cu scopul de a ajuta medicii s ia cea
mai bun decizie de tratament la pacientul cu o anumit patologie, innd seama de impactul pe prognostic
i, de asemenea, de raportul risc-beneficiu, analizat n
funcie de diagnostic sau de decizia terapeutic. Ghidurile nu se substituie, ci sunt complementare tratatelor
medicale i acoper toate capitolele curiculei Societii
Europene de Cardiologie. Ghidurile i recomandrile
ar trebui s ajute medicii s ia decizii n practica zilnic. Oricum, decizia final n cazul unui pacient intr n
responsabilitatea medicului curant.
n anii trecui, a fost elaborat un numr mare de ghiduri, att de SEC, ct i de alte societi i organizaii.
Din cauza impactului pe care l au n practica clinic,
au fost stabilite criterii de calitate n elaborarea ghidurilor, astfel nct toate deciziile s apar clar pentru
cel ce consult ghidul. Recomandrile de formulare i
redactare a ghidurilor SEC pot fi consultate pe site-ul
SEC (htpp://www.escardio.org/guidelines-surveys/escguidelines/about/Pages/rules-writing.aspx). Ghidurile
SEC exprim poziia oficial a SEC pe o tem dat i
sunt actualizate periodic.
Membrii comitetului de redactare sunt selectai de
SEC dintre profesionitii reprezentativi implicai n ngrijirea pacienilor cu patologia respectiv. Experii n
domeniu selectai fac o analiz comprehensiv a evidenelor publicate n legtur cu diagnosticul, tratamentul i/sau prevenia unei condiii date, n concordan cu reglementrile Comitetului SEC pentru Ghidurile Practice (CGP). Se realizeaz o evaluare critic
a diagnosticului i procedurilor terapeutice, inclusiv a
raportului risc-beneficiu. Acolo unde exist date, sunt
incluse i estimri de prognostic pentru populaii mai
mari. Nivelul de eviden i puterea recomandrilor pe

o anumit opiune de tratament sunt evaluate i stratificate n concordan cu scalele predefinite, aa cum sunt
prezentate n Tabelele 1 i 2.
Experii comitetelor de redactare i revizuire au
completat declaraii de interes, care pot fi percepute ca
surse reale sau poteniale de conflict de interese. Aceste
declaraii au fost comprimate ntr-una singur, ea putnd fi consultat pe site-ul SEC (htpp://www.escardio.
org/guidelines). Pe parcursul redactrii unui ghid, orice
schimbare a declaraiei de interes trebuie notificat ctre SEC i actualizat. Comitetul de redactare primete
suport financiar doar de la SEC, fr vreo implicare a
industriei farmaceutice.
Comitetul pentru ghiduri practice al ESC supervizeaz i coordoneaz pregtirea noilor ghiduri redactate de Grupurile de Specialitate, grupuri de experi sau
de consens. Comitetul este, de asemenea, responsabil
pentru procesul de aprobare a acestor ghiduri. Ghidurile ESC sunt supuse unei vaste revizuiri de ctre CPG
i experi din afara Grupului. Dup revizuirea atent,
Ghidul este aprobat de ctre toi experii din cadrul
Grupului de Specialitate. Documentul final este aprobat de CPG pentru publicarea n European Heart Journal. n redactarea ghidurilor se ia n considerare nu
numai integrarea celor mai recente cercetri, dar i
crearea unor instrumente educaionale i programe de
implementare a recomandrilor. Pentru implementarea ghidurilor sunt produse versiuni prescurtate de
buzunar, diapozitive, brouri cu mesaje eseniale, precum i versiunea electronic pentru aplicaii digitale
(smartphone etc.). Aceste versiuni sunt prescurtate,
recomandarea fiind de a consulta varianta in extenso
disponibil gratuit pe site-ul ESC.
Societile Naionale sunt ncurajate s-i nsueasc, s traduc i s implementeze ghidurile ESC. Implementarea programelor este necesar deoarece s-a dovedit c evoluia bolii poate fi influenat favorabil prin
aplicarea recomandrilor clinice.

Tabelul 1. Clasele de recomandri


Clasa de recomandare
Definiie
Clasa I
Dovezi sau/i acord general cu privire la faptul c un anumit tratament sau procedur sunt benefice, utile, eficiente.
Clasa II
Dovezi contradictorii sau/i divergen de opinii asupra utilitii/eficacitii unui anume tratament sau proceduri.
Clasa II a
Dovada/opinia este mai degrab n favoarea utilitii/eficienei
Clasa II b
Utilitatea/eficiena este mai puin susinut de dovezi/opinii.
Clasa III
Dovezi sau acord general c un anume tratament sau procedur nu este util/eficace i n anumite cazuri poate fi chiar
duntoare.
Tabelul 2. Niveluri de eviden
Nivel de eviden A
Nivel de eviden B
Nivel de eviden C

Date derivate din multiple trialuri clinice randomizate sau meta-analize.


Date derivate dintr-un singur trial clinic randomizat sau din studii largi non-randomizate.
Consens de opinii ale experilor sau/i studii mici, studii retrospective, registre.

Sugestii pentru utilizare


Este recomandat/este indicat.
Ar trebui luat n considerare.
Poate fi luat n considerare.
Nu este recomandat.

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Pentru a verifica cum se coreleaz practica zilnic cu


recomandrile din ghiduri, sunt necesare evaluri i registre, completnd astfel bucla ntre cercetarea clinic,
scrierea ghidurilor i implementarea lor n practica clinic. Ghidurile nu nlocuiesc responsabilitatea individual a cadrelor medicale n luarea celor mai adecvate
decizii, individualizate pentru fiecare pacient. De asemenea, intr n responsabilitatea cadrelor medicale s
verifice regulile i reglementrile aplicabile la medicaie
i dispozitive medicale, la momentul prescripiei.

2. CONSIDERAII GENERALE
2.1. Introducere
n prezent 0,2-4% dintre toate sarcinile din rile
industrializate sunt complicate de afeciuni cardiovasculare (CVD)1, iar numrul pacientelor care dezvolt
probleme cardiace n sarcin este n cretere. Cu toate
acestea, numrul pacientelor care se prezint la medic
este redus. Cunoaterea riscurilor asociate cu patologia
cardiovascular n timpul sarcinii i managementul lor
au o importan capital pentru consilierea pacientelor nainte de sarcin. De aceea, ghidul privind managementul afeciunilor cardiovasculare n sarcin are o
relevan foarte mare. Acest ghid trebuie s sublinieze
faptul c toate msurile privesc nu doar mama, ci i ftul. De aceea, trebuie intit tratamentul optim pentru
ambii. O terapie favorabil pentru mam poate fi asociat cu o afectare a copilului, iar, n cazuri extreme,
msurile de tratament care protejeaz supravieuirea
mamei pot cauza decesul ftului. Pe de alt parte, terapiile care protejeaz copilul pot conduce la un rezultat
suboptimal pentru mam. Deoarece studiile prospective sau randomizate lipsesc, cu cteva excepii, recomandrile din acest ghid corespund n cea mai mare
parte cu nivelul de eviden C.
Unele concluzii generale au fost desprinse din acest
ghid: consilierea i managementul femeii de vrst fertil la care se suspecteaz o afeciune cardiac trebuie
s nceap nainte de apariia sarcinii; acestea ar trebui
consiliate de echipe interdisciplinare; pacientele cu risc
nalt trebuie tratate n centre specializate; iar procedurile de diagnosticare i interveniile trebuie efectuate
de specialiti cu experien tehnic vast i n tratarea
pacientelor nsrcinate. Reprezint o prioritate crearea
de registre i studii prospective pentru a mbunti nivelul actual de cunotine n domeniu.
2.2. Metodologie
Ghidul se bazeaz pe o cercetare sistematic a literaturii din ultimii 20 de ani din baza de date a Institutelor
Naionale Medicale (PubMed). Publicaiile i recoman-

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cardiovascular diseases during pregnancy

drile societilor de cardiologie europene i americane


sunt de asemenea luate n considerare: American Heart
Association/American College of Cardiology (AHA/
ACC)2, ESC n 20033, Grupul de Lucru de Valvulopatii al ESC4, ghidul Societii Germane de Cardiologie
(German Society of Cardiology)5,6, i ESC Task Force
n Managementul Valvulopatiilor 20077.
2.3. Epidemiologie
Spectrul afeciunilor cardiovasculare n sarcin se
schimb i difer de la o ar la alta. n rile occidentale, riscul de afeciuni cardiovasculare n sarcin a
crescut din cauza vrstei tot mai avansate a femeii la
prima sarcin i a creterii prevalenei factorilor de risc
cardiovascular diabet, hipertensiune i obezitate. De
asemenea, tratamentul afeciunilor cardiace congenitale s-a mbuntit, contribuind la creterea numrului
de femei cu afeciuni cardiace care ajung la vrst fertil8. n rile vestice boala cardiac a mamei reprezint
acum principala cauz de deces matern n timpul sarcinii9.
Complicaiile hipertensive sunt cele mai frecvente
evenimente cardiovasculare n timpul sarcinii, acestea
ntlnindu-se n 6-8% din cazuri10. n rile occidentale, boala cardiac congenital este cea mai frecvent
afeciune cardiovascular n sarcin (75-82%), predominnd afeciunile cu unt (20-65%)11,12. Boala cardiac congenital se ntlnete doar n 9-19% din sarcini
n afara Europei i Americii de Nord. Boala valvular
reumatismal predomin n restul rilor, reprezentnd
56-89% din toate bolile cardiovasculare din sarcin11,12.
Cardiomiopatiile sunt rare, ns reprezint cauze severe de complicaii cardiovasculare n sarcin. Cardiomiopatia peri-partum (PPCM) este cea mai comun
cauz de complicaii severe13.
2.4. Modificrile hemodinamice, hemostatice i
metabolice n sarcin
Sarcina induce schimbri n sistemul cardiovascular
pentru a satisface cererea metabolic ridicat a mamei
i ftului. Acestea includ creterea volumului sanguin
i a debitului cardiac (CO), precum i reducerea rezistenei vasculare sistemice i a presiunii sangvine (BP).
Volumul de plasm ajunge la un maxim de 40% peste nivelul de referin la 24 de sptmni de gestaie. O
cretere de 30-50% a debitului cardiac apare n sarcina
normal. La nceputul sarcinii CO ridicat este cauzat n
principal de creterea debitului btaie; n sarcina avansat, debitul cardiac crete n principal prin creterea
frecvenei cardiace. Frecvena cardiac ncepe s creasc n sptmna 20 i crete pn n sptmna 32 de
gestaie. Ea rmne crescut 2-5 zile dup natere. Pre

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siunea arterial sistemic (SBP) scade n mod normal


n prima parte a sarcinii, iar presiunea arterial diastolic (DBP) este de obicei cu 10 mmHg sub valoarea de
referin n al doilea trimestru. Aceast scdere a presiunii arteriale este cauzat de vasodilataia activ obinut prin aciunea mediatorilor locali, precum prostaciclina i oxidul nitric. n al treilea trimestru, presiunea
arterial diastolic crete progresiv, putnd reveni pn
la termen la valorile din afara sarcinii.
Inima i poate crete dimensiunile cu pn la 30%,
fapt datorat parial vasodilataiei. Datele privind funcia sistolic i diastolic n sarcin sunt rare. Funcia
sistolic crete prima, ns poate scdea n ultimul trimestru. Rapoartele privind funcia diastolic sunt contradictorii.
Sarcina induce o serie de schimbri hemostatice, cu
o cretere a concentraiei de factori de coagulare, fibrinogen i o cretere a adezivitii trombocitelor, precum
i o scdere a fibrinolizei, care conduce la hipercoagulabilitate i un risc crescut de evenimente trombo-embolice. n plus, obstrucionarea ntoarcerii venoase prin
lrgirea uterului cauzeaz staz i o cretere adiional
a riscului de trombo-embolism.
Homeostazia glucidelor materne se poate schimba,
iar nivelurile de colesterol cresc pentru a se adapta necesitilor materno-fetale.
Schimbrile fiziologice, care apar n sarcin, pot
afecta absorbia, excreia i bio-disponibilitatea tuturor
medicamentelor14. Volumul sanguin intravascular crescut explic n parte dozele mai mari de medicamente
necesare pentru a obine concentraia plasmatic terapeutic i adaptrile de dozaj necesare n timpul tratamentului. Mai mult, perfuzia renal ridicat i metabolismul hepatic mai mare cresc eliminarea medicamentelor. Modificrile farmacokineticii medicamentelor
variaz n magnitudine n timpul diferitelor etape ale
sarcinii, fcnd necesar monitorizarea atent a pacientelor i ajustarea dozelor de medicamente.
Contraciile uterine, poziia (lateral stnga vs. decubit dorsal), durerea, anxietatea, efortul, sngerrile i
involuia uterin determin schimbri hemodinamice
semnificative n timpul travaliului i post-partum. Anestezia, analgezia, hemoragia i infecia pot induce un
stres cardiovascular adiional. Presiunea arterial sistolic i presiunea arterial diastolic cresc cu 15-25% i
respectiv 10-15% n timpul contraciilor uterine. Aceste
creteri sunt asociate cu o mrire a presiunii din lichidul amniotic i n venele intratoracice, precum i n lichidele cerebrospinale i extradurale. CO crete cu 15%
n etapa incipient a travaliului, cu 25% n prima etap
i cu 50% n timpul eforturilor de expulzie15. Totodat,

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CO atinge o valoare de 80% imediat post-partum, din


cauza auto-transfuziei asociate cu involuia uterin i
reabsorbiei edemelor de la nivelul membrelor inferioare.
n concluzie, adaptrile fiziologice la sarcin influeneaz evaluarea i interpretarea funciei cardiace i a
statusului clinic.
2.5. Testarea genetic i consilierea
Un aspect important n ngrijirea femeilor tinere cu
afeciuni cardiovasculare l reprezint consultul prin
care se evalueaz riscul de motenire a defectelor cardiace de ctre descendenii lor. Riscul este semnificativ
crescut n comparaie cu prinii fr afeciuni cardiovasculare, unde riscul este ~1%. n plus, exist diferene mari ntre bolile cardiace ereditare, iar riscul pentru
descendeni depinde de condiia n care numai mama,
numai tatl sau ambii prini sufer de defecte cardiace
ereditare. n general, riscul este mai mare atunci cnd
mama este afectat, mai degrab dect tatl16. Riscul de
recuren variaz ntre 3% i 50% n funcie de tipul de
afeciune cardiac matern.
Copiii prinilor cu o afeciune cardiac ce se transmite autozomal dominant (de ex. sindromul Marfan,
cardiomiopatia hipertrofic sau sindromul QT lung) au
un risc de motenire de 50% indiferent de sexul printelui afectat.
Fenotipul final va fi de asemenea determinat de penetrana incomplet i efectele pleiotropice i poate
varia semnificativ. Pentru defectele care se transmit poligenic, riscul de recuren este mai puin definit. Ereditatea autozomal recesiv i recesiv legat de cromozomul X sunt rare.
Testarea genetic poate fi util:
n cardiomiopatii i canalopatii, cum ar fi sindroamele de QT lung17.
atunci cnd sunt afectai ali membri ai familiei.
cnd pacientul are caracteristici dismorfice, retard mental/ ntrziere n dezvoltare sau cnd
sunt prezente alte anormalii congenitale noncardiace, n sindroamele precum Marfan, deleia
22q11, Williams-Beuren, Alagille, Noonan i
sindromul Holt-Oram.
Pentru un numr din ce n ce mai crescut de defecte
genetice, screening-ul genetic prin biopsie viloas corionic poate fi recomandat n a 12-a sptmn de sarcin. Toate femeile cu afeciuni cardiace congenitale ar
trebuie s efectueze o ecocardiografie fetal ntre sptmnile 19 i 22 de sarcin. Msurarea grosimii cutei
nucale ntre sptmnile 12 i 13 de sarcin reprezint
un test de screening precoce pentru femeile cu vrsta

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de peste 35 de ani. Sensibilitatea n detectarea unui defect cardiac este de 40%, n timp ce specificitatea metodei este de 99%. Incidena afeciunii cardiace congenitale n cazul unei grosimi a cutei nucale normale este
de ~1/100018.
Profilul ereditar difer de la o afeciune la alta, astfel nct consilierea genetic de ctre un genetician
este recomandat cu trie pentru pacieni i membrii
familiei lor17. Testarea genetic dup consilierea atent
se face pentru identificarea rudelor asimptomatice sau
fr boal dar la risc, pentru a dirija urmrirea clinic pentru apariia bolii, accentund astfel msurile de
prevenire i tratament. Este recomandat la pacienii
cu afeciuni genetice cunoscute, cu att mai mult dac
exist variante de tratament17.
2.6. Diagnosticul afeciunii cardiovasculare n
sarcin
Urmtoarele proceduri sunt semnificative pentru
diagnosticul i gestionarea afeciunilor cardiovasculare
n sarcin.
Istoricul i investigaia clinic
Multe afeciuni pot fi descoperite lund cu atenie
un istoric personal i familial, n spe cardiomiopatiile, sindromul Marfan, bolile cardiace congenitale,
moartea subit juvenil, sindromul QT lung i tahicardia ventricular catecolaminergic (VT) sau sindromul
Brugada. Este important s se insiste asupra eventualelor mori subite n familie. Aprecierea dispneei este
important pentru diagnosticul i prognosticul leziunilor valvulare i a insuficienei cardiace. O examinare fizic minuioas, lund n considerare schimbrile fiziologice care apar n sarcin (Seciunea 2.4), este
obligatorie, incluznd auscultaia pentru identificarea
unor sufluri noi sau schimbri ale caracteristicilor celor cunoscute, precum i cutarea semnelor de insuficien cardiac. Atunci cnd apare dispneea n sarcin
sau cnd se ascult un suflu nou patologic, se indic un
examen ecocardiografic. Este crucial s se msoare tensiunea arterial n poziie culcat pe stnga lateral (vezi
Seciunea 9), folosind o metod standardizat, i s se
caute proteinuria, n special n cazul unui istoric personal sau familial de hipertensiune sau pre-eclampsie.
Oximetria ar trebui verificat la pacienta cu afeciuni
cardiace congenitale.
Electrocardiograma
Marea majoritatea a pacientelor nsrcinate au o
electrocardiogram (ECG) normal. Inima este rotat
spre stnga i pe ECG de suprafa exist o deviaie axi-

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

al stng de 15-20. Modificrile obinuite sunt reprezentate de modificri tranzitorii ale segmentului ST i
ale undei T, prezena unei unde Q i unde T inversate
n derivaia III, o und Q micorat n derivaia AVF i
unde T negative n derivaiile V1, V2 i, ocazional, V3.
Modificrile ECG pot fi asociate unei schimbri graduale n poziia inimii i pot mima hipertrofia ventricular stng (LV) i alte afeciuni cardiace structurale.
Monitorizarea Holter trebuie recomandat pacientelor cunoscute anterior cu aritmie paroxistic, persistent documentat (tahicardie ventricular, fibrilaie
atrial (AF) sau flutter atrial) sau celor care descriu palpitaii.
Ecocardiografia
Deoarece ecocardiografia nu implic expunerea la
radiaii, este uor de efectuat i poate fi repetat ori de
cte ori este nevoie. n prezent, ecocardiografia a devenit o investigaie important n timpul sarcinii i reprezint metoda preferat de screening pentru evaluarea
funciei cardiace.
Ecocardiografia transesofagian
Transductoarele multiplanare au fcut din ecocardiografia trans-esofagian o metod util ecocardiografic n evaluarea adulilor, de exemplu, cu afeciune
cardiac complex congenital. Ecocardiografia transesofagian, dei este rar necesar, este relativ sigur pe
perioada sarcinii. Prezena coninutului gastric, riscul
de vom i aspiraia, i creterea brusc a presiunii intra-abdominale sunt elemente de luat n calcul. n plus,
dac se folosete sedarea trebuie realizat monitorizarea fetal.
Testul de efort
Testarea la efort este util pentru a evalua obiectiv
capacitatea funcional, rspunsul cronotropic i al
presiunii arteriale, precum i aritmiile induse de efort
fizic. A devenit o parte integral din urmrirea pacienilor cu afeciuni cardiace congenitale, precum i a
pacienilor cu afeciuni cardiace valvulare asimptomatice19,20. Testul de efort trebuie efectuat la pacientele cu
afeciuni cardiace cunoscute, preferabil nainte de sarcin pentru evaluarea riscului.
Comitetul recomand efectuarea testului de efort
submaximal pentru atingerea a 80% din frecvena cardiac maxim predictiv la pacientele nsrcinate asimptomatice cu suspiciunea de boal cardiovascular. Nu
exist dovezi care s arate c ar crete riscul de avort
spontan. Cicloergometrul n poziia nclinat pare s
fie cea mai confortabil modalitate, ns mersul pe ban

ESC Guidelines on the management of


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d sau cicloergometrul obinuit pot fi, de asemenea,


folosite. Testul de stres cu dobutamin trebuie evitat.
Dac se folosete analiza gazelor respiratorii, limita este
un raport de schimb respirator de 1.0. Ecocardiografia
de stres pe cicloergometru are o specificitate mai ridicat n detectarea prezenei i extinderii ischemiei la
pacientele cu risc nalt pentru boal coronarian ischemic. De asemenea, aceasta poate fi folosit i nainte
de concepie pentru a evalua rezerva miocardiac la
pacientele cu istoric de cardiomiopatie peripartum, dar
cu funcia ventriculului stng recuperat [(fracie de
ejecie ventricul stng (FEVS)], precum i la pacientele
cu alte cardiomiopatii, cu afeciuni cardiace congenitale sau valvulare, cu FEVS la limita normalului sau uor
redus. Scintigrafia nuclear trebuie evitat n timpul
sarcinii din cauza expunerii la radiaii.
Expunerea la radiaii
Efectele radiaiilor asupra ftului depind de doza de
radiaii i vrsta gestaional la care apare expunerea.
Dac este posibil, procedurile trebuie ntrziate pn
cel puin la finalul perioadei de organogenez major
(>12 sptmni de la ultima menstruaie). Nu exist
dovezi prin care s se evidenieze un risc fetal crescut
de malformaii congenitale, dizabilitate intelectual,
ntrziere n cretere sau pierderea sarcinii la doze de
radiaii administrate femeii nsrcinate de mai puin de
50 mGy22,23 (www.bt.cdc.gov/radiation/prenatalphysician.asp; date accesate n 31 octombrie 2007).
Poate exist o cretere redus a riscului (1:2000 vs.
1:3000) de cancer infantil. Pragul la care apare un risc
crescut de malformaii congenitale nu a fost determinat
cu precizie. Unele dovezi sugereaz c riscul de malformaii este ridicat la doze de peste 100 mGy, n timp ce
riscul ntre 50 i 100 mGy este mai puin clarificat. n
primele 14 zile de la fertilizare, expunerea la radiaii de
peste 50 mGy nu determin anomalii fetale sau deces,
supravieuirea fr anomalii fiind regula. Dup primele
14 zile, expunerea la radiaii de peste 50 mGy poate fi
asociat cu un risc crescut de malformaii congenitale,
ntrziere n cretere i dizabilitate intelectual.

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Cele mai multe proceduri medicale nu expun ftul


la nivele mari de radiaii (Tabelul 3). Pentru majoritatea procedurilor de diagnostic medical, implicnd doze
pentru ft de pn la ~1 mGy, riscul de cancer infantil
este foarte sczut. (Documente ale Health Protection
Agency, Radiation, Chemical and Environmental Hazards, martie 2009. RSE-9 Protecia pacientelor nsrcinate n timpul expunerii n scop diagnostic la radiaii ionizante. Consiliere din partea Health Protection
Agency, the Royal College of Radiologists, and the College of Radiographers).
Ca regul general, conform cu principiul ct mai
redus posibil (ALARA), toate dozele de radiaii cauzate de expunerile medicale trebuie pstrate la un nivel
ct mai mic24.
Radiografia toracic
Doza fetal de la o radiografie toracic este <0,01
mGy25. Oricum, o radiografie toracic trebuie fcut
numai dac alte metode nu sunt suficiente n clarificarea cauzei dispneei, tusei sau a altor simptome.
Dac informaiile de diagnostic necesare pot fi obinute cu o modalitate de imagistic ce nu folosete radiaie ionizant, aceasta trebuie folosit ca test de prima linie. Dac trebuie efectuat un studiu care folosete
radiaie ionizant, doza de radiaie pentru ft trebuie
pstrat ct mai redus posibil (preferabil <50 mGy).
Riscurile i beneficiile efecturii sau neefecturii examinrii trebuie comunicate. Se recomand documentarea dozei de radiaii primite de mam n evidenele
medicale, n special dac ftul este n cmpul de vizualizare26,27.
Imagistica prin rezonan magnetic i tomografia
computerizat
Imagistica prin rezonan magnetic (IRM) poate
fi util n diagnosticarea afeciunilor cardiace complexe sau a patologiei aortei28. Trebuie efectuat numai
dac alte msuri de diagnostic, inclusiv ecocardiografia transtoracic i transesofagian, nu sunt suficiente
pentru un diagnostic complet. Sunt disponibile puine

Tabelul 3. Doze efective estimate fetale i materne pentru diferite proceduri de diagnostic i intervenii radiologice
Procedura
Expunere fetal
Expunere matern
Radiografie toracic
<0,01 mGy
<0,01 mSv
0,1 mGy
(PA i lateral)
CT toracic
0,3 mGy
0,3 mSv
7 mGy
Angiografie coronarian
1,5 mGy
1,5 mSv
7 mGy
PCI sau ablaie prin cateter de radiofrecven
3 mGy
3 mSv
15 mGy
*Expunerea depinde de numrul de proiecii sau incidene
CT tomografie computerizat
PA post-anterior
PCI intervenie coronarian percutanat

0,1 mSv
7 mSv
7 mSv
15 mSv

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date despre efectul asupra organogenezei, ns IRM


este probabil sigur, n special dup primul trimestru29.
Se presupune c gadoliniul poate traversa bariera fetoplacentar, ns datele sunt limitate. Riscurile de expunere pe termen lung a ftului la ionii de gadoliniu
nu sunt cunoscute i de aceea gadoliniul trebuie evitat.
Tomografia computerizat (CT)31 nu este de obicei
necesar pentru diagnosticarea afeciunilor cardiovasculare n sarcin i, din cauza dozei de radiaii pe care
o implic examinarea, nu este recomandat. Excepia
este reprezentat de cazul n care poate fi necesar pentru un diagnostic cert sau excluderea definitiv a embolismului pulmonar. Pentru aceast indicaie CT se
recomand doar dac nu sunt suficiente alte modalitai
de diagnostic (vezi Seciunea 10). n aceste situaii se
poate folosi o doz mic de radiaii 1-3 mSv.
Cateterismul cardiac
n angiografia coronarian expunerea medie la radiaii
la nivel abdominal neprotejat prin scut este de 1,5 mGy.
Din acest doz <20% ajunge la ft datorit atenurii
produse de esuturi. Reducerea expunerii la radiaii se
face prin protejarea uterului gravid cu scut mpotriva
radiaiei directe i, n special, scurtarea timpului fluoroscopic. Abordarea radial este preferabil i trebuie
efectuat de un operator cu experien. Studiile electrofiziologice cu scop de ablaie trebuie efectuate numai
dac aritmiile sunt refractare la tratamentul medical
i dac determin degradare hemodinamic. Dac se
efectueaz, sistemele de mapping electroanatomic trebuie folosite pentru a reduce doza de radiaii32.
Recomandrile generale pentru diagnostic i msurile terapeutice n timpul sarcinii sunt listate n Tabelul
9.
2.7. Evaluarea fetal
Ecografia din primul trimestru permite o msurare precis a vrstei gestaionale i detectarea din timp
a sarcinii multiple i a malformaiilor. Diagnosticarea
malformaiilor cardiace congenitale poate fi realizat
mai devreme de 13 sptmni i, n familiile cu afeciuni cardiace, aceast limit de timp este adecvat pentru nceperea screening-ului afeciunilor cardiace congenitale. O analiz a acurateii ecografiilor din primul
trimestru pentru detectarea afeciunilor cardiace congenitale majore a artat o sensibilitate i o specificitate
de 85% [95% interval de confiden (CI) 78-90%] i respectiv 99% (95% CI 98-100%). Examinarea din timp
n sarcin permite prinilor s ia n considerare toate opiunile, inclusiv ntreruperea sarcinii, dac exist
malformaii majore33.

ESC Guidelines on the management of


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Perioada optim pentru screening-ul sarcinilor normale pentru afeciuni cardiace congenitale34 este 18-22
de sptmni de gestaie, atunci cnd vizualizarea inimii i a tracturilor de ieire este optim. Devine mai dificil dup 30 de sptmni, cnd ftul este mai strns n
cavitatea amniotic. Screning-ul din al doilea trimestru
(18-22 de sptmni) pentru detectarea anomaliilor
fetale trebuie efectuat de specialiti cu experien, n
special n cazul sarcinilor cu factori de risc pentru anomalii cardiace congenitale35.
Anatomia i funcia cardiac, fluxul arterial i venos
i ritmul trebuie evaluate. Atunci cnd se suspecteaz o
anomalie cardiac fetal, urmtoarele proceduri devin
obligatorii:
O ecocardiografie complet fetal pentru evaluarea structurii i funciei cardiace, fluxului venos
i arterial, i a ritmului.
Scanarea detaliat a anatomiei fetale pentru a
cuta anomalii asociate (n special la degete i
oase).
Istoricul familial pentru a cuta sindroame familiale.
Istoricul medical al mamei pentru a identifica
afeciuni medicale cronice, boli virale sau medicaiile teratogenice.
Cariotipul fetal (cu screening pentru deleie n
22q11.2 cnd sunt prezente anomaliile conotruncale)
Adresarea la un specialist n medicin maternofetal, cardiolog pediatru, genetician i/ sau neonatolog pentru a discuta prognosticul, opiunile
i managementul obstetrical i neonatal.
Naterea ntr-o instituie care poate asigura ngrijiri neonatale cardiologice, dac este necesar.
Velocimetria Doppler (uterin, ombilical, renal fetal i a arterelor cerebrale i aortei descendente)
asigur o apreciere non-invaziv a strii hemodinamice fetoplacentare. Modificri ale indexului Doppler n
artera ombilical se coreleaz cu dezvoltarea deficitar
vascular fetoplacentar, hipoxia fetal, acidoza i evoluia perinatal nefavorabil. Cele mai severe modificri pre-terminale ale undei Doppler la nivelul arterei
ombilicale sunt absena velocitii end-diastolice i velocitatea end-diastolic inversat. Prezena velocitii
end-diastolice inversate dincolo de sptmna 28 determin luarea deciziei de natere imediat prin cezarian. Dac velocitatea end-diastolic este absent trebuie s se ia n considerare naterea dup completarea
perioadei de 32 de sptmni36.

ESC Guidelines on the management of


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Testarea profilului biofizic fetal este indicat n sarcini cu risc de compromitere fetal. Testarea trebuie
efectuat o dat sau de mai multe ori pe sptmn, n
funcie de situaia clinic. Pentru determinarea unui
scor sunt folosite patru variabile biofizice ecografice
(micarea fetal, tonusul, respiraia i volumul de lichid
amniotic) i rezultatele testrii fr solicitare (nonstres testing). Prezena lor echivaleaz cu absena unei
hipoxemii/acidemii semnificative la nivelul sistemului
nervos central. Un ft compromis prezint pierderea
accelerrii frecvenei cardiace fetale, micri reduse
ale corpului i respiraiei, hipotonie i, mai puin acut,
reducerea volumului de lichid amniotic. ntre 70% i
90% din decesele fetale trzii prezint dovezi de compromitere cronic i/sau acut. Detectarea sonografic
a semnelor de compromitere fetal permite intervenii
rapide care pot preveni sechelele fetale37,38.
2.8. Intervenii asupra mamei n timpul sarcinii
2.8.1. Tratamentul percutanat
Se aplic aceleai restricii ca pentru angiografia diagnostic coronarian (vezi Seciunea 2.6). Dac intervenia este absolut necesar, cel mai bun moment pentru a interveni este considerat a fi dup a patra lun,
n al doilea trimestru. n acest moment, organogeneza
este complet, tiroida fetal este nc inactiv, iar volumul uterului este nc redus, astfel nct exist o distan mai mare ntre fetus i torace dect n ultimele luni
de sarcin. Timpii pentru fluoroscopie i cineangiografie trebuie s fie ct mai mici posibil, iar uterul gravidei trebuie s fie protejat cu scut de radiaia direct.
Heparina trebuie administrat n doz de 40-70 U/kg,
urmrind un timp de coagulare activat de cel puin 200
de s., dar fr s depeasc 300 de s.
2.8.2. Intervenia chirurgical cardiac cu bypass
cardio-pulmonar
Mortalitatea matern n timpul bypass-ului cardiopulmonar este acum similar cu aceea ntlnit n cazul
femeilor nensrcinate, care sufer proceduri cardiace
comparabile1. Totui, exist o morbiditate semnificativ, incluznd deteriorare neurologic tardiv la 3-6%
dintre copii, iar mortalitatea fetal rmne ridicat39.
Din acest motiv, chirurgia cardiac este recomandat
numai cnd terapia medicamentoas sau procedurile
intervenionale au euat, iar viaa mamei este ameninat. Cea mai bun perioad pentru intervenia chirurgical este ntre sptmnile 13 i 2840,41. Intervenia chirurgical n timpul primului trimestru se nsoete de
un risc ridicat de malformaii fetale, iar n timpul celui
de-al treilea trimestru, exist o inciden mai ridicat

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de natere prematur i complicaii maternale. Cunoatem, din studiile anterioare, faptul c vrsta de gestaie
are un mare impact asupra evoluiei neonatale42. mbuntirile recente n domeniul ngrijirii nou-nscuilor
au sporit rata de supravieuire a copiilor prematuri. La
26 de sptmni, rata supravieuirii este, n general, de
circa 80%, 20% avnd deteriorri neurologice severe.
Din acest motiv, poate fi luat n considerare naterea
prin cezarian nainte de operaia de bypass cardiopulmonar, dac perioada de gestaie este mai mare de
26 de sptmni43. Dac naterea este avantajoas sau
nu pentru copil la aceast perioad de gestaie, aceasta
depinde de mai muli factori: sex, greutatea estimat,
administrarea de corticosteroizi nainte de natere, precum i statistica rezultatelor unitii respective de maternitate. Atunci cnd perioada de gestaie este de 28
de sptmni sau mai mult, trebuie luat n considerare
naterea, nainte de intervenia chirurgical. nainte de
operaie, trebuie administrat mamei o cur complet
(cel puin 24h) de corticosteroizi. n timpul bypass-ului
cardio-pulmonar, trebuie monitorizate pulsul ftului i
tonusul uterin, n plus fa de monitorizarea standard a
pacientei. Debitul cardiac > 2,5 L/min./m2 i presiunea
perfuziei >70 mmHg sunt obligatorii pentru a menine
debitul sanguin utero-placentar corespunztor; debitul
pulsatil, dei controversat, pare mai eficient pentru pstrarea fluxului sanguin utero-placentar. Hematocritul
mamei >28% este recomandat pentru a optimiza alimentarea cu oxigen. Este recomandat perfuzia normo-termic, atunci cnd este posibil i, de asemenea,
este preferat gestionarea corect a pH-ului, pentru a se
evita hipocapnia rspunztoare pentru vasoconstricia
utero-placentar i hipoxia fatului. Trebuie minimizat
durata bypass-ului cardio-pulmonar44.
2.9. Momentul declanrii i modalitatea de
natere: risc pentru mam i copil
Natere cu mare risc
Inducerea, gestionarea travaliului, naterea i supravegherea post-natal necesit competen specific i
management prin colaborarea unor cardiologi, obstetricieni i anesteziti cu experien, n cadrul unitilor
experimentate de medicin materno-fetal45,46.
Declanarea naterii
nceputul spontan al travaliului este potrivit pentru
femei cu funcie cardiac normal i este preferat travaliului indus, pentru majoritatea femeilor cu boli cardiace. Aprecierea momentului declanrii travaliului se
face individualizat, n conformitate cu statusul cardiac
al gravidei, scorul Bishop (un scor bazat pe starea pri-

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mei pri ieite i 4 caracteristici ale cervixului: dilatare, estompare, consisten i poziie), starea ftului i
maturitatea plmnilor. Din cauza lipsei datelor prospective i a influenei caracteristicilor individuale ale
pacientei, nu exist instruciuni standard, prin urmare
managementul trebuie s fie individualizat. La femeile
cu patologie cardiac congenital uoar necorectat,
precum i la acelea care au suferit intervenii chirurgicale cardiace reuite, cu minime defecte restante, gestionarea travaliului i a naterii este aceeai ca i la femeile gravide normale.
Inducerea travaliului
Sunt indicate administrarea de oxitocin i ruperea
artificial a membranelor, atunci cnd scorul Bishop
este favorabil. Un timp ndelungat de inducere trebuie evitat dac cervixul este nefavorabil. Dei nu exist nici o contraindicaie absolut pentru misoprostol
sau dinoproston, exist un risc teoretic de vasospasm
coronarian i un risc redus de aritmii. Dinoprostonul
are efecte mai profunde asupra tensiunii arteriale dect prostaglandin E1 i, prin urmare, este contraindicat
n bolile cardiovasculare active. Metodele mecanice, de
pild un cateter Foley, ar fi de preferat fa de agenii
farmacologici, n mod special pentru pacientele cu cianoz, acolo unde o scdere a rezistenei vasculare sistemice i/sau a tensiunii arteriale ar fi duntoare47.
Naterea natural sau prin cezarian
Modul preferat de natere este cel natural, cu un
plan de natere individualizat, care informeaz echipa
despre declanarea naterii (spontan/indus), metoda de inducere, analgezia/anestezia regional, precum
i nivelul de monitorizare necesar. n cazul leziunilor
de mare risc, naterea trebuie s aib loc ntr-un centru teriar, cu o echip de ngrijire multidisciplinar,
format din specialiti. Naterea natural este asociat
cu o pierdere mai sczut de snge i un risc mai redus de infecie, comparativ cu naterea prin cezarian,
care, de asemenea, crete riscul de tromboz venoas
i trombo-embolism48. n general, naterea prin cezarian este rezervat indicaiilor obstetricale. Nu exist
niciun consens n legtur cu contraindicaiile absolute
pentru naterea natural, recomandrile depinznd de
starea mamei la momentul naterii i de tolerana cardio-pulmonar anticipat a pacientei. Naterea prin cezarian trebuie luat n considerare la pacientele crora
li se administreaz anticoagulant pe cale oral (OAC)
i crora li se declaneaz travaliul nainte de termen,
la pacientele cu sindromul Marfan i cu un diametru

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

aortic >45 mm, la pacientele cu disecie de aort acut


sau cronic, precum i la cele cu insuficien cardiac
acut refractar. Naterea prin cezarian poate fi luat
n considerare n cazul pacientelor cu sindromul Marfan, cu un diametru al aortei de 40-45 mm7,49,50 (vezi, de
asemenea, Seciunea 4.3).
n unele centre, naterea prin cezarian este recomandat femeilor cu stenoz aortic sever (SA) i
pentru pacientele cu forme severe de hipertensiune
pulmonar (incluznd sindromul Eisenmenger) sau cu
insuficien cardiac acut7,46 (vezi Seciunile specifice).
Naterea prin cezarian poate fi luat n considerare
pentru pacientele cu proteze mecanice valvulare cardiace, pentru a preveni problemele din cazul naterii
naturale planificate. n cazul unor asemenea paciente,
o trecere prelungit la heparin/heparin cu greutate
molecular mic (HGMM) ar putea, ntr-adevr, s fie
necesar pentru un timp ndelungat naintea naterii
naturale, n mod special atunci cnd situaia obstetrical este nefavorabil. Aceasta ar crete riscul maternal
(vezi, de asemenea, Seciunile 5.5 i 5.6).
Monitorizare hemodinamic
Sunt monitorizate presiunea arterial sistemic i
frecvena cardiac a mamei, deoarece anestezia epidural lombar poate cauza hipotensiune. Puls oximetria
i monitorizarea ECG continu sunt utilizate dac e necesar. Un cateter Swan-Ganz pentru monitorizare hemodinamic este rar utilizat, dac este indicat vreodat, din cauza riscului aritmogen, de sngerare i a complicaiilor trombo-embolice, la ndeprtarea acestuia51.
Anestezie/analgezie
Analgezia epidural lombar este recomandat adesea, deoarece ea reduce creterea activitii simpatice
determinate de durere, reduce imboldul de a mpinge
i ofer anestezie pentru operaie. Analgezia epidural
lombar continu, cu anestezice sau opioide locale, sau
anestezia spinal opioid continu pot fi administrate
n siguran. Totui, anestezia regional poate cauza
hipotensiune sistemic i trebuie utilizat cu precauie
la pacientele cu leziuni valvulare obstructive. Perfuzia
intravenoas (i.v.) trebuie monitorizat cu atenie52.
Travaliu
n travaliu, femeia trebuie aezat ntr-o poziie decubit-lateral, pentru a atenua impactul hemodinamic
al contraciilor uterine53. Contraciile uterine trebuie
s coboare capul ftului spre perineu, fr mpingerea
mamei, pentru a evita efectele nedorite ale manevrei
Valsalva54,55.

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Naterea poate fi asistat cu forceps jos sau extragere


prin aspirare. Nu este recomandat profilaxia antibiotic de rutin. Este recomandat monitorizarea electronic continu a pulsului ftului.

naterii i post-partum, cu excepia cazului n care


exist contraindicaii precise. Utilizarea de -blocant
n timpul travaliului nu previne contraciile uterine i
naterea natural61.

Naterea la femeile pe anticoagulant, cu proteze valvulare


Anticoagulantele orale trebuie schimbate cu HGMM
sau heparin nefracionat (HNF) din a 36-a sptmn. Femeile tratate cu HGMM trebuie s fie trecute pe
HNF i.v., cu cel puin 36 de ore nainte de inducerea
travaliului sau de naterea prin cezarian. Administrarea HNF trebuie ntrerupt cu 4-6 ore naintea naterii
planificate i reluat la 4-6 ore dup natere, dac nu
exist complicaii hemoragice (vezi, de asemenea, Seciunea 5.5). Poate fi necesar naterea de urgen, la o
pacient cu o valv mecanic, creia i se administreaz
anticoagulare terapeutic, i n aceast situaie exist
un risc major de hemoragie matern sever. Dac naterea de urgen este necesar, n timp ce pacienta se
afl nc sub tratament cu HNF sau HGMM, trebuie
luat n considerare protamina. Protamina va inversa
numai parial efectul anticoagulant al HGMM. n cazul
unei nateri urgente, la o pacient aflat sub tratament
cu anticoagulante orale n doz terapeutic, este de preferat naterea prin cezarian, pentru a reduce riscul de
hemoragie intra-cranian la ftul complet anticoagulat.
Dac este necesar naterea de urgen, trebuie administrat plasm proaspt congelat, nainte de naterea prin cezarian, pentru a obine un raport normalizat internaional (INR) de 24. Poate fi, de asemenea,
administrat oral vitamina K (0,5-1 mg), dar dureaz
4-6 ore pentru a influena INR. Dac mama a fost sub
tratament anticoagulat oral la momentul naterii, nounscutului anticoagulat i se poate administra plasm
proaspt congelat i trebuie s primeasc vitamina K.
Ftul poate rmne anticoagulat timp de 8-10 zile dup
ntreruperea anticoagularii orale la mam.

ngrijirea post-partum
Dup ndeprtarea placentei, se administreaz oxitocin i.v.lent (<2 U/min.), care previne hipotensiunea
sistemic, pentru a evita riscul de apariie a hemoragiei
materne. Analogii de prostaglandin F sunt utili n tratamentul hemoragiei post-partum, cu excepia situaiei
n care nu este de dorit o cretere a presiunii arteriale
pulmonare (PAP). Metilergonovina este contraindicat, din cauza riscului (>10%) de vasoconstricie i hipertensiune62,63. ngrijirea atent a picioarelor, ciorapii
cu suport elastic, precum i mobilizarea timpurie sunt
importante pentru reducerea riscului de trombo-embolism. Naterea este asociat cu modificri hemodinamice importante i schimbri de fluide, n special
n primele 12-24 de ore, care pot precipita insuficiena
cardiac la femeile cu boli cardiace structurale. Prin urmare, trebuie continuat monitorizarea hemodinamic
pentru cel puin 24 de ore dup natere64.

Aritmii ventriculare n timpul sarcinii i travaliului


Aritmiile sunt cele mai des ntlnite complicaii cardiace din timpul sarcinii, la femeile cu i fr boli cardiace structurale12,56,57. Ele se pot manifesta pentru prima dat n timpul sarcinii, sau sarcina poate exacerba
aritmii preexistente58-60. Ghidurile ACC/AHA/ESC din
2006 pentru managementul pacienilor cu aritmii ventriculare i prevenirea morii subite de cauz cardiac
recomand ca femeile nsrcinate, cu sindrom QT prelungit, care au avut simptome, s beneficieze de terapie
continu cu -blocant, de-a lungul sarcinii, n timpul

Alptarea
Lactaia este asociat cu un risc redus de bacteriemie, secundar mastitei. La pacientele cu simptome
puternice/suferinde, trebuie considerat hrnirea cu
biberonul.
2.10 Endocardita infecioas
Endocardita infecioas din timpul sarcinii este rar,
cu o inciden total estimat de 0,006% (1 la 100.000
de sarcini)65 i cu o inciden de 0,5% la pacientele cu
boli cardiace valvulare sau congenitale cunoscute66.
Incidena este mai ridicat n cazul dependentelor de
droguri. Pacientele cu riscul cel mai mare de endocardit infecioas sunt acelea cu o protez valvular sau
cu material protetic utilizat pentru reconstrucia valvular cardiac, cu un istoric de endocardit infecioas
anterioar i anumite paciente cu boal cardiac congenital.
2.10.1 Profilaxie
Se aplic aceleai msuri, specificate n ghiduri, ca
i pentru pacientele nensrcinate67. Profilaxia endocarditei este acum recomandat numai pacientelor cu un
risc nalt de dobndire a endocarditei, n timpul procedurilor cu grad ridicat de risc, cum ar fi procedurile
dentare. n timpul naterii, indicaia pentru profilaxie a
fost controversat i, dat fiind lipsa de dovezi convingtoare asupra faptului c endocardita infecioas este

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determinat fie de naterea natural, fie de cea prin cezarian, nu este recomandat profilaxia cu antibiotice,
n timpul naterii naturale sau prin cezarian67,68.
2.10.2 Diagnosticare i evaluarea riscului
Diagnosticarea endocarditei infecioase n timpul
sarcinii implic aceleai criterii ca la pacientele nensrcinate67. n ciuda progresului n diagnosticarea i
tratamentul endocarditei infecioase, morbiditatea i
mortalitatea matern rmn ridicate, fiind raportate la
33% n cadrul unui studiu (n principal, din cauza insuficienei cardiace i complicaiilor trombo-embolice)69.
Mortalitatea fetal este, de asemenea, ridicat, de 29%.
Insuficiena cardiac, datorat regurgitarii valvulare
acute este cea mai des ntlnit complicaie, necesitnd
o intervenie chirurgical de urgen, atunci cnd tratamentul medical nu poate stabiliza pacientul67. Embolizrile cerebrale i periferice reprezint, de asemenea,
complicaii frecvente.
2.10.3 Tratament
Endocardita infecioas trebuie tratat n acelai fel
ca i la pacienta nensrcinat, gndindu-ne la efectele
feto-toxice ale antibioticelor (vezi Seciunea 11). Dac
este diagnosticat endocardita infecioas, antibioticele trebuie administrate pe baza culturii i a rezultatelor
de sensibilitate fa de antibiotice, precum i a protocoalelor de tratament locale. Antibioticele care pot fi
administrate n timpul tuturor trimestrelor de sarcin
sunt penicilina, ampicilina, amoxicilina, eritromicina,
mezlocilina i cefalosporine70. Toate acestea sunt incluse n grupa B a clasificrii Food and Drug Administration (FDA). Vancomicina, imipenemul, rifampicina
i teicoplanina fac toate parte din grupa C, ceea ce nseamn c nu poate fi exclus riscul, iar raportul riscbeneficiu trebuie evaluat n mod atent. Exist un risc
definit pentru ft n toate trimestrele sarcinii, n ceea
ce privete medicamentele din grupa D (aminoglicozide, quinolone i tetracicline), prin urmare, acestea
trebuie utilizate numai n cazul unor indicaii vitale71.
Intervenia chirurgical de protezare valvular n timpul sarcinii trebuie rezervat cazurilor de insucces al
terapiei medicamentoase, ca i n cazul recomandrilor
pentru pacientele nensrcinate67. Un ftus viabil trebuie nscut naintea interveniei chirurgicale, acolo unde
este posibil (vezi Seciunea 2.8.2).
2.11 Estimarea riscului: contraindicaii pentru
sarcin
2.11.1 Consiliere pre-sarcin
Riscul sarcinii depinde de patologia cardiac specific i de starea clinic a pacientei. Este recomandat

consilierea individual efectuat de experi. Adolescentelor ar trebui s le fie oferite sfaturi referitoare la
contracepie, iar problemele legate de sarcin trebuie
discutate imediat ce tinerele devin active din punct de
vedere sexual. Se impune realizarea unei evaluri a riscului, nainte de sarcin, iar medicamentele trebuie verificate, astfel nct cele care sunt contraindicate n timpul sarcinii s fie oprite sau schimbate cu medicamente
similare, acolo unde este posibil (vezi Seciunea 11.2,
Tabelul 21). Planul de urmrire trebuie discutat cu pacienta i, dac este posibil, cu partenerul ei. Femeile cu
o patologie cardiac important ar trebui urmrite n
echip, de ctre un obstetrician i un cardiolog cu experien n tratamentul pacientelor nsrcinate i cu boal cardiac, din faz incipient. Pacientele cu risc nalt
ar trebui supravegheate de o echip multidisciplinar
experimentat, n cadrul unui centru specializat. Toate
femeile cu boli cardiace ar trebui evaluate cel puin o
dat nainte de sarcin i n timpul sarcinii, i ar trebui
recomandat naterea n spital.
2.11.2 Evaluarea riscului: estimarea riscului
matern i fetal
Exist cteva abordri disponibile, pentru estimarea
riscului de complicaii cardiovasculare materne. Riscul specific bolii poate fi evaluat, i este descris n acest
ghid n cadrul seciunilor specifice fiecrei boli. n general, riscul complicaiilor crete odat cu amplificarea
complexitii bolii56,72.
Tabelul 4. Predictori ai evenimentelor cardiovasculare materne i
scorul de risc din studiul CARPREG12
Eveniment cardiac anterior (insuficien cardiac, atac ischemic tranzitoriu, accident vascular
cerebral nainte de sarcin sau aritmie).
Clasa funcional NYHA bazal >II sau cianoz.
Obstrucie cardiac stng (aria valvei mitrale <2 cm2, aria valvei aortice <1,5 cm2, gradient
maxim n tractul de ejecie VS >30 mmHg, la ecocardiografie).
Funcie sistolic a ventriculului sistemic redus (fracie de ejecie <40%).
Tabelul 5. Predictori ai evenimentelor cardiovasculare materne identificate n bolile cardiace congenitale n studiile ZAHARA i Khairy
Predictori ZAHARA57
Istoric de evenimente aritmice.
Clasa funcional NYHA bazal >II.
Obstrucie cardiac stnga (gradient maxim la aort >50 mmHg).
Protez valvular mecanic.
Regurgitare moderat/sever la nivelul valvei atrioventriculare (posibil legat de disfuncia
ventricular).
Regurgitare moderat/sever la nivelul valvei atrioventriculare sub-pulmonare (posibil legat de
disfuncia ventricular).
Utilizarea unei medicaii cardiace pre-sarcin.
Boala cardiac cianogen corectat sau necorectat.
Predictori Khairy76
Istoric de fumat.
Funcie a ventriculului sub-pulmonar redus i/sau regurgitare pulmonar sever.
NYHA = New York Heart Association.

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Scor risc CARPREG: pentru fiecare predictor CAPREG prezent este acordat un punct. Estimarea riscului de complicaii materne cardiovasculare.
0 puncte 5%; 1 punct 27%; > 1 punct 75%
VS = ventricul stng; NYHA = New York Heart
Association.
Studiile referitoare la o afeciune specific sunt n general retrsopective i cu un numr prea mic de cazuri
pentru a identifica predictori ai unui prognostic negativ. Prin urmare, estimarea riscului poate fi perfecionat, prin luarea n considerare a indicatorilor de predicie care au fost identificai n cadrul studiilor care au
inclus populaii mai mari, cu diverse boli. Pe baza acestor indicatori de predicie au fost dezvoltate cteva scoruri de risc, dintre care scorul CARPREG este cel mai
cunoscut i cel mai larg utilizat. Acest scor de risc a fost
validat n cadrul ctorva studii i pare valoros pentru

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Tabelul 6. Clasificarea OMS modificat a riscului cardiovascular
matern: principii
Clasa de risc
Riscul sarcinii dup afeciunea medical
I
Fr un risc crescut identificat sau fr/cretere uoar a morbiditii.
II
Cretere uoar a mortalitii materne sau cretere moderat a morbiditii.
III
Cretere semnificativ a riscului mortalitii materne sau morbiditate sever.
Sfatul unui specialist este necesar. Dac se continu sarcina, este necesar
monitorizare intensiv cardiologic i obstetrical pe timpul sarcinii, naterii i
postpartum.
IV
Risc extrem de mortalitate matern sau morbiditate sever; sarcina este contraindicat. Dac sarcina apare, ntreruperea sarcinii trebuie pus n discuie. Dac
sarcina continu, se aplic msurile de la clasa a III-a.
Modificat dup Thorne et. al72
OMS = Organizaia Mondial a Sntii

predicia riscului matern, dei poate determina supraestimare57,73. Scorul de risc CARPREG este descris n
Tabelul 4. La femeile cu boli cardiace congenitale, scorul de risc CARPREG12 poate fi asociat, de asemenea,
cu un risc mai mare de evenimente cardiovasculare tardive, post-sarcin74. Indicatorii de predicie din studiul

Tabelul 7. Clasificarea OMS modificat a riscului cardiovascular matern: aplicare


Condiii medicale ce corespund riscului OMS I
Necomplicat, mic sau uoar
- stenoz pulmonar
- persisten de canal arterial
- prolaps de valv mitral
Leziuni simple corectate cu succes (defect septal atrial sau ventricular, persisten de canal arterial, drenaj venos pulmonar aberant)
Extrasistole atriale sau ventriculare, izolate
Condiii medicale ce corespund riscului OMS II sau III
OMS II (dac pacienta este bine i fr complicaii)
Defect septal atrial sau ventricular neoperat
Tetralogie Fallot corectat
Majoritatea aritmiilor
OMS II-III (n funcie de pacient)
Insuficien ventricular stnga uoar
Cardiomiopatie hipertrofic
Boal valvular ce nu corespunde OMS I sau IV
Sindrom Marfan fr dilatare aortic
Aorta <45 mm n boala aortic asociat cu valv aortic bicuspid
Coarctaie corectat
OMS III
Valv mecanic
Ventricul drept sistemic
Circulaie Fontan
Boli cardiace cianogene (necorectate)
Alte boli cardiace complexe
Dilatare aortic de 40-45 mm n sindromul Marfan
Dilatare aortic de 45-50 mm n boli aortice, asociate cu valva aortic bicuspid
Condiii medicale ce corespund riscului OMS IV (sarcin contraindicat)
Hipertensiune arterial pulmonar de orice cauz
Disfuncie sever a ventriculului sistemic (FEVS <30%, NYHA III- IV)
Cardiomiopatie peripartum anterioar cu disfuncie rezidual a ventriculului stng
Stenoz mitral sever, stenoz aortic simptomatic sever
Sindrom Marfan cu aorta dilatat >45 mm
Dilatare aortic >50 mm n insuficiena aortic, cu valv aortic bicuspid
Coarctaie sever nativ
Adaptat din Thorne et al.73
FEVS = fracie de ejecie a ventriculului stng
NYHA = New York Heart Association; OMS = Organizaia Mondial a Sntii.

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ZAHARA57 (Tabelul 5) nu au fost nc validai n alte


studii. Trebuie notat faptul c indicatorii de predicie
i scorurile de risc din studiile CARPREG i ZAHARA
sunt dependente n mare msur de populaie. Factori
importani de risc, cum sunt hipertensiunea arterial
pulmonar i dilatarea aortei, nu au fost identificai, deoarece au fost sub-reprezentai n cadrul acestor studii.
Studiul CARPREG a inclus bolile cardiace dobndite i
congenitale, n timp ce studiul ZAHARA a investigat
numai o populaie cu patologie cardiac congenital.
Grupul de Lucru recomand ca evaluarea riscului
matern s fie efectuat n conformitate cu clasificarea
riscului modificat a Organizaiei Mondiale a Sntii
(OMS)72. Clasificarea riscului integreaz toi factorii de
risc cardiovascular materni cunoscui, incluznd bolile
cardiace de baz i orice alt co-morbiditate. Aceasta
include contraindicaii pentru sarcin care nu sunt incluse n scorurile de risc CARPREG i ZAHARA. Principiile generale ale acestei clasificri sunt reprezentate
n Tabelul 6. O aplicaie practic este oferit n Tabelul
7. La femeile din clasa OMS I, riscul este foarte redus,
iar urmrirea cardiologic n timpul sarcinii poate fi limitat la una sau dou vizite. La cele din clasa OMS II,
riscul este redus sau moderat, putnd fi recomandat
urmrirea n fiecare trimestru. Pentru femeile din clasa
OMS III, exist un risc nalt de complicaii, fiind recomandat controlul cardiologic i obstetrical frecvent
n timpul sarcinii (lunar sau bilunar). Femeile din clasa
OMS IV trebuie sftuite mpotriva sarcinii dar, dac rmn gravide i nu vor lua n considerare ntreruperea
sarcinii, va fi necesar urmrirea lunar sau bilunar.
Complicaiile neonatale apar la 20-28% dintre pacientele cu boli cardiace12,56,57,75,76, cu o mortalitate neonatal ntre 1% i 4%12,56,57. Evenimentele materne i neonatale sunt strns corelate57. Predictorii complicaiilor
neonatale sunt enumerai n Tabelul 8.
Tabelul 8. Predictori maternali de evenimente neonatale la femeile cu
boli cardiace
1. Clas NYHA bazal >II sau cianoz12
2. Obstrucie la nivelul cordului stng al mamei12,76
3. Fumat n timpul sarcinii12,57
4. Sarcin multipl12,57
5. Utilizare de anticoagulante orale n timpul sarcinii12
6. Protez valvular mecanic57
Modificat din Siu et al.12 (investigatori CARPREG); Khairy et al.76; Drenthen/Pieper et al.57 (investigatori ZAHARA)
NYHA = New York Heart Association.

2.12 Metode de contracepie, de ntrerupere a


sarcinii i fertilizarea in vitro
2.12.1 Metode de contracepie
Metodele contraceptive includ anticoncepionale
hormonale combinate (estrogen/progesteron), metode

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

pe baz de progesteron exclusiv, dispozitive intrauterine i contracepia de urgen. Utilizarea lor trebuie s
fie echilibrat mpotriva riscului de sarcin.
n 2010, Centrele pentru Controlul Afeciunilor
(CDC) au modificat sugestiile OMS pentru criteriile
medicale de eligibilitate pentru utilizarea contraceptivelor la femeile cu boli cardiovasculare.[http://www.
cdc.gov/Mmwr/preview/mmwrhtml/rr59e0528a13.
htm]. Injeciile lunare cu medroxiprogesteron acetat
sunt nepotrivite pentru pacientele cu insuficien cardiac, din cauza tendinei de retenie a fluidelor. Contraceptivele orale n doz redus coninnd 20 g de
etil-estradiol sunt sigure pentru femeile cu un potenial
trombogenic redus, dar nu pentru femeile cu patologie
valvular complex77,78.
Pe lng metodele de barier (prezervativul), dispozitivul intrauterin cu eliberare de levonorgestrel este cel
mai sigur i cel mai eficient contraceptiv care poate fi
utilizat la femeile cu boli cardiace congenitale cianogene i patologie vascular pulmonar. Acesta reduce
pierderea de snge la menstruaie cu 40-50% i induce
amenoreea la un procent semnificativ de utilizatori79.
Trebuie reinut faptul c aproximativ 5% dintre paciente dezvolt reacii vasovagale la momentul implantului,
prin urmare, pentru acelea cu patologie cardiac complex (de exemplu, Fontan, Eisenmenger), implanturile
intrauterine sunt indicate doar cnd tabletele pe baz
numai de progesteron sau implanturile cutanate s-au
dovedit inacceptabile i, dac sunt utilizate, trebuie implantate numai ntr-un mediu spitalicesc. Un dispozitiv
intrauterin din cupru este acceptat la femeile non-cianotice sau uor cianotice. Profilaxia antibiotic nu este
recomandat la momentul introducerii sau ndeprtrii, din moment ce nu crete riscul de infecie pelvian.
Dac apare sngerarea abundent la momentul menstruaiei, dispozitivul trebuie ndeprtat. Este contraindicat la femeile cianotice, cu niveluri ale hematocritului
>55%, deoarece tulburrile hemostatice intrinseci cresc
riscul de sngerare menstrual abundent.
2.12.2 Sterilizarea
Ligaturarea trompelor este realizat de obicei n siguran, chiar i la femeile cu un risc relativ nalt. Din
cauza anesteziei asociate i a inflaiei abdomenului, nu
este, totui, lipsit de risc la pacientele cu hipertensiune
arterial pulmonar, cianoz i circulaie Fontan. Riscul poate fi mai redus prin folosirea tehnicilor histeroscopice minim invazive, cum ar fi dispozitivul Essure.
Sterilizarea histeroscopic este efectuat prin introducerea unei micro-inserii metalice sau a unei matrice
polimerice n poriunea interstiial a fiecrei trompe

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

uterine. La trei luni dup instalare, sunt confirmate


aezarea corect a dispozitivului i ocluzia bilateral a
trompelor prin imagistic pelvian. Avantajele sterilizrii histeroscopice includ capacitatea de a efectua procedura n ambulatoriu i fr o incizie. Un dezavantaj
l reprezint perioada de ateptare de 3 luni, pn cnd
ocluzia trompelor este confirmat80. Vasectomia pentru
partenerul masculin reprezint o alt opiune eficient,
dar prognosticul pe termen lung al partenerului femeii
trebuie luat n considerare, deoarece partenerul masculin poate s triasc mai muli ani dect ea. Dat fiind lipsa de date publicate despre contracepie n cazul
insuficienei cardiace, sfaturile trebuie oferite de ctre
medici sau ginecologi cu pregtire corespunztoare.
2.12.3 Metode pentru ntreruperea sarcinii
ntreruperea sarcinii trebuie discutat cu femeile a
cror gestaie reprezint un risc major pentru mam sau
ft. Primul trimestru este cel mai sigur moment pentru
ntreruperea electiv a sarcinii, care trebuie efectuat n
spital, mai degrab dect n ambulator, astfel nct s fie
disponibile toate serviciile de urgen. Metoda, inclusiv
necesitatea anesteziei, trebuie luat n considerare pe
baz individual. Pacientele cu risc nalt trebuie tratate ntr-un centru cu experien, cu secie de chirurgie
cardiac. Profilaxia endocarditei nu este recomandat
cu fermitate de ctre cardiologi81, dar tratamentul ar
trebui individualizat. Ginecologii recomand de obicei
profilaxia cu antibiotice pentru a preveni endometrita
post-avort, care apare la 5-20% dintre femeile care nu
iau antibiotice82,83.
Dilatarea i evacuarea sunt cele mai sigure proceduri
att n primul ct i n al doilea trimestru al sarcinii.
Dac evacuarea chirurgical nu este posibil n al doilea
trimestru, prostaglandinele E1 sau E2, sau misoprostol,
o prostaglandin sintetic asemntoare din punct de
vedere structural cu prostaglandina E1, pot fi administrate pentru a stimula evacuarea uterului84. Aceste medicamente sunt absorbite n circulaia sistemic i pot
scdea rezistena vascular sistemic i tensiunea arterial, crescnd de asemenea frecvena cardiac, efecte
care sunt mai importante pentru E2 dect pentru E1.
Pn n saptmna a aptea de gestaie, mifepriston
este o alternativ la chirurgie. n timpul administrrii
prostaglandinelor E, este necesar monitorizarea saturaiei arteriale n oxigen cu ajutorul puls-oximetrului
i administrarea norepinefrinei n perfuzie, la o doz
care s menin presiunea arterial diastolic ce reflect rezistena vascular sistemic. Prostaglandinele F ar
trebui evitate datorit creterii semnificative a presiunii

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din artera pulmonar i scderii perfuziei coronariene85.


Avortul prin administrarea de substane saline ar
trebui evitat deoarece absorbia salin poate determina
expansiunea volumului intravascular, insuficien cardiac i tulburri de coagulare.
2.12.4 Fertilizarea in vitro
Fertilizarea in vitro poate fi luat n considerare
atunci cnd riscul procedurii n sine, inclusiv a stimulrii hormonale i a sarciii sunt sczute. Fertilizarea in
vitro se poate complica cu tromboembolism, atunci
cnd nivelul ridicat de estradiol poate precipita statusul
protrombotic86.
2.13 Recomandri generale
Tabelul 6. Recomandri generale
Recomandri
Clasa
Evaluarea riscului i consilierea anterioar sarcinii este indicat la toate
femeile cunoscute sau la cele la care se suspecteaz boli cardiovasculare sau
I
aortice congenitale sau dobndite.
Evaluarea riscului trebuie realizat la toate femeile cu boli cardiace de
I
vrst fertil i dup concepie.
Pacientele cu risc nalt trebuie tratate n centre specializate de o echip
I
multidisciplinar.
Consilierea genetic trebuie oferit femeilor cu boli cardiace congenitale
sau aritmii congenitale, cardiomiopatii, boli aortice sau malformaii genetice
I
asociate cu BCV.
Ecocardiografia trebuie realizat la orice gravid cu semne i simptome
I
cardiovasculare nou aprute sau ce nu pot fi explicate.
Anterior operaiei cardiace, o cur complet de corticosteroizi trebuie
I
administrat mamei cnd este posibil.
Pentru profilaxia endocarditei infecioase n sarcin trebuie folosite aceleai
I
msuri ca n afara sarcinii.
Naterea vaginal este recomandat ca prim alegere pentru majoritatea
I
pacientelor.
IRM (fr gadolinum) este o alternativ la pacientele la care ecocardiografia
IIa
este insuficient.
La pacientele cu hipertensiune sever, naterea vaginal cu anestezie
IIa
epidural i naterea instrumental trebuie avute n vedere.
Cnd vrsta gestaional este de cel puin 28 de sptmni, naterea premaIIa
tur naintea operaiei cardiace trebuie luat n considerare.
Operaia de cezarian trebuie avut n vedere pentru indicaii obstetricale
sau pentru dilatarea aortei ascendente >45 mm, stenoz aortic sever,
IIa
natere prematur i anticoagulare oral, sindrom Eisenmenger sau
insuficien cardiac sever.
Operaia de cezarian trebuie avut n vedere n sindromul Marfan cu un
IIb
diametru aortic de 40-45mm.
Radiografia toracic cu protecia ftului poate fi realizat dac alte metode
IIb
de investigare a dispneei nu au avut succes.
Cateterizarea cardiac are indicaii foarte stricte i se realizeaz n timp
IIb
limitat i cu protecia ftului.
CT i studiile electrofiziologice, cu protecia ftului, pot fi avute n vedere la
IIb
anumite paciente pentru afeciuni vitale.
Operaia de bypass sau chirurgia valvular poate fi avut n vedere cnd
terapia conservativ i medical nu au dat rezultate, n situaii cu risc vital
IIb
pentru mam i n care tratamentul percutan nu se poate realiza.
Terapia antibiotic profilactic n timpul naterii nu este recomandat.
III
a = clasa de recomandare; b = nivelul de eviden
CT = computer tomograf; BCV = boli cardiovasculare; IRM = imagistic prin rezonan magnetic

Nivelb
C
C
C
C
C
C
C
C
C
C
C

C
C
C
C
C
C

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3. BOLILE CARDIACE CONGENITALE I HIPERTENSIUNEA PULMONAR


Multe femei cu boal cardiac congenital tolereaz
bine sarcina. Riscul sarcinii depinde att de boala cardiac de baz, ct i de factori adiionali precum funcia
ventricular i valvular, clasa funcional i prezena
cianozei. Rata sarcinilor pierdute este mai mare n bolile cardiace complexe (Figura 1)56. Complicaiile cardiace materne sunt prezente n 12% din sarcinile duse
la termen i, din nou, frecvena crete pe msur ce se
amplific i complexitatea bolii. Pacientele care prezint complicaii pe parcursul sarcinii pot prezenta de asemenea, un risc mai mare de evenimente cardiace tardive, dup sarcin74. Complicaiile fetale, inclusiv mortalitatea fetal (4%) sunt mai frecvente dect n rndul
populaiei generale.
Diagnostic
De obicei, bolile cardiace congenitale sunt cunoscute
i diagnosticate nainte de sarcin. Evaluarea pre-concepie, incluznd istoricul medical, ecocardiografia i
testarea capacitii de efort le sunt indicate tuturor pacientelor, cu teste diagnostice suplimentare recomandate n funcie de particularitile individuale. Statusul
funcional anterior sarcinii i istoricul evenimentelor
cardiace anterioare au o valoare prognostic particular

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

(vezi Tabelele 4 i 5). De asemenea, dozarea peptidului


natriuretic tip B (BNP)/pro-peptidului natriuretic tip B
N-terminal (NT-pro-BNP) poate fi util n stratificarea
riscului. Un test de efort anterior sarcinii n care este
atins o capacitate de efort <70% din valoarea prezis,
cu o scdere a presiunii arteriale, sau o scdere a saturaiei oxigenului, permite identificarea unor femei la risc
pentru dezvoltarea simptomelor, sau a complicaiilor,
pe perioada sarcinii. Procedurile diagnostice care pot
fi utilizate pe perioada sarcinii sunt enumerate n seciunea 2.621. Pentru evaluarea ulterioar a riscului, vezi
Seciunea 2.11.
3.1 Afeciunile cu risc matern crescut (Organizaia
Mondial a Sntii (III)-IV; vezi i Seciunea 2.11)
Pacientele cu clas NYHA III/IV sau cu scderea
marcat a funciei ventriculului sistemic prezint risc
crescut pe perioada sarcinii, mpreun cu alte condiii specifice discutate mai jos. n plus, anumite condiii
specifice prezint un risc crescut mai ales pe perioada
sarcinii.
3.1.1 Hipertensiunea pulmonar
Riscul matern
Hipertensiunea pulmonar cuprinde un grup de boli
cu fiziopatologii diferite, printre care hipertensiunea
arterial pulmonar, hipertensiunea pulmonar din
bolile cordului stng, hipertensiunea pulmonar core-

Figura 1. Distribuia pierderilor de sarcin, a sarcinilor duse la termen (> 20 de sptmni de durat a sarcinii) i a avorturilor elective pentru fiecare boal
cardiac congenital separat i n total. ASD = defect septal atrial; AVSD = defect septal atrioventricular; AOS = stenoz aortic; CC-TGA = transpoziie
corectat de vase mari; CHD = boal cardiac congenital; Coarctation = coarctaie de aort; Ebstein = anomalie Ebstein; Eisenmenger = sindrom Eisenmenger; Fontan = pacieni dup reparaie Fontan; PAVSD = atrezie pulmonar cu defect septal ventricular; PS = stenoz valvular pulmonar; TGA =
transpoziie complet de vase mari; TOF = tetralogie Fallot; VSD = defect septal ventricular.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

lat cu bolile pulmonare i/sau hipoxia, hipertensiunea


pulmonar cronic trombo-embolic i hipertensiunea
pulmonar cu mecanism neclar sau multifactorial. Hipertensiunea arterial pulmonar include formele idiopatice i ereditare, precum i hipertensiunea pulmonar asociat cu bolile cardiace congenitale, cu sau fr
intervenie chirurgical de corecie anterioar87. O presiune arterial pulmonar medie (PAPm) 25 mmHg
n repaus este un indicator al hipertensiunii pulmonare87. La pacientele cu hipertensiune arterial pulmonar sever i sindrom Eisenmenger este raportat un
risc crescut de mortalitate matern (30-50% n seriile
mai vechi i 17-33% n studiile mai recente)87,88. Decesul matern survine n ultimul trimestru de sarcin i n
primele luni dup natere din cauza crizelor hipertensive pulmonare, trombozei pulmonare, sau insuficienei
cardiace drepte refractare. Aceasta survine chiar i la
pacientele cu dizabiliti mici sau chiar fr dizabiliti
nainte sau pe perioada sarcinii. Factorii de risc pentru
mortalitatea matern sunt: spitalizarea tardiv, severitatea hipertensiunii pulmonare i anestezia general87.
Cel mai probabil, riscul crete n paralel cu severitatea
hipertensiunii pulmonare. Totui, chiar i formele cu
severitate moderat ale bolii vasculare pulmonare se
pot agrava pe perioada sarcinii, ca rezultat al scderii
rezistenei vasculare sistemice i a suprasarcinii ventriculului drept, fr a se cunoate valorile limit. Nu se
tie exact dac riscul este de asemenea crescut la pacientele cu boli congenitale, dup nchiderea cu succes
a untului i cu presiuni pulmonare uor crescute (ex:
dup nchiderea defectului septal atrial, cu o presiune
medie de 30 mmHg), dar aceste riscuri sunt probabil
mai mici i sarcina poate fi avut n vedere, dup evaluarea atent a riscului, pe baza tuturor metodelor de
diagnostic disponibile ntr-un centru specializat89.
Riscul obsterical i fetal
Ratele de supravieuire neonatal sunt raportate ntre 87-89%87.
Management
Urmrirea
Dac sarcina survine, posibilitatea ntreruperii ei
trebuie oferit pacientelor. Avnd n vedere riscurile pe
care le implic anestezia, ntreruperea sarcinii trebuie
efectuat ntr-un centru teriar, cu experien n managementul pacienilor cu hipertensiune pulmonar arterial. Dac pacienta dorete s continue sarcina, aceasta trebuie ndrumat spre un centru cu experien n
HTP arterial, cu toate opiunile terapeutice disponibi

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le68. Trebuie depuse toate eforturile pentru meninerea


volumului circulant i evitarea hipotensiunii sistemice,
hipoxiei i acidozei, care pot precipita insuficiena cardiac refractar. Pacientele trbuie s primeasc aport
suplimentar de oxigen, n caz de hipoxemie. Prostaciclina i.v. sau iloprost sub form de aerosoli au fost utilizai ocazional n perioada antenatal i peripartum
pentru a ameliora condiiile hemodinamice n timpul
naterii90. n cazul pacientelor care se afl pe tratament
specific pentru hipertensiune pulmonar arterial anterior sarcinii, se poate lua n considerare continuarea
acestei terapii, dup informarea prealabil asupra efectelor teratogene ale unor medicamente precum bosentanul. Monitorizarea hemodinamic cu cateter SwanGanz se poate asocia cu complicaii serioase, precum
ruptura de arter pulmonar, n timp ce utilitatea sa
nu a fost demonstrat; de aceea, se recomand rar, sau
chiar niciodat.
Tratamentul medical
n cazul pacientelor la care exist indicaie de terapie anticoagulant stabilit anterior sarcinii, anticoagularea ar trebui meninut i pe durata sarcinii89. n
hipertensiunea pulmonar arterial asociat cu unturi
cardiace congenitale, n absena hemoptiziei semnificative, tratamentul anticoagulant ar trebui luat n considerare la pacienii cu tromboz arterial pulmonar
sau semne de insuficien cardiac. n hipertensiunea
pulmonar arterial asociat cu boli ale esutului conjunctiv, tratamentul anticoagulant ar trebui avut n
vedere pe considerente individuale. n hipertensiunea
pulmonar arterial asociat cu hipertensiune portal,
anticoagularea nu este recomandat pacientelor cu risc
crescut de sngerare.
Pe perioada sarcinii, tipul tratamentului anticoagulant (HNF vs. HGMM) trebuie ales pe considerente individuale. Nu sunt disponibile studii randomizate care
s compare eficacitatea diferitelor tipuri de heparin
i nici studii referitoare la riscul asociat cu nlocuirea
tratamentului cu anticoagulante orale, fie cu heparin
nefracionat, fie cu heparine cu greutate molecular
mic, pe perioada sarcinii. Trebuie realizat o evaluare
a riscului n funcie de tipul de anticoagulant ales. Din
cauza riscului crescut de sngerare la aceste paciente,
administrarea subcutan a HGMM sau a HNF este
de preferat n comparaie cu anticoagularea oral pe
perioada sarcinii. Trebuie reinut faptul c pot aprea
interaciuni medicamentoase semnificative cu terapia
HTP-specific i este necesar monitorizarea cu atenie
a anticoagulrii (monitorizare INR pentru anticoagu-

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lante orale, monitorizarea timpului parial de tromboplastin activat-aPTT n caz de HNF; nivelele anti-Xa
n caz de HGMM).
Naterea
Tipul de natere trebuie individualizat. Naterea prin
operaie cezarian planificat sau naterea pe cale vaginal sunt de preferat, comparativ cu naterea prin operaie cezarian de urgen.
3.1.2. Pacientele cu sindrom Eisenmenger
Riscul matern
Pacientele cu Sindrom Eisenmenger necesit atenie
special, din cauza asocierii hipertensiunii pulmonare
cu cianoz secundar untului dreapta-stnga. Vasodilataia sistemic crete untul dreapta-stnga i scade fluxul pulmonar, ducnd la accentuarea cianozei i
eventual la un sindrom de debit cardiac sczut. Datele
din literatur raporteaz o mortalitate matern crescut de 20-50%, ce survine cel mai frecvent n perioada
peri- sau post-partum91.
Riscul obsterical i fetal
Cianoza determin creterea semnificativ a riscului
fetal, cu probabilitate redus de a da natere unui ft viu
(<12%), dac saturaia oxigenului este <85%.
Management
Urmrirea
Dac sarcina survine, posibilitatea ntreruperii ei
trebuie oferit pacientelor; totui i ntreruperea sarcinii comport un risc68. Dac pacienta dorete s continue sarcina, aceasta trebuie urmrit ntr-un centru
specializat. Repausul la pat poate fi benefic. Tromboembolismul reprezint un risc major la pacientele cianotice, motiv pentru care pacientele ar trebui s fac
profilaxia acestei afeciuni, dup evaluare hematologic
i investigarea hemostazei. Terapia anticoagulant trebuie utilizat cu precauie, pacientele cu Eisenmenger
fiind predispuse la hemoptizii i trombocitopenie. Riscurile i beneficiile anticoagulrii trebuie cntrite cu
atenie i decizia individualizat n fiecare situaie. La
pacientele cu insuficien cardiac, diureticele trebuie
utilizate judicios i n doza cea mai mic, eficient terapeutic, pentru a evita hemoconcentraia i depleia
volumului intravascular. Microcitoza i deficitul de fier
sunt frecvente i trebuie tratate cu suplimente de fier
orale sau i.v., evitnd un efect de rebound. Sunt indicate reevaluri clinice frecvente, cu msurarea saturaiei
oxigenului i hemoleucogram complet.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Naterea
Dac starea mamei sau a ftului se deterioreaz, trebuie planificat o natere prematur prin operaie cezarian. Avnd n vedere riscul pe care l presupune anestezia, aceasta trebuie realizat ntr-un centru teriar, cu
experien n managementul unor astfel de paciente. La
celelalte, internarea temporar, naterea electiv planificat i anestezia regional incremental pot ameliora
prognosticul matern68.
3.1.3. Bolile cardiace cianogene fr
hipertensiune pulmonar
Riscul matern
Bolile congenitale cardiace cianogene sunt n general
corectate nainte de sarcin, dar unele cazuri inoperabile, sau cu operaii paleative pot ajunge la vrsta fertil.
Complicaiile materne (insuficiena cardiac, tromboza
sistemic sau pulmonar, aritmiile supraventriculare,
endocardita infecioas) survin la 30% din pacientele
cianotice nsrcinate. Dac saturaia oxigenului n repaus este <85%, riscul mortalitii materno-fetale este
substanial i sarcina este contraindicat. Dac saturaia oxigenului n repaus este de 85-90%, se recomand
msurarea ei n timpul efortului. Dac saturaia scade
semnificativ i precoce, pacientele trebuie atenionate
c sarcina presupune un prognostic prost.
Riscul obsterical i fetal
Gradul hipoxemiei materne este cel mai important
predictor pentru evoluia ftului. Cu o saturaie a sngelui matern peste 90% msurat n condiii de repaus,
prognosticul fetal este bun (<10% mortalitate fetal).
Dac totui, saturaia n oxigen a sngelui matern este
sub 85%, ansa unui ft nscut viu este de 12%, motiv
pentru care sarcina ar trebui descurajat91.
Management
Urmrire
Pe perioada sarcinii se recomand restricionarea
activitii fizice i aportul suplimentar de oxigen (cu
monitorizarea saturaiei n oxigen). Din cauza riscului crescut de embolii paradoxale, combaterea stazei
venoase prin purtarea de ciorapi elastici i evitarea ortostatismului sunt importante. n cazul repaosului prelungit la pat, se ia n discuie administrarea profilactic
de heparin. Hematocritul i hemoglobina nu reprezint indicatori fideli ai hipoxemiei. Tromboembolismul
reprezint un risc major pentru pacienii cianotici, de
aceea pacienii trebuie consiliai pentru profilaxie dup
evaluarea hematologic i investigarea hemostazei.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Terapia medical
Tromboprofilaxia cu HGMM trebuie luat n considerare, dac hemostaza este normal. Diureticele i
terapia cu fier sunt indicate i manageriate n mod similar ca n cazul pacientelor cu sindrom Eisenmenger.
Naterea
Naterea pe cale vaginal este recomandat n majoritatea cazurilor. Dac apare deteriorarea condiiei
materne sau fetale, se impune planificarea unei operaii
cezariene timpurii. Avnd n vedere riscurile anesteziei, aceasta trebuie realizat ntr-un centru teriar cu
experien n managementul acestor paciente. La altele, internarea temporar, naterea electiv planificat
i anestezia regional incremental pot ameliora prognosticul matern68.
3.1.4 Obstrucia sever a tractului de ejecie a
ventriculului stng
Obstrucia sever a tractului de ejecie a ventriculului stng (LVOTO) constituie o contraindicaie pentru
sarcin i trebuie tratat anterior sarcinii, sau, femeile
trebuie consiliate s evite sarcina. Poate fi valvular, supravalvular sau cauzat de o stenoz aortic subvalvular membranoas, discret sau tipul tunelar. Managementul stenozei supravalvulare i subvalvulare este
descris doar n prezentri de cazuri din sarcin i este
probabil similar cu managementul pacientelor cu stenoz valvular, dei valvulotomia cu balon nu constituie o opiune terapeutic92. Managementul sarcinii n
stenoza aortic (sever) este descris n seciunea bolilor
cardiace valvulare (Seciunea 5).
3.2 Afeciunile cu risc matern sczut i moderat
(Organizaia Mondial a Sntii I, II i III; vezi i
Tabelele 6 i 7 )
La pacientele care au suferit anterior intervenii chirurgicale de corecie de succes, fr implantare de valv mecanic, sarcina este frecvent bine tolerat, dac
tolerana la efort este bun, funcia ventricular normal i statusul funcional sunt bune. Dei pacientele
trebuie informate cu privire la riscul adiional (adesea
mic), sarcina nu trebuie descurajat. Pacientele trebuie
evaluate pn la sfritul primului trimestru i stabilit
un plan de urmrire cu definirea intervalelor de timp
i a investigaiilor necesare (precum ecocardiografia).
Planul de urmrire trebuie individualizat innd cont
de complexitatea bolii cardiace i de statusul clinic al
pacientei. Unele afeciuni congenitale se pot agrava pe
perioada sarcinii, de aceea datele programate pentru

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reevaluare trebuie s fie flexibile. Naterea pe cale vaginal poate fi planificat n majoritatea cazurilor3,93,94.
3.3 Defecte congenitale specifice
3.3.1 Defectul septal atrial
Riscul matern
Sarcina este bine tolerat de majoritatea femeilor
cu DSA. Singura contraindicaie o constituie prezena
HTP sau a Sindromului Eisenmenger (vezi seciunile
3.2.1 i 3.2.2)95. nchiderea unui DSA semnificativ hemodinamic trebuie realizat naintea sarcinii. Complicaiile tromboembolice au fost descrise n pn la
5% din cazuri56. Aritmiile survin mai frecvent dect la
femeile sntoase, n special dac DSA este necorectat
sau nchis la o vrst mai avansat i femeia nsrcinat
are >30 de ani95,96.
Riscul obstetrical i fetal
La pacientele cu DSA necorectat exist un risc mai
mare de pre-eclampsie i ft mic pentru vrsta gestaional. n DSA corectat nu exist riscuri suplimentare.
Management
De obicei, pe parcursul sarcinii, dou evaluri sunt
suficiente. Pentru DSA tip ostium secundum, nchiderea intervenional cu device, poate fi realizat n timpul sarcinii, dar se indic doar n cazul n care exist o
deteriorare a strii mamei (cu ghidare ecocardiografic
transesofagian sau intracardiac). Nu se indic nchiderea unui DSA mic sau a unui foramen ovale patent,
n scopul prevenirii emboliilor paradoxale. Din cauza
riscului crescut de embolii paradoxale la pacientele
cu unt rezidual, este important prevenirea stazei venoase (utilizarea de ciorapi elastici i evitarea ortostatismului), precum i mobilizarea precoce dup natere. n cazul repausului prelungit la pat, administrarea
profilactic de heparin ar trebui avut n vedere97. Este
important ngrijirea minuioas, cu eliminarea bulelor
de aer din cile de abord i.v., care ar putea duce la embolizare sistemic, datorit untului dreapta-stnga, n
timpul travaliului.
Naterea spontan, pe cale vaginal este indicat n
majoritatea situaiilor.
3.3.2 Defectul septal ventricular
Riscul matern
Defectul septal interventricular (DSV) mare cu hipertensiune pulmonar (vezi situaiile de risc matern
crescut Seciunea 3.1). DSV mic, perimembranos
(fr dilatarea cavitilor stngi) are un risc mic de
complicaii n timpul sarcinii98. DSV corectat are un
bun prognostic n timpul sarcinii, cnd funcia VS este

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pstrat. Se recomand evaluarea prezenei unui posibil defect (rezidual), a dimensiunilor cardiace i estimarea presiunii pulmonare.
Riscul obstetrical i fetal
Pre-eclampsia poate surveni mai frecvent dect n
rndul populaiei generale98.
Management
De obicei, pe parcursul sarcinii, dou evaluri sunt
suficiente, iar naterea spontan, pe cale vaginal, este
recomandat.
3.3.3 Defectul septal atrio-ventricular
Riscul matern
Dup corecie, sarcina este n general bine tolerat,
dac regurgitarea valvular rezidual nu este sever i
funcia ventricular este normal (clas de risc OMS
II). Pacientele cu regurgitare valvular atrioventricular stng sever, simptomatice, sau cu disfuncie ventricular, ar trebui tratate chirurgical nainte de sarcin,
n special reparare valvular7. n cazul defectului atrioventricular cu hipertensiune pulmonar (vezi situaiile de risc matern crescut Seciunea 3.1.1). Corecia
nainte de sarcin a unui defect septal atrioventricular
semnificativ hemodinamic19 ar trebui avut n vedere.
Agravarea clasei NYHA, aritmiile, agravarea regurgitrii la nivelul valvei atrio-ventriculare, au fost descrise
pe perioada sarcinii99. Riscul de insuficien cardiac
este mic i apare doar la femeile cu regurgitare sever
sau disfuncie ventricular stng.
Riscul obstetrical i fetal
Complicaiile obstetricale sunt legate n general de
riscul de insuficien cardiac acut n timpul sau imediat dup natere i depind de prezena simptomelor i
de presiunea arterial pulmonar din timpul naterii.
Mortalitarea infantil a fost de 6%, cauzat mai ales de
prezena unei boli cardiace congenitale complexe99.
Management
Urmrirea
Pe perioada sarcinii, se recomand evaluare cel puin
o dat n fiecare trimestru. Evaluarea clinic i ecocardiografic este indicat lunar sau bilunar la pacientele
cu regurgitare valvular moderat, sever sau cu disfuncie ventricular. n defectele septale atrio-ventriculare necorectate, exist risc de embolie paradoxal
(vezi Seciunea 3.3.1 pentru msurile de prevenie a
tromboembolismului).

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Naterea
Naterea spontan, pe cale vaginal, este recomandat n majoritatea situaiilor.
3.3.4 Coarctaia de aort
Riscul matern
Sarcina este frecvent bine tolerat de paciente, dup
corecia coarctaiei de aort (CoA) (clas de risc OMS
II). (Re) coarctaia semnificativ trebuie corectat nainte de sarcin. Femeile cu CoA nativ, necorectat,
precum i cele cu CoA corectat dar cu hipertensiune
rezidual, cu CoA rezidual sau anevrism aortic, au un
risc crescut de ruptur aortic i ruptur a unui anevrism cerebral n timpul sarcinii sau al naterii. Ali
factori de risc pentru aceast complicaie sunt dilatarea
de aort i valva aortic bicuspid i ar trebui evaluai
nainte de momentul concepiei.
Riscul obstetrical i fetal
A fost raportat un numr crescut de boli hipertensive i avorturi spontane100,101.
Management
Monitorizarea atent a tensiunii arteriale este justificat i se indic reevaluarea regulat, cel puin o dat
pe trimestru. Hipertensiunea trebuie tratat, dei tratamentul agresiv la femeile cu coarctaie rezidual este
de evitat, pentru a preveni hipoperfuzia placentar. n
cazul recoarctaiei de aort, intervenia percutan este
posibil pe perioada sarcinii, dar se asociaz cu un risc
mai mare de disecie de aort i trebuie efectuat doar
n cazul hipertensiunii severe, persistente, n ciuda
terapiei medicale maximale, cu afectare matern sau
fetal. Utilizarea de stenturi acoperite, poate diminua
riscul de disecie.
Naterea
Naterea spontan, pe cale vaginal, este de preferat,
cu utilizarea anesteziei epidurale n special la pacientele
hipertensive.
3.3.5 Stenoza valvular pulmonar i regurgitarea
Riscul matern
Stenoza valvular pulmonar (PS) este n general
bine tolerat n timpul sarcinii102-104. Totui, n cazul
stenozei severe pot surveni complicaii precum insuficiena ventricular dreapt i aritmii. Corectarea stenozei pe perioada sarcinii (n general prin valvuloplastie
cu balon) ar trebui realizat n cazul stenozelor severe
(Gradient max Doppler >64 mmHg)19,68,105.
Regurgitarea pulmonar sever reprezint un predictor independent al complicaiilor materne, n special la pacientele cu disfuncie ventricular76,106. La

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

pacientele simptomatice sau cu disfuncie de VD din


cauza regurgitrii pulmonare severe, nlocuirea valvular pulmonar (preferabil bioprotez) este de luat n
considerare nainte de momentul concepiei.
Riscul obstetrical i fetal
La femeile cu stenoz pulmonar poate crete incidena complicaiilor obstetricale materne, n special
cele legate de hipertensiune, inclusiv (pre-) eclampsia103. Incidena complicaiilor fetale pare de asemenea mai mare dect n cadrul populaiei generale103. n
general, regurgitarea pulmonar nu aduce un risc fetal
suplimentar.
Management
Urmrire
Stenoza pulmonar uoar i moderat este considerat leziune cu risc sczut (clase de risc OMS I i II)
(Tabelele 6 i 7) i evaluarea trimestrial este considerat suficient. La pacientele cu stenoz pulmonar
sever, se recomand evaluarea cardiac lunar sau bilunar, inclusiv ecocardiografic pentru determinarea
statusului clinic i pentru monitorizarea funciei VD.
n timpul sarcinii, la pacientele cu stenoz pulmonar
sever simptomatic, neresponsivi la terapia medical
i la repausul la pat, se poate recurge la valvuloplastia
percutan.
Naterea
Naterea pe cale vaginal este recomandat pacientelor cu stenoz pulmonar non-sever, sau stenoz
pulmonar sever n clas NYHA I/II. Cezariana este
recomandat pacientelor cu stenoz pulmonar sever i clas NYHA III/IV, n ciuda terapiei medicale i a
repausului la pat, la care nu s-a putut efectua valvulotomie pulmonar percutan sau la care aceast procedur
a euat.
3.3.6 Stenoza aortic
Stenoza aortic congenital este cauzat cel mai frecvent de o valv aortic bicuspid. La pacienii tineri,
rata progresiei stenozei este mai mic comparativ cu
pacienii vrstnici107. Deoarece valva aortic bicuspid se asociaz cu dilatarea aortic i disecia de aort,
dimensiunile aortice ar trebui msurate nainte de sarcin i n timpul sarcinii. Riscul de disecie este crescut n timpul sarcinii (vezi i Seciunea 4.3)108,109. Toate
femeile cu valv aortic bicuspid ar trebui s aib o
evaluare imagistic a aortei ascendente nainte de sarcin i corecia chirurgical ar trebui indicat cnd diametrul aortei depete 50 de mm. Pentru recomandri

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n ceea ce privete managementul femeilor nsrcinate


cu stenoz aortic, a se vedea Seciunea 5 despre bolile
valvulare cardiace.
3.3.7 Tetralogia Fallot
Riscul matern
La pacientele care nu au suferit intervenie chirurgical de corecie, aceasta este indicat nainte de momentul concepiei. n general, femeile cu tetralogie Fallot
corectat tolereaz bine sarcina (clas de risc OMS II).
S-au raportat complicaii cardiace n timpul sarcinii la
pn la 12% din paciente. Aritmiile i insuficiena cardiac survin n mod particular110. Alte complicaii sunt
reprezentate de tromboembolism, dilatarea progresiv
a arcului aortic i endocardita. Disfuncia ventriculului
drept i/sau regurgitarea pulmonar moderat-sever
reprezint factori de risc pentru complicaiile cardiovasculare i sarcina se poate asocia cu creterea persistent a dimensiunii VD. La pacientele simptomatice cu
dilatare marcat a ventriculului drept cauzat de regurgitarea pulmonar sever, ar trebui indicat nlocuirea
valvular pulmonar (homograft) nainte de momentul
concepiei19.
Riscul obstetrical i fetal
Riscul complicaiilor fetale este crescut.
Management
Urmrire
Urmrirea trimestrial este suficient la majoritatea
pacientelor. La pacientele cu regurgitare pulmonar
sever, se indic evaluarea cardiac lunar sau bilunar, cu ecocardiografie. Dac insuficiena ventricular
dreapt survine pe parcursul sarcinii, trebuie iniiat
terapia diuretic i recomandat repausul la pat. Implantarea valvular transcateter sau naterea prematur ar
trebui luate n calcul la pacientele care nu rspund la
tratamentul conservator.
Naterea
Naterea pe cale vaginal este recomandat n majoritatea cazurilor.
3.3.8 Boala Ebstein
Riscul matern
Pacientele cu boal Ebstein fr cianoz i insuficien cardiac, tolereaz bine sarcina, n mod frecvent
(clas de risc OMS II). Pacientele simptomatice cu cianoz i/sau insuficien cardiac ar trebui tratate nainte de momentul concepiei i consiliate s nu rmn
nsrcinate. n cazul regurgitrii tricuspidiene severe,
simptomatice, corecia ar trebui efectuat nainte de

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momentul concepiei. Problemele hemodinamice survenite n perioada sarcinii depind att de severitatea regurgitrii tricuspidiene,precum i de capacitatea funcional a ventriculului drept111,112. Leziunile frecvent
asociate sunt reprezentate de DSA i Sindromul WolffParkinson-White. Incidena aritmiilor poate crete n
timpul sarcinii i se asociaz cu un prognostic prost111.
Riscul obstetrical i fetal
Riscul de natere prematur i mortalitate fetal este
ridicat112.
Management
Urmrire
Chiar i cazurile cu regurgitare tricuspidian sever
i insuficien cardiac pot fi de obicei controlate medical pe perioada sarcinii. Pacientele cu anomalie Ebstein
i unt interatrial pot prezenta pe perioada sarcinii inversarea untului i cianoz. Exist de asemenea un risc
crescut de embolii paradoxale (vezi Seciunea 3.4.2).
Naterea
Naterea pe cale vaginal este recomandat n majoritatea cazurilor.
3.3.9 Transpoziia de mari vase
Riscul matern
Dei multe femei tolereaz relativ bine sarcina, dup
o operaie de switch atrial (procedeul Senning sau Mustard), pacientele au un risc crescut de dezvoltare a complicaiilor precum aritmiile (uneori amenintoare de
via) i insuficien cardiac (clas de risc OMS III)93.
O parte din aceste femei au un ritm de baz bradicardic
sau un ritm joncional. n aceste situaii betablocantele
trebuie utilizate cu precauie sau chiar deloc. Un declin
ireversibil al funciei ventriculului drept a fost descris
n 10% din cazuri. Pacientele cu disfuncie de VD mai
mult dect moderat sau regurgitare tricuspidian sever ar trebui sftuite s evite sarcina.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

lunar din punct de vedere al simptomatologiei, funciei


VD i ritmului cardiac.
Naterea
Pacientelor asimptomatice cu funcie ventricular
bun sau moderat li se recomand naterea pe cale
vaginal. Dac funcia ventricular se deterioreaz, trebuie planificat naterea prematur, prin operaie cezarian, pentru a evita apariia sau agravarea insuficienei
cardiace113.
Operaia de switch arterial
Pn n prezent, au fost studiate doar serii mici de
paciente nsrcinate cu operaie de switch arterial114.
Riscul sarcinii pare mic la aceste paciente, dac exist
o stare clinic bun anterior momentului concepiei. Se
recomand naterea pe cale vaginal.
3.3.10 Transpoziia corectat a marilor vase
Riscul matern
n cazul pacientelor cu transpoziie corectat congenital a marilor vase (numit de asemenea discordan
atrioventricular i ventriculo-arterial), riscul depinde de statusul funcional, de funcia ventricular, de
prezena aritmiilor i leziunile asociate. Pacientele au
un risc crescut de a dezvolta complicaii precum aritmiile (uneori amenintoare de via) i insuficien
cardiac (clas de risc OMS III). Aceste paciente au
predispoziie pentru a dezvolta bloc atrio-ventricular,
motiv pentru care beta-blocantele trebuie utilizate cu
mare precauie. Un declin ireversibil al funciei VD a
fost descris n 10% din cazuri115, 116. Pacientele cu clas
funcional NYHA III sau IV, cu disfuncie ventricular important (fracie de ejecie <40%), sau regurgitare
tricuspidian sever, trebuie consiliate s evite sarcina.
Riscul obstetrical i fetal
Rata avorturilor spontane este crescut.

Riscul obstetrical i fetal


Pre-eclampsia i hipertensiunea indus de sarcin
precum i complicaiile fetale se ntlnesc mai frecvent
dect n cazul sarcinilor normale.

Management
Urmrire
Se recomand evaluarea ecografic repetat a funciei VD sistemic (la fiecare 6-8 sptmni) i evaluarea
simptomelor i ritmului cardiac.

Management
Urmrirea
Este recomandat ca pacientele cu intervenie chirurgical de corecie prin procedeul Mustard sau Senning
s fie urmrite cardiac i ecocardiografic lunar sau bi-

Naterea
Pacientelor asimptomatice cu funcie ventricular
bun sau moderat, li se recomand naterea pe cale
vaginal. Dac funcia ventricular se deterioreaz trebuie planificat naterea prematur, prin operaie ceza

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

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Vol. 23, No. 1, 2013

3.4 Recomandri pentru managementul bolilor


cardiace congenitale

rian, pentru a evita apariia sau agravarea insuficienei


cardiace.
3.3.11 Circulaia Fontan
Riscul matern
Dei exist cazuri de sarcin fr complicaii la paciente selecionate, cu monitorizare intensiv, acestea
sunt sarcini cu risc moderat sau nalt i pacientele trebuie urmrite atent (clas de risc OMS III sau IV). Exist probabil un risc matern mai mare n cazul unui circuit Fontan suboptimal i se recomand evaluarea cu
grij n perioada anterioar concepiei. Au fost descrise
aritmii atriale i deteriorarea clasei NYHA117,118. Pacientele cu saturaia oxigenului <85% n repaus, disfuncie
ventricular i/sau regurgitare atrio-ventricular moderat-sever sau cu enteropatie cu pierdere de proteine,
ar trebui consiliate s evite o eventual sarcin.
Riscul obstetrical i fetal
Riscul fetal include naterea prematur, ft mic pentru vrsta gestaional i mortalitate fetal n pn la
50% din cazuri.
Management
Urmrire
Se recomand ca pacientele cu circuit Fontan s fie
evaluate frecvent pe perioada sarcinii i n primele sptmni postpartum (la fiecare 4 sptmni) i ngrijire
ntr-o unitate specializat. Inhibitorii enzimei de conversie trebuie ntrerupi. Terapia anticoagulant constituie de asemenea o problem. Dei complicaiile tromboembolice nu au fost descrise n literatur la pacientele cu circuit Fontan n timpul sarcinii, riscul trebuie
considerat crescut i terapia anticoagulant ar trebui
luat n considerare119. Riscul tromboembolic poate fi
sczut la pacientele tratate prin corecie total Fontan
cavo-pulmonar.
Naterea
n general, naterea pe cale vaginal reprezint prima alegere. Dac funcia ventricular se deterioreaz,
trebuie planificat o operaie cezarian prematur, ntrun centru experimentat, pentru a evita dezvoltarea i
agravarea insuficienei cardiace.

Tabel 10. Recomandri pentru managementul bolilor cardiace congenitale


Recomandri
Clasa Nivelb
nlturarea stenozei anterior concepiei (n general prin valvulotomie cu
I
B68, 105
balon) trebuie realizat n stenoza pulmonar valvular sever (gradient
Doppler maxim > 64mmHg).
Ar trebui efectuat individualizarea programului de urmrire pe perioada
I
C
sarcinii, de la dou vizite pn la vizite lunare.
Pacientele cu boal Ebstein simptomatice, cu cianoz i/sau insuficien
I
C
cardiac trebuie tratate naintea sarcinii sau consiliate s evite o eventual
sarcin.
nlocuirea valvular pulmonar (bioprotez) ar trebui realizat naintea
I
C
sarcinii la pacientele simptomatice, cu dilatare marcat a ventriculului drept,
cauzat de regurgitarea pulmonar sever.
nlocuirea valvular pulmonar (bioprotez) ar trebui avut n vedere naintea IIa
C
sarcinii la pacientele asimptomatice, cu dilatare marcat a ventriculului drept,
cauzat de regurgitarea pulmonar sever.
C
Toate femeile cu valv aortic bicuspid ar trebui s aib o evaluare imagistiIIa
c a aortei ascendente nainte de sarcin i intervenia chirurgical ar trebui
avut n vedere dac diametrul aortic depete 50 de mm.
Terapia anticoagulant trebuie avut n vedere la pacientele cu circuit Fontan
IIa
C
pe perioada sarcinii.
Tratamentul anticoagulant asociat ar trebui avut n vedere n hipertensiunea
IIa
C
arterial pulmonar, la pacientele la care se suspecteaz embolia pulmonar
drept cauz a hipertensiunii pulmonare (sau cauz parial).
IIa
C
Pacientele care primesc terapie pentru hipertensiunea arterial pulmonar
nainte de a rmne nsrcinate trebuie s ia n considerare continuarea
terapiei, dup ce sunt informate asupra efectelor teratogene.
Femeile cu hipertensiune pulmonar trebuie sftuite s evite sarcinac.
III
C
Femeile cu o saturaie a oxigenului sub 85% n repaus trebuie sftuite s
III
C
evite sarcina.
Pacientele cu transpoziie de vase mari i un ventricul drept sistemic cu
III
C
disfuncie mai mult dect moderat i/sau regurgitare tricuspidian sever
trebuie sftuite s evite sarcina.
C
Pacientele cu circuit Fontan cu disfuncie ventricular i/sau regurgitare valvu- III
lar atrioventricular sever, sau cu cianoz, sau cu enteropatie cu pierdere
de proteine, trebuie sftuite s evite sarcina.
Clas de recomandare
Nivel de eviden
Vezi textul pentru descriere detaliat i excepii
VD = ventricul drept; RT = regurgitare tricuspidian
a
b
c

4. BOLILE AORTEI
Exist cteva afeciuni ereditare, cu interesarea aortei toracice, predispunnd pacienii att la formare de
anevrism, ct i la disecie de aort. Acestea includ
sindromul Marfan, valva aortic bicuspid, sindromul
Ehlers-Danlos, sindromul Turner i formele familiale
ale diseciei de aort, anevrismului, sau ectazia anuloaortic. De asemenea, alte forme de boli cardiace congenitale (ex: tetralogia Fallot, coarctaia de aort) se
pot nsoi de dilatare aortic sau formare de anevrisme,
sau poate fi vorba de o patologie aortic non-ereditar.
Factorii de risc pentru patologia aortic n populaia
general sunt hipertensiunea i vrsta matern avansat. Sarcina este o perioad cu risc crescut pentru toate
pacientele cu patologie aortic, patologia aortic fiind
raportat drept una dintre principalele cauze de morta-

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litate matern n raportul 2003-2005 a UK Confidential Enquiry into Maternal and Child Health9. Recent,
a fost publicat ghidul pentru diagnosticul i managementul pacienilor cu boal aortic toracic50.
Diagnostic
n prezent, sunt disponibile un numr de proceduri
imagistice i teste genetice discutate n Seciunile 2.5
i 2.6.
4.1 Riscul matern i fetal
Pe perioada sarcinii, pe lng modificrile hemodinamice, au loc i modificri hormonale, care duc la modificri histologice ale aortei, crescnd susceptibilitatea
pentru disecie120. Disecia survine cel mai frecvent,
n ultimul trimestru de sarcin (50%), sau n perioada
precoce post-partum (33%). Riscurile pe care le presupune sarcina trebuie discutate nainte de momentul
concepiei, cu toate pacientele cu boal aortic cunoscut i/sau diametru mrit al rdcinii aortice. Femeile
cu antecedente personale de disecie de aort au un risc
crescut de complicaii aortice pe perioada sarcinii. Din
pcate, nu toate pacientele cu patologie aortic contientizeaz riscul. De aceea, toate femeile cu sindrom
Marfan dovedit genetic, sau cu alt patologie aortic
familial, ar trebui consiliate asupra riscului de disecie i a recurenei riscului i s aib o evaluare complet, inclusiv de tip imagistic, a ntregii aorte nainte de
sarcin (vezi Seciunea 2.7). Nu a fost dovedit niciun
efect ireversibil al sarcinii asupra dilatrii aortice121. Diagnosticul de disecie de aort trebuie avut n vedere la
toate pacientele cu durere toracic pe perioada sarcinii,
deoarece acest diagnostic este frecvent omis.
4.2 Sindroame specifice
4.2.1 Sindromul Marfan
Pacientele cu sindrom Marfan122,123 i diametru normal al rdcinii aortice au un risc de 1% de disecie de
aort sau alte complicaii cardiace serioase pe parcursul
sarcinii124. La femeile nsrcinate cu sindrom Marfan,
diametrul rdcinii aortice >4 cm i creterea diametrului rdcinii aortice pe perioada sarcinii, reprezint factori de risc pentru disecie109,125. Dei sunt puine
date despre sarcin la femeile cu sindrom Marfan i
diametru al rdcinii aortice > 45 de mm, o eventual sarcin ar trebui descurajat la aceste paciente. Disecia este rar la un diametru aortic <40 de mm, dei
un diametru sigur nu exist126. La un diametru aortic
de 40-45 de mm, trebuie luai n calcul factorii de risc
pentru disecie (istoricul familial de disecie, creterea
rapid)121. Consideraii legate de aria suprafeei corporeale sunt de asemenea importante, n special la femei-

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le de statur mic. Chiar i dup procedura electiv de


nlocuire a rdcinii aortice, pacientele prezint risc de
disecie n aorta restant127.
n afar de disecia de aort amenintoare de via,
aceste paciente pot prezenta o agravare a regurgitrii
mitrale, ce poate duce la complicaii precum aritmiile
supraventriculare sau insuficiena cardiac, n special
la acele paciente care aveau deja regurgitare mitral
moderat-sever nainte de sarcin (vezi i Seciunea 5
despre bolile valvulare).
4.2.2 Valva aortic bicuspid
Aproximativ 50% din pacienii cu valv aortic bicuspid i stenoz aortic au dilatare de aort ascendent128. Frecvent, dilatarea este maximal n poriunea
distal a aortei ascendente, segment ce nu poate fi vizualizat adecvat ecocardiografic, de aceea IRM sau CT ar
trebui efectuate anterior sarcinii. Disecia survine mai
puin frecvent dect la pacienii cu sindrom Marfan109.
Riscul pe care l presupune sarcina la femeile cu bicuspidie aortic i dilatare de aort, nu a fost investigat
sistematic. La pacientele cu un diametru al rdcinii
aortice >50 de mm, trebuie luat n calcul o intervenie
chirurgical, nainte de o eventual sarcin19.
4.2.3 Sindromul Ehlers-Danlos
Afectarea aortei apare, aproape exclusiv, n sindromul Ehlers-Danlos tip IV, care este transmis ntr-un
mod autozomal dominant. Pe perioada sarcinii, femeile pot prezenta echimoze extinse, hernii i varicoziti
i pot suferi rupturi ale vaselor mari i ruptur uterin. Din cauza riscului de ruptur uterin, sindromul
Ehlers-Danlos tipul IV reprezint o contraindicaie
pentru sarcin. Disecia de aort se poate produce fr
dilataie. Rolul chirurgiei profilactice este mai puin
bine stabilit la acest grup de paciente, deoarece raportul
risc-beneficiu este influenat de faptul c intervenia de
corecie chirurgical poate fi complicat de fragilitatea
tisular, tendina la hemoragie extensiv i vindecarea
deficitar a cicatricilor129,130.
4.2.4 Sindromul Turner
Prevalena malformaiilor cardiovasculare n sindromul Turner este de 25-50% i, de asemenea, hipertensiunea este frecvent prezent. Dei nu exist dovezi
cantitative ale riscului de disecie ce pot fi atribuite sarcinii la femeile cu sindrom Turner, riscul probabil este
crescut i este mai mare la femeile care au factori de
risc adiionali precum valva aortic bicuspid, coarctaie de aort i/sau hipertensiune131. Femeile expuse la
cel mai mare risc sunt cele cu dilatare aortic, dar disecia poate surveni i n absena dilatrii. Diametrele
aortei toracice trebuie evaluate n relaie cu aria supra

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feei corporale, deoarece aceste paciente au n general


statur mic. Un diametru aortic indexat >27 de mm/
m2 se asociaz cu un risc crescut de disecie i chirurgia
profilactic ar trebui luat n considerare. Complicaiile
aortice pe perioada sarcinii se asociaz cu o mortalitate
matern de pn la 11%, ce poate fi atribuit n special
diseciei de tip A. Riscul de (pre)eclampsie este crescut
i tratamentul hipertensiunii este important, n special
pe durata sarcinii.
4.3 Management
Urmrire i terapie medical
n funcie de diametrul aortic, pacientele cu patologie aortic ar trebui urmrite prin ecocardiografii repetate la interval de 4-12 sptmni pe perioada sarcinii i ase luni postpartum. Sarcina trebuie urmrit
de un cardiolog i un obstetrician vigileni la posibilele
complicaii. Tratamentul cu ageni beta-blocani poate
reduce rata dilatrii aortice i poate ameliora supravieuirea. Totui, ntr-o metaanaliz recent132, care
includea majoritatea studiilor cu paciente care nu erau
nsrcinate, efectul benefic nu a fost confirmat. n ciuda acestor incertitudini, Grupul de Lucru recomand
utilizarea -blocantelor la pacientele cu sindrom Marfan pe perioada sarcinii, cu scopul de a preveni disecia.
Pacientelor cu sindrom Ehlers-Danlos tipul IV le este
recomandat celiprolol, din cauza riscului foarte nalt de
disecie i a beneficiului demonstrat la pacientele care
nu erau nsrcinate130. Creterea fetal trebuie monitorizat atunci cnd mama ia -blocant.
Intervenii
La pacientele cu sindrom Marfan sau alte sindroame
cu risc crescut de disecie, precum sindromul LoeysDietz, sindromul Ehlers-Danlos, sau mutaia genei
Smad-3133, se recomand chirurgia n perioada premergtoare sarcinii, dac aorta ascendent este 45 de mm,
depinznd i de caracteristicile individuale. Dac pe
perioada sarcinii survine dilatarea progresiv a aortei,
nainte ca ftul s fie viabil, repararea aortei cu ftul in
utero trebuie luat n considerare. Dac ftul este viabil,
se recomand naterea prin operaie cezarian, urmat
direct de chirurgia aortei (vezi Seciunea 2.8.2). Operaia cezarian trebuie realizat ntr-un spital cu faciliti
de tipul chirurgie toracic i terapie intensiv neonatal. Disecia aortei ascendente survenite n timpul sarcinii este o urgen chirurgical; medici cu experien
n chirurgie cardiovascular, cardiologie, obstetric i
anestezie trebuie s acioneze rapid pentru naterea ftului (dac este viabil) prin operaie cezarian, n sal
de chirurgie cardiovascular, pentru ca apoi s treac
direct la repararea diseciei.

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Naterea (vezi de asemenea Seciunea 2.9)


La pacientele cu dilatare de aort ascendent, scopul
primar al managementului intrapartum este s reduc
stresul cardiovascular generat de travaliu i natere.
Dac pacienta a urmat tratament cu -blocante pe perioada sarcinii, acesta ar trebui continuat i n perioada
peripartum. Dac diametrul aortei ascendente este ntre 40-45 de mm, naterea pe cale vaginal, cu o a doua
etap rapid i anestezie regional este recomandat,
pentru a preveni creterea tensional care poate induce
disecie. De asemenea, naterea prin operaie cezarian
poate fi luat n considerare la aceste paciente, n funcie de caracteristicile individuale. Tehnicile de anestezie
regional pot fi dificile la pacientele cu sindrom Marfan, n funcie de prezena i severitatea scoliozei, precum i de prezena ectaziei durale134. Naterea pe cale
cezarian trebuie luat n considerare dac diametrul
aortic depete 45de mm. Se recomand naterea prematur, prin operaie cezarian, la femeile cu sindrom
Ehlers-Danlos tipul IV.
4.4 Recomandri privind managementul bolii
aortice
Tabelul 11. Recomandri privind managementul bolii aortice
Recomandri
Clasa Nivelb
Femeile cu sindrom Marfan sau alte boli aortice cunoscute, ar trebui informate
I
C
cu privire la riscul diseciei de aort din timpul sarcinii i riscul de transmitere
al bolii la urmai.
Evaluarea imagistic a ntregii aorte (CT/IRM) ar trebui realizat la toate
I
C
pacientele cu sindrom Marfan sau alte boli aortice cunoscute.
Femeile cu sindrom Marfan i o aort ascendent de peste 45 de mm ar trebui
I
C
tratate chirurgical anterior sarcinii.
Se recomand controlul strict al tensiunii arteriale la pacientele nsrcinate,
I
C
cu dilatare aortic cunoscut, (istoric de) disecie de tip B, sau predispoziie
genetic pentru disecie.
La pacientele cu dilatare de aort ascendent ar trebui repetat evaluarea
I
C
imagistic ecocardiografic la fiecare 4-8 sptmni pe perioada sarcinii.
La pacientele nsrcinate cu dilatare a aortei ascendente distale, a arcului
I
C
aortic, sau a aortei descendente se recomand evaluare imagistic prin IRM
(fr gadolinium).
Se recomand evaluarea imagistic a aortei ascendente la femeile cu
I
C
bicuspidie aortic.
La pacientele cu diametru al aortei ascendente sub 40 de mm, se recomand
I
C
naterea pe cale vaginal.
I
C
Femeile cu dilatare de aort, sau (istoric de) disecie de aort, ar trebui s
nasc ntr-un centru unde este disponibil serviciul de chirurgie cardiotoracic.
La pacientele cu dilatare de aort ascendent de peste 45 de mm, naterea ar
I
C
trebui s se produc prin operaie cezarian.
IIa
C
La femeile cu boal aortic asociat cu bicuspidie aortic, tratamentul de
corecie chirurgical ar trebui avut n vedere naintea sarcinii, dac diametrul
2
aortic depete 50 de mm (sau > 27mm/m BSA).
Chirurgia profilactic ar trebui avut n vedere pe perioada sarcinii, dac
IIa
C
diametrul aortic este 50 de mm i cu rat rapid de cretere.
La pacientele cu sindrom Marfan sau alte boli cu diametrul aortic de 40-45 de
IIa
C
mm, ar trebui luat n considereare naterea pe cale vaginal, cu anestezie
epidural i a doua faz accelerat.
La pacientele cu sindrom Marfan sau alte boli cu diametrul aortei de 40-45 de
IIb
C
mm, operaia cezarian poate fi avut n vedere.
Pacientele cu (istoric de) disecie de tip B ar trebui sftuite s evite sarcina.
III
C
Clas de recomandare
Nivel de eviden
CT = tomografie computerizat; IRM = imagistic prin rezonan magnetic
a
b

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5. VALVOLUPATIILE
Bolile valvulare cardiace att dobndite ct i congenitale sunt cauze importante de morbiditate i mortalitate matern i fetal. Boala cardiac postreumatismal
rmne o problem major n rile n curs de dezvoltare i este nc observat i n rile occidentale, n
special la imigrani. Stenozele valvulare au un risc
mai mare n sarcin dect regurgitrile valvulare i
afeciunile valvulare ale cordului stng au un risc mai
mare de complicaii dect cele ale cordului drept12,
56,57,135
. Probleme specifice, n principal legate de tratamentul anticoagulant, sunt prezente la femeile
cu proteze valvulare mecanice.
5.1 Leziuni valvulare stenozante
n stenozele valvulare, debitul cardiac crescut determin o cretere a gradientului transvalvular i, prin urmare, a presiunilor din amonte, existnd un risc crescut
de complicaii materne i fetale12, 102.
5.1.1 Stenoza mitral
Stenoza mitral moderat sau sever (SM) este prost
tolerat n timpul sarcinii. SM este responsabil de cea
mai mare rat a morbiditii i a mortalitatii n timpul
sarcinii legate de boala cardiac postreumatismal. Diagnosticul se bazeaz pe ecocardiografie7,136. PHT este
mai puin sigur dect planimetria direct, dar poate fi
utilizat n timpul sarcinii136. Gradientul i PAP nu reflect n mod direct severitatea SM n timpul sarcinii,
dar au o important valoare prognostic136. Evaluarea
morfologiei valvei mitrale i cuantificarea regurgitrii
asociate sau evaluarea altor afeciuni valvulare sunt deosebit de importante atunci cnd se ia n considerare
comisurotomia percutan7,136. Testul de efort este util
pentru relevarea simptomatologiei i evaluarea toleranei la efort.
Riscul matern
Riscul de decompensare depinde de severitatea
SM102,137. Insuficiena cardiac apare frecvent la femeile
gravide cu SM moderat sau sever (aria valvei mitrale
<1,5 cm2), n special n timpul trimestrelor al doilea i
al treilea, chiar i la femeile anterior asimptomatice102,
135,137
. Insuficiena cardiac este deseori progresiv. Edemul pulmonar poate s apar, n special atunci cnd
SM nu este cunoscut sau n cazul instalrii fibrilaiei
atriale. Fibrilaia atrial, dei rar (<15%), aduce un
risc suplimentar de evenimente tromboembolice102,137.
Mortalitatea este ntre 0 i 3%102,135,137. Se poate ntlni
precipitarea simptomelor la femeile cu SM uoar, dar

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acestea, n general, nu sunt severe i sunt bine tolerate102,135.


Riscul obstetrical i al ftului
Complicaiile obstetricale sunt legate n principal de
riscul de insuficien cardiac acut n timpul sau imediat dup natere, i depind de simptomele i de PAP
din timpul sarcinii135. Ratele de prematuritate sunt de
20-30%, retard de cretere intrauterin 5-20%, i de
natere a unui copil mort de 1-3%102,137. Riscul fetal este
mai mare la femeile n clas NYHA III /IV n timpul
sarcinii12,135.
Management
Toate pacientele cu SM moderat sau sever (chiar
i asimptomatic) ar trebui s fie consiliate mpotriva
sarcinii i interveniile, de preferin interveniile percutane7, ar trebui efectuate naintea sarcinii.
Urmrirea
Este indicat urmrirea clinic i ecocardiografic
lunar sau bilunar, n funcie de tolerana hemodinamic. n SM uoar, evaluarea este recomandat n fiecare
trimestru i nainte de natere.
Terapia medicamentoas
n cazul apariiei simptomelor sau a HTP (presiunea
sistolic n artera pulmonar estimat prin ecocardiografie >50 mmHg) se recomand restricionarea activitii fizice i iniierea terapiei cu beta blocante beta-1
selective7,64. n cazul n care simptomele persist se pot
folosi diureticele, cu evitarea dozelor mari64. n caz de
fibrilaie atrial paroxistic sau permanent, tromboz
de atriu stng sau embolie n antecedente, se recomand terapie anticoagulant7,64. Aceast terapie ar trebui
luat n considerare i la femeile cu stenoz mitral
moderat sau sever i contrast spontan n atriul stng
ecocardiografic, atriu stng mrit (40 ml/m2), debit
cardiac sczut sau insuficien cardiac congestiv,
deoarece aceste femei prezint un risc tromboembolic
foarte nalt.
Intervenii n timpul sarcinii
Comisurotomia mitral percutanat este preferabil a
se realiza dup sptmna 20 de sarcin. Ar trebui luat
n considerare doar la femeile din clasa NYHA III/IV
i/sau PAPs estimat ecocardiografic >50 mmHg, care
nu rspund la tratament medical optimal, n absena contraindicaiilor i n cazul n care caracteristicile
pacientei permit intervenia7,64. Aceasta trebuie reali

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zat de un operator cu experien, rata complicaiilor


fiind n acest context redus. Se recomand protecia
abdomenului cu un or de plumb7,64. Doza de radiaii trebuie redus la minim prin realizarea unui timp
de screening ct mai scurt posibil7,64. Avnd n vedere
riscul complicaiilor, comisurotomia mitral percutan
nu trebuie realizat la pacientele asimptomatice. Comisurotomia digital rmne o alternativ n rile aflate
n curs de dezvoltare, unde comisurotomia percutan
nu este disponibil. Chirurgia pe cord deschis trebuie
rezervat cazurilor n care celelate msuri nu au dat rezultate i n care viaa mamei este n pericol.
Naterea
La pacientele cu stenoz mitral uoar i la cele
cu stenoz mitral moderat sau sever n clasa I/II
NYHA fr HTP, ar trebui luat n considerare naterea
pe cale vaginal. Operaia cezarian este recomandat
la pacientele cu SM moderat sau sever, care sunt n
clasa III/IV NYHA sau cu HTP, dei au primit terapie
medical optimal, i la care nu se poate realiza comisurotomia percutan sau aceasta a euat.
5.1.2. Stenoza aortic valvular
La femeile de vrst fertil, principala cauz de SA
este reprezentat de valva aortic bicuspid congenital. Afeciunea poate rmne asimptomatic chiar i
n cazurile severe7, primele simptome putnd aprea n
timpul sarcinii. Ecocardiografia este obligatorie pentru diagnostic7,136. Se recomand efectuarea testului de
efort la pacientele asimptomatice naintea sarcinii, pentru a confirma statusul asimptomatic i pentru a evalua
tolerana la efort, rspunsul TA, riscul de aritmii i/sau
necesitatea interveniei. La femeile cu valv aortic bicuspid, diametrele aortei trebuie evaluate nainte i n
timpul sarcinii.
Riscul matern
Morbiditatea cardiac n timpul sarcinii se coreleaz
cu severitatea SA i cu simptomatologia. Sarcina este
bine tolerat n cazul SA asimptomatice uoare sau
moderate. De asemenea, pacientele cu stenoz aortic
sever pot susine sarcina dac la testul de efort rmn
asimptomatice i au rspuns tensional normal19,139.
Creterea debitului cardiac poate duce la o cretere
marcat a gradientului135,139. Insuficiena cardiac apare
la aproximativ 10% dintre pacientele cu SA sever, iar
aritmiile la 3-25%140. Mortalitatea este astzi rar dac
tratamentul este adecvat8,56,74,102,135,139,140. Femeile cu val

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v aortic bicuspid au risc de a dezvolta dilatare de


aort i disecie (vezi Seciunea 4.3.2).
Riscul obstetrical i fetal
Complicaiile obstetricale pot s apar mai frecvent
la femeile cu SA sever (evenimente legate de HTA n
13% din cazuri, natere prematur)140. Naterea nainte
de termen, ntrzierea n creterea intrauterin i greutatea mic la natere se ntlnesc n pn la 25% din
nou-nscuii din mame cu stenoz aortic moderat i
sever.
Management
Toate pacientele simptomatice cu SA sever, precum
i cele asimptomatice dar cu afectarea funciei VS sau
cu test de efort patologic, trebuie sftuite s evite sarcina, iar valvuloplastia sau intervenia chirurgical trebuie s fie efectuate pre-sarcin, conform ghidurilor7,19.
Sarcina nu trebuie descurajat la pacientele asimptomatice, chiar cu SA sever, atunci cnd mrimea i
funcia VS sunt normale, testul de efort este de asemenea normal i a fost exclus o hipertrofie sever de VS
(perete posterior >15 mm). De asemenea, nu trebuie s
existe evidene a unei progresii recente a SA74,139-141. La
pacientele cu aorta ascendent >50 de mm (27,5 mm/
m2) se recomand intervenia chirurgical nainte de
sarcin, indiferent de simptomatologie.
Urmrire
Urmrirea regulat n timpul sarcinii trebuie efectuat de o echip cu experien. n SA sever, se recomand control lunar sau bilunar, inclusiv ecocardiografie, pentru a evalua simptomatologia, progresia SA
sau alte complicaii.
Terapia medicamentoas
La pacientele care dezvolt semne sau simptome de
insuficien cardiac n timpul sarcinii, se indic tratament medicamentos i restricionarea activitii fizice.
Pentru simptome de congestie se pot administra diuretice. Tratamentul cu un betablocant sau cu un antagonist de canal de calciu de tip nondihidropiridinic ar
trebui luat n considerare pentru controlul frecvenei
cardiace la pacientele cu fibrilaie atrial. Dac ambele
sunt contraindicate, se poate administra digoxin142.
Intervenii n timpul sarcinii
La pacientele cu simptomatologie sever care nu
rspund la terapia medicamentoas, se poate efectua
valvuloplastie percutan pe valve necalcificate i cu re-

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gurgitare minim143. Dac intervenia nu este posibil,


iar pacientele prezint simptome amenintoare de via, se recurge la cezarian, urmat de nlocuirea valvei,
dac aceasta reprezint o opiune (vezi Seciunea 2.7.2).

Riscul obstetrical i fetal


Nu a fost raportat un risc crescut de complicaii obstetricale. n cazul regurgitrilor valvulare simptomatice riscul de complicaii fetale este crescut12.

Naterea
n SA sever, simptomatic n special n a doua jumtate a sarcinii, se prefer operaia cezarian cu intubaie orotraheal i anestezie general. n SA nonsever se prefer naterea pe cale vaginal, cu evitarea
scderii rezistenei vasculare periferice n timpul anesteziei i analgeziei regionale.

Management
Femeile cu regurgitare valvular sever simptomatic, cu disfuncie VS sau cu dilatare de VS (conform criteriilor din ghidurile de valvulopatii) ar trebui supuse
interveniei chirurgicale nainte de sarcin, preferabil
reparrii valvulare7.

5.2. Regurgitrile valvulare


5.2.1 Regurgitarea mitral i regurgitarea aortic
La femeile de vrst fertil, regurgitarea mitral i
regurgitarea aortic pot fi congenitale, reumatismale
sau degenerative. Endocardita infecioas n antecedente i o valvulotomie anterioar pot fi factori asociai. O cauz rar de insuficien valvular acut aprut n timpul sarcinii este sindromul antifosfolipidic.
Regurgitrile valvulare stngi sunt asociate cu un risc
mai mic n timpul sarcinii fa de leziunile valvulare
stenotice, datorit faptului c rezistena vascular sistemic sczut reduce volumul regurgitant. Regurgitarea
valvular sever cu disfuncie de VS este prost tolerat,
la fel cum este i regurgitarea sever acut. Evaluarea
se face, de preferat, naintea concepiei i trebuie s includ aprecierea simptomatologiei, evaluarea ecocardiografic a severitii regurgitrii (n conformitate cu
criteriile ESC), precum i aprecierea dimensiunilor i
funciei VS7. n cazul leziunilor moderate/severe, se recomand efectuarea unui test de efort nainte de sarcin. Diametrele aortei ascendente ar trebui msurate la
femeile cu regurgitare aortic, mai ales la cele cu valve
bicuspide.
Riscul matern
Riscul cardiovascular matern depinde de severitatea regurgitrii, simptome i funcia VS135. Femeile
cu insuficien valvular sever simptomatic sau cu
disfuncie de VS au un risc nalt de insuficien cardiac135. La femeile asimptomatice cu funcie VS pstrat,
cea mai frecvent complicaie o reprezint aritmiile.
La femeile cu boal cardiac congenital, regurgitarea
semnificativ valvular atrio-ventricular pe partea
stng s-a raportat a fi asociat cu complicaii cardiace n timpul sarcinii. Aceast asociere poate fi atribuit
parial disfunciei ventriculare. Se poate ntlni, de asemenea, o accentuare persistent a regurgitrii57, 99.

Urmrire
n regurgitrile uoare/moderate controlul se face
trimestrial i mai frecvent n cazurile severe. Calendarul de urmrire se stabilete individualizat, n funcie
de statusul clinic i de simptomatologie.
Terapia medicamentoas i interveniile n timpul
sarcinii
Simptomele de retenie lichidian se trateaz de obicei medical. n regurgitarea acut sever cu insuficien
cardiac rezistent la tratament, chirurgia este uneori
inevitabil n timpul sarcinii. Dac ftul este suficient
de matur, se recomand declanarea naterii naintea
unei intervenii chirugicale (vezi Seciunea 2.8.2).
Naterea
Se prefer naterea pe cale vaginal; la pacientele simptomatice se recomand anestezia epidural i
scurtarea celei de-a doua etape.
5.2.2. Regurgitarea tricuspidian
Regurgitarea tricuspidian (RT) este, de cele mai
multe ori, funcional (dilatarea inelului tricuspidian
determinat de creterea presiunii n VD sau de suprancrcare volemic); endocardita sau malformaia
Ebstein sunt cauze rare. Diagnosticul se pune clinic
i ecocardiografic7. Riscul cardiovascular matern este,
de obicei, determinat de leziunile valvulare stngi primare sau de HTP. Totui, riscul matern poate fi crescut
n cazurile cu RT sever simptomatic sau la femeile
cu disfuncie de VD76. La femeile cu boal cardiac
congenital, RT moderat/sever poate fi asociat cu
complicaii cardiace materne (posibil dependente de
funcia ventricular), n special aritmii57.
Conduita medical conservatoare poate fi aplicat n
timpul sarcinii chiar i n cazurile de RT sever, asociat cu insuficien cardiac (Tabelul 12). Este recomandat repararea tricuspidian n caz de RT sever i ar
trebui luat n considerare i n RT moderat i n RT

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

moderat secundar cu dilatare de inel (>40 de mm),


atunci cnd este necesar intervenia chirurgical pentru leziunile valvulare ale cordului stng7. n cazurile
de RT sever simptomatic, se recomand repararea
nainte de sarcin. n aproape toate cazurile se prefer
naterea pe cale natural.
5.3. Fibrilaia atrial (FA) valvular (valve native)
FA valvular este asociat cu un risc tromboembolic ridicat, n special la pacientele cu SM sever. Tratamentul anticoagulant se iniiaz imediat cu heparin
nefracionat i.v. urmat de heparin cu greutate molecular mic (HGMM) n primul i ultimul trimestru i
anticoagulant oral sau HGMM n al doilea trimestru.
Dozele de heparin cu greutate molecular mic trebuie ajustate n funcie de greutate (administrate de 2 ori
pe zi), administrate pn la 36 de ore anterior naterii.
n cazul tratamentului anticoagulant oral, valoarea INR
trebuie s se situeze n intervalul 2-2,5, minimiznd
astfel riscul fetal.
5.4. Proteze valvulare
5.4.1. Alegerea tipului de protez valvular
Alegerea unei valve protetice la femeile care doresc o
sarcin este dificil.
Valvele mecanice au durabilitate mare, ofer performan hemodinamic excelent, dar necesitatea terapiei anticoagulante crete mortalitatea i morbiditatea
matern i fetal. Valvele biologice ofer de asemenea
performan hemodinamic bun i sunt mai puin
trombogenice. Totui, utilizarea lor la femeile tinere
este asociat cu un risc crescut de deteriorare structural valvular, aprnd la aproximativ 50% din femeile
sub 30 de ani la 10 ani de la implantare, i este mai frecvent n cazul valvelor implantate n poziie mitral dect la cele din poziie aortic sau tricuspidian. Pentru
valvele din poziie pulmonar, implantarea transcateter
este o opiune la un numr din ce n ce mai mare de
pacieni, n special la cei cu antecedente de implantare
a unei proteze biologice. Exist preri contradictorii n
ceea ce privete influena sarcinii asupra accelerrii degradrii valvelor biologice144. Totui, pacientele tinere
cu protez biologic vor necesita, aproape sigur, o reintervenie, cu un risc de mortalitate de 0-5%, n funcie
de poziia valvei i de gradul de urgen.
n cazul pacientelor cu boal valvular aortic, alternativa este reprezentat de procedura Ross (autogref
pulmonar transferat n poziie aortic i nlocuirea
valvei pulmonare cu homogref). n acest caz, hemodinamica valvular este excelent, fr risc de tromboz. Totui, aceast intervenie bivalvular necesit

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experien chirurgical mare, cu o rat semnificativ


de reintervenie dup 10 ani. n plus, se cunosc puine
date despre evoluia sarcinii la femeile cu antecedente
de intervenie Ross145. Dorina unei sarcini reprezint o
indicaie de clasa IIb pentru implantarea unei valve biologice7. Alegerea unui anumit tip de protez ar trebui
s se fac dup informarea detaliat a pacientei i dup
discuia cu pacienta.
5.4.2. Protezele biologice
n general, sarcina este bine tolerat la femeile cu
proteze biologice. Riscul cardiovascular matern depinde, n principal, de funcionalitatea protezei. Riscul este
sczut la pacientele fr disfuncia protezei sau cu disfuncie minim i cu funcie ventricular bun144.
Evaluarea i consilierea presarcin, la fel ca i urmrirea, tratamentul medical i indicaiile pentru intervenie sunt comparabile cu cele pentru gravidele cu
disfuncie de valv nativ.
5.5. Protezele mecanice i tratamentul
anticoagulant
Din punct de vedere hemodinamic, femeile cu valve
mecanice, fr simptomatologie important, tolereaz
bine sarcina. Cu toate acestea, nevoia de anticoagulare
ridic probleme specifice, din cauza riscului crescut de
tromboz valvular, complicaii hemoragice, precum i
complicaii la ft. Sarcina este asociat cu un risc matern crescut. Caracterul i magnitudinea riscului depind de regimul de anticoagulare utilizat n timpul sarcinii i calitatea controlului anticoagulrii. Evaluarea n
pre-sarcin ar trebui s includ evaluarea simptomelor
i evaluarea ecocardiografic a funciei ventriculare, a
protezei i a valvelor native.
Riscul matern
Valvele mecanice prezint risc de tromboz valvular, risc crescut n timpul sarcinii. ntr-o recenzie ampl,
riscul a fost de 3,9% cu ACO pe tot parcursul sarcinii,
de 9,2% atunci cnd a fost folosit heparina nefracionat n primul trimestru i ACO n al doilea i a treilea
trimestru i de 33% la pacientele ce au avut heparin
nefracionat pe toat durata sarcinii146. Decesul matern a fost nregistrat n aceste grupuri n 2%, 4%, i
respectiv 15% din cazuri, i a fost, de obicei cauzat de
tromboza valvular146. O trecere n revist a literaturii recente de specialitate a confirmat riscul sczut de
tromboz valvular n cazul utilizrii terapiei cu ACO
pe tot parcursul sarcinii (2,4%, 7/287 de sarcini), comparativ cu heparina nefracionat n primul trimestru
(10,3%, 16/156 sarcini)147. Riscul este, probabil, mai

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mic la dozare adecvat i depinde de tipul i poziia


valvei mecanice, precum i de factorii de risc suplimentari7. Utilizarea heparinei nefracionate pe tot parcursul
sarcinii se asociaz n plus cu trombocitopenie i osteoporoz. HGMM sunt, de asemenea, asociate cu risc de
tromboz valvular148,149. Riscul este mai mic, dar totui
prezent, dac se ajusteaz dozele n conformitate cu nivelul anti-Xa147,148,150-152. La un lot de 111 gravide, la care
s-a ajustat doza de HGMM n funcie de nivelurile antiXa pe toat durata sarcinii, tromboza valvular a aprut
la 9% din cazuri147,150-152. Valoarea prea mic de anti-Xa
sau compliana redus, probabil, a contribuit la apariia
trombozei n aproape toate cazurile (mai puin unul).
O recenzie a raportat o frecven mai mic a trombozei
la pacientele care au primit HGMM doar n primul trimestru, dar studiul cuprinde un numr mic de pacieni
(3,6%, 2/56 sarcini)147.
Folosirea HGMM n timpul sarcinii la femeile cu
proteze mecanice este nc controversat, deoarece dovezile sunt insuficiente. Problemele nerezolvate se refer la nivelul optim de anti-Xa, importana peak-ului vs
nivelurile pre-doz i intervalele de timp optime pentru monitorizarea anti-Xa. Este nevoie imperioas de
studii pe aceast tem.
Exist o cretere marcat a necesarului de doze n
timpul sarcinii pentru a menine nivelurile de anti-Xa
n intervalul terapeutic151,153, din cauza volumului crescut de distribuie i al creterii clearance-ului renal.
Prin urmare, monitorizarea periodic a nivelului anti-Xa este necesar. S-a demonstrat c nivelele de anti-Xa pre-doz sunt adesea subterapeutice atunci cnd
nivelurile de vrf se situeaz n intervalul 0,8 i 1,2 U/
mL153,154. Chiar i atunci cnd sunt monitorizate nivelurile de anti-Xa predoz i dozarea mai frecvent, determin niveluri predoz mai crescute asociate cu niveluri
de vrf mai mici, nu exist date disponibile pentru a
demonstra c prin aceast abordare se obine o anticoagulare stabil i consistent i c va preveni tromboza
valvular i sngerarea152-154.
Dovezile actuale indic faptul c anticoagularea oral pe tot parcursul sarcinii, sub controlul strict al INRului, este cel mai sigur tratament pentru mam146, 147,155.
Totui, studii randomizate adecvate care s compare
diferitele regimuri nu sunt disponibile. Superioritatea
heparinei nefracionate sau HGMM n primul trimestru nu este dovedit, dei un studiu recent sugereaz
o eficacitate mai mare a HGMM147. Nicio HGMM nu
este oficial aprobat pentru femeile nsrcinate cu valve
mecanice.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Riscul obstetrical i al ftului


Toate regimurile de anticoagulare prezint un risc
crescut de avort spontan i de complicaii hemoragice,
inclusiv sngerare retroplacentar, ce determin natere prematur i deces fetal144,146,148,150-152. Comparaia
studiilor este dificil, totui, dat fiind c se constat diferene. Anticoagulantele orale traverseaz placenta i
utilizarea lor n primul trimestru de sarcin poate duce
la embriopatie n 0,6-10% din cazuri146,156-158. Heparina
nefracionat i HGMM nu traverseaz placenta nedeterminnd embriopatie. nlocuirea ACO cu heparin
nefracionat n sptmnile 6-12 scade foarte mult
acest risc. ntr-un studiu mic, incidena embriopatiei
a fost redus (2,6%), cnd doza de warfarin a fost <5
mg i 8% cnd doza de warfarin a fost >0,5 mg/zi159.
Aceast dependen n funcie de doza utilizat a fost
confirmat ntr-un studiu recent155. Anomaliile de la
nivelul sistemului nervos central au fost constatate la
1% dintre copiii a cror mame au utilizat anticoagulante orale n primul trimestru de sarcin158. Exist un risc
redus de anomalii minore la nivelul sistemului nervos
central i la utilizarea anticoagulantelor orale n afara
primului trimestru158. Naterea pe cale natural n timp
ce mama se afl sub terapie cu anticoagulante orale este
contraindicat din cauza riscului de sngerare intracranian fetal.
Management
Ar trebui luate n considerare disfuncia ventricular
i valvular, precum i tipul i poziia valvei, i antecedentele de tromboz valvular. Avantajele i dezavantajele diferitelor regimuri de anticoagulare ar trebui s
fie discutate pe larg. Mama i partenerul ei trebuie s
neleag c n conformitate cu dovezile actuale, anticoagulantele orale sunt cele mai eficiente n prevenia
trombozei valvulare, i, prin urmare, sunt cel mai sigur
regim pentru mam, iar riscurile aduse mamei pun n
pericol i copilul. Pe de alt parte, riscul de embriopatie
i de hemoragie fetal trebuie s fie discutat, n funcie
de doza de anticoagulant oral. Managementul regimului ce va fi ales ar trebui planificat n detaliu.
Urmrire
Eficacitatea regimului anticoagulant ar trebui monitorizat sptmnal, iar urmrirea clinic i ecocardiografic ar trebui efectuate lunar.
Terapia medicamentoas
Scopul principal al tratamentului anticoagulant la
aceste femei este de a preveni apariia trombozei val

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

vulare i consecinele sale letale, att pentru mam ct


i pentru ft. Urmtoarele recomandri ar trebui s fie
vzute n aceast perspectiv. Tratamentul cu anticoagulante orale ar trebui s fie meninut pn la apariia
sarcinii. Heparina nefracionat sau HGMM pe tot parcursul sarcinii nu sunt recomandate din cauza riscului
ridicat de tromboz valvular, comparativ cu riscul fetal sczut n cazul utilizrii anticoagulantelor orale n
al doilea i al treilea trimestru. Continuarea terapiei cu
anticoagulante orale pe parcursul sarcinii ar trebui s
fie luat n considerare atunci cnd doza de warfarin
este <5 mg pe zi (sau fenprocumon <3 mg sau acenocoumarol <2 mg pe zi), deoarece riscul de embriopatie
este sczut, iar regimul este cel mai eficient n prevenirea trombozei valvulare146,147. Dup ce mama a primit
informaii complete despre faptul c utilizarea anticoagulantelor orale pe tot parcursul sarcinii este cel mai sigur tratament pentru ea i c riscul de embriopatie este
<3%, ntreruperea tratamentului cu anticoagulante orale i schimbarea cu heparin nefracionat sau HGMM
ntre sptmnile 6 i 12 sub control strict al dozei i
supraveghere (astfel cum este indicat mai jos), ea poate fi ncadrat n categoria pacienilor care va necesita
doze sczute de anticoagulant oral. Atunci cnd o pacient necesit o doz mai mare de anticoagulant oral,
trebuie s se aib n vedere ntreruperea anticoagulantului ntre sptmnile 6 i 12 i nlocuirea cu heparin
nefracionat (aPTT dou ori controlul, la pacientele
cu risc nalt administrat sub form de infuzie i.v.) sau
HGMM de dou ori pe zi, cu ajustarea dozei n funcie
de greutate i conform cu nivelul anti-Xa (Tabelul 12).
Nivelul de anti-Xa ar trebui s fie meninut ntre 0,8
i 1,2 U/ml, determinat la 4-6 ore dup administrarea
substanei (Tabelul 12)4,7. Grupul de Lucru recomand
controlul sptmnal al nivelului de anti-Xa din cauza
necesitii de cretere a dozelor de HGMM n timpul
sarcinii2,4,7,147,151,153. Ca o alternativ, continuarea terapiei cu anticoagulante orale poate fi luat n considerare
la aceste paciente dup consimmntul informat. Importana monitorizrii nivelului de anti-Xa predoz i
necesitatea de a menine acest nivel peste 0,6 UI/ml, nu
a fost studiat suficient, mai ales din punct de vedere
al evenimentelor trombo-embolice i sngerrii, pentru a face recomandri ferme. Doza de nceput pentru
HGMM este de 1 mg/kg corp n cazul n care se utilizeaz enoxaparin i 100UI/ kg pentru dalteparin, administrate de dou ori pe zi, subcutanat. Doza trebuie
ajustat n funcie de greutate, care crete pe perioada
sarcinii160 i de nivelul anti-Xa. Grupul de Lucru nu
recomand adugarea de aspirin la acest regim, de

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oarece nu exist date care s demonstreze eficacitatea


i sigurana la femeile gravide. Utilizarea de HGMM
n primul trimestru este limitat de numrul redus de
date referitoare la eficien147 i siguran, incertitudini
n ceea ce privete dozarea optim att pentru a preveni
tromboza valvular, ct i sngerarea, precum i disponibilitatea variabil de a testa nivelul anti-Xa.
Indiferent de regimul folosit, efectul anticoagulantelor ar trebui s fie monitorizat foarte atent, iar n cazul
anticoagulantelor orale INRul ar trebui s fie determinat la interval de o sptmn. Valoarea INR ar trebui
s fie aleas n funcie de tipul i amplasarea valvei
protetice, n conformitate cu ghidurile4,7. O educaie
intens referitoare la anticoagulante i auto-monitorizarea este recomandat pacientelor. n cazul n care
este utilizat heparina nefracionat i aPTT este stabil,
acesta ar trebui monitorizat sptmnal, la 4-6 ore dup
administrarea primei doze, cu o cretere de dou ori
normalul.
Diagnosticul i managementul trombozei valvulare
Atunci cnd o femeie cu protez mecanic prezint
dispnee i/sau un eveniment embolic, ecocardiografia transtoracic imediat este indicat pentru a cuta
tromboza valvular, de obicei, urmat de ecocardiografie transesofagian. Dac este necesar, fluoroscopia
poate fi efectuat cu un risc fetal limitat. Managementul
trombozei valvulare este comparabil cu managementul
pacienilor n afara sarcinii. Acesta include optimizarea
nivelului de anticoagulant cu heparin i.v. i reluarea
anticoagulrii orale la bolnavii care nu sunt n stare critic i au avut anticoagulare recent subterapeutic, i
intervenie chirurgical atunci cnd anticoagularea nu
e eficient i pentru pacienii n stare critic cu tromboz obstructiv7. Majoritatea agenilor fibrinolitici nu
traverseaz placenta, dar riscul de embolizare (10%) i
de sngerare subplacentar trebuie luat n considerare,
experiena utilizrii acestora n timpul sarcinii fiind limitat. Fibrinoliza ar trebui aplicat la pacienii n stare
critic atunci cnd chirurgia nu este disponibil imediat. Deoarece riscul pierderii ftului este ridicat n cazul
interveniei chirurgicale, fibrinoliza poate fi o opiune
la pacientele n stare non-critic la care anticoagularea
a euat. Fibrinoliza este terapia de elecie a trombozei
valvelor protetice ale cordului drept7. Mama trebuie informat asupra riscurilor.
Naterea (a se vedea i Seciunea 2.9)
Naterea planificat pe cale natural este de obicei
preferat, cu trecerea prealabil pe heparin. O cezari-

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an planificat poate fi o alternativ, n special la pacientele cu risc crescut de tromboz valvular, pentru a
menine pacienta ct mai puin timp fr anticoagulante orale. Cezariana ar trebui efectuat dac travaliul se
declaneaz i pacienta se afl nc sub terapie cu anticoagulante orale.
5.6. Recomandri pentru managementul
valvulopatiilor

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

6. BOALA ARTERIAL CORONARIAN I SINDROAMELE


CORONARIENE ACUTE
Criteriile de diagnostic ale sindromului coronarian
acut (SCA) n timpul sarcinii sau n perioada peripartum sunt similare cu cele pentru pacientele nensrcinate i constau n dureri n piept, modificri ECG i
biomarkeri cardiaci pozitivi. Cu toate acestea, undele
T negative pot aprea la un numr crescut de paciente

Tabelul 12. Recomandri pentru managementul valvulopatiilor


Recomandri
Clasa
Stenoza mitral
I
La pacientele simptomatice sau cu hipertensiune pulmonar sunt recomandate restricionarea activitii i betablocantele 1-selective.
I
Diureticele sunt recomandate cnd simptomele de congestie persist n timpul terapiei cu -blocante.
Pacientele cu SM sever trebuie supuse inteveniei chirurgicale anterior sarcinii.
I
Anticoagularea terapeutic este recomandat n caz de fibrilaie atrial, tromboz atrial stng sau antecedente de embolism.
I
Comisurotomia mitral percutan ar trebui luat n considerare la gravidele cu simptome severe sau cu presiunea sistolic n artera pulmonar >50 mmHg n ciuda tratamentului
IIa
medicamentos.
Stenoza aortic
La pacientele cu SA sever este necesar intervenia chirurgical anterior sarcinii dac:
sunt simptomatice
I
disfuncia VS (FEVS <50%) este prezent
I
Pacientele asimptomatice cu SA sever trebuie tratate chirurgical anterior sarcinii dac dezvolt simptome specifice la testul de efort.
I
Pacientele asimptomatice cu SA sever ar trebui luate n considerare pentru tratament chirurgical anterior sarcinii dac la testul de efort se nregistreaz o scdere a tensiunii arteriale.
IIa
Regurgitrile valvulare
Pacientele cu regurgitare sever aortic sau mitral simptomatice sau disfuncie sau dilatare ventricular ar trebui tratate chirurgical anterior sarcinii.
I
Terapia medical este recomandat la femeile gravide cu leziuni de regurgitare odat cu apariia simptomelor.
I
Valve mecanice
ACO este recomandat n timpul celui de-al doilea i al treilea trimestru pn n sptmna 36 de sarcin.
I
Modificrile tratamentului ACO n timpul sarcinii trebuie realizate n spital.
I
Dac travaliul se declaneaz n timpul tratamentului cu ACO, operaia de cezarian este indicat.
I
ncepnd cu sptmna 36 de gestaie, ACO trebuie ntrerupt i nceput terapia cu doze ajustate de HNF (aPTT2 x control) sau HGMM (nivel anti-Xa la 4-6 ore post-doz de 0,8-1,2 U/
I
mL).
La femeile nsrcinate sub tratament cu HGMM, nivelul seric anti-Xa post-doz trebuie evaluat sptmnal.
I
HGMM ar trebui nlocuite cu HNF intravenos cu cel puin 36 de ore anterior travaliului. HNF ar trebui ntrerupt cu 4-6 ore anterior travaliului i reluat la 4-6 ore dup natere dac nu
I
exist complicaii hemoragice.
Ecocardiografia imediat este indicat la femeile cu valv mecanic ce se prezint cu dispnee i/sau un eveniment embolic.
I
Continuarea ACO n primul trimestru trebuie luat n considerare la pacientele la care doza necesar de warfarin pentru anticoagulare n limite terapeutice este <5 mg/zi (sau phenproIIa
coumon <3 mg/zi sau acenocumarol <2 mg/zi), dup informarea i consimmntul pacientei.
Oprirea ACO ntre sptmnile 6-12 de sarcin i nlocuirea cu doze ajustate de HNF (aPTT2 x control; la pacientele cu risc nalt administrat ca perfuzie intravenoas) sau de HGMM de
dou ori pe zi (cu doza ajustat n funcie de greutate i de nivelul anti-Xa int la 4-6 ore post-doz de 0,8-1,2 U/mL) ar trebui luat n considerare la pacientele la care doza necesar de
IIa
warfarin pentru anticoagulare n limite terapeutice este >5 mg/zi (sau phenprocoumon >3 mg/zi sau acenocumarol >2 mg/zi).
Oprirea ACO ntre sptmnile 6-12 de sarcin i nlocuirea cu HGMM sau HNF sub control strict (descris mai sus) poate fi luat n considerare la anumite paciente la care doza necesar de
IIb
warfarin pentru anticoagulare n limite terapeutice este <5 mg/zi (sau phenprocoumon <3 mg/zi sau acenocumarol <2 mg/zi).
Continuarea ACO ntre sptmnile 6-12 de sarcin poate fi luat n considerare la pacientele la care doza necesar de warfarin pentru anticoagulare n limite terapeutice este >5 mg/
IIb
zi (sau phenprocoumonol >3 mg/zi sau acenocumarol >2 mg/zi).
HGMM trebuie evitate dac nivelul plasmatic anti-Xa nu poate fi monitorizat.
III

Nivelb
B7,64
B64
C
C
C

B7
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C

a = clasa de recomandare
b = nivel de eviden
aPTT = activated partial thromboplastin time (Timpul de tromboplastin parial activat); SA = Stenoz aortic; HGMM = heparin cu greutate molecular mic; FEVS = fracia de ejecie a ventricului stng; SM = stenoz mitral; ACO =
anticoagularea oral; HNF = heparin nefracionat

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

n timpul sarcinii n condiii non-ischemice. O cretere


a nivelului troponinei I ar trebui investigat i luat n
considerare diagnosticul de ischemie chiar n prezena
pre-eclampsiei161. Diagnosticul este de multe ori ntrziat, deoarece simptomele pot fi atribuite sarcinii. Diagnosticele difereniale principale ale durerii toracice
acute ischemice sunt pre-eclampsia, embolia pulmonar acut i disecia de aort. Ecocardiografia poate fi folosit n siguran pentru a evalua prezena tulburrilor
de cinetic. Testul ECG de efort sau ecocardiografia de
efort pot fi efectuate la pacientele stabile; testele de stres
cu radionuclizi ar trebui evitate din cauza radiaiilor.
Hemoragia post-partum sever cu oc hemoragic, poate duce de asemenea la niveluri crescute ale troponinei
cu modificri ischemice pe ECG i anomalii de cinetic
ale peretelui VS.
6.1 Riscul matern i fetal
Odat cu creterea n vrst a mamelor i cu creterea numrului de femei cu risc nalt care rmn nsrcinate, sindromul coronarian acut (SCA) la femeile
nsrcinate este de ateptat s creasc. Sarcina poate fi
luat n considerare la femeile cu boal coronarian
cunoscut n absena ischemiei reziduale i a semnelor clinice de disfuncie de VS. Se recomand evaluarea riscului cardiac naintea concepiei (vezi Seciunea
2.11). SCA sunt rare n timpul sarcinii i sunt estimate
la 3-6 la 100 000 de nateri162-164. Sunt strns legate de
prezena factorilor de risc coronarieni majori, cum ar fi
fumatul, hipertensiunea, dislipidemia, vrsta naintat,
diabetul zaharat i istoricul familial pozitiv. Alte condiii care contribuie la riscul de SCA sunt (pre) eclampsia,
trombofilia, infeciile post-partum i hemoragia sever postpartum161,163-165. SCA din timpul sarcinii poate
aprea n oricare dintre etapele de gestaie. Diseciile
spontane de artere coronare sunt mai frecvente la femeile nsrcinate dect la restul femeilor, i sunt n mare
parte raportate n apropierea naterii sau n perioada
imediat post-partum163. Acestea pot fi legate de nivelurile ridicate de progesteron cu modificri ulterioare
structurale ale colagenului din pereii vaselor. Ergometrina administrat pentru sngerarea post-partum poate duce la vasospasm coronarian i la ischemie. Trombii
i diseciile apar mai frecvent n perioada peripartum
dect naintea naterii163.
Mortalitatea matern dup SCA este estimat la
5-10% i este mai mare n perioada peripartum. Supravieuirea s-a mbuntit din cauza interveniei coronariene percutane primare (PCI)162-164. Prognosticul matern pe termen lung depinde n principal de mrimea
infarctului i de profilul de risc cardiovascular. nainte

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de natere, SCA poate duce la mortalitate fetal i prematuritate, risc, care este legat n principal de gradul de
severitate al bolii cardiace materne.
6.2. Management
Primul pas n caz de SCA cu supradenivelare ST este
s se trimit imediat pacienta ntr-un centru cu faciliti de angiografie diagnostic i PCI primar.
Intervenii n timpul sarcinii
Angiografia coronarian cu posibilitatea de PCI este
preferat fa de tromboliz, deoarece poate diagnostica, de asemenea, existena diseciei arterei coronare.
Riscul de dunare potenial asupra ftului ar trebui
luat n considerare, n special n primul trimestru. Toate studiile au raportat utilizarea de stenturi metalice n
timpul fazei acute a infarctului miocardic cu supradenivelare de ST din timpul sarcinii; sigurana utilizrii
DES (drug-eluting stent) la femeile gravide este nc necunoscut. Deoarece DES necesit utilizarea prelungit
a terapiei duale antiplachetare, acestea ar trebui evitate.
Dei activatorul tisular al plasminogenului recombinant nu traverseaz placenta, acesta poate determina
complicaii hemoragice (sngerare subplacentar); prin
urmare, tratamentul trombolitic ar trebui s fie rezervat pentru SCA amenintoare de via cnd nu exist
acces la PCI166. La femeile cu SCA fr supradenivelare
de ST, cu risc intermediar sau nalt, este indicat abordarea invaziv pentru a evalua anatomia coronarian,
n timp ce la pacientele stabile cu simptome de efort
tratamentul de ales este reprezentat de supraveghere
atent i tratament medicamentos167. n cazul n care
exist o deteriorare a strii clinice, strategia invaziv
este indicat la toi pacienii. n caz de disecie coronarian recurent, poate fi luat n considerare naterea nainte de termen n funcie de viabilitatea fetal.
Datele privind chirurgia de bypass aorto-coronarian
n urgen, n timpul sarcinii, sunt puine, cu o rat de
mortalitate potenial ridicat163,164.
Tratamentul medicamentos
Utilizarea de IECA, blocani de receptori ai angiotensinei (BRA) i inhibitori ai reninei este contraindicat n timpul sarcinii (a se vedea Seciunea 11). Beta-blocantele i aspirina n doz mic sunt considerate
relativ sigure, n timp ce sigurana tienopiridinelor este
necunoscut. Prin urmare, clopidogrelul ar trebui s fie
folosit n timpul sarcinii numai cnd este strict necesar
(de exemplu, dup implantare de stent) i pentru cea
mai scurt perioad posibil. n absena datelor privind
sigurana inhibitorilor glicoproteinei IIb/IIIa, bivaliru-

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dinei, prasugrelului i ticagrelorului, acestea nu sunt


recomandate n timpul sarcinii.
Naterea
n majoritatea cazurilor, naterea natural este adecvat. Naterea este discutat n Seciunea 2.9.
6.3. Recomandri pentru managementul bolii
arteriale coronariene
Tabelul 13. Recomandrile pentru managementul bolii arteriale
coronariene
Recomandri
Clasaa Nivelb
ECG i nivelul troponinei ar trebui s fie efectuate n cazul apariiei
I
C
durerilor toracice la o femeie gravid.
Angioplastia coronarian este de preferat ca terapie de reperfuzie n
I
C
STEMI din timpul sarcinii.
Managementul conservator ar trebui s fie luat n considerare pentru SCA
IIa
C
fr supradenivelare de ST fr criterii de risc.
Un management invaziv ar trebui s fie luat n considerare pentru SCA fr
IIa
C
supradenivelare de ST cu criterii de risc (inclusiv NSTEMI).
a = clasa de recomandare
b = nivel de eviden
STEMI = infarct miocardic cu supradenivelare de ST; NSTEMI = infarct miocardic fr supradenivelare de ST;
SCA= sindrom coronarian acut.

7. CARDIOMIOPATIILE I INSUFICIENA CARDIAC


Incidena actual n Europa a cardiomiopatiilor asociate cu sarcina nu este cunoscut. Etiologia cardiomiopatiilor care apar n asociere cu sarcina este divers; pot
fi dobndite i ereditare (cardiomiopatia peripartum
(CMPP), cardiomiopatia toxic, hipertrofic (CMH),
dilatativ (CDM), boli de depozitare etc). Cardiomiopatiile sunt boli rare, dar pot cauza complicaii severe
n sarcin168.
7.1. Cardiomiopatia peripartum
CMPP a fost analizat recent168. Cele mai importante aspecte sunt descrise pe scurt aici. Incidena variaz
ntre 1:300 i 1:4000 de nateri, n funcie de factorii
genetici i/sau factorii culturali168,169. Factori de risc
par a fi multiparitatea, naterile multiple, istoricul familial, etnia, fumatul, diabetul zaharat, hipertensiunea
arterial, pre-eclampsia, malnutriia, vrsta naintat a
mamei sau sarcina la adolescen, precum i utilizarea
ndelungat a -agonitilor168,169. Etiologia CMPP (Cardiomiopatia Peripartum) este incert, dar infeciile,
inflamaia i procesele autoimune pot juca un rol170.
CMPP este considerat a fi consecina dezechilibrului
stresului oxidativ care conduce la clivarea proteolitic a
hormonului prolactin ntr-un factor potent angiostatic i n fragmente pro-apoptotice171.
Conform definiiilor actuale, PPCM este o cardiomiopatie idiopatic ce se manifest prin insuficien
cardiac secundar disfunciei sistolice a VS care apare spre sfritul sarcinii sau n urmtoarele luni dup

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

natere. Aceasta este un diagnostic de excludere atunci


cnd nu este gsit nicio alt cauz de insuficien cardiac. VS poate s fie nedilatat, dar FE este aproape ntotdeauna redus sub 45%168.
Semnele i simptomele sunt de obicei tipice pentru
insuficiena cardiac, dar, din cauza strii fiziologice
speciale datorate sarcinii i perioadei post-partum, la
pacientele cu CMPP este raportat un spectru larg de
simptome. CMPP ar trebui s fie suspectat la toate
femeile cu o revenire ntrziat la starea fiziologic de
dinaintea sarcinii. Frecvent, pacientele se prezint cu
insuficien cardiac acut. Aritmiile ventriculare complexe precum i moartea subit de cauz cardiac sunt,
de asemenea, descrise.
n unele cazuri, nu toate criteriile de diagnostic sunt
strict ndeplinite. Ecocardiografia este metoda preferat pentru evaluarea funciei VS. CMD (cardiomiopatia
dilatativ) cu transmitere genetic se poate manifesta
n acelai interval de timp ca i CMPP i nu se poate
distinge de aceasta172,173.
Management
Insuficiena cardiac n CMPP se poate dezvolta
foarte rapid, de aceea se aplic msurile pentru managementul insuficienei cardiace acute174.
Intervenii
Dac o pacient este dependent de suportul inotrop, n ciuda tratamentului medical optimal, ar trebui
transferat ntr-o unitate specializat unde exist posibilitatea implantrii unui balon de contrapulsaie aortic, a unui dispozitiv de asisten ventricular, precum
i prezena unei echipe de medici n vederea transplantului cardiac. Decizia de utilizare a balonului de contrapulsaie aortic i de implantare a unui dispozitiv de
asisten ventricular ar trebui s fie discutat n colaborare cu medicii specialiti. Este important de reinut
c prognosticul CMPP este diferit de cel al CMD, cu o
rat important de ameliorare sau normalizare a funciei VS n primele 6 luni de la diagnosticare. Rata relativ ridicat (aproximativ 50%) de recuperare spontan
trebuie s fie luat n considerare atunci cnd se decide
diagnosticul175.
Dispozitive i transplantul cardiac
Pentru femeile care prezint simptome i disfuncie
sever de VS la 6 luni de la prima prezentare, n ciuda
tratamentului medical optimal maxim i QRS cu durata >120 ms, cei mai muli clinicieni ar recomanda terapia de resincronizare cardiac sau implantarea de ICD
(cardiodefibrilator implantabil). Transplantul cardiac

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

trebuie s fie rezervat pacienilor la care folosirea dispozitivelor mecanice de suport circulator nu este posibil sau nu este dorit, precum i pacienilor care nu
se recupereaz dup 6-12 luni de asistare ventricular
stng. Pacienii cu CMPP au un prognostic similar cu
cei cu CMD dup transplantul cardiac176.
Terapia medicamentoas
Prezena sarcinii este important pentru tratamentul
insuficienei cardiace cronice. Cele mai multe paciente
prezint CMPP peri- sau postpartum. Femeile care se
prezint cu CMPP n timpul sarcinii necesit ngrijire
medical pluridisciplinar, cardiologic i obstetrical.
Efectele adverse posibile asupra ftului trebuie s fie
luate n considerare atunci cnd se stabilete schema
de tratament. Naterea n urgen, indiferent de vrsta
sarcinii, trebuie s fie luat n considerare la femeile
care se prezint sau la care persist insuficiena cardiac avansat cu instabilitate hemodinamic. Imediat ce
naterea a avut loc, iar pacienta este stabil din punct
de vedere hemodinamic, terapia standard pentru insuficiena cardiac poate fi aplicat (Seciunea 7.4).
Tratamentul anticoagulant trebuie administrat cu
atenie n perioada imediat postpartum dar, odat ce
sngerarea este oprit, acesta trebuie luat n considerare la pacientele cu FE foarte mic deoarece accidentele embolice periferice, inclusiv embolismul cerebral
i trombii ventriculari sunt fenomene frecvente n
CMPP168. Accidentele embolice sunt frecvente ca urmare a activitii procoagulante crescute n perioada
peripartum177.
Insuficiena cardiac trebuie s fie tratat conform
ghidurilor de insuficien cardiac acut i cronic174.
Tratamentul cu IECA, BRA i inhibitori ai reninei este
contraindicat n timpul sarcinii din cauza fetotoxicitii178,179. Cnd este necesar folosirea IECA n timpul
alptarii, benazepril, captopril sau enalapril ar trebui s
fie preferai. Hidralazina i nitraii pot fi folositi n loc
de IECA/ BRA pentru reducerea postsarcinii. Dopamina i levosimendanul pot fi utilizai n cazul n care sunt
necesare medicamentele inotrop pozitive. Tratamentul
cu beta blocante este indicat la toate pacientele cu insuficien cardiac, dac sunt tolerate3. Blocantele 1selective (de exemplu, metoprolol) ar trebui s fie preferate. Atenolol nu ar trebui s fie folosit180. Nou-nscuii ar trebui supravegheai timp de 24-48 de ore dup
natere pentru a exclude hipoglicemia, bradicardia i
insuficiena respiratorie. Diureticele ar trebui s fie folosite numai dac este prezent congestia pulmonar,
deoarece acestea pot scdea fluxul de snge la nivelul

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placentei169. Furosemidul i hidroclorotiazida sunt cele


mai utilizate diuretice. Antagonitii de aldosteron ar
trebui evitai181. Tratamentul cu spironolacton poate
asocia efecte antiandrogenice n primul trimestru. Nu
exist date despre folosirea eplerenonei.
Activitatea de coagulare este crescut n timpul sarcinii (a se vedea Seciunea 2.4)177. n contextul unei
FE reduse n CMPP, trebuie considerat tratamentul cu
HGMM sau cu anticoagulante orale. Anticoagularea
este recomandat la pacientele cu trombi intracardiaci
detectai prin tehnici imagistice sau cu dovezi de embolie sistemic174, precum i la pacientele cu insuficien cardiac sau fibrilaie atrial paroxistic sau persistent. HGMM sau antagonitii de vitamina K sunt
recomandai n funcie de perioada sarcinii pentru a
preveni accidentele embolice142,174,182. Cnd sunt folosite HGMM ar trebui monitorizate nivelurile serice de
anti-Xa.
Naterea
Naterea pe cale natural este ntotdeauna de preferat n cazul n care pacienta este stabil din punct de vedere hemodinamic i nu exist motive obstetricale pentru intervenia cezarian. Este necesar monitorizarea
atent din punct de vedere hemodinamic. Analgezia
epidural este de preferat. Naterea prematur a fost
raportat la 17% dintre paciente, fr efecte negative
marcate asupra nou-nscutului183. Naterea de urgen,
indiferent de vrsta gestaional ar trebui s fie luat n
considerare la femeile cu insuficien cardiac avansat
i instabilitate hemodinamic n ciuda tratamentului.
Se recomand combinaia de rahianestezie i anestezie
epidural n caz de cezarian184. Este necesar prezena unei echipe interdisciplinare format din medici cu
experien.
Alptatul la sn
Unii IECA (benazepril, captopril, enalapril) au fost
testai la femeile care alpteaz i utilizarea lor de ctre
mame este sigur pentru copii185. Monitorizarea greutii copilului n primele 4 sptmni este un indicator
esenial al disfunciei renale. Un mic studiu pilot recent
randomizat i prospectiv susine ipoteza c adugarea
de bromocriptin la terapia standard a insuficienei
cardiace, are efecte benefice asupra FE ventriculare i
asupra rezultatelor clinice la femeile cu CMPP acut
sever186. n plus, din cauza cerinelor metabolice crescute din timpul lactaiei i alptrii, prevenirea lactaiei
poate fi luat n considerare.

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Prognosticul i consilierea pentru o sarcin ulterioar


Datele la nivel mondial cu privire la ratele de mortalitate variaz de la 0% la 9% n populaia alb din Statele Unite ale Americii, pn la 15% la afro-americani i
populaiile din Africa de Sud i Haiti. Studiile sistematice efectuate n ri europene nu sunt disponibile pn
n prezent. Deteriorarea funciei VS este raportat n
maxim 50% din cazuri, n ciuda tratamentului medicamentos optimal maximal187.
O sarcin ulterioar implic un risc de recuren a
CMPP de aproximativ 30-50%169,175. n cazul n care FE
nu s-a normalizat, o sarcin ulterioar ar trebui s fie
descurajat. Chiar dac FE a revenit la normal, consilierea este nc necesar din cauza riscului de recuren
care se instaleaz odat cu o nou sarcin.
7.2 Cardiomiopatia dilatativ (CDM)
CDM este definit de prezena simptomelor tipice de
insuficien cardiac, dilatare VS i disfuncie sistolic
VS de cauz necunoscut. Diferenierea de CMPP se
face n funcie de momentul manifestrii. Dac afeciunea nu este cunoscut nainte de concepie, cel mai
adesea este demascat n timpul primului sau celui deal doilea trimestru atunci cnd solicitrile hemodinamice sunt n cretere. Un istoric familial de CDM pledeaz pentru diagnosticul de CDM i mpotriva celui
de CMPP. Puinele cazuri clasice de CDM din timpul
sarcinii s-au nsoit de deteriorare marcat pe timpul
sarcinii188.
Cardiomiopatiile secundare, cum ar fi cardiomiopatiile infiltrative sau toxice, bolile de depozitare i alte
forme rare, se pot, de asemenea, manifesta n timpul
sarcinii. Cardiomiopatiile hipertensiv sau ischemic
pot provoca, de asemenea, un tablou clinic similar.
Riscul matern i fetal
Femeile cu CMD ar trebui informate cu privire la
riscul de deteriorare a strii de sntate n perioada de
gestaie i n perioada peripartum (a se vedea Seciunea 2). Acestea ar trebui consiliate n funcie de riscul
individual. Dac sarcina survine, o FEVS sub 40% este
un predictor de risc nalt i se sftuiete monitorizarea
atent ntr-un centru teriar. Dac FEVS este de sub
20%, riscul de mortalitate matern este foarte mare i
ar trebui luat n considerare decizia de ntrerupere a
sarcinii.
Management
Tratamentul anticoagulant cu HGMM sau cu antagoniti de vitamin K, n funcie de stadiul sarcinii ar
trebui luat n considerare pentru pacientele care prezint aritmii atriale.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

CMD se trateaz n conformitate cu ghidurile ESC/


European Society of Intensive Care Medicine (ESICM)
de insuficien cardiac174, cu adaptrile pe timpul sarcinii descrise mai sus pentru CMPP.
7.3 Cardiomiopatia hipertrofic (CMH)
CMH este cea mai frecvent boal cardiac cu transmitere genetic189. Boala este frecvent diagnosticat
pentru prima dat n timpul sarcinii prin ecocardiografie. Cele mai frecvente complicaii apar din cauza
disfunciei diastolice cauzate de miocardul hipertrofiat
non-compliant, de obstrucia sever la nivelul tractului
de ejecie al VS i a aritmiilor.
Simptomele sunt tipice insuficienei cardiace, cu fenomene de congestie pulmonar din cauza creterii
presiunii la sfritul diastolei sau sincopei aprute n
timpul activitii fizice, ca rspuns la obstrucia tractului de ejecie. Ecocardiografia este metoda de elecie pentru diagnosticare. Aritmiile supraventriculare i
ventriculare sunt comune.
Riscul matern i fetal
De obicei, femeile cu CMH tolereaz bine sarcina.
Riscul este crescut la femeile care sunt simptomatice
nainte de sarcin i la cele care prezint un gradient
crescut n tractul de ejecie. Pacientele cu un profil clinic corespunztor unui risc nalt nainte de sarcin prezint un risc mai mare i au nevoie de ngrijire obstretical specializat pe parcursul sarcinii34,190. Cazurile cu
risc sczut ar putea avea travaliu spontan i natere pe
cale normal.
Management
Beta-blocantele ar trebui luate n considerare la pacientele care prezint obstrucie mai mult dect uoar
la nivelul tractului de ejecie a VS i/sau grosimea pereteilor >15 mm, pentru a preveni congestia pulmonar
brusc din timpul stresului fizic sau emoional189. Beta-blocantele pot fi utilizate pentru controlul frecvenei
n fibrilaia atrial i pentru a suprima aritmiile ventriculare. Verapamilul poate fi folosit ca o a doua alegere
atunci cnd beta-blocantele nu sunt tolerate (atenie la
riscul de producere de bloc AV la ft). Cardioversia ar
trebui luat n considerare pentru cazurile cu aritmie
persistent, deoarece fibrilaia atrial nu este bine tolerat. Terapia anticoagulant cu HGMM sau antagoniti
ai vitaminei K n conformitate cu stadiul sarcinii este
recomandat pacientelor cu FA paroxistic sau persistent. Pacientele cu antecedente personale sau heredocolaterale de moarte subit au nevoie de supraveghere
atent i de investigare prompt dac apar simptome
precum palpitaii sau pre-sincop.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Naterea
Cazurile care prezint risc sczut ar putea avea travaliu spontan i natere pe cale normal. Cu toate acestea, pot aprea complicaii; prin urmare se recomand
o natere planificat n toate celelalte cazuri. Gravitatea
obstruciei de la nivelul tractului de ejecie a VS stabilete dac se poate efectua anestezie regional. Anestezia epidural cauzeaz vasodilataie sistemic i hipotensiune arterial, i, prin urmare, trebuie s fie utilizat cu precauie la pacientele cu obstrucie sever la
nivelul tractului de ejecie a VS. Perfuziile i.v. trebuie
administrate judicios pentru a evita creterea volumului circulant care este prost tolerat n prezena disfunciei diastolice. Syntocinon poate determina hipotensiune arterial, aritmii i tahicardie, de aceea trebuie
administrat numai n perfuzie lent.
7.4 Recomandri pentru managementul
insuficienei cardiace
Tabelul 14. Recomandri pentru managementul cardiomiopatiilor i
insuficienei cardiace
Recomandri
Clasaa Nivelb
Anticoagularea este recomandat la pacientele cu tromb intracardiac detecI
A174
tat de ctre explorrile imagistice sau cu dovezi de embolie sistemic.
Femeile cu IC n timpul sarcinii trebuie tratate conform ghidurilor actuale
I
B168
pentru non-gravide, cu respectarea contraindicaiilor pentru unele medicamente n sarcin - vezi Seciunea 11 Tabelul 21.
Femeile cu CMD trebuie informate cu privire la riscul de agravare a bolii n
I
C
timpul sarcinii i n perioada peripartum.
La pacientele cu antecedente personale sau heredo-colaterale de moarte
I
C
subit, este nevoie de supraveghere atent i de investigare prompt dac
apar simptome precum palpitaiile sau pre-sincopa.
Terapia anticoagulant cu HGMM sau antagoniti ai vitaminei K n conformiI
C
tate cu stadiul sarcinii este recomandat pacientelor cu fibrilaie atrial.
Naterea la pacientele cu CMH trebuie s aib loc sub protecie cu betaIIa
C
blocante.
IIa
C
Beta-blocantele ar trebui luate n considerare la toate pacientele cu CMH
care prezint obstrucie mai mult dect uoar la nivelul tractului de
ejecie a VS i/sau grosimea peretelui >15 mm, pentru a preveni congestia
pulmonar brusc.
n CMH, cardioversia trebuie luat n considerare la pacientele cu fibrilaie
IIa
C
atrial persistent.
Din cauza cerinelor metabolice ridicate ale lactaiei i alptrii, prevenirea
IIb
C
lactaiei poate fi luat n considerare n CMPP.
III
C
Sarcinile ulterioare nu sunt recomandate dac FEVS nu se normalizeaz la
pacientele cu CMPP.
a = clasa de recomandare
b = nivel de eviden
CMD = cardiomiopatie dilatativ; CMH = cardiomiopatie hipertrofic; IC = insuficien cardiac; HGMM =
heparin cu greutate molecular mic; FEVS = fracia de ejecie a VS; CMPP = cardiomiopatia peripartum;
LVOTO = obstrucie la nivelul tractului de ejecie a VS.

8. ARITMIILE
Att extrasistolele ct i tahiaritmiile susinute pot deveni mai frecvente sau se pot manifesta pentru prima
dat n timpul sarcinii. Exacerbri simptomatice produse de pusee de tahicardie supraventricular paroxistic (TPSV) apar n timpul sarcinii n aproximativ 20
pn la 44% din cazuri60. Chiar dac cele mai multe pal

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pitaii sunt benigne, apariia de episoade de tahicardie


ventricular este ngrijortoare i pacientele ar trebui
investigate pentru prezena unei boli cardiace structurale de baz.
Preocuparea major n ceea ce privete utilizarea de
medicamente antiaritmice n timpul sarcinii este dat
de potenialele efecte adverse produse asupra ftului.
Toate medicamentele antiaritmice ar trebui s fie luate
n considerare ca potenial toxice pentru ft. n timp
ce primul trimestru este asociat cu cel mai mare risc
teratogen, expunerea la medicamente antiaritmice mai
trziu, n timpul sarcinii poate produce efecte adverse
asupra creterii i dezvoltrii fetale i amplific riscul
proaritmogen al acestora. Lipsesc studiile majore controlate efectuate asupra medicamentelor antiaritmice
n timpul sarcinii. Medicamentele antiaritmice sunt
enumerate n Seciunea 11.
Decizia asupra continurii sau opririi administrrii
medicamentelor antiaritmice trebuie s fie luat dup o
analiz atent, datorit posibilitii recurenei tahiaritmiilor n timpul sarcinii. Aceste decizii sunt individualizate i sunt bazate pe natura i tipul aritmiilor, dar i
a bolii cardiace de baz. Este important ca tahiaritmiile
simptomatice s fie tratate prin ablaie nainte de apariia sarcinii, acolo unde este posibil.
8.1 Aritmii asociate cu boli cardiace structurale i
congenitale
Aritmiile supraventriculare i ventriculare care necesit tratament apar la pn la 15% (n medie 5%) din
pacientele cu boli cardiace congenitale n timpul sarcinii56. Episoadele de tahicardie susinut, n special de
flutter atrial, nu sunt bine tolerate i pot provoca hipoperfuzie fetal la pacientele cu boli cardiace structurale.
Conversia electric ar trebui efectuat pentru a restabili
ritmul sinusal. Digoxinul poate fi folosit pentru a controla frecvena ventricular, dar nu are efect profilactic
antiaritmic. Beta-blocantele, medicamentele antiaritmice de clasa I i sotalolul trebuie utilizate cu precauie
dac funcia VS sau VD este afectat (vezi Seciunea
11). Amiodarona ar trebui s fie utilizat numai atunci
cnd celelalte tratamente au euat i doar la cea mai
mic doz eficace (vezi Seciunea 11).
8.2 Aritmii specifice
8.2.1 Tahicardii supraventriculare
Tahicardia prin reintrare nodal atrio-ventricular i
tahicardia prin reintrare atrioventricular
Tahicardia prin reintrare nodal atrio-ventricular i
tahicardia prin reintrare atrioventricular care implic
existena unei ci accesorii pot fi oprite prin manevre

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vagale sau, n cazul n care acestea eueaz, prin adenozin i.v.191. Adenozina i.v. este medicamentul de elecie
n cazul n care manevrele vagale nu reuesc a opri un
episod de TPSV191. Metoprololul i.v. se recomand n
cazul n care adenozina nu reuete s opreasc un episod de tahicardie. Terapia profilactic cu medicamente
antiaritmice ar trebui instituit numai n cazul n care
simptomele sunt prost tolerate sau dac tahicardia cauzeaz instabilitate hemodinamic (Tabelul 15). Digoxinul sau beta-blocantele selective (metoprolol) sunt
ageni de prim linie, urmai de sotalol, flecainid sau
propafenon192. Agenii care acioneaz la nivelul nodului AV nu trebuie utilizai la pacientele care prezint sindrom de pre-excitaie pe ECG de repaus. Ablaia
prin cateter trebuie luat n considerare pe timpul sarcinii numai n cazuri speciale.
Tahicardia atrial focal
Tratamentul cazurilor de tahicardie atrial pe timpul
sarcinii este, n general, mai dificil din cauza rezistenei
la medicamente, tendinei de a fi persistente i a asocierii lor cu boli cardiace structurale. Folosirea betablocantelor i/sau a digitalicelor pentru controlul frecvenei, este indicat pentru evitarea apariiei cardiomiopatiei induse de tahicardie. Terapia profilactic cu
medicamente antiaritmice, ce include flecainida, propafenona sau sotalolul, ar trebui s fie utilizat pentru
pacientele cu simptomatologie clar. Amiodarona ar
trebui folosit numai n cazul n care aritmia nu poate
fi controlat cu alte medicamente.
Cardioversia electric nu se recomand n general,
din cauza recurenei tahicardiei. Aproximativ 30% din
tahicardiile atriale pot fi controlate cu ajutorul adenozinei. Ablaia prin cateter poate fi luat n considerare
n cazurile rezistente la medicamente i prost tolerate.
8.2.2 Flutterul atrial i fibrilaia atrial
Flutterul atrial i fibrilaia atrial sunt foarte rare n
timpul sarcinii, excepie fcnd cazurile care prezint
boli cardiace structurale sau hipertiroidie. Un rspuns
ventricular rapid poate duce la consecine hemodinamice severe, att pentru mam ct i pentru ft. Prioritatea este prin urmare diagnosticul i tratamentul bolii
de baz. Cardioversia electric ar trebui s fie efectuat
n caz de instabilitate hemodinamic.
La pacienii stabili hemodinamic cu cord structural
normal trebuie luat n considerare conversia medicamentoas a flutterului atrial i a fibrilaiei atriale. Terapia cu ibutilid sau flecainid i.v. este de obicei eficient
i poate fi luat n considerare, dar experiena pentru
aceste medicamente n timpul sarcinii este foarte limi-

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

tat193. Deoarece experiena pentru conversia farmacologic a FA n timpul sarcinii cu propafenon i.v. i cu
noul antiaritmic de clasa III, vernacalant, este foarte limitat sau nu exist, aceste medicamente pot fi utilizate
numai n cazul n care toate celelalte msuri de cardioversie au euat. Amiodarona nu este recomandat din
cauza efectelor sale fetotoxice, cu excepia cazului n
care toate celelalte opiuni eueaz.
Cardioversia flutterului i fibrilaiei atriale, indiferent dac se efectueaz electric sau medicamentos,
necesit terapie anticoagulant anterioar i/sau examinare ecocardiografic transesofagian pentru excluderea trombilor atriali stngi182. Anticoagularea (warfarin, nlocuit cu HNF sau HGMM n primul i ultimul
trimestru) este considerat obligatorie pentru cel puin
3 sptmni anterior de cardioversia electiv a FA sau a
flutterului atrial cu debut de 48 de ore sau mai mult, sau
n cazul n care durata FA este necunoscut182, i trebuie
s fie continuat cel puin 4 sptmni dup efectuarea
cardioversiei datorit riscului de trombo-embolism datorat stunningului atrial.
Pentru pacienii cu FA cu debut <48 de ore i fr factori de risc tromboembolici, heparina i.v. sau HGMM
n doze adaptate la greutate pot fi utilizate pericardioversie, fr a fi necesar anticoagularea oral dup
cardioversie. Indicaiile pentru terapia profilactic
antiaritmic i anticoagulant sunt legate de prezena
simptomelor i a factorilor de risc trombo-embolici182.
La pacienii cu factori de risc pentru accidente vasculare cerebrale sau pentru recurena FA, tratamentul
antitrombotic trebuie continuat pe tot parcursul vieii,
indiferent dac aparent se menine ritmul sinusal dup
cardioversie182.
Terapia anticoagulant n fibrilaia atrial
Riscul accidentelor trombo-embolice n FA depinde
de prezena factorilor de risc. Pacienii fr boal cardiac structural sau fr factori de risc (episod unic
de fibrilaie atrial) au cel mai mic risc de evenimente
tromboembolice i nu necesit tratament anticoagulant
sau antiagregant plachetar n afara sau n timpul sarcinii (nu sunt studii disponibile n timpul sarcinii). Gradul riscului trombo-embolic n FA non-valvular este
evaluat cu ajutorul criteriilor CHADS2182 i a scorului
CHA2DS2VASC142 la pacientele non-gravide. n aceste cazuri, un beneficiu al terapiei anticoagulante orale
este documentat atunci cnd riscul tromboembolic este
4.0 evenimente pe 100 de ani-pacient (se coreleaz cu
scorul CHADS2 2, sau dou puncte de risc cu scorul CHA2DS2VASC). Prin urmare, i la gravidele cu

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

risc ridicat este recomandat profilaxia evenimentelor


trombo-embolice. Alegerea terapiei anticoagulante se
face n funcie de stadiul sarcinii. Antagonitii vitaminei K sunt recomandai, n cele mai multe cazuri din al
doilea trimestru pn cu o lun nainte de natere142. n
primul trimestru i n ultima lun de sarcin se recomand administrarea subcutanat de doze terapeutice
de HGMM ajustate n funcie de greutate. Noii antagonitii orali ai trombinei, cum ar fi dabigatranul au artat
fetotoxicitate la doze mari i nu ar trebui utilizai. Terapia antiagregant plachetar, unic sau dual (clopidogrel i aspirin) nu a fost la fel de eficient ca warfarina
la pacienii cu FA care prezint risc ridicat142,194.
Studiile efectuate la paciente n vrst, non- gravide,
au artat c administarea de HGMM este eficient i
poate fi utilizat dac este posibil monitorizarea adecvat. Administrarea subcutanat a dozelor terapeutice
ajustate n funcie de greutate este recomandat n primul trimestru i n ultima lun de sarcin.
Controlul frecvenei cardiace
Ar trebui luat n considerare controlul frecvenei
ventriculare cu ajutorul medicamentelor ce acioneaz
la nivelul nodului AV, precum digoxinul, beta-blocantele i antagonitii non-dihidropiridinici ai canalelor de
calciu (verapamil, diltiazem)182. Pentru controlul frecvenei cardiace n FA, betablocantele sunt recomandate ca medicamente de prim alegere. Digoxinul poate
fi, de asemenea, utilizat, dar este mai puin eficace n
timpul efortului intens195. Msurarea digoxinmiei este
nesigur n timpul sarcinii din cauza interferenelor
dogoxinului cu componente serice imunoreactive196.
Verapamilul ar trebui s fie medicamentul de a doua
alegere.
Terapia antiaritmic profilactic (sotalol, flecainid
sau propafenon) poate fi luat n considerare n cazul
simptomatologiei severe n ciuda medicaiei de control a frecvenei cardiace182. Flecainida i propafenona
ar trebui combinate cu ageni blocani ai nodului AV.
Dronedarona, un nou medicament antiaritmic, nu ar
trebui utilizat n timpul sarcinii.
8.2.3 Tahicardia ventricular
Aritmiile ventriculare amenintoare de via n
timpul sarcinii sunt rare. Ar trebui luat ntotdeauna n
considerare existena afeciunilor aritmogene ereditare
n la nivelul unui istoric familial pozitiv i diagnosticate cu ajutorul unor teste specifice n timpul sau dup
sarcin61.
La pacienii sntoi, tahicardia idiopatic din tractul de ejecie al ventriculului drept este cea mai frecven

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t form i trebuie tratat conform ghidurilor utiliznd


profilactic, fie verapamil, fie un beta-blocant, dac se
asociaz cu simptomatologie sever sau cu instabilitate hemodinamic61,197. Ablaia prin cateter a tahicardiei
idipatice din tractul de ejecie VD poate fi luat n considerare dac se asociaz cu instabilitate hemodinamic i dac tratamentul medicamentos eueaz.
TV asociat cu boli cardiace structurale prezint un
risc crescut de moarte subit cardiac pentru mam198.
CMPP trebuie ntotdeauna exclus la femeile cu tahicardie ventricular debutat n timpul ultimelor 6 sptmni de sarcin sau n perioada timpurie post-partum.
Pentru tratamentul TV cu instabilitate hemodinamic, se recomand cardioversie imediat, care se pare
c este sigur n orice stadiu al sarcinii. Restaurarea n
timp util a ritmului sinusal este de dorit, chiar dac TV
este bine tolerat, i se poate realiza cu ajutorul medicamentelor antiaritmice sau, n cazuri selecionate, prin
pacing overdrive. La femeile cu TV susinut fr QT
lung, stabile hemodinamic, administrarea i.v. de sotalol
poate remite tahicardia. La pacientele cu TV monomorf stabil, procainamida i.v., dei nu este disponibil n multe ri, poate fi luat n considerare. Administrarea de amiodaron i.v. ar trebui luat n considerare
la pacientele cu TV susinut monomorf, instabile hemodinamic, care sunt refractare la conversia electric,
sau cu recurene n ciuda altor medicaii. Amiodarona
i.v. nu este terapia ideal pentru conversia precoce a TV
monomorfe stabile. Monitorizarea atent a tensiunii
arteriale este recomandat n prezena disfunciei VS.
Tratamentul profilactic cu un agent beta-blocant
cardioselectiv, cum ar fi metoprololul, poate fi eficace.
Sotalolul sau antiaritmicele de clas IC pot fi administrate n absena unei boli cardiace structurale dac
beta-blocantele sunt ineficiente. Amiodarona i/sau
implantarea de ICD ar trebui luate n considerare de
asemenea n timpul sarcinii n caz de TV rezistente la
tratament pentru protecia vieii mamei61,199.
La femeile cu sindrom de QT lung congenital, riscul
de stop cardiac este mai mare n timpul perioadei postpartum fa de riscul de dinaintea sau din timpul sarcinii200. Beta-blocantele au un beneficiu major n perioada post-partum, dar sunt, de asemenea, recomandate i
n timpul sarcinii.
8.3 Terapia intervenional: ablaia pe cateter
Ablaia pe cateter poate fi necesar n caz de tahicardii refractare la terapia medicamentoas i prost tolerate. Din cauza expunerii crescute la radiaii, ablaia ar
trebui amnat dac este posibil n trimestrul al doilea

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i ar trebui realizat ntr-un centru cu experien n


efectuarea ablaiilor, cu protecie abdominal adecvat
i utilizarea maximal a sistemelor de mapping echoi electro-anatomic. Au fost calculate doza de radiaii
fetal i riscul procedurilor de ablaie prin cateter n
timpul sarcinii25 (vezi Seciunea 2.5).
8.4 Defibrilatorul cardiac implantabil
Prezena unui ICD nu contraindic prin el nsui o
sarcin viitoare. Tratamentul cu ICD ar trebui luat n
considerare n timpul sarcinii pentru protecia vieii
mamei61,199. n general, dac sarcina este planificat,
implantarea unui ICD ar trebui avut n vedere la pacientele cu risc nalt de moarte subit199.
8.5 Bradiaritmiile
Bradiaritmiile i tulburrile de conducere sunt rare
n timpul sarcinii. Bradiaritmiile asimptomatice pot
deveni simptomatice ca urmare a necesitii unei frecvene cardiace i a unui debit cardiac mai crescute la
pacientele cu boli cardiace structurale201. Cu toate acestea, de obicei, bradiaritmiile au un prognostic favorabil
n lipsa unei boli cardiace de baz.
8.5.1 Disfuncia de nod sinusal
Bradicardia sinusal poate aprea din cauza scderii reflexe a frecvenei cardiace (manevr Valsalva) n
timpul naterii. Cazurile rare de bradicardie sinusal
au fost atribuite sindromului hipotensiv de decubit din
sarcin, cauzat de compresia venei cave inferioare de
ctre uter, ce oprete ntoarcerea venoas i produce ncetinirea paradoxal a nodului sinusal. n cazurile rare
n care apare bradicardia simptomatic, este necesar
schimbarea poziiei mamei n decubit lateral stng.
Pentru simptomele persistente, poate fi necesar implantarea unui stimulator cardiac temporar.
8.5.2 Blocurile atrio-ventriculare
Blocul AV de grad I poate fi ntlnit n timpul sarcinii n absena unei boli cardiace subiacente. Locul de
ntrziere a conducerii AV, este situat, de obicei, deasupra fasciculului Hiss i nu progreseaz spre bloc AV
complet. Blocul AV de grad II apare rar i este de obicei
asociat cu boli cardiace structurale sau cu terapie medicamentoas. n majoritatea cazurilor sunt blocuri AV
de gradul II tip I Wenckebach, neasociate cu bradicardie simptomatic. La pacienii cu boli cardiace congenitale, blocul AV de gradul II apare cel mai frecvent n
cazurile cu tetralogie Fallot reparat chirurgical i mai
puin frecvent dup repararea DSV.
Blocul AV complet dobndit, cel mai adesea ntlnit
n bolile cardiace congenitale dup intervenia chirurgical de corectare, este rar n timpul sarcinii. 30% din

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

blocurile AV congenitale rmn nedescoperite pn la


vrsta adult i pot fi diagnosticate n cursul sarcinii201.
Blocurile AV complete congenitale izolate au un prognostic favorabil n timpul sarcinii, mai ales n cazul n
care ritmul de scpare prezint complex QRS ngust.
Stimularea cardiac n timpul sarcinii nu este necesar
de obicei. Naterea pe cale vaginal nu prezint riscuri
suplimentare dac mama are bloc AV complet congenital, cu excepia cazului n care este contraindicat din
motive obstetricale.
8.5.3 Stimularea cardiac n timpul sarcinii
Pacingul temporar n timpul naterii este recomandat la paciente selectate cu bloc AV complet i simptomatologie prezent, din cauza riscului de bradicardie
i sincop.
Riscurile implantrii unui cardiostimulator permanent (de preferat unicameral) sunt n general sczute.
Implantarea poate fi efectuat n condiii de siguran,
n special dac ftul are vrsta gestaional de peste opt
sptmni. Ghidarea ecografic poate fi util pentru
implantare202.
8.6 Recomandri pentru managementul aritmiilor
Tabelul 16. Recomandri pentru managementul aritmiilor
Recomandri
Clasa
Managementul Tahicardiei Supraventriculare (TSV)
Pentru conversia acut a TSV paroxistic sunt recomandate manevrele
I
vagale urmate de administrarea adenozinei i.v.
Cardioversia electric imediat este recomandat pentru tratamentul acut
I
al oricrei tahicardii cu instabilitate hemodinamic.
Pentru managementul pe termen lung al TSV sunt recomandate digoxinulc
I
sau metoprololul/propranololulc,d.
Pentru conversia acut a TSV paroxistic, metoprololul i.v. sau propranoloIIa
lul ar trebui luate n considerare.
Pentru managementul pe termen lung al TSV sotalolule sau flecainidaf
oral ar trebui luate n considerare cnd terapia cu digoxin sau -blocante
IIa
nu d rezultate.
Pentru conversia acut a TSV paroxistic verapamilul i.v. poate fi luat n
IIb
considerare.
Pentru managementul pe termen lung al TSV, propafenona oralf sau
IIb
procainamida pot fi folosite ca ultim opiune dac ali ageni terapeutici
nu au avut efect i naintea folosirii amiodaroneie.
Pentru managementul pe termen lung al TSV, verapamilul oral poate fi
folosit pentru controlul frecvenei dac ali blocani ai nodului AV nu au
IIb
avut efect.
Atenololuld nu ar trebui folosit pentru nicio aritmie.
III
Managementul Tahicardiei Ventriculare (TV)
Implantarea de ICD, dac exist indicaie clinic, este recomandat
anterior sarcinii dar, este de asemenea recomandat n timpul sarcinii
I
oricnd exist indicaie.
Pentru managementul pe termen lung al sindromului de QT lung congenital, agenii -blocani sunt recomandai n timpul sarcinii i de asemenea
I
postpartum cnd au un efect benefic major.
Pentru managementul pe termen lung al TV susinute idiopatice este recoI
mandat tratamentul oral cu metoprololc,d, propranololc,d sau verapamilc,f.
Se recomand cardioversia electric imediat a TV susinute instabile i
I
stabile.

Nivelb
C
C
C
C
C
C
C

C
C

C
C
C

ESC Guidelines on the management of


cardiovascular diseases during pregnancy
Pentru conversia acut a TV susinut, stabil hemodinamic i monomorf
ar trebui luat n considerare administrarea de sotalole sau procainamid
i.v.
Implantul de cardiostimulatoare permanente sau ICD (preferabil unicamerale) ar trebui luat n considerare sub ghidaj ecocardiografic, mai ales
dac vrsta de gestaie este > 8 sptmni.
Pentru conversia acut a TV susinut, monomorf instabil hemodinamic,
refractar la cardioversia electric sau care nu rspunde la alte medicamente, ar trebui luat n considerare administrarea de amiodaron i.v.e
Pentru managementul pe termen lung al TV susinute idiopatice, n cazul
n care alte medicamente eueaz ar trebui luat n considerare tratamentul oral cu sotalole, flecainidf sau propafenonf.
Ablaia prin cateter poate fi luat n considerare n cazul tahicardiilor
refractare la tratament sau slab tolerate.

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IIa

IIa

IIa

IIa

IIb

Pentru informaii referitoare la dozajul medicamentelor va rugm sa consultai cele trei ghiduri publicate referitoare la managementul pacienilor cu fibrilaie atrial, aritmii supraventriculare i aritmii ventriculare61,142,192.
a
Clasa de recomandare
b
Nivel de eviden
c
Medicamentele care blocheaz nodul AV nu trebuie folosite la pacienii cu sindrom de pre-excitaie pe ECG-ul
de repaus.
d
-blocantele trebuie folosite cu precauie n primul trimestru; vezi Seciunea 11.
e
Antiaritmicele de clasa a III-a nu trebuie folosite n cazurile de QTc alungit.
f
n cazul anumitor tahicardii atriale luai n considerare agenii blocani ai nodului AV n asociere cu flecainida
i propafenona.
AV = atroventricular; ECG = electrogardiogram; ICD = defibrilator cardiac implantabil; i.v. = intravenos; TSV
= tahicardie supraventricular; TV = tahicardie ventricular.

9. AFECIUNILE HIPERTENSIVE
Tulburrile hipertensive din timpul sarcinii rmn o
cauz major de morbiditate i mortalitate matern,
fetal i neonatal n rile dezvoltate i n cele n curs
de dezvoltare. Aceste femei au un risc mai mare pentru
apariia de complicaii severe, cum ar fi abruptio placentae, accidente cerebrovasculare, insuficien de organ i coagulare intravascular diseminat. Ftul este
la risc de cretere intrauterin ntrziat, prematuritate
i moarte intrauterin. Hipertensiunea arterial este
cea mai frecvent problem medical n timpul sarcinii, complicnd pn la 15% din sarcini i reprezentnd
aproximativ un sfert din toate internrile prenatale203.
9.1.Diagnostic i evaluarea riscului
Valori crescute ale TA trebuie confirmate la dou
evaluri diferite204, folosind tensiomentrul cu mercur
(Korotkoff V pentru determinarea TA distolice) sau
cu dispozitiv aneroid, cu pacientul n poziie eznd.
Msurarea valorilor tensionale n decubit lateral stng
este o alternativ rezonabil. Trebuie folosite doar dispozitive de msurare i aparate de msurare a TA n
ambulator valide (vezi: www.dableducational.org). Hipertensiunea n sarcin, diagnosticat prin monitorizare ambulatorie a TA este superioar n prezicerea evoluiei fa de cea diagnosticat n cabinet205,206.
Analizele de laborator uzuale recomandate pentru
monitorizarea pacientelor gravide cu hipertensiune
arterial includ: sumar urin, hemoleucogram, hematocrit, enzime hepatice, creatinin seric i acid uric.

Proteinuria trebuie msurat n urina pe 24 de ore


(pentru valori >2 g/zi se indic monitorizare atent;
pentru valori >3 g/zi ar trebui luat n considerare naterea). Ecografia glandelor suprarenale i determinarea
metanefrinelor urinare i a normetanefrinei pot fi luate n considerare la femeile gravide cu HTA, pentru a
exclude feocromocitomul, care poate fi asimptomatic,
i dac nu este diagnosticat nainte de natere poate fi
fatal207. Ecografia Doppler a arterelor uterine, efectuat
n timpul celui de-al doilea trimestru de sarcin (>16
sptmni), este util pentru detectarea hipoperfuziei
utero-placentare care este asociat cu un risc crescut de
pre-eclampsie i ntrziere a creterii intrauterine, att
la femeile cu risc crescut ct i la cele cu risc sczut208.
9.2. Definiia i clasificarea hipertensiunii n
sarcin
Definiia hipetensiunii n sarcin se bazeaz pe
msurarea valorilor tensionale (TAS 140mmHg
sau TAD 90 mmHg)209,210 i se disting: HTA uoar
(140- 159/90-109 mmHg) sau HTA sever (160/ 110
mmHg), n contrast cu clasele utilizate de Societatea
European de Hipertensiune (ESH)/ ESC210 sau de alte
societi.
Hipertensiunea n sarcin nu este o entitate unic, ci
cuprinde212:
hipertensiunea preexistent;
hipertensiunea de sarcin;
hipertensiunea preexistent cu hipertensiuna de
sarcin suprapus i cu proteinurie;
hipertensiunea neclasificat prenatal.
9.2.1. Hipertensiunea preexistent
Hiperensiunea preexistent apare la 1-5% din pacientele gravide i este definit ca TA 140/90 mmHg
descoperit naintea sarcinii sau n primele 20 de sptmni de gestaie. Hipertensiunea persist de obicei >42
de zile post-partum. Poate fi asociat cu proteinuria.
Femeile hipertensive nediagnosticate pot prea normotensive la nceputul sarcinii din cauza scderii fiziologice a valorilor tensionale n primul trimestru. Acest
lucru poate masca hipertensiunea preexistent, iar valorile tensionale crescute descoperite trziu n timpul
sarcinii, pot fi interpretate drept HTA gestaional.
9.2.2. Hipertensiunea de sarcin
Hipertensiunea gestaional este hipertensiunea
indus de sarcin, cu sau fr proteinurie, i complic 6-7% din sarcini. Cnd este asociat cu proteinurie
semnificativ (0,3 g/zi n urina pe 24 ore sau 30 mg/
mmol creatinin urinar n urina emis spontan) este
cunoscut ca pre-eclampsie.

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Hipertensiunea de sarcin apare dup sptmna 20


de gestaie i dispare n cele mai multe cazuri n primele
42 de zile post-partum. Este caracterizat prin hipoperfuzie organic.
Pre-eclampsia este un sindrom specific n sarcin ce
apare n a doua parte a sarcinii, definit prin valori tensionale crescute aprute de novo, nsoite de proteinurie
semnificativ >0,3 g/24h. Este o afeciune sistemic, nsoit de manifestri materne i fetale. Edemele nu mai
sunt considerate criteriu de diagnostic, deoarece apar n
pn la 60% din sarcinile normale. n total, pre-ecalmpsia complic 5-7% din sarcini213, dar poate aprea la
pn la 25 % din femeile cu hipertensiune preexistent.
Pre-eclampsia apare mai frecvent n timpul primei sarcini, n sarcina multipl, mola hidatiform sau diabet
zaharat. Este asociat cu insuficien placentar, reflectat deseori n retard de cretere fetal. n plus, preeclampsia este una dintre cele mai frecvente cauze de
prematuritate, fiind responsabil pentru 25% din copiii
cu greutate foarte mic la natere (<1500 g)214.
Simptomele i semnele de pre-eclampsie sever includ:
durere n hipocondrul drept/epigastru din cauza
edemului hepatic hemoragie hepatic;
cefalee tulburri de vedere (edem cerebral);
tulburri de vedere cauzate de afectarea lobilor
occipitali;
hiperreflexie clonus;
sindromul HELLP: hemoliz, valori crescute ale
enzimelor hepatice, trompocitopenie.
Managementul pre-eclampsiei se bazeaz n primul
rnd pe recunoaterea afeciunii i n final pe eliminarea placentei, care este soluia curativ.
Avnd n vedere c proteinuria poate fi o manifestare
tardiv a pre-eclampsiei, aceasta ar trebui suspicionat
cnd HTA de novo este asociat cu cefalee, tulburri de
vedere, dureri abdominale sau analize de laborator modificate: specific trombocitopenie i valori crescute ale
enzimelor hepatice; se recomand tratamentul acestor
paciente ca i cum ar avea pre-eclampsie.
9.2.3. Hipertensiunea preexistent cu
hipertensiune de sarcin suprapus i cu
proteinurie
Cnd hipertensiunea preexistent este asociat cu
creterea valorilor tensionale i cu proteinurie 3g/zi
n urina/24h dup cea de-a 20-a sptmn de gestaie este clasificat drept hipertensiune preexistent cu
hipertensiune de sarcin suprapus i cu proteinurie.
9.2.4. Hipertensiunea neclasificat prenatal
Cnd TA este msurat pentru prima dat dup
cea de-a 20-a sptmn de gestaie i hipertensiunea

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

(cu sau fr manifestri sistemice) este diagnosticat,


se numete hipertensiune neclasificat prenatal. Este
necesar reevaluare la/dup 42 de sptmni post-partum.
9.3. Managementul hipertensiunii n sarcin
Majoritatea femeilor cu hipertensiune preexistent
sarcinii au HTA uoar pn la moderat (140-160/90109 mmHg) i au un risc sczut de complicaii cardiovasculare n timpul sarcinii. Femeile cu HTA esenial
i cu funcie renal normal au un prognostic bun att
pentru mam ct i pentru ft i sunt candidate pentru tratament non-farmacologic, pentru c nu exist
dovezi c tratamentul farmacologic ar mbunti prognosticul neonatal. Unele femei cu HTA preexistent
sarcinii pot chiar opri administrarea medicaiei antihipertensive n prima parte a sarcinii din cauza scderii
fiziologice a TA n aceast perioad. Cu toate acestea,
este necesar o monitorizare atent i reluarea tratamentului la nevoie.
Singurul studiu despre tratamentul hipertensiunii
n timpul sarcinii, cu o urmrire adecvat a copiilor
(7,5 ani) a fost efectuat n urm cu >30 de ani pentru
-metildopa215,216.
9.4. Tratamentul non-farmacologic i prevenia
hipertensiunii n sarcin
Tratamentul non-farmacologic ar trebui luat n considerare n cazul femeilor nsrcinate cu TAS 140-150
mmHg i/sau TAD 90-99 mmHg. O spitalizare de scurt durat poate fi necesar pentru a confirma diagnosticul i pentru a exclude hipertensiunea sever de sarcin
(pre-eclampsia), caz n care singurul tratament curativ
este reprezentat de declanarea naterii. Managementul
depinde de valorile tensionale, de vrsta gestaional
i de prezena factorilor de risc materni i fetali asociai, i include o monitorizare atent, limitarea activitilor i repaus n decubit lateral stng. Se recomand
un regim alimentar normal fr restricie de sare, n
special n preajma naterii deoarece restricia de sare
poate induce hipovolemie. Suplimentarea dietei cu cel
puin 1 g de calciu/zi n timpul sarcinii a redus riscul de
pre-eclampsie cu 50%, fr un risc adiional. Efectul a
fost mai mare la femeile cu risc nalt217. Cu toate acestea, dovezile legate de administrarea de calciu pentru
prevenia afeciunilor hipertensive sunt contradictorii.
Suplimentarea dietei cu ulei de pete218, vitamine i suplimente nutritive nu au niciun rol n prevenia hipertensiunii. Dozele mici de aspirin (75-100 mg/zi) sunt
administrate profilactic la femeile cu antecedente de
pre-eclampsie precoce (<28 de sptmni)219. Ar trebui administrat seara la culcare ncepnd din perioa

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

da preconcepional sau din momentul diagnosticrii


sarcinii, dar nainte de sptmna 16 de gestaie i ar
trebui continuat pn la natere. Scderea n greutate nu este recomandat n timpul sarcinii la pacientele obeze, deoarece poate determina o greutate mic la
natere i o cretere ulterioar ncetinit a copilului. Cu
toate acestea, avnd n vedere c obezitatea mamei poate determina un prognostic negativ att pentru mam
ct i pentru ft, au fost stabilite ghiduri cu limitele de
cretere n greutate pe parcursul sarcinii. Pentru femeile nsrcinate cu IMC normal (IMC <25 kg/m2) creterea n greutate recomandat este de 11,2- 15,9 kg; pentru cele supraponderale (IMC 25-29,9 kg/m2) creterea
n greutate recomandat este de 6,8- 11,2 kg; i pentru
femeile obeze (IMC 30 kg/m2) creterea n greutate
recomandat este <6,8 kg220.
9.5. Managementul farmacologic al hipertensiunii
n sarcin
Tratamentul medicamentos al hipertensiunii severe
n sarcin este necesar i benefic, dar tratamentul formelor mai puin severe de HTA este controversat. Cu
toate c scderea valorilor tensionale poate fi benefic
pentru mam, aceasta poate determina hipoperfuzie
utero-placentar, punnd astfel n pericol dezvoltarea
fetal.
Femeile cu HTA preexistent i pot continua schema terapeutic, cu excepia IECA, BRA i inhibitori
direci ai reninei, care sunt strict contraindicate din
cauza toxicitii fetale severe n special n al doilea i
al treilea trimestru (Tabelul 21). Dac totui sunt luate
n primul trimestru de sarcin, este necesar i de obicei suficient nlocuirea acestora i monitorizarea atent
prin ecografie inclusiv a ftului.
-Metildopa este medicamentul de elecie pentru
tratamentul pe termen lung al hipertensiunii n sarcin216. Labetalolul (/-blocant) are o eficacitate comparabil cu -metildopa. Dac HTA este sever acesta
se poate administra i.v. Metropololul este de asemenea
recomandat221. Blocantele canalelor de calciu, cum ar fi
nifedipina (oral) sau isradipina i.v. sunt medicamentele
de linia a doua n tratamentul hipertensiunii222. Aceste
medicamente pot fi administrate n urgenele hipertensive sau n pre-eclampsie. Potenialul sinergism al
acestora cu sulfatul de magneziu poate induce hipotensiune matern i hipoxie fetal. Urapidilul poate fi
de asemenea folosit n urgenele hipertensive. Sulfatul
de magneziu i.v. este medicamentul de elecie n tratamentul convulsiilor i prevenia eclampsiei. Diureticele
trebuie evitate n tratamentul hipertensiunii deoarece

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pot determina hipoperfuzie placentar. Sunt contraindicate n pre-eclampsie.


9.5.1. Tratamentul formelor uoare i moderate
de hipertensiune
Beneficiile i riscurile terapiei antihipertensive n
formele uoare i moderate (TAS 140-160mmHg i
TAD 90-109mmHg) sunt controversate. Ghidurile actuale ESH/ESC210 recomand ca valori int ale tratamentului antihipertensiv TAS de 140 mmHg sau TAD
de 90 mmHg, la femeile cu:
hipertensiune gestaional (cu sau fr proteinurie);
hipertensiune preexistent asociat cu hipertensiunea gestaional;
hipertensiune cu afectare subclinic de organ
sau cu simptome n orice moment al sarcinii.
n orice alte circumstane, valorile int ale TAS i
TAD recomandate de ghidurile ESH/ESC sunt 150
mmHg, respectiv 95 mmHg. Recomandm urmarea
acestor ghiduri.
9.5.2. Tratamentul formelor severe de
hipertensiune
Nu exist un acord asupra definiiei hipertensiunii
severe, cu valori variind ntre 160-180 mmHg />110
mmHg. Acest Grup de Lucru recomand considerarea
valorilor TAS 170 mmHg sau TAD 110 mmHg la
femeile nsrcinate a fi o urgen i indicaie de spitalizare. Selectarea antihipertensivelor i modul de administrare depinde de durata pn la natere. Tratamentul farmacologic cu labetalol i.v. sau metildopa po sau
nifedipina po ar trebui iniiate. Hidralazina i.v. nu mai
este indicat din cauza efectelor adverse perinatale mai
importante dect ale altor medicamente. Medicamentul de elecie n tratamentul crizei hipertensive este nitroprusiatul de sodiu n perfuzie i.v. cu 0,25-5 g/kg/
min. Tratamentul prelungit cu nitroprusiat de sodiu
este asociat cu un risc crescut de intoxicaie fetal cu
cianuri din cauz c nitroprusiatul este metabolizat n
thiocianat i este excretat prin urin223. Tratamentul de
elecie n pre-eclampsia asociat cu edem pulmonar
este nitroglicerina administrat n perfuzie i.v. cu 5 g/
min, cu cretere treptat la fiecare 3-5 min. pn la o
doz maxim de 100 g/min.
Naterea
Inducerea naterii este indicat n hipertensiunea de
sarcin asociat cu proteinurie cu manifestri adverse
precum tulburri de vedere, anomalii de coagulare sau
suferin fetal.

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Alptarea
Alptarea nu crete TA. Bromocriptina, care este utilizat pentru suprimarea lactaiei poate induce HTA224.
Toi agenii antihipertensivi se excret n lapte. Majoritatea medicamentelor antihipertensive se gsesc n
concentraie foarte sczut n laptele matern, exceptnd propanololul i nifedipina, ale cror concentraii
sunt similare cu cele plasmatice.
9.6 Prognosticul postnatal
9.6.1 Valorile tensionale postpartum
Postpartum, HTA este comun. Valorile tensionale
cresc de obicei pe parcursul primelor 5 zile postpartum. Femeile hipertensive n timpul sarcinii pot fi normotensive dup natere, dar redevin hipertensive pe
parcursul primei sptmni postnatale. Metildopa ar
trebui evitat postpartum din cauza riscului de depresie postnatal.
9.6.2 Riscul de reapariie a hipertensiunii la
sarcinile ulterioare
Femeile ce au dezvoltat hipertensiune pe parcursul
primei sarcini au un risc crescut de HTA la o sarcin
ulterioar225. Cu ct instalarea HTA n prima sarcin
este mai precoce, cu att riscul de recuren este mai
mare226.
9.6.3 Consecine cardiovasculare pe termen lung
ale hipertensiunii induse de sarcin
Femeile care dezvolt hipertensiune gestaional sau
pre-eclampsie au un risc crescut de hipertensiune i de
accident vascular cerebral mai trziu ca adult227, precum i de boal cardiac ischemic228,229. Riscul relativ
de a dezvolta boala cardiac ischemic dup pre-eclampsie este de dou ori mai crescut fa de femeile normotensive pe parcursul sarcinii i riscul de a dezvolta HTA
ulterior este de aproape patru ori mai mare229. Femeile
cu pre-eclampsie precoce (natere nainte de 32 de sptmni de gestaie), natere de ft mort sau retard de
cretere fetal sunt considerate cu risc crescut229. Factorii de risc naintea sarcinii pentru dezvoltarea HTA
sunt: vrsta naintat a mamei, valori tensionale crescute, dislipidemia, obezitatea, antecedente heredocolaterale cardiovasculare, sindrom antifosfolipidic i scderea toleranei la glucoz. Tulburrile hipertensive n
sarcin sunt recunoscute drept un factor de risc important pentru bolile cardiovasculare la femei230. Prin urmare, modificrile stilului de via, controlul regulat al
TA i al factorilor metabolici dup natere, sunt recomandate pentru a evita complicaiile ce pot aprea la
sarcinile ulterioare i pentru a reduce riscul cardiovascular matern.

9.7 Recomandri pentru managementul


hipertensiunii
Tabelul 16. Recomandri pentru managementul hipertensiunii
Recomandri
Clas
Este recomandat tratamentul nefarmacologic al gravidelor cu TAS 140-150
I
mmHg sau TAD 90-99 mmHg.
n cazul femeilor cu HTA gestaional sau HTA preexistent sarcinii cu HTA
gestaional suprapus sau cu hipertensiune i afectare subclinic a organelor
int sau cu simptome aprute n orice moment pe perioada sarcinii, iniierea
I
tratamentului farmacologic se recomand la valori tensionale de 140/90
mmHg. n orice alte circumstane, iniierea tratamentului farmacologic se
recomand dac TAS 150 mmHg sau TAD 95 mmHg.
La o gravid,TAS 170 mmHg sau TAD 110 mmHg reprezint urgene i se
I
recomand spitalizarea.
Provocarea naterii este recomandat n HTA gestaional cu proteinurie care
I
evolueaz cu tulburri de vedere, anomalii de coagulare sau suferin fetal.
n preeclampsia asociat cu edem pulmonar acut, se recomand nitroglicerina
I
n perfuzie i.v.
n hipertensiunea sever se recomand administrarea intravenoas de
I
labetalol sau administrarea oral de metildopa sau nifedipin.
Femeile cu HTA preexistent sarcinii ar trebui s continue tratamentul cu
medicaia curent exceptnd IECA, BRA i inhibitorii direci ai reninei, sub
IIa
atenta monitorizare a TA.

Nivel
C

C
C
C
C
C

Clasa de recomandare
Nivel de eviden
IECA = inhibitori ai enzimei de conversie a angiotensinei; BRA = blocant al receptorului de angiotensin; TA =
tensiune arterial; TAS = tensiunea arterial sistolic; TAD = tensiunea arterial diastolic.
a
b

10. TROMBOEMBOLISMUL VENOS N TIMPUL SARCINII I POSTPARTUM


10.1. Epidemiologie i riscul matern
Sarcina i perioada postpartum sunt asociate cu o
inciden crescut de tromboembolism venos (TEV),
ce apare n aproximativ 0,05-0,20% din toate sarcinile231-235. TEV, cuprinznd embolismul pulmonar i
tromboza venoas profund (TVP) reprezint o cauz important de morbiditate i mortalitate n sarcin.
Embolismul pulmonar este cauza cea mai frecvent de
deces matern n Marea Britanie, cu o inciden de 1,56
decese la 100 000 de sarcini, respectiv cea de-a doua cauz de deces matern n celelalte regiuni9. Rata fatalitii
este 3,5%236. Riscul de TEV este mai mare imediat postpartum232, n special dup cezarian235 i revine la riscul
dinainte de sarcin dup 6 sptmni postpartum231,232.
10.2 Factorii de risc pentru tromboembolismul
venos asociat sarcinii i stratificarea riscului
Prezena factorilor de risc (vezi Tabelele 17 i 18)
contribuie la creterea riscului de TEV pe parcursul
sarcinii i postpartum. 79% din femeile decedate n
Marea Britanie din cauza embolismului pulmonar survenit prenatal au factori de risc identificai9,236. Cei mai
importani factori de risc pentru TEV n sarcin sunt
antecedentele de TVP neprovocat sau de embolism
pulmonar237 i trombofiliile (Tabelul 18). ntre 15-25%

ESC Guidelines on the management of


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din TEV sunt evenimente recurente. Jumtate dintre


femeile ce au dezvoltat un eveniment trombotic pe perioada sarcinii sufer fie de o tulburare trombofilic fie
au antecedente de TEV idiopatic.
Tabelul 17. Lista factorilor de risc pentru tromboembolismul venos,
modificat dup Royal College of Obstetrician and Gynaecologists238
Factori preexisteni
Antecedente de TEV recurenta
Antecedente de TEV neprovocat sau asociat cu estrogenib
Antecedente de TEV provocat
Istoric familial de TEV
Trombofilie cunoscutc
Comorbiditi, ex.: boli cardiace sau pulmonare, LES, cancer, afeciuni inflamatorii, sindrom nefritic,
anemie falciform, consumul de droguri i.v.
Vrsta >35 de ani
Obezitate, IMC >30 kg/m2 d
Numr de sarcini 3
Fumtoare
Vene varicoase mari
Factori de risc obstetricali
Pre-eclampsia
Deshidratare/ Disgravidia/Sindromul hiperstimulrii ovariene
Sarcini multiple sau terapie reproductiv asistat
Operaie cezarian de urgen
Operaie cezarian electiv
Natere prin aplicare de forceps mid-cavity sau rotaional
Travaliu prelungit (>24 de ore)
Hemoragie peripartum (>1l sau transfuzie)
Factori de risc tranzitorii
Infecie sistemic curent
Imobilizare
Intervenie chirurgical n sarcin sau <6 sptmni postpartum
Pacientele cu antecedente de TEV recurent (>1) sau cu b antecedente de TEV neprovocat sau asociat cu
estrogeni, aparin grupului cu risc nalt de TEV (vezi Tabelul 19).
c
Vezi Tabelul 18.
d
Obezitate bazat pe greutatea de dinaintea sarcinii.
Ex.: la o femeie nsrcinat cu istoric familial de TEV, vrsta >35 de ani i obezitate (IMC >30 kg/m2), numrul
total al factorilor de risc este de 3; Aceast pacient aparine grupului de risc intermediar i necesit profilaxia
corespunztoare TEV (vezi Tabelul 19).
IMC = indice de mas corporal; LES = lupus eritematos sistemic; TEV = tromboembolism venos.
a

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pentru TEV nainte de sarcin sau precoce n timpul


sarcinii. Tabelul 17 sugereaz o list pentru documentarea riscului238. Pe baza tipului i a numrului total de
factori de risc prezeni la fiecare pacient, se identific
trei grupe de risc (risc nalt, intermediar i sczut) conform crora se aplic msurile de prevenie (vezi Tabelul 19). Antecedentele de TEV recurent i de TEV
neprovocat sau asociat cu estrogeni sunt considerate
factori de risc nalt. Influena exact a altor factori de
risc individuali sau nsumarea a civa factori de risc
asupra riscului de TEV nu este cunsocut.
10. 3 Prevenia tromboembolismului venos
Studii prospective nerandomizate au artat c la
femeile cu factori de risc care nu au primit tratament
anticoagulant, rata recurenelor de TEV a variat de la
2,4% la 12,2%, n comparaie cu 0-2,4% la pacientele
care au primit terapie anticoagulant241.
HGMM a devenit medicaia de elecie pentru profilaxia i tratamentul TEV la femeia gravid242, determinnd o pierdere osoas mai puin important dect n
cazul utilizrii HNF, iar rata fracturilor osteoporotice
este mai sczut (0,04% din femeile gravide tratate cu
HGMM)242.
Doza de HGMM folosit pentru profilaxia TEV se
bazeaz pe greutatea corporal. Nu exist date pentru
a ghida dozele corespunztoare de HGMM pentru femeile gravide obeze sau pentru lehuze. S-a stabilit c
femeile cu greutate mai mare trebuie s primeasc doze
mai mari, fr ns a exista studii privind doza optim
necesar n funcie de greutatea pacientei. Pacientele cu
risc crescut de TEV (vezi Tabelul 19) ar trebui s primeasc o doz uzual profilactic de 0,5 UI/kg de enoxaparin sau 50 UI/kg de dalteparin de dou ori pe zi.
10.4 Managementul tromboembolismului venos
acut

Tabelul 18. Prevalena trombofiliei congenitale i riscul asociat de


tromboembolism venos pe parcursul sarcinii ntr-un grup de populaie
european, bazat pe Marik i Plante239
Factor de risc
Prevalen
Odds ratio
(%)
(interval de confiden)
Mutaia factorului V Leiden
Heterozigoi
2,0-7,0
8.32 (5,44; 12,70)
Homozigoi
0,2-0,5
34,40 (9,86; 120,05)
Mutaia protrombinei G20210A
Heterozigoi
2,0
6,80 (2,46; 18,77)
Homozigoi
Rar
28,36 (1,24; 559,29)
Deficit de antitrombin (activitate <80%)
<0,1-0,6
4,76 (2,15; 10,57)
Deficit de Protein C (activitate <75%)
0,2- 0,3
4,76 (2,15; 10,57)
Deficit de Protein S (activitate <65%)
<0,1-0,1
2,19 (1,48; 6,00)

Tablou clinic
Simptomele i semnele clinice de embolie pulmonar n timpul sarcinii sunt similare cu cele prezente
n afara sarcinii (dispnee, durere toracic, tahicardie,
hemoptizii i colaps). Evaluarea clinic n embolia pulmonar este mai dificil din cauza faptului c dispneea
i tahicardia pot fi prezente n mod normal n timpul
sarcinii.

De aceea, identificarea factorilor de risc la fiecare


pacient este important pentru aprecierea riscului i
alegerii strategiei de prevenie. Toate femeile trebuie
s dein o evaluare documentat a factorilor de risc

Diagnostic
Regulile de predicie clinic pentru aprecierea probabilitii pretest de TEV au fost validate pentru paciente n afara sarcinii, la fel ca i testatea D-dimerilor,

10.4.1 Embolia pulmonar

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ecografia cu compresie, angio-CT pulmonar i scintigrafia de ventilaie-perfuzie pentru diagnosticul emboliei pulmonare243. Acestea nu se aplic ns la femeia
gravid244. De asemenea, algoritmul de diagnostic pentru TEV, care este bine stabilit pentru populaia general, dar nu a fost validat la pacientele gravide. Acest
fapt complic recomandrile i urgenteaz necesitatea
efecturii unor studii prospective multicentrice. Un
indice ridicat de suspiciune este important pentru diagnosticarea la timp a TEV. Toate femeile gravide cu
semne i simptome sugestive pentru TEV. Toate femeile nsrcinate cu semne i simptome sugestive pentru
TEV, n special dispnee brusc instalat sau agravat, ar
trebui supuse testrii paraclinice ct mai rapide similar
cu femeile n afara sarcinii.
D-dimerii si compresia ecografic
Nivelul D-dimerilor prezint o cretere fiziologic
n fiecare trimestru de sarcin. ntr-un studiu, concentraia medie a D-dimerilor preconcepional a fost
0,43 (SD 0,46) mg/l i a crescut n primul, al doilea i
al treilea trimestru de sarcin la 0,58 mg/l (SD 0,36),
0,83 mg/l (SD 0,46) i respectiv 1,16 mg/l (SD 0,57),
indicnd o cretere relativ de 39% a concentraiilor
D-dimerilor pentru fiecare trimestru comparativ cu
precedentul245. Astfel, un test pozitiv pentru D-dimeri
avnd drept referin nivelul convenional al acestora
nu este n mod obligatoriu indicator pentru TEV, fiind
necesar stabilirea de noi valori de referin. Teste suplimentare obiective sunt necesare pentru confirmarea
diagnosticului.
Cu toate acestea, un test al D-dimerilor negativ este
util pentru a exclude TEV, dei exist cteva cazuri de

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

TEV cu D-dimeri normali246. Recomandarea de dozare


a D-dimerilor la toate femeile gravide cu suspiciune clinic de TEV este nc controversat243. Cu toate acestea,
ndemnul acestui Grup de Lucru este de a doza concentraia D-dimerilor la pacientele suspectate de embolie
pulmonar, urmat de ecografie cu compresie bilateral. Dac aceasta este normal n prezena D-dimerilor negativi, embolia pulmonar este puin probabil i
anticoagularea cu HGMM nu se justific.
La pacientele cu suspiciune de embolie pulmonar, D-dimeri pozitivi i ultrasonografia cu compresie
pozitiv, tratamentul anticoagulant este indicat. Dac
nivelul D-dimerilor este ridicat i ecografia de compresie este negativ la pacientele cu suspiciune de embolie
pulmonar, testele suplimentare sunt necesare. IRM-ul
nu implic expunerea la radiaii, nu este probabil duntoare pentru ft, i are o mare sensibilitate i specificitate pentru diagnosticul de tromboz venoas iliac.
Angiografia CT pulmonar ar trebui s fie efectuat
n cazul n care diagnosticul nu poate fi confirmat sau
exclus cu explorrile de mai sus. La aceste paciente se
prefer fa de scintigrafia pulmonar ventilaie-perfuzie pentru stabilirea diagnosticului de embolism pulmonar243; ambele sunt asociate cu expunerea ridicat la
radiaii a ftului, cu o doz mai mare de radiaii n cazul
scintigrafiei de ventilaie-perfuzie fa de angiografia
CT pulmonar (a se vedea Tabelul 3 din Seciunea 2).
Cu toate acestea, dozele de radiaii se situeaz sub limita considerat ca fiind periculoas pentru ft243,247.
Tratament
HGMM. HGMM a devenit, de asemenea, drogul de
elecie pentru tratamentul TEV n timpul sarcinii i

Tabelul 19. Grupurile de risc n funcie de factorii de risc, definiie i msuri de prevenie modificate n acord cu Royal College of Obstetricians and
Gynaecologists238
Grupurile de risc
Definiie n funcie de factorii de risc menionai n Tabelul 17
Msuri de prevenie n funcie de grupa de risc
Pacientele cu:
Pacientele cu risc nalt ar trebui s primeasc profilaxie prenatal cu HGMM, precum i post(i) Antecedente de TEV recurente (> 1)
partum pe o durat de 6 sptmni.
sau
(ii) TEV neprovocat/asociat cu estrogeni
Ciorapii elastici cu compresie gradat sunt de asemenea recomandai n timpul sarcinii i
Risc nalt
sau
post-partum.
(iii) un singur episod anterior de TEV + trombofilie sau antecedente familiale
Pacientele cu:
La pacientele cu risc intermediar, profilaxia antenatal cu HGMM ar trebui luat n considerare.
(i) 3 sau mai muli factori de risc n afara celor enumerai ca fiind de risc nalt
(ii) 2 sau mai muli factori de risc n afara celor enumerai ca fiind de risc nalt,
Profilaxia este recomandat dup natere timp de cel puin 7 zile sau mai mult dac persist
dac pacienta este internat n spital
> 3 factori de risc.
Risc intermediar
Ciorapii elastici cu compresie gradat ar trebui luai n considerare n timpul sarcinii i post
partum.
La pacientele cu risc sczut mobilizarea precoce i evitarea deshidratrii sunt recomandate.
Pacientele cu:
< 3 factori de risc.
Risc sczut
Au fost dezvoltate mai multe scoruri de risc pentru identificarea gradului de risc240, dar toate scorurile de risc, inclusiv cel de mai sus, au nevoie de validare prin studii prospective.
HGMM = heparin cu greutate molecular mic; TEV = tromboembolism venos.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

postnatal. Eficacitatea i sigurana diferitelor HGMM


a fost demonstrat ntr-o recenzie ce cuprinde 2777 de
femei gravide, tratate pentru embolie pulmonar sau
TVP. Riscul de TEV recurente n timpul tratamentului
cu HGMM a fost de 1,15%. Rata de sngerare major
observat a fost de 1,98%. Trombocitopenia indus de
heparin este semnificativ mai mic cu HGMM dect
cu heparina nefracionat, la fel ca i osteoporoza indus de heparin (0,04%)242. n suspiciunea clinic de
embolie pulmonar sau TVP, tratamentul cu HGMM
ar trebui administrat pn la excluderea diagnosticului
prin teste obiective.
Doze
Doza terapeutic recomandat este calculat n
funcie de greutatea corporal (ex.: enoxaparina 1 mg/
kg de dou ori pe zi, Dalteparina 100 UI/kg de dou ori
pe zi) cu o int a valorilor anti-Xa la 4-6 h de 0,6-1,2
IU/mL248.
Monitorizare
Necesitatea monitorizrii regulate a nivelului antiXa la pacienii cu TEV este nc controversat. Dei
monitorizarea este considerat necesar la pacientele
cu valve mecanice aflate sub terapie cu HGMM (a se
vedea Seciunea 5), acest lucru nu este la fel de bine stabilit pentru pacientele cu TEV. Avnd n vedere necesitatea de a crete dozele pe msur ce sarcina progreseaz pentru a menine nivelul terapeutic de anti-Xa153,154,
pare rezonabil a determina nivelul anti-Xa i la pacienta gravid cu TEV. Determinarea pare justificat n
special avnd n vedere faptul c embolismul pulmonar
a aprut i la femeile care au primit HGMM n doze de
profilactice236. Acest subiect necesit studii suplimentare. Un ghid simplu sugereaz ajustarea dozelor odat cu
creterea greutii n timpul sarcinii.
Heparina nefracionat (HNF)
HNF, de asemenea, nu traverseaz placenta, dar este
asociat cu apariia mai frecvent a trombocitopeniei, osteoporozei i a necesitii de doze mai frecvente
atunci cnd se administreaz subcutanat comparativ
cu HGMM. Este preferat n tratamentul pacienilor cu
insuficien renal i a celor la care este nevoie de anularea urgent a anticoagulrii cu protamin, precum i
n tratamentul acut al emboliilor pulmonare masive.
Doze
La pacienii cu embolie pulmonar acut cu compromitere hemodinamic, este recomandat adminis

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

trarea de HNF i.v. (bolus 80U/kg, urmat de perfuzie


continu i.v. cu 18 U/kg/h).
Monitorizare
APTT trebuie determinat la 4-6h dup bolus, 6 ore
dup orice schimbare a dozelor i apoi cel puin zilnic
atunci cnd este n intervalul terapeutic. Nivelul int al
aPTT este, de obicei, de 1,5-2,5 ori fa de valoarea de
control a laboratorului. Doza este titrat pentru a obine un aPTT terapeutic, definit ca aPTTul care coresponde unui nivel de anti-Xa ntre 0,3-0,7 UI/ml. Atunci
cnd hemodinamica este mbuntit i pacientul este
stabilizat, HNF poate fi schimbat cu HGMM n doze
terapeutice i meninute pe toat perioada sarcinii.
HGMM ar trebui schimbat cu HNF i.v. cu cel puin 36
de ore nainte de inducerea travaliului sau de cezarian.
HNF trebuie ntrerupt cu 4-6h nainte de natere i reluat la 6 ore dup, n cazul n care nu exist complicaii
hemoragice. Nici HNF, nici HGMM nu au fost depistate n laptele matern ntr-o cantitate semnificativ i nu
reprezint o contraindicaie a alptrii.
Tromboliza
Tromboliticele sunt considerate relativ contraindicate n timpul sarcinii i peripartum i ar trebui utilizate
numai la pacientele cu risc nalt cu hipotensiune arterial sever sau oc243. Riscul de hemoragie, n special la nivelul tractului genital, este ~8%249. La ~200 de
paciente raportate s-a folosit mai ales streptokinaz i,
mai recent, activator tisular al plasminogenului recombinant. Ambele trombolitice nu traverseaz placenta
n cantiti semnificative. Au fost raportate un procent
de 6% pierderi fetale i 6% nateri nainte de termen250.
Cnd tromboliza a fost efectuat, nu s-a efectuat doza
de ncrcare de HNF i s-a nceput cu o perfuzie cu o
rat de 18 U/kg/h. Dup stabilizarea pacientului, HNF
poate fi schimbat cu HGMM pe durata restului sarcinii.
Fondaparina
Exist foarte puine studii despre fondaparin n timpul sarcinii; unul a artat pasajul minor transplacentar
al fondaparinei251. Din cauza datelor limitate, aceasta
nu ar trebui s fie utilizat n timpul sarcinii (a se vedea
Seciunea 11).
Rivaroxaban
Rivaroxaban traverseaz bariera placentar i, prin
urmare, nu a fost evaluat i nu este recomandat la pacientele gravide.

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Filtrele de ven cav


Indicaiile pentru filtre de ven cav sunt aceleai
ca i la pacientele negravide. Cu toate acestea, riscurile
asociate cu procedura pot fi crescute243,250.
Managementul post-partum
La pacientele cu embolism pulmonar recent, terapia
cu heparin ar trebui reluat la 6 ore dup o natere pe
cale normal sau la 12 ore dup cezarian, n cazul n
care nu a aprut o sngerare semnificativ, cu suprapunerea ulterioar a antagonitilor de vitamin K pentru
cel puin 5 zile. Antagonitii de vitamina K se pot ncepe a doua zi dup natere i pot fi continuai timp de
cel puin 3 luni sau 6 luni dac embolismul pulmonar
a aprut trziu n timpul sarcinii. INRul ar trebui s fie
ntre 2 i 3, i necesit monitorizare periodic, n mod
ideal o dat la 1-2 sptmni. Antagonitii de vitamin
K nu sunt excretai n laptele matern n formele active
i sunt siguri pentru mamele care alpteaz.
10.4.2 Tromboza venoas profund acut
Prezentare clinic
Mrirea de volum a membrelor inferioare este o constatare frecvent n timpul sarcinii, ducnd la suspiciunea de TVP. Avnd n vedere c TVP este localizat n
>85% din cazuri pe partea stng, din cauza compresiei venei iliace stngi de ctre artera iliac dreapt i
uterul gravid, creterea diametrului membrului inferior stng este suspect. Tromboza izolat a venei iliace
se poate manifesta prin durere izolat la nivelul fesei,
zon inghinal, flanc sau abdomen. O strategie de decizie clinic, ce ia n considerare trei variabile: aspectul
membrului inferior stng, o diferen de circumferin
ntre cele dou gambe >2 cm i apariia modificrilor
n primul trimestru de sarcin, a prezentat o valoare
predictiv negativ de 100% (95% CI 95,8 - 100%) n cazul n care niciuna dintre cele trei variabile nu au fost
prezente i explorarea echografic a membrelor a fost
negativ86. Aceste constatri clinice necesit validare n
studii prospective.
Diagnostic
D-dimerii
A se vedea diagnosticul embolismului pulmonar.
Ecografia cu compresie a venelor membrelor inferioare
Ecografia cu compresie este procedura imagistic de
elecie pentru diagnosticul TVP suspectat n timpul
sarcinii, cu sensibilitate i specificitate nalt pentru
TVP proximal, dar mai puin sensibil pentru TVP

distal i TVP la nivelul vascularizaiei bazinului. Evaluri seriate prin ecografie cu compresie n zilele 0, 3
i 7 n sarcin are o mare valoare predictiv negativ
99,5% (95% IC 97-99%%)240.
Toate femeile suspectate de TVP n timpul sarcinii
ar trebui s fie evaluate pentru probabilitatea pretest,
determinat valoarea D-dimerilor i apoi supuse ecografiei cu compresie.
n cazul n care se constat prezena TVP proximale, tratamentul trebuie continuat. La femeile cu probabilitate pretest nalt, D-dimeri pozitivi i o ecografie
cu compresie iniial normal, se recomand efectuarea
venografiei prin rezonan magnetic pentru a exclude
o TVP pelvin izolat. Femeile cu probabilitate pretest
joas i D-dimeri normali ar trebui s fie supuse la ecografii cu compresie seriate n ziua 3 i dup o sptmn, fr a i se administra anticoagulant. Dac ecografia
rmne negativ, se va exclude diagnosticul de TVP.
Tratament
n TVP acut, ar trebui administrat tratamentul cu
HGMM n doze terapeutice, ajustate n funcie de greutate, de dou ori pe zi (vezi tratamentul embolismului
pulmonar).
10.5 Recomandri pentru prevenia i
managementul tromboembolismului venos n
timpul sarcinii i postnatal
Tabelul 20. Recomandri pentru prevenia i managementul tromboembolismului venos n timpul sarcinii i postnatal
Recomandri
Clasa Nivelb
Se recomand evaluarea factorilor de risc pentru TEV la toate femeile
I
C
gravide sau la femeile care i doresc o sarcin.
Mamele ar trebui informate despre semnele i simptomele TEV n sarcin i
I
C
necesitatea contactrii unui medic n cazul apariiei acestora.
Pacientele cu risc crescutc ar trebui s primeasc profilaxie antenatal cu
I
C
HGMM, precum i postnatal pe o durat de 6 sptmni.
n cazul pacientelor cu risc intermediard profilaxia postpartum cu HGMM ar
I
C
trebui fcut cel puin 7 zile sau mai mult, dac 3 factori de risc persist.
n cazul pacientelor cu risc sczute se recomand mobilizarea precoce i
I
C
evitarea deshidratrii.
Ciorapii cu compresie gradat sunt recomandai tuturor femeilor cu risc
I
C
crescut att n perioada antepartum, ct i postpartum.
Dozarea D-dimerilor i ultrasonografia compresiv se recomand pacienteI
C
lor cu suspiciune de TEV pe perioada sarcinii.
Pentru tratamentul TEV acut n sarcin se recomand HNF pacientelor cu risc
I
C
crescut i HGMM pacientelor fr risc crescut.
Utilizarea ciorapilor cu compresie gradat ar trebui luat n considerare n
IIa
C
cazul femeilor cu risc intermediar, n sarcin i postpartum.
n cazul pacientelor cu risc intermediar ar trebui luat n considerare profilaIIa
C
xia antenatal cu HGMM.
Nu ar trebui realizat screeningul de rutin al trombofiliei.
III
C
Clasa de recomandare
Nivel de eviden
HGMM = heparin cu greutatea molecular mic; HNF = heparin nefracionat; TEV = tromboembolism venos.
Pentru definirea riscului naltc, riscului intermediard i a riscului sczute, vezi Tabelul 19.
a
b

ESC Guidelines on the management of


cardiovascular diseases during pregnancy

11. TERAPIA MEDICAMENTOAS N TIMPUL SARCINII


I ALPTRII
11.1 Principii generale
Aceast seciune rezum toate medicamentele pertinente i posibilitatea utilizrii lor n timpul sarcinii i
alptrii. Nu exist nc nicio recomandare unanim
pentru tratamentul femeilor gravide. n aceast seciune se va face referire i la momentul iniierii tratamentului i selectarea medicaiei. Avnd n vedere c
tratamenul medicamentos n timpul sarcinii afecteaz
att mama ct i ftul, trebuie ales tratamentul optim
pentru amndoi. Dac este necesar tratamentul medicamentos, administrarea lui depinde de urgena indicaiei.
n caz de urgen, medicamentele care nu sunt recomandate de ctre industria farmaceutic a fi utilizate
n timpul sarcinii i alptrii nu ar trebui s fie reinute
mamei. Trebuie cntrit raportul risc/beneficiu al terapiei.
Dovezi din diferite surse pot fi utilizate pentru clasificarea riscului de administrare a medicamentelor n
timpul sarcinii.
11.1.1 Clasificarea US Food and Drug
Administration
Aceast clasificare a fost publicat de ctre Departmentul de Sntate i Servicii Umane al SUA (Sursa:
Drug Information for the Health Care Professional;
USDPI Vol 1, Micromedex 23rd edn., 01.01.2003).
Adaptat i modificat dup Bonow et al.46.
Clasificarea conine categorii de la A (cel mai sigur)
i la X (pericol cunoscut a nu se utiliza!). Urmtoarele
categorii sunt utilizate pentru medicamente n timpul
sarcinii i alptrii.
Categoria B: niciun studiu privind reproducerea la
animale nu a demonstrat un risc fetal, dar nu exist studii controlate la femeile gravide sau studiile pe animale
gestante au artat un efect advers care nu a fost confirmat n studii controlate la femei nsrcinate.
Categoria C: fie studiile pe animale au artat efecte
adverse asupra ftului i nu exist studii controlate la
femei nsrcinate, fie studiile pe femei sau animale nu
sunt disponibile. Medicamentele ar trebui s fie administrate numai dac beneficiile justific riscul potenial
pentru ft.
Categoria D: exist dovezi de risc asupra ftului
uman, dar beneficiile aduse de utilizare la femeile gravide pot fi acceptabile, n ciuda riscurilor (ex.: tratamentul afeciunilor amenintoare de via).

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Vol. 23, No. 1, 2013

Categoria X: studiile pe animale sau oameni au demonstrat anomalii fetale sau exist dovezi de risc fetal
bazate pe experiena uman, sau ambele, i riscul de
utilizare a medicamentului la femeia gravid depete
n mod clar orice beneficiu posibil. Medicamentul este
contraindicat la femeile care sunt sau pot deveni gravide.
11.1.2 Baze de date pe Internet
Autorii bazei de date www.embryotox.de a Pharmakovigilanz und Beratungszentrum fr Embryonaltoxikologie of the Berliner Betrieb fr Zentrale Gesundheitliche Aufgabe i bazeaz recomandrile pe o
combinaie de surse tiinifice, opinii ale experilor, n
principal fondate pe date observaionale i pe experiena personal a femeilor n timpul sarcinii i n timpul
alptrii.
Baza de date englez www.safefetus.com este relativ
similar cu baza de date german.
11.1.3 Industria farmaceutic
Prospectul realizat de firma productoare se bazeaz
n principal pe faptul c medicamentele nu sunt testate
suficient n timpul sarcinii i alptrii. Din acest considerent i din motive juridice, medicamentele sunt frecvent considerate interzise n timpul sarcinii i alptrii.
11.2 Recomandri pentru utilizarea
medicamentelor
12. Mulumiri
A fost un mare privilegiu pentru preedintele acestui Grup de Lucru s poat s lucreze cu cei mai buni
i mai renumii experi i oameni de tiin n domeniu la nivel european i s ofere aceste ghiduri
comunitii de cardiologi, chirurgi cardiovasculari,
ginecologi, i tuturor specialitilor implicai n ngrijirea femeilor gravide. Cu aceast ocazie, a dori s
mulumesc tuturor membrilor Grupului de Lucru, care
au mprtit cu generozitate cunotinele lor, precum
i referenilor pentru contribuia lor extraordinar. A
dori, de asemenea, s mulumesc ESC pentru c a fcut posibil realizarea acestor ghiduri. n sfrit, a ar
dori s-mi exprim enorma apreciere pentru echipa de
ghiduri de la Casa Inimii, n special Veronica Dean i
Nathalie Cameron pentru sprijinul lor extrem de util.
Textul CME Ghidul ESC pentru managementul
bolilor cardiovasculare n timpul sarcinii este acreditat de Consiliul European pentru Acreditare n
Cardiologie (EBAC). EBAC lucreaz n conformitate cu standardele de calitate ale Consiliului European
de Acreditare pentru Educaie Medical Continu
(EACCME), care este o instituie a Uniunii Europene

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Vol. 23, No. 1, 2013
Tabelul 21. Recomandri pentru utilizarea medicamentelor
Clasificarea
Permeabilitate
Medicamente
(Vaughan Wiliams pen- Categoria FDA
placentar
tru medicamentele AA)
Anticorp monoclonal cu
Abciximab
C
Necunoscut
efecte antitrombotice

Transferul prin laptele


matern (doza fetal)
Necunoscut

Efecte Adverse
Studii umane neadecvate; ar trebui folosit doar dac potenialul beneficiu depete potenialul risc fetal.
Embriopatii (mai ales n primul trimestru), sngerri (vezi
discuii suplimentare n Seciunea 5 pentru utilizarea n timpul
sarcinii).
Fr efecte teratogene cunoscute (studii ample).
Nu s-au raportat efecte adverse fetale (studii umane limitate).
Necunoscute (experien limitat).
Insuficien tiroidian (9%), hipertiroidism, gu, bradicardie,
retard n cretere, natere prematur.

Acenocoumarola

Antagonist de vitamin K

Da

Da (Nu s-au raportat efecte


adverse)

Acid acetilsalicilic (doze mici)


Adenozinb
Aliskiren

Antiplachetar
Antiaritmic
Inhibitor de renin

B
C
D

Da
Nu
Necunoscut

Bine tolerat
Nu
Necunoscut

Amiodaron

Antiaritmic (de clas a III-a)

Da

Da

Da

Da

Nu s-au raportat efecte adverse fetale.

Necunoscut

Necunoscut

Riscul nu poate fi exclus (studii umane limitate).

Necunoscut

Necunoscut

Exist risc pentru ft (rezervat pentru indicaii vitale).

Da

Ampicilin, amoxicilin,
cefalosporine, eritromicin,
Antibiotice
mezlocilin, penicilin
Imipenem, rifampicin, teicoplaAntibiotice
nin, vancomicin,
Aminoglucozide, quinolone,
Antibiotice
tetracicline
Atenololc

-blocant (clasa a II-a)

Da

Benazeprild

IECA

Da

Bisoprolol

-blocant (clasa a II-a)

Da

Da

Candesartan

Antagonist al receptorilor de
angiotensin

Necunoscut

Necunoscut; nu este
recomandat

Captoprild

IECA

Da

Dae (maximum 1,6%)

Clopidogrel
Colestipol,
Colestiramin
Danaparoid
Digoxinf

Antiplachetar

Necunoscut
Dae scad vitaminele liposolubile
Nu
Dae

Dae (maximum 1,6%)

Hipospadias (primul trimestru); defecte congenitale, greutate


mic la natere, bradicardie i hipoglicemie la ft (n trimestrul al II-lea i al III-lea).
Displazie renal sau tubular, oligohidramnios, retard n cretere, defecte de osificare ale craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Bradicardie i hipoglicemie fetal.
Displazie renal sau tubular, oligohidramnios, retard n cretere, defecte de osificare ale craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Displazie renal sau tubular, oligohidramnios, retard n cretere, defecte de osificare ale craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Nu exist informaii referitoare la sarcin.
Poate afecta absorbia vitaminelor liposolubile, ex.: vitamina
K => hemoragii cerebrale (neonatale).
Fr efecte adverse (studii umane limitate).
Nivelurile serice nesigure; sigur de folosit.

Necunoscut

Medicamente hipolipemiante C

Necunoscut

B
C

Nu
Da

Nu

Dae

Posibil efect teratogen.

Disopiramid

Anticoagulant
Glicozid cardiac
Blocant al canalelor de calciu
(clasa a IV-a)
Antiaritmic (clasa IA)

Da

Dae

Enalaprild

IECA

Da

Dae (maxim 1,6%)

Eplerenon
Fenofibrat
Flecainid
Fondaparinux

Antagonist de aldosteron
Medicament hipolipemiant
Antiaritmic (clasa IC)
Anticoagulant

C
C

Necunoscut
Da
Da
Da (max 10%)

Contracii uterine
Displazie renal sau tubular, oligohidramnios, retard n cretere, defecte de osificare ale craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Necunoscut (experien limitat).
Date insuficiente asupra efectelor la oameni.
Necunoscut (experien limitat).
Medicament nou (experien limitat).

Diltiazem

Furosemid

Diuretic

Da

Gemfibrozil
Gliceril trinitrat

Medicament hipolipemiant
Nitrat

C
B

Da
Necunoscut

Necunoscut
Da
Dae
Nu
Bine tolerat; producia de
lapte poate fi diminuat.
Necunoscut
Necunoscut

Heparin (greutate molecular


mic)

Anticoagulant

Nu

Nu

Heparin (nefracionat)

Anticoagulant

Nu

Nu

Hidralazin

Vasodilatator

Da

Dae (maximum 1%)

Hidroclorotiazid

Diuretic

Da

Irbesartan

Antagonist al receptorilor de
angiotensin

Necunoscut

Isosorbid dinitrat

Nitrat

Necunoscut

Isradipin

Blocant de canale de calciu

Da

Oligohidramnios.
Date insuficiente asupra efectelor la oameni.
Bradicardie, efect tocolitic.
Utilizare pe termen lung: rareori osteoporoz i semnificativ
mai puine cazuri de trombocitopenie dect n cazul utilizrii
HNF.
Utilizare pe termen lung: osteoporoz i trombocitopenie.
Efecte adverse materne: simptome lupus-like; tahiaritmii
fetale (utilizare matern).

Da; producia de lapte poate


Oligohidramnios.
fi diminuat.
Displazie renal sau tubular, oligohidramnios, retard n cretere, defecte de osificare ale craniului, hipoplazie pulmonar,
Necunoscut
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Necunoscut
Bradicardie.
Potenialul sinergism cu sulfatul de magneziu poate induce
Necunoscut
hipotensiune.

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Vol. 23, No. 1, 2013

Labetalol

-/-blocant

Da

Dae

Lidocain

Antiaritmic (clasa IB)

Da

Dae

Metildopa
Metoprolol
Mexiletin

-agonist central
-blocant (clasa a II-a)
Antiaritmic (clasa IB)

B
C
C

Da
Da
Da

Dae
Dae
Dae

Nifedipin

Blocant de canale de calciu

Da

Dae (maxim 1,8%)

Phenprocoumona

Antagonist de vitamin K

Da

Procainamid
Propafenon
Propranolol

Antiaritmic (clasa IA)


Antiaritmic (clasa IC)
-blocant (clasa a II-a)

C
C
C

Da
Da
Da

Da (maxim 10%), bine


tolerat ca metabolit inactiv.
Da
Necunoscut
Dae

Chinidin

Antiaritmic (clasa IA)

Da

Dae

Ramiprild

IECA

Da

Da (maxim 1,6%)

Sotalol

Antiaritmic (clasa a III-a)

Da

Spironolacton

Antagonist de aldosteron

Da

Statineg
Ticlopidin

Medicament hipolipemiant
Antiplachetar

X
C

Da
Necunoscut

Dae
Da (maximum 1,2%);
producia lactat poate fi
diminuat.
Necunoscut
Necunoscut

Valsartand

Blocant al receptorilor de
angiotensin II

Necunoscut

Necunoscut

Da

Dae

Da

Da

Vernakalant

Blocant al canalelor de calciu


C
(clasa a IV-a)
Blocant al canalelor de calciu
C
(clasa a IV-a)
Antiaritmic (clasa a III-a)

Necunoscut

Warfarin

Antagonist de vitamin K

Da

Necunoscut
Da (maxim 10%), bine
tolerat ca metabolit inactiv.

Verapamil oral
Verapamil i.v.
a

Retard de cretere intrauterin (trimestrul al II-lea i al IIIlea), bradicardie i hipotensiune fetal (utilizat n apropierea
naterii).
Bradicardie, acidoz, toxicitate la nivelul sistemului nervos
central la ft.
Uoar hipotensiune neonatal.
Bradicardie i hipoglicemie la ft.
Bradicardie fetal.
Tocolitic; administrarea s.l. i potenialul sinergism cu sulfatul
de magneziu pot induce hipotensiune (la mam) i hipoxie
fetal.
Embriopatie cumarinic, hemoragii (discuii suplimentare
referitoare la folosirea n sarcin n Seciunea 5).
Necunoscut (experien limitat).
Necunoscut (experien limitat).
Bradicardie i hipoglicemie fetal.
Trombopenie, natere prematur, toxicitate la nivelul nervului
VIII.
Displazie renal sau tubular, oligohidramnios, retard n
cretere, osificare anormal a craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Bradicardie i hipoglicemie fetal (experien limitat).
Efecte antiandrogenice, despicturi orale (primul trimestru)
Anomalii congenitale.
Necunoscut (experien limitat).
Displazie renal sau tubular, oligohidramnios, retard n
cretere, osificare anormal a craniului, hipoplazie pulmonar,
spasme musculare, articulaii mari, anemie, moarte fetal
intrauterin.
Bine tolerat (experien limitat n sarcin).
Administrarea intravenoas poate fi asociat cu un risc mai
mare de hipotensiune i implicit de hipoperfuzie fetal.
Fr experien n utilizarea n sarcin.
Embriopatie cumarinic, hemoragii (discuii suplimentare
referitoare la utilizarea n sarcin n Seciunea 5).

Comitetul pentru ghiduri a adugat acenocumarolul i phenprocumonul la aceast list prin analogie cu warfarina. Necesitatea evalurii riscului se aplic i acestor dou ACO. Anterior, warfarinei i-a fost atribuit categoria de risc X46. n
opinia Grupului de Lucru, dovezile disponibile sugereaz c warfarina, ca i ali antagoniti de vitamina K, ar trebui s se afle n categoria de risc D (pentru referine i discuii urmrii Seciunea 5.5).
b
Adenozina: cea mai mare experien n folosirea acestui medicament este pentru trimestrele al II-lea i al III-lea de sarcin. Timpul de njumtire scurt poate preveni ajungerea la ft.
c
Atenololul este clasificat de FDA n categoria de risc D252, totui, unii autori o clasific n grupa de risc C253.
d
Datele disponibile n legtur cu folosirea n primul trimestru nu ofer dovezi puternice asupra potenialului teratogen178,179. Deoarece IECA, BRA, antagonitii receptorilor de aldosteron i inhibitorii de renin trebuie evitai n sarcin
i pe durata alptrii, li s-a atribuit categoria de risc D. S-au descris situaii pozitive n urma folosirii IECA n sarcin, astfel nct sarcina nu trebuie s fie ntrerupt dac pacienta a fost expus la aceste medicamente, dar ar trebui
supravegheat atent.
e
Alptarea este posibil cnd mama este tratat cu acest medicament.
f
Digoxin: experiena cu digoxin n timpul sarcinii este vast i este considerat cel mai sigur antiaritmic n timpul sarcinii. O eficien antiaritmic profilactic nu a fost demonstrat.
g
Statinele: nu ar trebui prescrise n sarcin i n perioada de alptare deoarece sigurana administrrii acestora nu a fost demonstrat, iar n cazul ntreruperii tratamentului n perioada sarcinii, nu se ateapt dezavantaje pentru
mam.
IECA = inhibitori ai enzimei de conversie a angiotensinei.
a

a Specialitilor Medicale (UEMS). n conformitate cu


ghidurile EBAC / EACCME, toi autorii care particip la acest program au dezvluit potenialele conflicte de interese care ar putea cauza o prtinire n articol. Comitetul de Organizare este responsabil pentru
asigurarea conform creia toate potenialele conflicte de interese relevante pentru program sunt declarate participanilor nainte de activitile de CME.
ntrebri CME pentru acest articol sunt disponibile la
adresa: European Heart Journal http://cme.oxfordjournals. org/cgi/hierarchy/oupcme_node;ehjv i Societatea European de Cardiologie http://www.escardio.
org/guidelines.

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Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

NATIONAL AND INTERNATIONAL CARDIOLOGICAL AGENDA 2013


MANIFESTRILE CARDIOLOGICE INTERNE
LUNA

DENUMIREA MANIFESTRII
Controverse i soluii n HTA
Directori de curs: Prof. Dr. M. Cintez, Prof. Dr. Ctlina Arsenescu Georgescu

Lipid school ghidul dislipidemii 2012 (LIPS)


Aprilie

Directori de curs: Prof. Dr. D. Gai, Prof. Dr. D. Vinereanu

Angina pectoral stabil


Directori de curs: Prof. Dr. Doina Dimulescu, Conf. Dr. S. Blnescu

Conferina naional de aterotromboz


Moderatori: Prof. Dr. E. Apetrei, Prof. Dr. C. Popa

DATA

LOCAIA

12 aprilie

Trgu-Mure

12 aprilie

Brila

12 aprilie

Bucureti

26 aprilie

Bucureti

16-18 mai

Poiana Braov

31 mai

Constana

27-29 iunie

Sinaia

20 septembrie

Constana

25 septembrie

Trgu-Mure

4-6 octombrie

Sinaia

18 octombrie

Suceava

19 octombrie

Craiova

25 octombrie

Cluj-Napoca

25 octombrie

Iai

31 octombrie
2 noiembrie

Iai

noiembrie

Sibiu

noiembrie

Cluj-Napoca

1 noiembrie

Piteti

1 noiembrie

Oradea

Conferina naional a grupurilor de lucru


Mai

Prima Conferin Naional a Alianei Romne de Combatere a Hipertensiunii


Arteriale

Particulariti ale bolilor cardiovasculare la vrstnic (CARDIOSEN)


Directori de curs: Conf. Dr. F. Mitu, Conf. Dr. Dana Pop, Dr. D. Gherasim

Iunie
Septembrie

Expert meeting CARDIODIAB


Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. D. Gai

Lipid school ghidul dislipidemii 2012 (LIPS)


Directori de curs: Prof. Dr. D. Gai, Prof. Dr. D. Vinereanu

Aritmiile cardiace la copil o abordare practic


Directori de curs: Dr. Ioana Ghiorghiu, Prof. Dr. Rodica Toganel

Congresul Naional de Cardiologie


S analizm noile ghiduri de HTA
Directori de curs: Prof. Dr. M. Cintez, Prof. Dr. Ctlina Arsenescu Georgescu

Particulariti ale bolilor cardiovasculare la vrstnic (CARDIOSEN)


Octombrie

Directori de curs: Conf. Dr. F. Mitu, Conf. Dr. Dana Pop, Dr. D. Gherasim

Actualiti n aritmologie (ARCA 3)


Directori de curs: Dr. R. Vtescu, Prof. Dr. D. Dobreanu, Prof. Dr. G. A. Dan

Angina pectoral stabil


Directori de curs: Prof. Dr. Doina Dimulescu, Conf. Dr. S. Blnescu

Zilele Cardiologice Prof. Dr. George I. M. Georgescu


Cazuri clinice n insuficiena cardiac
Directori de curs: Prof. Dr. C. Macarie, Prof. Dr. D. Vinereanu, Dr. O. Chioncel

Soluii terapeutice n infarctul miocardic acut de la teorie la practic


cazuri clinice n direct
Noiembrie Directori de curs: Dr. D. Deleanu, Dr. A. Iancu, Dr. M. Croitoru
Imagistica bolilor valvulare
Directori de curs: Conf. Dr. Adriana Ilieiu, Conf. Dr. B. A. Popescu

S analizm noile ghiduri de HTA


Directori de curs: Prof. Dr. M. Cintez, Prof. Dr. Ctlina Arsenescu Georgescu

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Agenda

INTERNATIONAL CARDIOLOGICAL EVENTS


MONTH

NAME OF THE EVENT


79th Annual Congress of the German Cardiac Society

April

5th International Congress on Prediabetes and the Metabolic


Syndrome
EuroPRevent 2013
8th Congress of Vascular Access Society
EuroValve Congress
ICNC 11, Nuclear Cardiology and Cardiac CT

May

May

Venice, Italy

Association for European Paediatric and Congenital Cardiology


(AEPC 2013)

22nd-25th May

London,
United
Kingdom

EuroCMR2013
The Working Group on Cardiovascular Magnetic Resonance of the
European Society of Cardiology (ESC)

23rd-25th May

Heart Failure 2013

25th-28th May

EHRA EUROPACE 2013


Case-based Arrhythmia and Device Practice

August
ESC Congress 2013

October

Computing in Cardiology 2013


Scientific programme endorsed byWorking Group on e-Cardiology
Venice Arrhythmias 2013
Acute Cardiac Care 2013
10th International Congress on Coronary Artery Disease - ICCAD

Mannheim,
Germany
Vienna,
18th-20th April
Austria
Rome, Italy
18th-20th April
Prague,
25th-27th April
Czech Republic
3rd-4th May
Ibiza, Spain
Berlin,
5th-8th May
Germany
3rd-6th April

8th-10th May

23rd European Meeting on Hypertension and Cardiovascular


Protection

September

PLACE

Course: The Role of Advanced Cardiac Imaging: Clinical decision


making in Coronary artery disease
Scientific programme endorsed byEuropean Association of
Echocardiography (EAE)

Rhythm Congress 2013

June

DATE

Florence, Italy
Lisbon,
Portugal
Marseille,
France

30th May1 June 2013


14th-17th June
Milan, Italy
2013
23rd June-26th
Athens, Greece
June 2013
th
th
Amsterdam,
29 -30
August
Netherlands
st
th
31 August- 4
Amsterdam,
September
Netherlands
2013
Zaragoza,
22nd-25th
September
Spain
6th-9th October Venice, Italy
12th-14th
Madrid, Spain
October
13th-16th
Florence, Italy
October
st

Romanian Journal of Cardiology


Vol. 23, No. 1, 2013

Agenda

ESC CONGRESS 2013


will be held from August 31st to September 4th 2013
at the Amsterdam RAI.
This year the congress spotlight is on:

The heart interacting with systemic organs.


This largest gathering of cardiovascular professionals in the world is a major
occasion to discuss the latest achievements in cardiology. Moreover, this
unique scientific conference is an important opportunity to network,
exchange and enrich our daily practice to improve patient care.
The abstract submission deadline on February 14th 2013.
http://www.escardio.org/congresses/esc-2013/Pages/welcome.aspx

ROMANIAN JOURNAL OF CARDIOLOGY


acord, n acest an,
un premiu pentru cel mai bun articol original din anul 2012
(prim-autori sub 40 de ani).

Romanian Journal of Cardiology | Vol. 23, No. 1, 2013

INSTRUCIUNI PENTRU AUTORI


Informaii generale
Romanian Journal of Cardiology public articole originale din domeniul fiziologiei i patologiei cardiovasculare sub forma studiilor
clinice, de laborator, experimentale, epidemiologice etc. Autorii vor respecta principiile eticii i adevrului tiinific n realizarea studiului,
obinerea datelor i prezentarea rezultatelor.
Pentru publicare, articolele vor fi trimise ntr-un exemplar, mpreun cu toate fiierele pentru text (n format MS Word) i imaginile pe
CD. Formatul manuscrisului este de tip A4, scris la dou rnduri, cu caractere Times New Roman 12.
Articolele vor fi redactate n limba engleza. Cele trimise n limba romn vor fi traduse de redacie n limba englez (contra cost).
Fiecare manuscris trebuie s fie nsoit de o scrisoare de intenie a autorilor, semnat n original, care s afirme c articolul nu a mai fost
trimis simultan niciunei alte publicaii i nu a mai fost publicat n alt revist ntr-o form substanial similar. Responsabilitatea asupra
coninutului articolului aparine n ntregime autorilor.
Articolele vor fi semnate de toi autorii. Toi autorii vor semna o declaraie privind conflictul de interese i contribuia avut la elaborarea
lucrrii. Primul autor are obligaia de a colecta declaraiile de la toi co-autorii.

Pregtirea manuscrisului

Titlu: Pe pagina de titlu se va scrie titlul articolului n limba englez i romn, numele complet al autorilor, gradul academic, afilierea
acestora, adresa de coresponden, precum i un titlu scurt n limba englez (ntre 3-6 cuvinte) pentru paginile urmtoare ale articolului, i
cuvintele cheie ale articolului. Vor fi precizate sursele de finanare ale lucrrii (acolo unde este cazul).
Rezumatul: Rezumatul, n limba englez i romn, va cuprinde cel mult 200 de cuvinte. Va fi alctuit din urmtoarele subtitluri: obiectivele studiului, metodologia folosit, rezultate i concluziile studiului.
Textul manuscrisului: Textul manuscrisului nu va depi 12 pagini pentru studiile originale sau referatele generale i 5 pagini pentru
prezentrile de caz. Prescurtrile vor fi definite la prima lor folosire. Pentru denumirile medicamentelor sau ale altor substane folosite n
studiile prezentate vor fi utilizate denumirile comune internaionale. Aparatele utilizate n studii vor fi prezentate cu denumirea comercial,
cu indicarea productorului. Eventualele mulumiri pentru colaborare vor fi inserate la sfritul textului.
Bibliografia: Bibliografia se va nota cu cifre arabe n ordinea cresctoare a apariiei n text, unde vor fi notate superscript. Referinele bibliografice vor cuprinde numele autorilor, titlul complet al articolului, revista, anul apariiei, volumul, paginile. Prescurtarea numelui revistei
se va face dup cea folosit n Index Medicus.
Recomandm introducerea referinelor bibliografice actuale. Se recomand citarea referinelor bibliografice romneti, iar n cazul n
care autorii au mai publicat n Romanian Journal of Cardiology, citarea acestor publicaii.
Ex: Ridker PM, Rifai N, Pfeffer M et al. Elevation of TNF-a and increased risk of recurrent coronary events aft er myocardial infarction. Circulation, 2000; 101: 2149-53 [pentru articole din reviste] Madahi J. Myocardial perfusion imaging for the detection and evaluation of coronary
artery disease.In Cardiac Imaging: A Companion to Braunwalds Heart Disease, Second edition. Eds: DJ Skorton, HR Schelbert, GL Wolf et al.
WB Saunders, London, 1996, 193-203 [capitole n cri]
Figurile: Calitatea figurilor trebuie s fie excelent pentru a permite reproducerea corect. Ele nu vor fi inserate n interiorul textului manuscrisului, ci vor fi prezentate separat. n format electronic vor fi trimise separat ca fiiere imagine (JPG, TIFF etc.). Fiecare figur va fi nsoit de o legend n care vor fi explicate, n mod concis, principalele date referitoare la respectiva figur si eventualele prescurtari. Figurile vor
fi numerotate cu cifre arabe n ordinea apariiei lor n text. n text va fi precizat ntre paranteze rotunde numrul figurii la care se face referire
(Ex: Fig. 3). Dac este cazul, n parantez va fi precizat sursa bibliografic a figurii i, n acest caz, utilizarea figurii trebuie fcut cu avizul
de copyright. Prezentarea sursei bibliografice va fi urmat de cifra corespunztoare din bibliografie. Figurile color vor fi publicate contra cost.
Tabelele: Tabelele vor fi numerotate cu cifre arabe n ordinea apariiei n text i vor fi nsoite de titlul concis al tabelului i eventualele
explicaii. Vor fi precizate prescurtrile utilizate n tabel. Dac este cazul, n parantez va fi precizat sursa bibliografic a tabelului i avizul
de copyright.
Textele trimise pentru a fi publicate vor fi referate de ctre 2 refereni fr cunoaterea autorilor. Recomandrile referenilor sunt comunicate
autorilor pentru refacerea articolului. Dac articolul este aprobat pentru publicare, va fi transmis data publicrii. Refuzul publicrii va fi motivat i comunicat n scris autorilor. Manuscrisele nepublicate nu se returneaz autorilor.
Manuscrisele i suportul lor electronic (CD) vor fi trimise prin pot sau e-mail la urmtoarea adres:
Romanian Journal of Cardiology
n atenia dlui Prof. Dr. Eduard Apetrei, redactor-ef
Institutul de Urgen pentru Boli Cardiovasculare Prof. Dr. C. C. Iliescu, os. Fundeni, nr. 258, 022328, Bucureti, Romnia.
Tel./Fax: +40-21-318.35.92
E-mail: eapetrei@gmail.com, mihaela_salagean@yahoo.com

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