Introduction
Maternal conditions complicate the pregnancy in 1–4% of cases. Only limited data on the prevalence and incidence of heart diseases complicating pregnancy are still currently available [1]. Knowledge of cardiovascular risks during pregnancy and how to address them is crucial for preconception counselling [2]. As all available treatment methods affect not only the mother but also the foetus, the aim must be to optimise management from the perspective of both the mother and the child. Treatment that is beneficial to the mother may be associated with potential harm to the developing baby or, in extreme cases, treatment allowing the mother to survive may cause fetal death. On the other hand, management that protects the child may lead to suboptimal treatment outcomes for the mother. As there are no prospective or randomised studies, it seems more difficult to establish uniform rules of management for the difficult issue of the provision of care for pregnant women with a history of cardiac disease. In order to improve the current state of knowledge, further registries and prospective observational data on epidemiology and drug exposure during pregnancy are needed, provided by the European Society of Cardiology (ESC) guidelines and the Registry of Pregnancy and Cardiac Disease (ROPAC), run by the ESC and the European Surveillance of Congenital Anomalies (EUROCAT) network of registers.
Epidemiology
In Western European countries, the risk of cardiovascular disease during pregnancy has increased due to the older age of women at the time of their first pregnancy. However, this fact alone — pregnancy at a more mature age — does not explain the increased incidence of cardiovascular diseases (CVD) during pregnancy [1]. However, late pregnancies falling towards the end of the childbearing age (40–50 years) are statistically more likely to be associated with an increased prevalence of cardiovascular risk factors, especially diabetes, hypertension and obesity. Moreover, an increasing number of women with congenital heart defects are reaching childbearing age [3]. In Western countries, maternal heart disease is the leading cause of maternal death during pregnancy [4].
The most common cardiac condition complicating pregnancy is hypertension which occurs in 5–10% of all pregnancies. Congenital heart defects are next in line. In non-Western countries, rheumatic valvular defects predominate, representing 56–89% of all CVD during pregnancy [5].
Sources of knowledge on the management of patients with cardiovascular diseases during pregnancy
In terms of the publications on the management of cardiovascular diseases in pregnant women, the ESC guidelines occupy a special position. It is possible primarily thanks to the fact that they are among the few recommendations that still somehow escape the rules of evidence-based medicine which still prevails, especially in cardiology. For obvious ethical reasons, pregnant women have always been disqualified from participating in clinical trials, and those who are not pregnant are required to use effective contraception during the trial. Consequently, expert opinions remain the basis for almost all recommendations on this topic. The source of those opinions, apart from indirect indications obtained from animal testing, can only be the clinical experience gained in daily work with patients as well as the registers of pregnant women with a history of cardiac disease, such as ROPAC.
The first guidelines published by the ESC on pregnant women with cardiovascular diseases appeared in 2003 [1]. Those guidelines have been the foundation of knowledge in this difficult topic of pre-, peri- and postnatal care of pregnant women with a history of cardiac disease. The latest update of the ESC Guidelines on the care of pregnant women with heart diseases was published in 2018 [1]. Large amount of knowledge contained therein is based on the authors’ own experience. The second component that provides a valuable source of information on the management of the analysed group of patients are the registers maintained, among others, by the ESC. The most important of those are:
ROPAC – Registry of Pregnancy and Cardiac Disease
The register was established at the initiative of the ESC in 2007 [6]. Initially, it included patients with a structural heart defect. Recruitment is currently underway for Part III of the study — female patients with aortic pathology or a genetic predisposition to its development, as well as pregnant women with at least one valve prosthesis (biological or mechanical). By the end of 2018, 5739 pregnant patients with all types of structural heart disease had been included in ROPAC. That contributed to expanding the current literature and management protocols for this type of patients as well as it allowed identification of further gaps in knowledge about this problem [6]. Aortic abnormalities are among the most common causes of heart disease-related maternal mortality [7]. In the case of valve prostheses, a high rate of complications during pregnancy are observed. The most common ones include: caesarean delivery, increased hospitalisation days during pregnancy, maternal heart failure (HF), pre-term delivery or intrauterine growth retardation [8]. For those reasons, as of February 2019, the ROPAC study is continuing with a particular focus on two types of structural heart disease: pathology within the aorta (as well as genetic predisposition to its development) and the status post replacement of at least one heart valve [9].
The partial results of the ROPAC are now published [10]. In the years 2007–2011, 1321 women were included in the study. Congenital heart defects were found in 66% of patients, valvular defects in 25%, cardiomyopathies in 7% and coronary artery disease in 2% of patients. Maternal mortality was 1% (0.007% in the normal population based on literature data). A total of 338 female patients were hospitalised during pregnancy (26%), including 133 due to HF. Caesarean section was performed in 41% of patients. Maternal and child mortality was higher in developing countries compared to developed countries. Fetal mortality was 1.7% and neonatal mortality was 0.6% [10].
The ROPAC is currently one of the most valuable sources of knowledge used for the purposes of formulating guidelines on the management of pregnant women with a positive cardiac history.
PPCM registry – PeriPartum CardioMyopathy registry
This register was created in 2016. The first results were published in 2017 [11]. This study aims to compare clinical data of patients with PPCM from ESC member countries compared to non-ESC countries. The study began in 2016 and will be continued until the number of 1000 female patients is reached. This publication aims to present preliminary results after the inclusion of the first 500 women in the study. Out of those women, 411 pregnant women from 43 countries with complete records were analysed. Pharmacological treatment initiated after pregnancy was found
to be similar in both study groups, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, mineralocorticoid receptor antagonists. In contrast, drugs such as beta-blockers and ivabradine were used less frequently in non-ESC countries while diuretics, digoxin and bromocriptine were used more frequently (32.6% vs. 7.1%; p < 0.001). After 1 month, persistence of HF symptoms was more common in the non-ESC group (92.3% vs. 81.3%; p < 0.001). Thromboembolic complications from the venous system, arterial emboli and cerebrovascular incidents occurred in 28 out of 411 patients (6.8%) [11]. The neonatal mortality rate was 3.1%; a detailed analysis was not included in the register. The study is part of the EURObservational Research Programme and is an initiative of the Study Group on PPCM of Herat Failure Association.
Organisation of care for women of childbearing age with cardiovascular disease — general recommendations
Preconception counselling
When providing cardiovascular care to a woman planning a pregnancy or during pregnancy, it is important to remember that it is a long-term and comprehensive process, including follow-up visits, decisions on necessary hospitalisation, tests, the inclusion of pharmacotherapy, suggestions for premature termination of pregnancy or normal termination of pregnancy, the method of termination of pregnancy — spontaneous labour or caesarean labour, breastfeeding or withholding lactation. It is crucial for the patients that the cardiologist and gynaecologist work together to develop a coherent action plan. The provision of care does not end with the childbirth; on the contrary, it must extend up to approximately six months after the birth. It is often prolonged to fulfil the planned treatment, taking advantage of the period between pregnancies.
It is clear that all women diagnosed with heart or aortic disease and planning a pregnancy need preconception counselling [12]. If there is a high risk of complications or possible contraindications to pregnancy, the risks of pregnancy and the need for careful planning should be discussed with the woman at a sufficiently young age. At the same time, it should be noted that in many cases pregnancy does not significantly increase cardiovascular risk. There is only a small group of cardiac conditions in which the pregnancy should be terminated by caesarean section (Figure 1). The minimum diagnostic tests that are necessary to estimate the risk of pregnancy in CVD women include electrocardiogram, echocardiography and cardiac diagnostic test [13]. However, in the event of aortic disorders, full imaging of this vessel by computed tomography or magnetic resonance scanning must be carried out to enable giving appropriate advice before pregnancy. Predictive factors for cardiac events in pregnant women include heart rate limit and peak oxygen uptake (in the spiroergometric test). Exercise capacity in pregnant women > 80% of maximal value is associated with successful pregnancy termination [1]. Genetic counselling should be considered in women with congenital heart disease or congenital arrhythmias, cardiomyopathy, aortic disease or genetic abnormalities associated with CVD [1].
Maternal cardiovascular risk assessment
In a group of patients with a suspected or positive history of CVD, it is recommended that the risk of complications be assessed and counselling be given before pregnancy. The mWHO classification (Table 1), which can be used in both the pre- and post-conceptional periods, will be helpful in this regard [14].
|
Factor |
Class |
||||
|
mWHO I |
mWHO II |
mWHO II–III |
mWHO III |
mWHO IV |
|
|
Risk |
No appreciable increase in the risk of maternal death and at most a slight increase in the risk of other complications |
A small increase in the risk of maternal death or a moderate increase in the risk of other complications |
A moderate increase in the risk of maternal death or a moderate/major increase in the risk of other complications |
A significant increase in the risk of maternal death or a high increase in the risk of other complications |
An extremely high risk of maternal death or a high increase in the risk of other complications |
|
Rate of cardiac events in the mother |
2.5–5% |
5.7–10.5% |
10–19% |
19–27% |
40–100% |
|
Counselling |
Yes |
Yes |
Yes |
Yes — expert advice required |
Yes — pregnancy contraindicatedb |
|
Place of care during pregnancy and childbirth |
Community hospital |
Community hospital |
Referral centre |
Experienced obstetrics and cardiology centre |
Experienced obstetrics and cardiology centre |
|
Minimum number of visits during pregnancy |
1–2 |
In each trimester |
1 ×/2 mth |
1 ×/1–2 mth |
1 ×/mth |
The risk of cardiovascular complications in pregnancy depends on the type of heart disease, ventricular and valvular function, functional class, the presence of cyanosis, pulmonary artery pressure values and other factors, including comorbidities.
The following should be considered in the risk assessment: interview findings (including functional class), arterial blood haemoglobin oxygen saturation (SaO2), serum natriuretic peptide levels, echocardiographic assessment of ventricular and valvular function, pulmonary artery pressure and aortic dimensions, exercise capacity and the presence of arrhythmias [15].
The risk associated with a specific heart disease should be estimated based on the modified mWHO classification, although this probably performs better in populations in developed countries than in developing countries. According to this classification, heart diseases are classified into five classes (Table 2), which are associated with different risks of complications and need different management [14].
|
Class I according to mWHO |
Class II according to mWHO |
Class II–III according to mWHO |
Class III according to mWHO |
Class IV according to mWHO |
|
|
Diagnosis (if the patient is otherwise in good health status and the course |
Minor cardiac dysfunction(s):
Atrial or ventricular single ectopic beats |
Uncorrected ASD or VSD Tetralogy of Fallot after corrective surgery Mostly (supraventricular) arrhythmias Turner syndrome without aortic dilatation |
Slight LV dysfunction (EF > 45%) Hypertrophic cardiomyopathy Defective native valve or biological prosthesis not classified as WHO class I or IV (minor MS, moderate AS) Marfan syndrome or other HTAD without aortic dilatation Aorta < 45 mm in patients with bicuspid aortic valve Corrected aortic coarctation. AVSD |
Moderate LV dysfunction (EF 30–45%) A history of PPCM without residual LV impairment Mechanical valve Systemic RV with good or slightly impaired function Fontan circulation if patient is otherwise in good health status and cardiac course is uncomplicated Uncorrected cyanotic heart defect Other complex heart defect Moderate MS Severe asymptomatic AS Moderate aortic dilatation (40–45 mm in Marfan syndrome or HTAD; 45–50 mm in patients with bicuspid aortic valve, ASI 20–25 mm/m2 in Turner syndrome, < 50 mm in tetralogy of Fallot) Ventricular tachycardia |
Pulmonary arterial hypertension Severe systemic ventricular dysfunction (EF < 30% or NYHA class III–IV) A history of PPCM with any residual LV dysfunction Severe MS Severe symptomatic AS Systemic RV with moderate to severe dysfunction Significant aortic dilatation (> 45 mm in Marfan syndrome or HTAD; > 50 mm in patients with bicuspid aortic valve, ASI > 25 mm/m2 in Turner syndrome, > 50 mm in tetralogy of Fallot) Vascular form of Ehlers-Danlos syndrome Severe aortic (re)coarctation Fontan circulation with any complications |
As the risk can vary over time, it should be reassessed at each pre-pregnancy visit.
Risk of obstetric and neonatal complications
Pregnant women with cardiac disease are at increased risk of obstetric complications, including preterm birth, pre-eclampsia and postpartum haemorrhage. Neonatal complications occur with a frequency of 18–30%, including a mortality rate of 1–4% [16]. Predictive factors for adverse maternal and neonatal events are shown in Table 3.
|
Risk factors for cardiovascular events in the mother |
Predictive factors of adverse neonatal events |
|
|
Diagnosis of cardiovascular diseases in pregnancy
It is possible that some women will only be diagnosed with a cardiac condition during pregnancy. The physiological changes in the cardiovascular system that occur during pregnancy can sometimes cause symptoms that raise the suspicion of CVD (e.g., swelling), making it difficult to diagnose, for example, HF.
Diagnostic evaluation for CVD in pregnant women include:
- medical interview and physical examination;
- echocardiography – in case of inadequate or unexplained dyspnoea during pregnancy and/or a new pathological cardiac murmur (e.g. any diastolic murmur);
- measurement of blood pressure using a validated device;
- assessment of proteinuria, especially in the case of a personal or family history of hypertension or pre-eclampsia;
- oximetry in women with congenital heart disease.
If there is an increased risk of fetal abnormalities, fetal echocardiography performed by an experienced specialist is recommended for any pregnant woman with unexplained or new cardiovascular signs and symptoms. If echocardiography is insufficient to establish a definitive diagnosis, a gadolinium-free cardiac magnetic resonance scan should be considered.
In addition, if required, the following can be done:
- chest radiography;
- cardiac catheterisation (only for very strict indications);
- computed tomography (in selected women) and electrophysiological study (only for vital indications) [17].
Treatment and delivery recommendations [18]
- It is recommended that patients at high risk of complications be treated in referral centres where a multidisciplinary team of specialists is available.
- If cardiac surgery is necessary in a pregnant woman, it is advisable to administer a glucocorticosteroid to the pregnant woman between 24 and 37 week of pregnancy.
- In most cases, vaginal delivery is recommended.
- Induction of labour after the 40th completed week of pregnancy should be considered in all women with heart disease .
- In women with severe hypertension, natural labour with epidural anaesthesia should be considered.
- If the gestational age has exceeded 26 weeks, pregnancy termination should be considered before the necessary surgical intervention.
- Consideration may be given to coronary artery bypass grafting or valve surgery during pregnancy if conservative management (including pharmacotherapy) has failed and if the mother’s life is at risk or if percutaneous treatment is not available. Prophylactic antibiotic therapy during labour to prevent infective endocarditis is not recommended [18].
- In patients with severe cardiac dysfunction, full resuscitation and intensive care in the delivery room or operating theatre (intensive obstetric care room) must be provided.
These conditions include:
- anaesthetic care;
- possibility of monitoring: electrocardiogram monitoring, haemodynamic monitoring and pulse oximetry monitoring;
- full resuscitation care: drugs, intubation kit and mechanical ventilation kit, defibrillator, pacemaker and electrodes for transcutaneous and endocavitary stimulation.
Centres that are unable to provide the listed conditions of delivery should not provide obstetric care for pregnant women at risk of cardiac complications. The poor prognosis is usually related to the lack of adequate specialist care, the absence of a clear diagnosis and defined management principles. A well-prepared patient giving birth under intensive care is able to give birth successfully even with very advanced heart disease.
Conclusions
The provision of care for pregnant women with heart disease represents a major challenge in daily medical practice. When organising the management of such patients, a multidimensional approach to the problem – which involves close collaboration between the cardiology team and gynaecology team — is crucial. Despite the numerous publications, more studies are still needed to expand the knowledge of cardiac care for pregnant women. Data obtained from the Registries set up at the initiative of the ESC seem promising. These data are now the main source of knowledge for formulating recommendations on the topic of the provision of care to pregnant women with history of a cardiac disease.
Conflict of interest
None declared.
