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Rheumatic Heart Disease in Pregnancy
Introduction
Heart disease is the highest indirect (nonobstetric) cause of mortality for pregnant women in both high-income countries (HICs) and low- and middle-income countries (LMICs). Valvular heart disease is an important contributor to the burden of maternal disease, accounting for 15% of pregnancy-related complications in HICs, although this figure is significantly higher in LMICs owing to the much higher prevalence of rheumatic heart disease (RHD). In these resource-limited populations, RHD accounts for 50%–90% of maternal cardiac complications, with rheumatic mitral stenosis (MS) being the single most common cause of cardiac maternal mortality.
Damage to the cardiac valves, which is the hallmark of RHD, often leads to significant valvular heart disease and left ventricular dysfunction. These changes, coupled with the marked physiological adaptations associated with pregnancy, impose an increased hemodynamic stress on the cardiovascular system, increasing the risk of cardiovascular complications and poorer outcomes for both the mother and fetus. Nevertheless, pregnancy complicated by nonsevere valvular heart disease is generally associated with a favorable prognosis, providing that the risks are managed appropriately. For many patients living in LMICs, however, adequate preconception and prenatal care are not available.
Over the last number of years new data have emerged relating to pregnant women with heart disease and the recently updated European Society of Cardiology (ESC) guidelines on cardiovascular disease in pregnancy have introduced a number of important updates and recommendations. In particular, counseling is stressed as a crucial intervention for all women with heart disease who are contemplating pregnancy or are already pregnant. Moreover, those with moderate or greater risk heart disease should receive counseling and a full risk assessment by a “pregnancy heart team,” ideally in an expert center using modified WHO (mWHO) criteria. Other important new recommendations include the introduction of the Pregnancy and Lactation Labeling Rule (PLLR) drug table, which replaces the FDA's A to X categorial system with a more narrative approach, and the recommendation to consider inducing labor at 40 weeks' gestation for all women with cardiac disease (to reduce obstetric risk).
The 2014 American Heart Association and American College of Cardiology (AHA/ACC) guidelines on the management of valvular heart disease also make important recommendations on the management of pregnant women. It must be stressed however that most of the data on which the ESC and AHA/ACC recommendations are based are not from randomized control trials, so the guidelines' recommendations are mostly level C (expert opinion). Furthermore, these guidelines have been developed by experts in HICs, where resource limitation is usually not an issue.
This chapter will focus on the main issues surrounding preconception evaluation and management of RHD in stable pregnant patients. The medical ( Chapter 6 ), interventional ( Chapter 7 ), surgical ( Chapter 8 ), and emergency ( Chapter 16 ) management of nonpregnant RHD patients is discussed in detail elsewhere, with important differences in the management of pregnant patients discussed here.
Epidemiology of Rheumatic Heart Disease in Pregnancy
The scarcity of data on RHD in pregnancy is in part due to underdiagnosis as well as a lack of adequate antenatal care in most endemic settings. Although RHD and other cardiac diseases (such as hypertensive diseases and cardiomyopathies) are recognized as a major health burden in LMICs, a systematic search for these conditions is usually not performed during pregnancy in these settings.
Prevention and control programs for acute rheumatic fever (ARF) and RHD have not been implemented in many endemic areas. The lower a country's income category, the younger the median age and more advanced the disease is at presentation, and this epidemiological pattern has direct implications for the maternal health of a country's population. Poor countries with a high prevalence of RHD usually have a low human development index, poor provision of family planning, high fertility rates, weak prepregnancy advice for women with heart disease, and a 14 times higher maternal mortality ratio than HICs.
The Registry of Pregnancy and Cardiac Disease (ROPAC) data, which aimed to determine the variation in structural heart disease in pregnant patients, is the largest prospective cohort of pregnant women with RHD, and included 390 pregnant women with rheumatic mitral valve disease and no prepregnancy valve replacement. Three quarters of the patients (75%) came from LMICs. MS with or without mitral regurgitation (MR) was present in 273 women, and was moderate to severe in 59.0% of patients. One maternal death occurred during pregnancy in a patient with severe MS.
The first prospective global registry of RHD (REMEDY), which collected data from 12 African countries, India and Yemen, provides a contemporary description of the presentation, complications, and treatment of RHD. Young females were highly represented (median age 28 years, females 66.2%) among the 3343 patients enrolled at the 25 participating hospitals, and had a higher prevalence of major cardiovascular complications. Female predominance was seen across all income groups, varying from 63.0% in lower middle-income countries (Egypt, India, Mozambique, Nigeria, Sudan, and Yemen) to 71.3% in upper middle-income countries (Namibia and South Africa). Among the 1825 women of childbearing age (12–51 years), only 65 (3.6%) were on contraception, which can be explained by low level of education and awareness, poor access to healthcare, culturally inadequate care provision, and health systems that do not meet the needs of pregnant women with RHD.
With current management practices, maternal and fetal mortality can be reduced, and the incidence of complications is predictable based on known risk factors. Available data demonstrate that pregnancy outcomes in RHD patients are determined by the development status of a country and its health system, and the studies summarized here highlight these health disparities. In a study to determine maternal cardiac complications and obstetric outcomes among the 52 indigenous women of childbearing age in northern Australia with RHD, there were no maternal or neonatal deaths. Despite four patients being first diagnosed with RHD after developing acute pulmonary edema during the peripartum period, this study showed that a very low incidence of cardiac complications and no deaths is possible with expert and skilled care. In comparison, Diao et al. report on maternal and fetal outcomes in 50 Senegalese pregnant women with heart disease, of which 46 had RHD. Pulmonary edema (36), arrhythmias (18), and pulmonary embolism (2) were major complications found on admission among the 39 unoperated females (32 of whom had MS). There were 17 maternal deaths (34%) and the fetal outcomes were also poor: six fetal deaths, five therapeutic abortions, and four stillbirths (neonatal mortality was 7.6%). It is not possible to clearly assess to what extent these results are influenced by differences in the severity of cases at presentation and quality of care in the two countries. However, they do suggest that late presentation of patients and lack of access to specialized care for diagnosis and management might explain the high frequency of pregnancy-related hemodynamic decompensation and poor outcomes in women with rheumatic MS in studies from developing countries. This contrasts with a number of recent series from Western countries, which reported maternal mortality rates below 3%.
Maternal Cardiac Physiology
Given that pregnancy is akin to a physiological stress test, the period following conception can unmask previously silent maternal heart disease or exacerbate previously well-controlled preexisting conditions. The major hemodynamic changes that occur in pregnancy are summarized in Fig. 9.1 . A 30% increase in stroke volume and 10%–20% increase in heart rate result in a 30%–50% increase in cardiac output above the nonpregnant state. These changes begin in early pregnancy and plateau between the second and third trimesters. Systemic vasodilation and the low-resistance utero-placental circulation facilitate a drop in systemic vascular resistance (SVR) by 35%–40%, which helps accommodate for the increase in cardiac output. SVR reaches the nadir by the end of the second trimester and then slowly begins to increase until term. By the sixth week of pregnancy, the plasma volume also begins to increase and by the second trimester is 50% above baseline. Although there is a corresponding rise in red cell mass, this is not in proportion to the plasma volume, resulting in physiological anemia.
Together, each of these changes culminates in a hyperdynamic circulation leading to increased flow, and thus increased gradients, across heart valves. In normal valves, this results in physiological murmurs but in stenotic valves, gradients can increase significantly, particularly at the mitral valve level, and result in heart failure (HF) symptoms. For example, in MS any further elevation of the transmitral gradient is transmitted upstream, increasing both the left atrial and pulmonary venous pressures and resulting in breathlessness on exertion, orthopnea, paroxysmal dyspnea, or even frank pulmonary edema. The increased heart rate associated with pregnancy also decreases the time for diastolic filling, reducing both left ventricular volumes and cardiac output. Because pregnancy is an arrhythmogenic state, in patients with MS any further increase in the ventricular rate and/or loss of atrial filling (in the context of atrial fibrillation (AF)) can also precipitate acute HF (see Chapter 16 ). In contrast to stenotic lesions, regurgitant valve lesions are typically well tolerated because the fall in SVR compensates for the volume loading conditions of pregnancy.
Pregnancy also results in a highly thrombogenic state. This is in part mediated by an increased concentration of clotting factors, resulting in a 20% reduction of both the prothrombin time and activated partial thromboplastin time (aPTT), but also through increased platelet adhesiveness and decreased fibrinolysis. The risk of thrombosis is higher in the puerperium (particularly during the first 6 weeks) than during pregnancy. This increased thrombotic status is clearly a hazard for patients with mechanical heart valves (MHVs), significant MS, and AF. Meticulous management of anticoagulation is therefore particularly important during this period.
Regarding labor and delivery, a 30% increase in cardiac output occurs during the first stage of labor and a 60%–80% increase immediately postdelivery. These changes are driven by an increase in heart rate (due to pain and anxiety) and stroke volume (300–500 mL of blood is “autotransfused” into the systemic circulation with each uterine contraction). When spinal anesthesia is used a significant reduction in SVR also occurs, necessitating compensatory increases in heart rate and stroke volume. At delivery, the baby no longer mechanically compresses the inferior vena cava, resulting in a further increase in preload, unless there has been significant postpartum hemorrhage. Shifts in maternal hemodynamics peak within the first 24–72 h postpartum and are more rapid when delivery is by cesarean section. Therefore, women with heart disease are at increased risk of developing HF within this period, particularly if cesarean section was the mode of delivery. The period of increased risk of HF, thrombotic events, and bleeding lasts up to 1 year postpartum leading to late maternal death.
Preconception Evaluation
Given the potential for increased risk of cardiovascular complications while pregnant, preconception counseling should be offered to all women with RHD, and is strongly recommended based on current ESC and AHA/ACC guidelines. Individualized care and informed decision-making are both central to this process, taking into account the severity of the valvular lesions and cardiac function, as well as emotional, cultural, psychological, and ethical issues.
The reality, however, is that many newly pregnant women with RHD living in LMICs often present after 20 weeks' gestation, and a considerable number are unaware that they have RHD until hemodynamic decompensation occurs due to pregnancy. Delayed diagnosis is a risk factor for maternal death: in a report from the UK, most deaths occurred in those women who had undiagnosed preconception heart disease, a situation that is also true for women in LMICs. Unplanned pregnancies, which are widely acknowledged as both a cause and consequence of socioeconomic inequality, are also seen in many women with RHD and are associated with poorer outcomes for both the mother and fetus.
Issues that may be discussed during counseling include helping the woman understand the risk of death during pregnancy, the risk of embryopathy, need to cease or commence medications, the risks of thrombosis, and risks of peripartum bleeding. In more complex cases, interventional or surgical treatment may also be recommended before any planned pregnancy. Women at the highest risk should be counseled against pregnancy.
Risk Stratification
Risk stratification is an important part of preconception evaluation. In addition to a thorough assessment of symptoms and cardiac status, routine booking tests should include chest X-ray, full blood count, urine analysis, and HIV testing. The minimum cardiac investigations for maternal risk stratification for women with RHD are an electrocardiogram (ECG), echocardiogram, and an exercise test. Other tests, such as exercise echocardiography, cardiac computed tomography or magnetic resonance imaging may also be utilized if further information is required. Exercise testing can objectively estimate functional capacity: favorable outcomes are predicted by a pregnancy exercise capacity >80% (see individual valve lesions section).
The following factors should be considered during pregnancy risk stratification: maternal cardiac and obstetric risk, fetal and neonatal risks, long-term effects of pregnancy on the heart, maternal life expectancy, and modification of cardiac drugs.
Pregnancy risk should be determined using general and lesion-specific risk factors. General risk factors for adverse maternal cardiac events in those with heart disease include baseline New York Heart Association (NYHA) class III/IV (see Chapter 5 ), cyanosis, previous cardiac event (e.g., pulmonary edema, transient ischemic attack, or stroke), arrhythmia, systemic ventricular ejection fraction (EF) <40%, left heart obstruction (echocardiographic mitral valve area (MVA) <2 cm 2 , aortic valve area (AVA) <1.5 cm 2 , or peak left ventricular (LV) outflow tract gradient >30 mmHg), pulmonary regurgitation, mechanical heart valve, as well as significant mitral or tricuspid regurgitation. It is worth noting that the most frequent complications during pregnancy are HF, arrhythmias, and thromboembolic events. CARPREG (Cardiac Disease in Pregnancy) is an established general risk index based on these predictors and was derived from an observational prospective cohort study of pregnant women with congenital and acquired heart disease ( Box 9.1 ).
Box 9.1
The Cardiac Disease in Pregnancy (CARPREG) Risk Score
NYHA, New York Heart Association; EF, ejection fraction.
Another established risk index is the mWHO classification, which incorporates both general and lesion-specific diagnoses and is considered the most accurate system for risk assessment currently in use ( Table 9.1) , although it is probably better suited to patients from HICs rather than LMICs. For example, van Hagen and colleagues recently validated the mWHO classification in advanced and emerging countries and identified additional risk factors for cardiac events during pregnancy using data from ROPAC, which included more than 2500 pregnant women. The mWHO classification showed only a moderate performance of predicting risk between women with or without cardiac events (c-statistic 0.711, 95% CI 0.686–0.735) with a better performance in HICs versus LMICs. Prepregnancy signs of HF, and in HICs, AF, added prognostic value.
Table 9.1
Modified World Health Organization (mWHO) classification of maternal cardiovascular risk. a,2,6
Adapted from Regitz-Zagrosek et al
| mWHO I | mWHO II | mWHO II-III | mWHO III | mWHO IV | |
|---|---|---|---|---|---|
| Diagnosis (If otherwise well and uncomplicated) |
|
|
|
||
| Risk | No detectable increased risk of maternal mortality and no/mild increased risk in morbidity | Small increased risk of maternal mortality or moderate increase in morbidity | Intermediate increased risk of maternal morality or moderate to severe increase in maternal morbidity | Significantly increased risk of maternal mortality or severe morbidity | Extremely high risk of maternal mortality or severe morbidity |
| Maternal Cardiac Event Rate | 2.5-5% | 5.7-10.5% | 10-19% | 19-27% | 40-100% |
| Counselling | Yes | Yes | Yes | Expert counselling required | Pregnancy is contraindicated. If pregnancy occurs, termination should be discussed |
| Care During Pregnancy and Delivery | Local hospital | Local hospital | Referral hospital | Expert center for pregnancy and cardiac disease | Expert center for pregnancy and cardiac disease |
| Minimal Follow-Up Visits During Pregnancy | Once or twice | Once per trimester | Bimonthly | Monthly or bimonthly | Monthly |
MS mitral stenosis; MR mitral regurgitation; AS aortic stenosis; AR aortic regurgitation; TS tricuspid stenosis; TR tricuspid regurgitation; PS pulmonary stenosis; PR pulmonary regurgitation; LVSD left ventricular systolic dysfunction; EF ejection fraction; NYHA New York Heart Association
a Please see Regitz-Zagrosek for full list of risk factors; only those most relevant to patients with RHD are presented here
When using the mWHO index, it is important to remember that risks are additive. Therefore, risks are higher if, for example, the woman has mixed or multivalve disease (the most common RHD phenotype), concomitant left ventricular dysfunction, or noncardiac risk factors such as hypertension, obesity, or chronic kidney disease.
Women with low-risk valvular heart disease can usually be managed by their local cardiology and obstetric team. It is important to avoid anxiety and overtesting and reassurance plays an important role here. Those at higher risk should be managed within a pregnancy heart team, an important concept highlighted by the 2018 ESC guidelines that emphasizes the importance of expert and individualized care delivered in a specialist center for those women who are at moderate-to-extremely high-risk of complications (mWHO class II–III, III, or IV). Women with RHD that falls within these higher risk classes should ideally be referred to a tertiary centre before pregnancy where they can be appropriately assessed and managed. Centres that perform percutaneous mitral balloon commissurotomy (PMBC) and cardiac surgery, as well as other diagnostic and interventional procedures, should be chosen.
The minimum team requirements within a pregnancy heart team are a cardiologist, obstetrician, and anesthetist, and may include others: a nurse specialist, a cardiothoracic surgeon, pediatric cardiologist, neonatologist, and hematologist. Each of these experts should have experience in the management of high-risk pregnancies in women with heart disease. The pregnancy heart team should be involved in all aspects of care, from preconception evaluation and counseling to management during pregnancy and around delivery. It is recognized, however, that in many LMICs, these resources are simply not available.
In addition to the mWHO index, further considerations are given below regarding valve-specific risk stratification.
Mitral Stenosis
Even with ideal care, 35%–74% of women with rheumatic MS show clinical deterioration with pregnancy . Women with asymptomatic mild MS (MVA >1.5 cm 2 ) usually do well and are considered low risk (mWHO II), although elevated event rates are still seen in this group. Recent ROPAC data showed that although mortality was only 1.9% in those with MS during pregnancy, nearly half of patients with severe MS (<1 cm 2 ) and one-third of patients with moderate MS (1.0–1.5 cm 2 ) developed heart failure (HF), even if the patient was asymptomatic before pregnancy. Those with mixed mitral valve disease (moderate-to-severe MS and MR) had adverse pregnancy outcomes similar to those with isolated severe MS. HF due to MS is most likely to occur in the second trimester as cardiac output nears its peak.
Those with severe MS are likely to decompensate and should be advised to avoid pregnancy, at least until they receive successful intervention/surgical treatment. Other predictors of increased maternal complications in MS include NYHA III–IV, systolic pulmonary artery pressure (PAP) >30 mmHg, history of cardiac complications (pulmonary edema, transient ischemic attack, or stroke), reduced left ventricular EF (LVEF), and older age. Mortality is higher in LMICs (although data is lacking here) compared to HICs, where the death rate is between 0% and 3%. Persistent AF may also precipitate HF, although this occurs in <10% of pregnancies. Pulmonary hypertension (pHT), which is a contraindication to pregnancy, may occur secondary to pulmonary venous hypertension (in patients with RHD, this is almost always due to severe left-sided valve disease) and carries a high maternal risk, with mortality rates ranging from 16-30%. pHT is discussed in detail in chapter 5 .
The rapid fluid shifts and tachycardia associated with labor and the immediate postpartum period can cause pulmonary edema and a low output state. Fetal risks include prematurity (20%–30%), intrauterine growth restriction (5%–20%), and fetal death (1%–5%). These risks are higher if the mother is NYHA III or IV during pregnancy.
Aortic Stenosis
Women with asymptomatic mild or moderate AS or asymptomatic severe AS with a previously normal exercise tolerance usually tolerate pregnancy well, with a low risk of HF (<10%). In contrast, one quarter of patients with symptomatic AS will experience HF and those with severe symptomatic AS should be advised to avoid pregnancy until they undergo valve intervention. Arrhythmias and maternal mortality are now rare, providing high-quality management is offered, although this is not always possible in most LMICs. Obstetric risk may be increased in severe AS. Miscarriage and fetal death risk are both <5%. Other fetal risks include prematurity, intrauterine growth restriction, and low birth weight, which occur in 20%–25% of those with moderate AS and are increased in severe AS.
Mitral and Aortic Regurgitation
Mild regurgitation is usually well tolerated in pregnancy. Women are at high risk for HF if there is severe regurgitation with associated symptoms, reduced LVEF, severe LV dilatation, or pHT. The risk of developing HF in those with moderate or severe MR is 20%–25%. Women with LVEF <30% or any degree of pHT should be advised to avoid pregnancy. There appears to be no increased obstetric risk associated with regurgitant lesions. Intrauterine growth restriction is seen in 5%–10%.
Tricuspid Regurgitation
Maternal risk is usually determined primarily by the severity of left-sided valve lesions or the presence of pHT. Mild or moderate TR is tolerated well during pregnancy. Women with severe TR, although they can do well in pregnancy, are at increased risk for right-sided HF and atrial arrhythmias.
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