In women with valvular heart disease, pregnancy-associated cardiovascular changes can contribute to maternal, foetal and neonatal complications. Ideally, a woman with valvular heart disease should receive preconception assessment and counselling from a cardiologist with expertise in pregnancy. For women with moderate- and high-risk valve lesions, appropriate risk stratification and management during pregnancy will optimise outcomes. Pregnancy in women with high-risk lesions, such as severe aortic stenosis, severe mitral stenosis and those with mechanical valves, requires careful planning and coordination of antenatal care by a multidisciplinary team. The purpose of this overview is to describe the expected haemodynamic changes in pregnancy, review pregnancy risks for women with valvular heart disease and discuss strategies for management.
Introduction
Pregnancy in women with valvular heart disease can be associated with maternal and foetal complications. Most women are aware of their valve disease before pregnancy; however, in some cases, the haemodynamic changes of pregnancy unmask previously unrecognised lesions. For women with high-risk valve lesions, appropriate risk stratification and management during pregnancy by a multidisciplinary team will optimise outcomes. Even for women with low-risk lesions, preconception counselling is important for reassurance and to prevent unnecessary treatment during pregnancy. The purpose of this overview is to describe the expected haemodynamic changes in pregnancy, review pregnancy risks for women with valvular heart disease and discuss strategies for management.
Valvular heart disease in women of childbearing age
Even though more common in men, congenital bicuspid aortic valve disease (BAV) is a common cause when aortic stenosis is found in women of child-bearing age. Moreover, success in paediatric congenital cardiac surgery has resulted in increases in the number of young women with other congenital heart lesions, some of whom have valvular lesions. Rheumatic heart disease remains common in developing countries, although it is seen with diminishing frequency in developed countries. Other valve lesions found in young women include myxomatous mitral valve disease, valve damage from previous infective endocarditis and valvular lesions secondary to systemic diseases, such as systemic lupus erythematosus or those associated with inherited genetic disorder syndromes such as Marfan syndrome. Women of childbearing age may have had a valve replacement with either bioprosthetic tissue or mechanical prosthetic valves.
Valvular heart disease in women of childbearing age
Even though more common in men, congenital bicuspid aortic valve disease (BAV) is a common cause when aortic stenosis is found in women of child-bearing age. Moreover, success in paediatric congenital cardiac surgery has resulted in increases in the number of young women with other congenital heart lesions, some of whom have valvular lesions. Rheumatic heart disease remains common in developing countries, although it is seen with diminishing frequency in developed countries. Other valve lesions found in young women include myxomatous mitral valve disease, valve damage from previous infective endocarditis and valvular lesions secondary to systemic diseases, such as systemic lupus erythematosus or those associated with inherited genetic disorder syndromes such as Marfan syndrome. Women of childbearing age may have had a valve replacement with either bioprosthetic tissue or mechanical prosthetic valves.
Haemodynamic effects of pregnancy
Pregnancy-associated changes in cardiovascular physiology are well tolerated in healthy women. In women with valvular heart disease, however, such changes may provoke maternal, foetal or neonatal complications.
During pregnancy, cardiac output rises 30–50% above the non-pregnant level owing to increases in stroke volume and heart rate . Blood volume begins to increase by the sixth week of gestation, and reaches a level averaging 50% above pre-pregnancy volume by the end of pregnancy, with considerable inter-individual variation of between 20% and 100% . Blood volume increases towards the end of the second trimester; some studies report a plateau thereafter, whereas others describe a further increase until term . Systemic vascular resistance falls during pregnancy as a result of the low-resistance utero-placental circulation and systemic vasodilatation . The mechanisms of systemic vasodilatation in pregnancy may involve decreased vasoconstrictor effect of angiotensin II and norepinephrine, the effect of vasodilators such as prostaglandins, oestrogens, progesterone and prolactin, or both. In response to these changes, systolic and diastolic blood pressure falls by an average of 10 mm Hg, with nadir at the end of the second trimester, before rising again to or just above pre-pregnancy levels at term.
During labour and delivery, cardiac output increases further, transiently rising during contractions up to as much as 80% above levels seen at the end of the third trimester . At the time of delivery, increased sympathetic tone provoked by associated pain and anxiety provokes increases in blood pressure and heart rate while central blood volume is augmented by auto-transfusion from the contracting uterus . After delivery, a further increase in preload takes place as a result of relief of inferior vena cava compression, allowing return of sequestered fluids from the abdomen and extremities to the central blood pool.
General management of the pregnant woman with valvular heart disease
Preconception assessment
Ideally, a woman with valvular heart disease should receive preconception assessment and counselling so that valve lesions that may require treatment before pregnancy might be addressed. Some women may be well compensated and asymptomatic, but it can be predicted that they will develop symptoms in response to the expected haemodynamic changes of pregnancy. Women with mitral and aortic stenosis, in particular, are at risk of pregnancy-related complications. The maternal and foetal risk of the pregnancy for the individual may be estimated at preconception assessment by identifying risk factors that confer a poor outcome. The functional capacity of the individual, the type and severity of valvular disease, the systolic function of the ventricles, and the presence of pulmonary hypertension are important prognostic factors. As a general rule, stenotic valve lesions are less well tolerated during pregnancy than regurgitant lesions. The expected increased cardiac output and stroke volume of pregnancy will cause an increase in gradient across a stenotic valve. Decompensation may ensue in women with moderate to severely stenotic valves. In women with aortic or mitral regurgitation, the lower afterload effected by the fall in systemic vascular resistance mitigates the effect on the ventricle of the increased volume load. Risk stratification for multivalve and combined disease is compromised by lack of data. Many women with valvular heart disease will nevertheless present to the clinician already pregnant; under these circumstances, they will benefit from comprehensive assessment as early as possible during pregnancy .
Two common risk assessment tools are the CARPREG (Cardiac Disease in Pregnancy) and the ZAHARA (Zwangerschap bij vrouwen met een Aangeboren HARtAfwijking-II translated as Pregnancy in women with congenital heart disease II) scoring systems. The CARPREG score derives from a prospective study of 599 women with both acquired and congenital heart disease. Four predictors of adverse maternal cardiac event during pregnancy were identified: prior cardiac event, baseline New York Heart Association (NYHA) functional class over 2, or cyanosis, left heart obstruction and systemic ventricular systolic function <40% . A point is allocated for each risk factor identified, and the risk is then estimated on the basis of the total score ( Fig. 1 ). The ZAHARA score was based on 1302 completed pregnancies in women with congenital heart disease. Nine risk factors were identified that predicted adverse maternal cardiac events and a weighted scoring system was constructed . These scoring systems are helpful in assessing pregnancy risk in general; in addition, it is important to incorporate lesion-specific risk information when this is available. A classification of cardiac risk during pregnancy based on specific valve lesions is presented in Table 1 .
| Modified WHO classification of maternal risk |
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Conditions in which pregnancy risk is WHO class I: risk not significantly higher than the general population
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Conditions in which pregnancy risk is WHO class II-III: depending on the individual
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Conditions in which pregnancy risk is WHO class III: significantly increased risk of maternal morbidity and mortality compared with the general population
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Conditions in which pregnancy risk is WHO class IV: extremely high risk of maternal morbidity and mortality should be counseled against pregnancy
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Further investigations that may aid risk assessment include an exercise stress test, because an abnormal blunted heart rate chronotropic response to exercise has been associated with adverse outcomes in pregnancy . Serum levels of the biomarker brain natriuretic peptide (BNP) have been shown to be helpful in non-pregnant women in determining late cardiac risk of valvular heart disease . During pregnancy in women without cardiac disease, BNP levels are higher than in non-pregnant women . In pregnant women with heart disease, a normal BNP is helpful to exclude a cardiac cause of symptoms. Elevated BNP levels are more difficult to interpret in pregnant women with heart disease because BNP can be elevated even in uncomplicated pregnancies .
On the basis of an initial risk stratification, further management can be planned. Low-risk women can be reassured and will often be managed by their primary cardiologist and obstetrician. Women determined to be at medium or high risk will benefit from management at a high-risk centre with specialist cardiologists, high-risk obstetricians (e.g., maternal foetal medicine specialists) and obstetric anaesthetists with expertise in pregnancy and heart disease, and should be referred accordingly.
Women with high-risk lesions, such as severe and symptomatic aortic or mitral stenosis that are identified during preconception counselling, should be advised to proceed to treatment of the valve problem before pregnancy. If the valve is not suitable for a catheter balloon dilatation, and valve replacement is required, a detailed discussion about the different treatment options and choice of valve replacement options is required. This is because mechanical valves are associated with a high risk of pregnancy-related thromboembolic complications, even when anticoagulation is optimally managed, whereas tissue valves have a limited durability and will require earlier replacement and the need for redo surgery. Prosthetic valves are discussed in more detail subsequently.
Medications that are potentially teratogenic (i.e., warfarin, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors) should be discontinued or substituted with an alternative medication, although an appropriate substitute may not be available. The withdrawal of a necessary maternal medication is another risk of pregnancy .
Clinical evaluation during pregnancy
A detailed history, physical examination and transthoracic echocardiogram underpin the assessment of women with valvular heart disease. The history should assess for symptoms and determine the woman’s functional capacity before pregnancy. The details of previous interventional or surgical procedures should be documented. Pregnancy-related changes should be considered when interpreting findings on physical examination. Heart sounds and murmurs can change during pregnancy. A functional systolic ejection murmur caused by increased flow is common. A third heart sound is sometimes reported. The mammary soufflé is a systolic or continuous murmur heard over the breasts in late gestation, and is also common post partum in lactating women. Diastolic murmurs are not found solely as a consequence of pregnancy, so the detection of any diastolic murmur should prompt further investigation with an echocardiogram . Transthoracic echocardiography is essential in evaluating pregnant woman with valvular heart disease. It can accurately assess valvular structure and function, lesion severity, ventricular function and pulmonary artery systolic pressure.
Management during pregnancy
The frequency of clinical follow-up during pregnancy should be individualised, and will be dependent upon the lesion, its severity and the clinical status of the patient. Women with poor functional capacity, severe stenotic valve lesions, ventricular dysfunction or pulmonary hypertension are at highest risk of pregnancy-related complications, and warrant frequent follow-up. For some women, clinical decompensation will occur because of superimposed pregnancy complications such as pre-eclampsia or anaemia, which require prompt identification and treatment.
The haemodynamic shifts that occur during labour and delivery pose further challenges. In almost all instances, a vaginal delivery with adequate analgesia is recommended. A caesarean delivery is recommended for women who present in labour while on an oral anticoagulant that was not withdrawn in favour of heparin at least 2 weeks earlier . For women with high-risk valve lesions, blood pressure monitoring with an arterial line may be considered for monitoring of haemodynamics. An assisted second stage of labour helps attenuate the haemodynamic effect of vigorous maternal expulsive efforts and should be considered for any severe valve lesion.
In women with mitral stenosis, beta-blockers are first-line treatment for symptoms, because a slower heart rate increases the diastolic emptying time of the left atrium allowing the left atrial pressure to fall. In general, pulmonary oedema should be treated conventionally with diuretics, although, in the case of mitral stenosis, heart rate control may be all that is needed. In some circumstances, bed rest may be useful to reduce cardiac demand. When symptoms are not controlled by medical treatment, a percutaneous catheter balloon dilatation or cardiac surgery may need to be considered. During a balloon dilatation valvuloplasty, abdominal shielding should be used, and the procedure should be carried out by an expert operator. If possible, the procedure should be delayed until after the first trimester because of the potential effect of radiation on the developing foetus. In women unsuitable for percutaneous valvuloplasty, open-heart surgery may be required. Cardiopulmonary bypass during pregnancy is associated with a significant risk to the foetus, with reported mortality of 19–29%, although maternal risk is not significantly increased compared with the same procedure on a non-pregnant woman . In general, transmission of heart disease to offspring of women with congenital cardiac disease is about 3–6%; higher rates in the range of 10% are found when the mother has a left-sided outflow tract lesion. Foetal echocardiography should be offered to women at 18–22 weeks gestation when a parent has congenital cardiac disease .
Specific valve lesions
Mitral stenosis
The most common cause of mitral stenosis is rheumatic heart disease . Congenital mitral stenosis occurs rarely . In mitral stenosis, the restricted valve leaflets limit the flow of blood from the left atrium to the left ventricle in diastole. In pregnancy, the increased heart rate limits diastolic flow and ventricular filling time (atrial emptying time) and, in combination with increase in blood volume, will result in increased left atrial pressure. Maternal cardiac complications include functional deterioration, pulmonary oedema, atrial arrhythmias (i.e., atrial fibrillation), transient ischaemic attacks or stroke.
In women with severe mitral stenosis, complications are common; the incidence of atrial tachyarrhythmias or pulmonary oedema, or both, during pregnancy is >60% . Even women with mild mitral stenosis can develop atrial arrhythmias and pulmonary oedema ( Fig. 2 ). No maternal deaths were reported in four large contemporary studies of pregnant women with mitral stenosis from North America and Europe (total of 300 pregnancies) . By contrast, in a South American study of 88 women with rheumatic mitral stenosis (54 of whom had moderate to severe mitral stenosis), eight maternal deaths occurred as a result of heart failure . In a study of 50 pregnancies in women with heart disease in sub-Saharan Africa, most of whom had rheumatic mitral stenosis, maternal mortality was high at 32% . Only one stroke was reported in North American and European studies . In the South American study, eight episodes of thromboembolism were reported . Women with mitral stenosis are also at an increased risk of adverse foetal and neonatal outcomes, such as prematurity, low birth rate and, rarely, foetal and neonatal death .
Management should be aimed at slowing the heart rate and thereby lengthening the diastolic filling period using beta-blockers . Any factor that increases the heart rate, such as anaemia or infection, should be aggressively treated. Atrial fibrillation or atrial flutter may lead to an abrupt increase in heart rate, which may be more important than the loss of atrial transport, but both reasons can provoke acute pulmonary oedema. Atrial fibrillation and atrial flutter should be treated promptly with rate control, and early cardioversion should be considered. In women who remain symptomatic despite medical treatment, percutaneous balloon valvuloplasty should be considered if the valve is suitable for the procedure . The selection of whether a woman is suitable for mitral valvotomy is determined by echocardiographic assessment of the mitral valve apparatus. The mobility, thickness and degree of calcification of the leaflets are assessed as is the structure of the subvalvular apparatus. Those with calcification of the commissures or significant mitral regurgitation are generally unsuitable for the procedure.
Aortic stenosis
In women of childbearing age, the most frequent cause of aortic stenosis is BAV . This disease can be associated with dilatation of the ascending aorta (aortopathy) or coarctation of the aorta, or both. Aortic stenosis may also be secondary to rheumatic heart disease, in which case it is often found in combination with mitral valve disease. Subvalvular and supravalvular congenital aortic stenosis may occasionally be seen. The increased cardiac output during pregnancy may cause decompensation owing to increased left ventricular pressure overload.
Preconception assessment and counselling is important for women with aortic stenosis to identify women with symptoms or high-risk features (e.g., reduced left ventricular systolic function or a drop in blood pressure at exercise testing). Those with adverse features may need to have a catheter balloon dilatation or surgical valve replacement before pregnancy . In asymptomatic women with normal left ventricular systolic function, mild and moderate aortic stenosis is usually well tolerated. Severe aortic stenosis is associated with adverse maternal cardiac events. In a study of pregnancy outcomes in 49 women with congenital aortic stenosis, cardiac complications occurred in 10% of pregnancies in women with severe aortic stenosis ( Fig. 3 ) . In another study of 12 pregnancies in women with aortic stenosis, one woman had an arrhythmia and five had heart failure . Recent studies rarely report maternal deaths, but they have been described . Foetal and neonatal risks are also increased in aortic stenosis, including prematurity, intrauterine growth restriction and low birth weight .
