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European Journal of Heart Failure 2008 10(9):855-860; doi:10.1016/j.ejheart.2008.07.017
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© 2008 European Society of Cardiology

Maternal heart disease and pregnancy outcome: A single-centre experience

Verena Stangla,*, Johanna Schada, Gabriele Gossingb, Adrian Borgesa, Gert Baumanna and Karl Stangla

a Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie Charitéplatz 1, D-10117 Berlin, Germany
b Klinik für Geburtsmedizin Universitätsmedizin Berlin Charité Campus Mitte, Germany

* Corresponding author. Tel.: +49 30 450 513 153; fax: +49 30 450 513 932. E-mail address: verena.stangl{at}charite.de (V. Stangl).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Background: Maternal and neonatal complication rates are increased in pregnant women with heart disease. Cardiac risk assessment may be improved by defining low and high-risk groups.

Aims: To analyze pregnancy risks in low and high-risk women with cardiovascular diseases.

Methods and results: Pregnancy outcomes were analyzed in 93 consecutive women with heart disease, monitored in a single-centre cohort between 1996 and 2006. Women were classified according to pre-defined risk predictors as high-risk (left ventricular [LV] ejection fraction <50%, NYHA class>II or cyanosis, peak LV outflow gradient >60 mmHg) or low-risk (not meeting these criteria). Mean age was 28.1±5.7 years. 81.7% presented with congenital, 10.8% with acquired heart disease, and 7.5% with myocardial diseases. Severe maternal complications developed in 12.9% of all women: 6.5% heart failure, 3.2% arrhythmias, and 2.2% thrombotic complications. Maternal mortality was 1.1%. Women at high-risk (24.7%) had a 6.1-fold higher maternal complication rate and a 6.1 times higher foetal/neonatal event rate (abortion and stillbirth). 64.7% of the high-risk women delivered prematurely, before the 37th week, compared to 16.4% in the low-risk group.

Conclusions: Despite pronounced clinical variability of congenital and acquired heart diseases, a small number of risk conditions can effectively characterize women in whom pregnancy is associated with appreciably increased maternal and foetal risk.

Key Words: Pregnancy • Heart disease • Maternal • Foetal • Risk

Received February 11, 2008; Revised June 30, 2008; Accepted July 24, 2008


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
The number of women with heart disease who reach childbearing age in a good functional state increases continuously as advances in diagnosis and treatment improve overall health and prognosis. As a result, pregnancy becomes a realistic option for many of these young women. In western countries, maternal heart disease complicates 1-3% of pregnancies and is the third common cause of maternal death during pregnancy [1,2].

Increased cardiac demands during the course of pregnancy potentially increase morbidity and mortality in women with underlying heart disease. Pregnancy-associated cardiocirculatory changes—primarily, increase in heart rate, stroke volume, and cardiac output, as well as reduction in systemic vascular resistance—may threaten maternal outcome: which in turn holds foetal implications. Whereas pregnancy is associated with high maternal morbidity under some conditions (e.g., cyanosis), others such as valve insufficiencies generally follow a benign course during gestation if myocardial function is not compromised [3]. It is consequently essential to thoroughly evaluate patients for underlying cardiovascular disease in order to provide optimal care during pregnancy.

Most data concerning pregnancy course in heart disease patients are anecdotal reports or are in small series; only a few comprehensive studies are available [4-9]. The primary objective of the present study was, accordingly, to analyze maternal and foetal pregnancy risks in women with cardiovascular diseases in a real-life cohort from a tertiary university hospital in Germany.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
From 1996 to 2006 pregnancy course and foetal outcome were assessed in patients with congenital or acquired heart disease who were monitored in the Charité University Hospital Center, Campus Mitte, Berlin, Germany. More than 90% of the patients came to medical attention in their first trimester, a small proportion of them already prior to conception, for the purpose of planning their pregnancy. According to the underlying aetiology, diseases were classified into congenital and acquired heart diseases, and a further group comprising primary myocardial diseases. If patients presented with more than one diagnosis, the one with the highest severity was selected for classification. Cardiovascular history, functional and clinical evaluation (New York Heart Association [NYHA] functional class, dyspnoea, oedema, syncope, etc.), ECG, and echocardiography were assessed at the onset of pregnancy. As a protocol, care of the patients during pregnancy and delivery was realized in a multidisciplinary approach by cardiologists, gynaecologists, and anaesthesiologists. This retrospective analysis of maternal and foetal outcome during pregnancy in women was approved by the Ethics Committee of the Charité University Hospital Center.

From a cardiovascular and clinical point of view—as proposed earlier by Siu et al. [6]—pregnant women were categorized in a high-risk group if at least one of the following risk conditions was present: left ventricular (LV) ejection fraction (EF) <50%, NYHA class>II or cyanosis, or left heart obstruction; women without these risk conditions were classified in the low-risk group.

Maternal cardiovascular endpoints during pregnancy were defined as follows: clinically significant symptomatic heart failure, thromboembolic events, and arrhythmias requiring treatment (according to the attending cardiologist); mortality.

The following parameters of obstetrical and foetal outcomes were analyzed: abortions (spontaneous abortion referred to any spontaneous foetal loss before 20 weeks of gestation; therapeutic abortion included all medically indicated terminations before 20 weeks of gestation; stillbirths were defined as foetal loss past 20 weeks of gestation), pregnancy duration (gestational age), bleedings (defined as prepartum vaginal haemorrhage or postpartum haemorrhage requiring therapy), perinatal outcome (live births; preterm delivery defined as birth before 37 weeks of gestation), mode of delivery (spontaneous; induction of labour; caesarean), and birth weight. Premature delivery comprises cases of spontaneous preterm delivery and of scheduled premature caesarean section.

2.1. Data analyses
To investigate the relationship between the severity of maternal heart disease and maternal and foetal/neonatal as well as obstetrical event rates total patient sample was divided into a high and low-risk group depending on the presence or absence of the following risk factors: left ventricular ejection fraction <50%, NYHA functional class>II or cyanosis, and peak gradient in the LVOT >60 mmHg. Event rates were compared between high and low-risk groups by {chi}2, and t-tests wherever appropriate.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1. Characteristics of the study population
A total of 93 patients with 93 pregnancies were included in the study. There were no twin pregnancies. Maternal baseline characteristics are outlined in Table 1.


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  		Table 1 Maternal baseline characteristics

 
In total, 76 (81.7%) women presented with congenital heart disease and 10 (10.8%), with acquired heart disease. The 3 patients with coronary heart disease had experienced myocardial infarction a number of years before becoming pregnant. All had pronounced cardiovascular risk factors at the time of infarction, with one woman also demonstrating circulating antiphospholid antibodies. Seven (7.5%) pregnant patients had primary myocardial disease. The cardiac lesions and maternal risk conditions are depicted in Table 2.


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  		Table 2 Cardiac lesions and risk stratification

 
3.2. Pregnancy course
In 52.7%, pregnancy course was uneventful without cardiovascular, foetal/neonatal or obstetrical complications. Of the total, 16.1% were hospitalised during pregnancy for cardiac reasons and 23.7% for obstetric.

Severe maternal complications developed in 12.9% of all women (Table 3): 6.5% heart failure, 3.2% arrhythmias, and 2.2% thrombotic complications. Maternal mortality was 1.1%. Women at high-risk (n=23, 24.7%) had a 6.1-fold higher maternal complication rate (34.8% vs. 5.7%) than did low-risk women (n=70, 75.3%): 21.7% developed heart failure (vs. 1.4% in the low-risk group), 8.7% suffered thrombotic complications (vs. 0%), and mortality was 4.3% (vs. 0%).


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  		Table 3 Maternal, foetal/neonatal and obstetrical outcome in high-risk versus non-high-risk women

 
In detail, the following severe maternal cardiovascular events occurred:
  1. During pregnancy, 6 women (6.5%) experienced heart failure. During the first trimester there was one case of severe pulmonary congestion that was refractory to medical therapy and that required urgent surgical intervention (aortic valve replacement for severe congenital aortic stenosis). In the perioperative period, spontaneous abortion occurred in this patient. A total of 5 women suffered heart failure in the final trimester of the pregnancy: 1 tetralogy of Fallot, 1 coarctation of the aorta, 1 severe mitral stenosis, 1 severe tricuspidal insufficiency (following endocarditis and drug addiction), and 1 non-compaction cardiomyopathy. In these 5 women, caesarean was performed for cardiac reasons.
  2. Two severe thrombotic complications occurred (2.2%): in 1 patient, this involved partial thrombosis of the aortic valve prosthesis during therapy with low molecular weight heparin (LMWH) during pregnancy. The ensuing restenosis of the prosthesis was partially reversible after changing the regimen to oral anticoagulation. In another woman with coronary artery disease (CAD, earlier myocardial infarction) and reduced LV-function, a large LV thrombus emerged under LMWH therapy. In this patient, abortion was required owing to intrauterine death in early pregnancy.
  3. A total of 3 (3.2%) patients developed relevant arrhythmias/conduction defects: 1 tachyarrhythmia (atrial fibrillation) requiring cardioversion during pregnancy, 1 symptomatic sinus bradycardia (30/min) and syncopes, and 1 women with binodal disease (corrected ASD) and syncopes in which pacemaker implantation was performed immediately after caesarean.
  4. Maternal mortality was 1.1% (1 patient). Death occurred following acute heart failure secondary to severely reduced ejection fraction in a woman with patent foramen ovale who had successfully undergone primary interventional ablation for WPW syndrome years before to pregnancy. The patient died as a result of cardiocirculatory arrest during emergency caesarean section.

Of the 12 patients (12.9%) with cardiovascular events during the study, the majority responded satisfactorily to clinical management. Two women were refractory to clinical therapy: as described earlier, one patient with congenital aortic stenosis required surgery during pregnancy, and one died following heart failure. Most cardiovascular complications occurred during the third trimester of pregnancy, with 30.7% leading to indicated delivery (for cardiac reasons).

During the period under observation, there were 3 cases (mitral regurgitation, atrioventricular septal defect, and severe aortic regurgitation) of preeclampsia and one case (mitral regurgitation) of HELLP (haemolysis, elevated liver enzyme, and low platelet) syndrome. There were no cases of acute myocardial infarction or endocarditis.

3.3. Foetal/neonatal and obstetrical outcome
The foetal and neonatal outcomes are shown in Table 3. There were 5 (5.4%) therapeutic abortions, 4 of them for perceived cardiac risk. One termination occurred after diagnosis of trisomy 21. Spontaneous abortion was recorded in 3 women and stillbirth, in 1 case. In high-risk patients, foetal event rate (abortion and stillbirth) was 6.1 times higher than in low-risk women (26.1% vs. 4.3%). Moreover, 64.7% of the women at high-risk delivered prematurely before the 37th week, compared to 16.4% in the low-risk group. A total of 16.1% (15 newborns) were admitted to the ICU. Birth weight was at the low level of 2592±721 g (mean±SD) in the high-risk patients (low-risk: 3049±563). β-blocker use (n=15), on the other hand, was not associated with significantly reduced birth weight 2914±501 g.

Six haemorrhagic complications occurred during pregnancy: retroplacental bleeding, vaginal bleeding, and bleeding after sectio caesaria requiring transfusion. Two of these patients were on LMWH. Vaginal delivery occurred in 45.2% of the women, and 36.6% had induction of labour. Caesarean section was performed on 46 (54.8%) of the women, with significantly more in the high-risk (76.5%) than in the low-risk group (49.3%) (Table 3).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
Despite undisputed advances in diagnosis and treatment, maternal heart disease—which complicates around 1-3% of pregnancies in Western countries—still represents an interdisciplinary medical challenge.

Our single tertiary-centre experience documented a 12.9% incidence of maternal cardiovascular events during pregnancy in women with congenital and acquired heart disease. Foetal event rate was 9.7%. Nevertheless, due to exhaustive interdisciplinary care, 90.3% of the pregnancies resulted in healthy live births. Event rates in our study are comparable to those of other studies. A recent literature review with analysis of more than 2000 pregnancies in women with structural congenital heart disease, reported cardiac complications in 11% of pregnancies [10].

Accurate assessment of the individual maternal and foetal risk in pregnant women with heart disease is of fundamental importance for optimal patient care. Despite the diversity and broad morphological and functional variability of heart diseases, few predictors for complications during pregnancy have been recently described. In a prospective multicentre study enrolling 562 women with heart disease monitored in 13 Canadian hospitals, Siu et al. identified poor functional NYHA class or cyanosis, left ventricular systolic dysfunction, and left heart obstruction as major determinants for maternal cardiac complications [6]. In the clinical setting, this classification proved to be basically useful and enabled reliable assessment not only of maternal but also of foetal/neonatal risk. In our study, a total of 34.8% of the high-risk group suffered from maternal complications in comparison to only 5.7% of the women at low-risk. Accordingly, the high-risk group (24.7%) had a 6.1-fold greater severe maternal event rate; the only death also occurred in this group.

Review of the literature indicates that mortality among minimally symptomatic pregnant women with cardiac disease is about 1%: i.e., within the range of the incidence among the healthy general population [11,12]. In contrast, pregnant women with severe symptoms have been reported to experience a mortality risk up to 5-15% [13]. The relatively low mortality rate in our cohort may be associated with the intensive interdisciplinary care of the patients during pregnancy and delivery. The most frequently encountered cardiac complication in our study was clinically significant heart failure assuredly related to marked haemodynamic changes occurring during gestation [3]. In our study, all but one patient developed heart failure in the last trimester of the pregnancy. Most episodes resolved without sequelae.

Pregnancy is a hypercoagulable state in which thromboembolic complications occur at an incidence of 1/1000-2000 normal pregnancies [14]. In our study, thrombotic events complicated 2.2% of the pregnancies; these complications appeared in women under high-risk of thromboembolism (reduced LV-function, mechanical valve) despite heparin therapy. Similarly, Drenthen et al. found in his overview a rate of 2.2% (n=15) thromboembolic complications in 688 completed pregnancies in women with congenital heart disease [10].

Arrhythmias during pregnancy may cause significant haemodynamic compromise to both mother and fetus, and may impair outcomes [5,15,16]. In our study, 3.2% of the patients with heart disease presented arrhythmias/conduction defects during pregnancy. These rhythm disorders were not associated with further maternal or foetal complications.

In our study, maternal risk stratification also allowed assessment of foetal/neonatal and obstetrical risk. In low-risk women, abortion and stillbirth rates as well as birth weights were comparable to those reported for the general healthy population [17,18]. However, preterm birth rate (16.4%) in our low-risk group was slightly higher than in healthy women (reported to be 10-12%), but comparable to other studies in women with congenital or acquired heart disease [6,9,13,19]. In the high-risk group, however, foetal event rates were significantly higher: abortions and stillbirths occurred 6.1-fold more often than in low-risk women. This high miscarriage rate is probably even underestimated because abortions occurring before medical attention and referral may not have been detected. "High-risk" in this context was also associated with a 3.9-fold increased preterm rate and significantly reduced birth weight compared to low-risk women with heart disease. Reduced uterine blood flow secondary to haemodynamic compromise and associated with left ventricular obstruction or reduced myocardial function may explain this impaired intrauterine foetal growth. Finally, obstetric events also accumulated in the high-risk group (more frequent bleeding and more caesareans).

Several limitations of our study must be considered. The retrospective design that necessitates a review of the patients' medical records may be associated with potential source of error. However, information bias was minimized by the uniformity of obstetric and cardiology caregiving from the same centre. In addition, our study cohort from a tertiary university hospital may not have provided a representative patient sample.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
Pregnancy of women with heart disease is still a challenging condition: one associated with elevated maternal and foetal morbidity and mortality. In the clinical setting, accurate individual risk assessment is of fundamental importance. Despite the diversity of cardiac lesions presented by pregnant women with heart disease, even only a small number of clinical parameters—including poor functional NYHA class, left ventricular systolic dysfunction, and left heart obstruction—allow clinically useful dichotomic classification into high-risk and low-risk patients. Data from literature as well as our own experience indicate that low-risk women not meeting one of these criteria generally tolerate pregnancy well. Maternal and neonatal event rates, however, dramatically increase in high-risk patients. Consequent interdisciplinary approach, to include specialized cardiologic care, high-risk obstetric support, and neonatologic expertise with close monitoring of patients, are prerequisite for successful management of high-risk pregnancies with maternal heart disease.


   Acknowledgement
 
We sincerely appreciated Ulrike Günther in preparing the manuscript.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

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