Beruflich Dokumente
Kultur Dokumente
1, 2013
EDITORIAL
ORIGINAL ARTICLES
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
Long QT Syndrome
29
37
44
L. Lucaci
CASE REPORTS
51
54
56
UPDATES IN CARDIOLOGY
Updates in Cardiology
58
ESC GUIDELINES
63
IMAGES IN CARDIOLOGY
Ileana Arsenescu
AGENDA
123
INSTRUCTIONS FOR
AUTHORS
126
EDITORIAL
ARTICOLE ORIGINALE
REFERATE GENERALE
12
21
Sindromul de QT lung
29
37
44
47
51
54
56
ACTUALITI N
CARDIOLOGIE
Actualiti n cardiologie
58
GHID ESC
63
AGENDA
123
INSTRUCIUNI PENTRU
AUTORI
126
PREZENTRI DE CAZ
IMAGINI N CARDIOLOGIE
Ileana Arsenescu
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
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:
EDITORIAL
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.
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.
ORIGINAL ARTICLES
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
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
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
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
(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
A. Petris et al.
Romanian cardiologist: happiness questionnaire
(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-
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)
A. Petris et al.
Romanian cardiologist: happiness questionnaire
A. Petris et al.
Romanian cardiologist: happiness questionnaire
Table 3. Least happy respondents (score 1+2) versus happiest respondents (score 4+5) comparison
Least happy Romanian cardiologists
(score 1+2, n= 28)
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%)
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
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-
A. Petris et al.
Romanian cardiologist: happiness questionnaire
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-
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.
REVIEWS
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
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
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-
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
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.
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
Van der Linde D, Konings EE, Slager MA, et al. Birth prevalence of
congenital heart disease worldwide: a systematic review and metaanalysis. J Am Coll Cardiol 2011;58:2241-7.
3. Tararbit K, Houyel L, Bonnet D, et al. Risk of congenital heart defects
associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J 2011;32:500-8.
4. Van Engelen K, Topf A, Keavney BD, et al. 22q11.2 Deletion Syndrome is underrecognised in adult patients with tetralogy of Fallot and
pulmonary atresia. Heart 2010;96:621-4.
5. Griffin HR, Tpf A, Glen E, et al. Systematic survey of variants in
TBX1 in nonsyndromic tetralogy of Fallot identifies a novel 57 base
pair deletion that reduces transcriptional activity but finds no evidence for association with common variants. Heart 2010;96:1651-5.
6. Caleshu C, Day S, Rehm HL, et al. Use and interpretation of genetic
tests in cardiovascular genetics. Heart 2010;96:1669-75.
7. De Luca A, Sarkozy A, Consoli F, et al. Familial transposition of the
great arteries caused by multiple mutations in laterality genes. Heart
2010;96:673-7.
8. Keavney B. Left, right: a step forward in understanding transposition
of the great arteries. Heart 2010;96:653-5.
9. Zhao JY, Yang XY, Gong XH, et al. Functional variant in methionine
synthase reductase intron-1 significantly increases the risk of congenital heart disease in the Han Chinese population. Circulation 2012;
125:482-90.
10. Marek J, Tomek V, Skovrnek J, et al. Prenatal ultrasound screening
of congenital heart disease in an unselected national population: a 21year experience. Heart 2011;97:124-30.
11. Stressig R, Fimmers R, Eising K, et al. Preferential streaming of the
ductus venosus and inferior caval vein towards the right heart is associated with left heart underdevelopment in human fetuses with leftsided diaphragmatic hernia. Heart 2010;96:1564-8.
12. Eliasson H, Sonesson SE, Sharland G, et al; Fetal working group of the
European association of pediatric cardiology. Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study
of 175 patients. Circulation 2011;124:1919-26.
13. Baruteau AE, Fouchard S, Behaghel A, et al. Characteristics and longterm outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study. Eur Heart J
2012;33:622-9.
14. Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry
of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 2011;
124:1927-35.
15. Trucco SM, Jaeggi E, Cuneo B, et al. Use of intravenous gamma globulin
and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol 2011;57:715-23.
16. Jaeggi ET, Silverman ED, Laskin C, et al. Prolongation of the atrioventricular conduction in fetuses exposed to maternal anti-Ro/SSA
and anti-La/SSB antibodies did not predict progressive heart block. A
prospective observational study on the effects of maternal antibodies
on 165 fetuses. J Am Coll Cardiol 2011;57:1487-92.
17. Jaeggi ET, Carvalho JS, De Groot E, et al. Comparison of transplacental treatment of fetal supraventricular tachyarrhythmias with digoxin,
flecainide, and sotalol: results of a nonrandomized multicenter study.
Circulation 2011;124:1747-54.
18. Migliore F, Zorzi A, Michieli P, et al. Prevalence of cardiomyopathy
in Italian asymptomatic children with electrocardiographic T-wave
inversion at preparticipation screening. Circulation 2012;125:529-38.
19. Alvarez JA, Orav EJ, Wilkinson JD, et al; Pediatric cardiomyopathy
registry Investigators. Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy: results from the
pediatric cardiomyopathy registry. Circulation 2011;124:814-23.
20. Giardini A, Fenton M, Andrews RE, et al. Peak oxygen uptake correlates with survival without clinical deterioration in ambulatory children
with dilated cardiomyopathy. Circulation 2011;124:1713-18.
21. Irving C, Parry G, OSullivan J, et al. Cardiac transplantation in adults
with congenital heart disease. Heart 2010;96:1217-22.
22. Burch M. Is heart transplantation for adult congenital heart disease an
appropriate use of a scarce resource? Heart 2010;96:1172-3.
REVIEWS
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
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
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.
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acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA 2011;306:2110-9.
Traverse JH, Henry TD, Vaughan DE, et al. Rationale and design for
TIME: a phase II, randomized, double-blind, placebo-controlled pilot trial evaluating the safety and effect of timing of administration
of bone marrow mononuclear cells after acute myocardial infarction.
Am Heart J 2009;158:356-63.
Srder D, Schwitter J, Moccetti T, et al. Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale
and study design of the Swiss multicenter Intracoronary Stem cells
Study in Acute Myocardial Infarction (SWISSAMI). Am Heart J 2010;
160:58-64.
Miettinen JA, Ylitalo K, Hedberg P, et al. Determinants of functional recovery after myocardial infarction of patients treated with bone
marrow-derived stem cells after thrombolytic therapy. Heart 2010;
96:362-7.
Reffelmann T, Knemann S, Kloner RA. Promise of blood- and bone
marrow-derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy. J Am Coll Cardiol
2009;53:305-8.
Roncalli J, Mouquet F, Piot C, et al. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction:
results of the randomized multicenter BONAMI trial. Eur Heart J
2011;32:1748-57.
Grajek S, Popiel M, Gil L, et al. Influence of bone marrow stem cells
on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial:
impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur Heart J 2010;31:691-702.
Strauer BE, Yousef M, Schannwell CM. The acute and long-term
effects of intracoronary stem cell transplantation in 191 patients with
chronic heARt failure: the STAR-heart study. Eur J Heart Fail 2010;
12:721-9.
Perin EC, Silva GV, Henry TD, et al. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells
and cell function analysis in ischemic heart failure (FOCUS-HF). Am
Heart J 2011;161:1078-87.e3.
Hu S, Liu S, Zheng Z, et al. Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft
vessel for patients with previous myocardial infarction and chronic
heart failure: a single-center, randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 2011;57:2409-15.
Seth S, Bhargava B, Narang R, et al. The ABCD (Autologous Bone
Marrow Cells in Dilated Cardiomyopathy) trial a long-term follow-up
study. J Am Coll Cardiol 2010;55:1643-4.
Losordo DW, Henry TD, Davidson C, et al. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 2011;109:42836.
Chih S, Macdonald PS, McCrohon JA, et al. Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a
placebo controlled crossover trial. Heart 2012;98:282-90.
Houtgraaf JH, den Dekker WK, van Dalen BM, et al. First experience
in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J
Am Coll Cardiol 2012;59:539-40.
Perin EC SPL, Ruiz R, Perez-Cano R, et al. Abstract 17966: first in
man transendocardial injection of autologous adiPose-derived stem
cells in patients with non revascularizable ischemic myocardium
(PRECISE). Circulation 2010;122:A17966.
Hare JM, Traverse JH, Henry TD, et al. A randomized, double-blind,
placebocontrolled, dose-escalation study of intravenous adult human
mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 2009;54:2277-86.
Bolli R, Chugh AR, DAmario D, et al. Cardiac stem cells in patients
with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 2011;378:1847-57.
Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction
(CADUCEUS): a prospective, randomised phase 1 trial. Lancet
2012;379:895-904.
Bartunek J, Wijns W, Dolatabadi D, et al. C-CURE Multicenter trial:
lineage specific bone marrow derived cardiopoietic mesesnchymal
stem cells for treatment of ischaemic cardiomyopathy. J Am Coll Cardiol 2011;57:E200.
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
L. Lucaci
Long QT Syndrome
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.
L. Lucaci
Long QT Syndrome
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
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.
CAUSES
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
Figure 2. The onset of the pause-dependent torsade de pointes. VPB = ventricular premature beat. Data in references 30,32.
L. Lucaci
Long QT Syndrome
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.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
L. Lucaci
Long QT Syndrome
15. Schwartz PJ, Spazzolini C, Crotti L et al. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis and clinical outcome.
Circulation 2006;113:783-790.
16. Zareba W, Goldenberg I, Moss AJ. The role of the implantable cardioverter-defibrillator in the long QT syndrome. Long QT syndrome.
Cardiac electrophysiology clinics, volume 4, number 1. Editors: Priori
SG, Thakur RK, Natale A. Saunders, Philadelphia, 2012,89-95.
17. Schwartz PJ, Priori SG, Spazzolini C et al. Genotype-phenotype correlation in the long QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001;103:89-95.
18. Zareba W, Moss AJ, Schwartz PJ et al. Influence of the genotype on the
clinical course of the long QT syndrome. N Engl J Med 1998;339:960965.
19. Splawski I, Timothy KW, Sharpe LM et al. Cav1.2 Calcium channel
dysfunction causes a multisystem disorder including arrhythmia and
autism. Cell 2004;119:19-31.
20. Goldenberg I, Moss AJ, Paterson DR et al. Risk factors for aborted
cardiac arrest and sudden cardiac death in children with long QT
syndrome. Circulation 2008;117:2184-2191.
21. Priori SG, Schwartz PJ, Napolitano C et al. Risk stratification in the
long QT syndrome. N Engl J Med 2003;348:1866-1874.
22. Hobbs JB, Peterson DR, Moss AJ. Risk of aborted cardiac arrest or
sudden cardiac death during adolescence in the long QT syndrome.
JAMA 2006;296(10):1249-1254.
23. Ziv O, Kaufman ES. Age and gender modulation of the long QT
syndrome phenotype. Long QT syndrome. Cardiac electrophysiology
clinics, volume 4, number 1. Editors: Priori SG, Thakur RK, Natale A.,
Saunders, Philadelphia, 2012,39-51.
24. Buber J, Mathew J, Moss AJ et al. Risk of recurrent cardiac events after
onset of menopause in women with congenital LQTS types 1 and 2.
Circulation 2011;123 (24):2784-2791.
25. Moss AJ, Zareba W, Kaufman ES et al. Increased risk of arrhythmic
events in long QT syndrome with mutations in the pore region of the
human ether-a-go-go-related gene potassium channel. Circulation
2002;105(7):794-799.
26. Migdalovich D, Moss AJ, Lopes CM et al. Mutation and gender-specific risk in type 2 LQTS: implications for risk stratification for lifethreatening cardiac events in patients with long QT Syndrome. Heart
rhythm 2011;8(10):1537-1543.
27. Goldenberg I, Horr S, Moss AJ et al. Risk for life-threatening cardiac
events in patients with genotype-confirmed long QT syndrome and
normal range corrected QT intervals. J Am Coll Cardiol 2011; 57(1):
51-59.
28. Roden DM. Drug-induced prolongation of the QT interval. N Engl J
Med 2004;350:1013-1022.
29. Roden DM, Viswanathan PC. Genetics of acquired long QT syndrome. J Clin Invest 2005;115(8):2025-2032.
30. Surawicz B, Knilans T. Torsade de pointes, ventricular fibrillation and
differential diagnosis of ventricular tachycardia. Chous electrocardiography in clinical practice, 6th edition. Saunders Elsevier, Philadelphia, 2008,440-455.
31. Shantsila E, Watson T, Lip GYH. Drug induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.
Europace 2007;9(suppl 4):iv37-iv44.
32. Drew B, Ackerman MJ, Funk M et al. Prevention of torsade de pointes
in Hospital settings: a scientific statement from the AHA and ACCF.
Circulation 2010;121(8):1047-1060.
33. Antzelevitch C. Mechanisms of cardiac arrhythmias and conduction disturbances. Hursts the Heart, 12th edition. Editors: Fuster V,
ORourke RA, Walsh RA et al. McGraw Hill, New York, 2008,913-945.
34. Murray KT, Roden DM. Disorders of cardiac repolarization: the long
QT sSyndromes. Cardiology, 2nd edition. Editors. Crawford MH, DiMarco JP, Paulus WP et al. Mosby, Edinburgh, 2004,765-774.
35. Rautaharju PM, Surawicz B, Gettes LS. AHA / ACCF / HRS Recommendations for the standardization and interpretation of the electrocardiogram. Part IV: The ST segment, T and U waves and the QT
interval: a scientific statement from the AHA electrocardiography and
arrhythmias committee, Council on Clinical Cardiology; the ACCF
and the HRS: Endorsed by the International Society for Computerized Electrocardiology. Circulation 2009;119:e241-e250.
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36. Mirvis DM, Goldberger AL. Electrocardiography. Braunwalds heart
disease: a textbook of cardiovascular medicine, 9th edition. Editors:
Bonow RO, Mann DL, Zipes DP et al. Elsevier Saunders, Philadelphia,
2012,126-167.
37. Vetter VL. Clues or Miscues: how to make the right interpretation
and correctly diagnose long QT syndrome Editorial. Circulation
2007;115:2595-2598.
38. OConnor M, McDaniel M, Brady WJ. The pediatric electrocardiogram. Part I. Age-related interpretation. Am J Emerg Med 2008;26:
221-228.
39. Rubart M, Zipes DP. Genesis of cardiac arrhythmias. electrophysiologic considerations. Braunwalds heart disease: a textbook of cardiovascular medicine, 9th edition. Editors: Bonow RO, Mann DL, Zipes
DP et al. Elsevier Saunders, Philadelphia, 2012,653-686.
40. Akar FG, Yan GX, Antzelevitch C, Rosenbaum DS. Unique topographical distribution of M cells underlies reentrant mechanism of
torsade de pointes in Long QT syndrome. Circulation 2002;105:12471253.
41. Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long
QT syndrome. Curr Opin Cardiol 2002;17: 43-51.
42. Issa ZF, Miller JM, Zipes DP. Electrophysiological mechanisms of cardiac arrhythmias. Clinical arrhythmology and electrophysiology a
companion to Braunwalds heart disease, Saunders Elsevier, Philadelphia, 2009,1-26.
43. Ciudin R. Aritmiile cardiace. Mic Tratat de Cardiologie. Editor Ginghin C. Editura Academiei Romne, Bucureti, 2010, 679-710.
44. Pellizzon OA, Kalaizich L, Ptacek LJ, Tristani-Firouzi M, Gonzalez
MD. Flecainide suppresses bidirectional ventricular tachycardia and
reverses tachycardia-induced cardiomyopathy in Andersen-Tawil
syndrome. J Cardiovasc Electrophysiol 2008;19(1):95-97.
45. Noda T, Shimizu W, Satomi K et al. Classification and mechanisms
of torsade de pointes initiation in patients with congenital long QT
syndrome. Eur Heart J 2004;25:2149-2154.
46. Shimizu W. Diagnostic evaluation of long QT syndrome. Long QT
Syndrome. Cardiac electrophysiology clinics, volume 4, number 1.
Editors: Priori SG, Thakur RK, Natale A. Saunders, Philadelphia,
2012,29-37.
47. Zhang L, Benson DW, Tristani-Firouzi M et al. Electrocardiographic
features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic TU wave pattern pPredict the KCNJ2 phenotype.
Circulation 2005;111:2720-2726.
48. Napolitano C, Antzelevitch C. Phenotypical manifestations of mutations in the genes encoding subunits of the cardiac voltage-dependent
L-Type calcium channel. Circ Res 2011;108:607-618.
49. Moss AJ. Fragmented QRS is associated with torsade de pointes in
patients with acquired long QT syndrome. Heart Rhythm 2010;
7(12):1815-1816.
50. Goldenberg I, Mathew J, Moss AJ et al. Corrected QT variability in
serial electrocardiograms in long QT syndrome: the importance of
the maximum corrected QT for risk stratification. J Am Coll Cardiol
2006;48(5):1047-1052.
REVIEWS
Contact address:
Dr. Iancu Mdlina, Delta Hospital, 6A Racari Street, District no. 3,
Postal code: 031828, Bucharest, Romania. E-mail: madalina.iancu@gmail.
com
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
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-
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
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.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
World Health Organization. Preventing and managing the global epidemic: report of a WHO Consultation on Obesity, Geneva, Switzerland: World Health Organization 1997.
Ogden CL, Carroll MD, Curtin LR et al. Prevalence of overweight and
obesity in the United States, 1999-2004. JAMA 2006; 295(13):15491555.
Macarie C, Stoica E. Obezitatea i insuficiena cardiac relaia dintre
dou epidemii ale secolului 2007; XXII(2):79-83.
Apetrei E, Kulcsar I, Matei C et al. Studiul Urziceni Studiu populaional prospectiv de depistare a factorilor de risc pentru bolile
cardiovasculare. Partea a II-a Rezultate 2008; XXIII(4):305-316.
European Charter on Counteracting Obesity. [http://www.euro.who.
int/en/what-we-do/health-topics/noncommunicable-diseases/obesity/publications/pre-2009/european-charter-on-counteracting-obesity].
Perk J, De Backer G and Authors/Task Force Members: et al. European Guidelines on cardiovascular disease prevention in clinical
practice (version 2012). European Heart Journal 2012.
Whitlock G, Lewington S, Sherliker P et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57
prospective studies. Lancet 2009;373(9669):1083-1096.
Apetrei E. Paradoxul Obezitii? Revista Romn de Cardiologie
2009; XXIV(3):165.
Abel ED, Litwin SE, Sweeney G. Cardiac Remodeling in Obesity. Physiological Reviews 2008;88(2):389-419.
CASE REPORTS
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
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
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
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.
CASE REPORTS
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
N. Asan et al.
Hypertrophic obstructive cardiomyopathy and mitral valve abnormalities
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.
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.
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
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
IMAGES IN CARDIOLOGY
56
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.
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.
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 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.
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.
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.
IMAGES IN CARDIOLOGY
Figure 2. Acute right coronary artery thrombotic lesion in the Ist segment.
Timi 0 flux (continuous arrow).
Contact address:
Negoita Adrian, MD, Prof. Dr. C. C. Iliescu Emergency Institute
of Cardiovascular Diseases, 258 Fundeni Street, District no. 2, 022328,
Bucharest, Romania.
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.
IMAGES IN CARDIOLOGY
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].
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.
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.
UPDATES IN CARDIOLOGY
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)
Updates in cardiology
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.
Updates in cardiology
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.
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.
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
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
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.
ABREVIERI I ACRONIME
ABPM
ACC
ACE
ACS
FA
AHA
aPTT
AV
BRA
SA
DSA
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
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.
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-
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-
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
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
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.
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
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-
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
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.
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
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.
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
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
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
Nivelb
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
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.
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.
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.
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
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
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).
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
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.
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
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-
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-
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
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.
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
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
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
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-
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
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
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-
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
Nivelb
C
C
C
C
C
C
C
C
C
C
C
C
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.
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.
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
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.
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,
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
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.
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
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
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
Antiplachetar
Antiaritmic
Inhibitor de renin
B
C
D
Da
Nu
Necunoscut
Bine tolerat
Nu
Necunoscut
Amiodaron
Da
Da
Da
Da
Necunoscut
Necunoscut
Necunoscut
Necunoscut
Da
Ampicilin, amoxicilin,
cefalosporine, eritromicin,
Antibiotice
mezlocilin, penicilin
Imipenem, rifampicin, teicoplaAntibiotice
nin, vancomicin,
Aminoglucozide, quinolone,
Antibiotice
tetracicline
Atenololc
Da
Benazeprild
IECA
Da
Bisoprolol
Da
Da
Candesartan
Antagonist al receptorilor de
angiotensin
Necunoscut
Necunoscut; nu este
recomandat
Captoprild
IECA
Da
Clopidogrel
Colestipol,
Colestiramin
Danaparoid
Digoxinf
Antiplachetar
Necunoscut
Dae scad vitaminele liposolubile
Nu
Dae
Necunoscut
Medicamente hipolipemiante C
Necunoscut
B
C
Nu
Da
Nu
Dae
Disopiramid
Anticoagulant
Glicozid cardiac
Blocant al canalelor de calciu
(clasa a IV-a)
Antiaritmic (clasa IA)
Da
Dae
Enalaprild
IECA
Da
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
Anticoagulant
Nu
Nu
Heparin (nefracionat)
Anticoagulant
Nu
Nu
Hidralazin
Vasodilatator
Da
Hidroclorotiazid
Diuretic
Da
Irbesartan
Antagonist al receptorilor de
angiotensin
Necunoscut
Isosorbid dinitrat
Nitrat
Necunoscut
Isradipin
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).
Labetalol
-/-blocant
Da
Dae
Lidocain
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
Da
Phenprocoumona
Antagonist de vitamin K
Da
Procainamid
Propafenon
Propranolol
C
C
C
Da
Da
Da
Chinidin
Da
Dae
Ramiprild
IECA
Da
Da (maxim 1,6%)
Sotalol
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
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
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DENUMIREA MANIFESTRII
Controverse i soluii n HTA
Directori de curs: Prof. Dr. M. Cintez, Prof. Dr. Ctlina Arsenescu Georgescu
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
Iunie
Septembrie
Directori de curs: Conf. Dr. F. Mitu, Conf. Dr. Dana Pop, Dr. D. Gherasim
Agenda
April
May
May
Venice, Italy
22nd-25th May
London,
United
Kingdom
EuroCMR2013
The Working Group on Cardiovascular Magnetic Resonance of the
European Society of Cardiology (ESC)
23rd-25th May
25th-28th May
August
ESC Congress 2013
October
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
September
PLACE
June
DATE
Florence, Italy
Lisbon,
Portugal
Marseille,
France
Agenda
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
www.mediamed.ro