Effect of maternal heart disease on pregnancy outcomes

Abstract

The presence of maternal heart disease has an adverse effect on pregnancy outcomes. The most recent triennial confidential enquiry confirmed that heart disease is now the most common cause of maternal death in the UK. Maternal and neonatal morbidity are also significant. This article details the causes of heart disease and why maternal mortality is increasing. The marked physiological changes to the cardiovascular system during pregnancy are outlined. The effects of pregnancy on heart disease are discussed for specific cardiac lesions/conditions and basic management principles are described.

Keywords::

• arrhythmia
• cardiomyopathy
• congenital heart disease
• ischemic heart disease
• pregnancy
• valvular heart disease

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Learning objectives

Upon completion of this activity, participants should be able to:

• • Identify causes of cardiac morbidity and death in pregnancy, including predictors of primary cardiac events during pregnancy in women with heart disease

• • Examine appropriate anticoagulation regimens in pregnancy for women with mechanical heart valves and strategies for their incorporation into management

• • Describe effects of maternal heart disease and its treatment on fetal outcomes

Heart disease is now the leading cause of maternal mortality in the UK with a mortality rate of 2.27 per 100,000 maternities; double that reported in 1990 [1]. However, the incidence of heart disease during pregnancy has remained constant at 0.9% over several decades [2], implying that the severity of heart disease and/or the risk it poses during pregnancy is increasing. The main cause of this appears to be an increased incidence in previously undiagnosed ischemic heart disease. This is due to lifestyle changes, with increasing numbers of pregnancies in women with risk factors such as obesity, diabetes and smoking, and also pregnancies in older women. In addition, women with complex pre-existing heart disease are surviving into adulthood and considering pregnancy.

Pregnancy in women with heart disease not only poses a risk of maternal death but also of serious morbidity such as heart failure, stroke and cardiac arrhythmia. The fetus is not spared, with neonatal morbidity and mortality due to fetal growth retardation and prematurity also markedly increased. The causes of maternal heart disease are diverse and its management complex.

Financial & competing interests disclosure

EDITOR

Elisa Manzotti,Editorial Director, Future Science Group, London, UK.

Disclosure:Elisa Manzotti has disclosed no relevant financial relationships.

CME AUTHOR

Désirée Lie, MD, MSEd

Clinical Professor, Family Medicine, University of California, Irvine, Orange, California; Director of Research and Patient Development, Family Medicine, University of California, Irvine, Medical Center, Rossmoor, CA, USA.

Disclosure:Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship: she served as a nonproduct speaker for: ‘Topics in Health’for Merck Speaker Services.

AUTHORS AND CREDENTIALS

Emily Gelson, BSc (Hons)

Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.

Disclosure:Emily Gelson has disclosed no financial relationships.

Mark Johnson, PhD

Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.

Disclosure:Mark Johnson has disclosed no financial relationships.

Causes of maternal heart disease

In the developed world, congenital heart disease is now more common in the pregnant population than acquired heart disease. This reflects the fact that with advances in cardiac surgery and medication, 85% of infants with congenital heart disease now survive into adult life [3, 4]. In the UK, the prevalence of congenital heart disease at birth remains constant at seven per 1000 live infants but the number of adults with congenital heart disease is increasing by 1600 per year with a 50% increase in those with complex disease [5]. By contrast, the rates of maternal death related to structural congenital heart disease have declined progressively, suggesting that the level of awareness may have increased and, thus, may have led to improved management of pregnant women with various congenital heart defects [6, 7].

Ischemic heart disease is rapidly increasing in the pregnant population and is now the commonest cause of cardiac death in pregnancy in the UK [2]. This is likely due to increased maternal age, smoking, the adoption of a sedentary lifestyle and poor diet leading to greater rates of obesity, diabetes and hypertension. Acute myocardial infarction accounts for the majority of deaths and is most commonly due to coronary atherosclerosis, although coronary artery dissection and consequent occlusion is also relatively frequent [8]. The risk of an acute myocardial infarction during pregnancy is small but increasing, with an estimated incidence of one in 35,700 deliveries between 1991 and 2000 [9] and one in 16,100 deliveries between 2000 and 2002 [10].

Consistent with the decline in rheumatic fever in the developed world, the prevalence of pregnancies complicated by rheumatic heart disease in the UK has significantly decreased. Rheumatic heart disease remains prevalent in many developing countries [101]. The current level of immigration to the UK means that we are experiencing a resurgence in these cases and it seems inevitable that the number of pregnant women with rheumatic heart disease will increase over the coming years. Indeed, the latest confidential enquiry reported the first maternal deaths due to rheumatic heart disease since 1991–1993 and both were in recent immigrants [1].

Pregnancy-induced cardiomyopathy is a disorder in which left ventricular systolic dysfunction and heart failure present in the last month of pregnancy and the first 5 months postdelivery, in the absence of all other causes of dilated cardiomyopathy with heart failure. It is a rare condition with an estimated incidence of 1 case per 5000–10,000 live births [11]. However, it is one of the most common causes of maternal death in the UK [1].

Cardiac arrhythmias are also an important cause of maternal morbidity. Pregnancy increases the incidence of cardiac arrhythmia. This is due to hormonal changes, alterations in autonomic tone, increased hemodynamic demands and mild hypokalemia. These factors act to precipitate cardiac arrhythmias not present prior to pregnancy or exacerbate pre-existing arrhythmias. The risk is highest during labor and delivery.

Physiological changes in normal pregnancy

During normal pregnancy there are dramatic alterations in cardiovascular physiology, initiated by a fall in systemic vascular resistance to 30–70% of its preconception value by 8 weeks of gestation (Box 1)[12]. The mechanism(s) responsible for triggering such widespread vasodilatation is unclear but increased circulating levels of estrogens, vasodilatory peptides or factors such as nitric oxide and calcitonin gene-related peptide have all been suggested to be responsible. The fall in systemic vascular resistance results in fluid retention and an increased blood volume. Since there is a relatively greater expansion in plasma volume, this results in a fall in hematocrit and plasma osmolality. The increase in cardiac output is secondary to a greater stroke volume and higher heart rate. It rises to a peak between the 20th and 24th weeks and remains stable until term. Arterial blood pressure falls until mid pregnancy, gradually returning to prepregnancy levels late in the second trimester. Prolonged volume overload results in progressive physiological left ventricular hypertrophy.

Labor, particularly the second stage, is associated with a further increase in cardiac output. Pain induces a sympathetic response causing an increase in heart rate. Stroke volume is augmented by autotransfusion during contractions. Following delivery the return of uterine blood into the systemic circulation results in a further increase in cardiac output. Stroke volume, heart rate and cardiac output remain high for 24 h postdelivery with rapid intravascular volume shifts in the first 2 weeks postpartum. Thus, the later stages of labor and early postpartum are periods of high risk of pulmonary edema.

Effect of pregnancy on heart disease

In the presence of maternal heart disease, such a dramatic alteration in the cardiovascular system may ultimately lead to cardiac decompensation or death. Risk to the mother with heart disease appears to be determined primarily by the ability of their cardiovascular system to adapt to pregnancy. As such, different cardiac lesions carry specific mortality risks, dependent on current hemodynamic status, previous operations and anatomical features [13]. The cardiac conditions of highest risk are pulmonary vascular disease, Marfan syndrome with a dilated aortic root, left-sided obstructive lesions and a dilated poorly functioning left ventricle.

Pregnancy also poses the risk of serious maternal morbidity. The only large prospective study of pregnancy outcomes in women with congenital heart disease to date identified 546 women with congenital heart disease with 599 pregnancies. This showed a combined maternal, fetal and neonatal mortality of 3% [6]. The rate of primary cardiac event, the most common of which was pulmonary edema, was 13%. In a multivariate analysis, the most significant predictor of morbidity and mortality was the presence of left ventricular dysfunction. Predictors of adverse maternal outcomes are listed in Box 2.

Other studies combining congenital and acquired heart disease have mainly arisen from the developing world, where rheumatic heart disease is the most predominant cardiac lesion encountered [14–22]. These retrospective studies demonstrate a high rate of cardiac complication ranging from 11.11 to 30% and a maternal mortality rate of 2–3.3%. Higher rates of both maternal morbidity and mortality were seen in women with poorer cardiac New York Heart Assiciation (NYHA) functional class at baseline [14–16].

Pregnancy in specific conditions

Left to right shunts

In pregnancy, increased cardiac output and blood volume are counterbalanced by a decrease in peripheral vascular resistance. Left-to-right shunting in patients with atrial septal defects (ASDs), ventricular septal defects and patent ductur arteriosus is therefore reduced. In the absence of pulmonary hypertension, pregnancy, labor and delivery are well tolerated [23]. Patients with ASDs are at risk of atrial arrhythmia and paradoxical embolism. As such there is a low threshold for prophylaxis with either aspirin alone or with heparin if other risk factors are present.

Right-sided heart lesions

Right-sided heart lesions lead to abnormal loading of the right ventricle (Table 1). During pregnancy, increased blood volume and heart rate put a considerable strain on the right side of the heart, leading to enlargement of the right ventricle [24].

Pulmonary stenosis

Isolated pulmonary stenosis is usually well tolerated during pregnancy [25]. However, the increased cardiac output of pregnancy can lead to increased right-ventricular pressure and, in severe pulmonary stenosis, this may lead to right-ventricle failure and/or atrial arrhythmia.

Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. It is characterized by a nonrestrictive ventricular septal defect, aortic override, pulmonary stenosis and right-ventricular hypertrophy. In developed countries, TOF is usually corrected surgically in infancy, well before pregnancy is contemplated, and it is generally accepted that pregnancy in women with repaired TOF is well tolerated in this context [26]. However, complications such as arrhythmias and right-ventricular failure do occur, particularly in the presence of residual shunts, right-ventricular outflow obstruction and pulmonary hypertension. Careful assessment including echocardiography is advisable prior to pregnancy. Many TOF patients will have significant pulmonary regurgitation. The presence of severe pulmonary regurgitation and/or subpulmonary ventricular systolic function has been shown to be associated with adverse maternal and neonatal outcomes [27, 28]. This needs to be discussed prior to pregnancy, and in some cases pulmonary valve replacement may be advisable.

Ebstein’s anomaly of the tricuspid valve

Ebstein’s anomaly is a malformation of the tricuspid valve consisting of apical displacement of the tricuspid valve, resulting in tricuspid regurgitation and enlargement of the right atrium. In the absence of cyanosis, right-sided heart failure or arrhythmias (Ebstein’s is often associated with a re-entrant tachycardia) pregnancy is usually well tolerated [29].

Transposition of the great arteries

In transposition of the great arteries, the aorta arises from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. The atrial switch procedure introduced in the 1950s has enabled survival beyond infancy. In this procedure, venous blood flow is redirected within the atrial compartment leaving the morphological right ventricle and tricuspid valve supporting the systemic circulation. Although survival rates are favorable, a number of potential long-term complications exist. These include failure of the systemic right ventricle, tricuspid regurgitation, sinus node dysfunction, arrhythmias and baffle obstruction (venous pathway obstruction). Pregnancy is well tolerated following an uncomplicated repair; however, right ventricular dysfunction and/or atrial arrhythmia may still occur [30]. In patients with long-term complications, pregnancy is poorly tolerated with an increased risk of cardiac complications [31]. Many patients with corrected transposition of the great arteries are on angiotensin convertase (ACE) inhibitors, which should ideally be stopped preconception, as they are associated with fetal nephrotoxicity and congenital malformations [32]. More recently, complete repair has been by the Jatene procedure, in which the great vessels are transplanted to their correct anatomical sites. The outcome of pregnancy in these patients remains to be seen but recent case reports are promising [33].

Univentricular hearts after Fontan-type procedure

The Fontan-type procedures have become recognized as the definitive palliative procedure available for complex cyanotic heart defects characterized by a single functional ventricle. Atrial separation divides the systemic and pulmonary circulations, and with the construction of atrio–pulmonary connections blood enters the pulmonary circulation without pulsatile ventricular flow. Increasing numbers of patients with a Fontan circulation are reaching childbearing age. The major concern regarding pregnancy in women with a Fontan circulation is their ability to augment, maintain and adjust cardiac output and heart rate. There is also a tendency towards atrial arrhythmias, which are poorly tolerated. Recent studies suggest that the maternal risk of pregnancy is low in NYHA class I–II patients, provided ventricular function is good [34].

Left-sided heart lesions

Owing to a fall in peripheral vascular resistance, left-sided valvular regurgitant abnormalities are generally well tolerated in pregnancy. However, the increased stroke volume of pregnancy and delivery can have profound effects in the presence of left-sided stenotic valvular abnormalities.

Mitral stenosis

Rheumatic mitral stenosis is the most common clinically significant valvular lesion in pregnancy. During pregnancy, the rise in heart rate and stroke volume increases the pressure gradient across the narrowed mitral valve. This leads to an increase in left atrial pressure and potentially the development or worsening of symptoms, including dyspnea, decreased exercise capacity, orthopnea, paroxysmal nocturnal dyspnea and pulmonary edema. The risk of deterioration persists into the puerperium. Increased left-atrial pressure also increases the risk of atrial fibrillation, which may lead to an uncontrolled ventricular rate and heart failure. Mortality among pregnant women with minimal symptoms is less than 1% [35]. Women with severe symptoms (NYHA class III or IV) or severe stenosis (valve area <1 cm) should delay conception until surgical correction. During pregnancy, medical therapy is directed at minimizing volume overload with bed rest and diuretics and optimizing ventricular filling with β-blockade. Atrial fibrillation requires prompt treatment with direct current (DC) cardioversion, β-blockers or digoxin. Balloon mitral valvuloplasty is indicated with refractory symptoms despite optimal medical therapy and is safe and effective during pregnancy, with favorable long-term results [36].

Mitral valve prolapse

Mitral valve prolapse (MVP) is the most common cardiac abnormality in the pregnant population, affecting 12–17% of women of childbearing age. MVP without regurgitation does not affect the cardiovascular response to pregnancy and thus seldom gives rise to cardiovascular complications [37].

Mitral regurgitation

Mitral regurgitation during pregnancy is usually a result of rheumatic valvular disease or MVP. Owing to the fall in systemic vascular resistance and reduced left-ventricular afterload, mitral regurgitation in the absence of left ventricular dysfunction is usually well tolerated during pregnancy [38]. Asymptomatic patients do not require therapy during pregnancy. Symptomatic heart failure can be treated with nitrates, hydralazine, diuretics and digoxin.

Aortic stenosis

In young women, aortic stenosis (AS) is usually congenital in origin. The limited ability of the left ventricle to augment cardiac output results in an abnormal elevation of left-ventricular systolic and filling pressures, leading to a compensatory left-ventricular hypertrophy. During pregnancy, the increase in stroke volume and fall in systemic vascular resistance lead to an increase in the gradient across the aortic valve [39]. The clinical consequences of the increased aortic gradient depend on the degree of pre-existing left-ventricular hypertrophy and left-ventricular systolic function. When compensatory changes in the left ventricle are inadequate to meet the demands imposed by the need for increased cardiac output late in pregnancy, symptoms develop. Moderate-to-severe AS (valve area <1.5 cm²) has a significant impact on pregnancy outcome. Recent studies report no maternal or neonatal deaths; however, moderate-to-severe AS is associated with significant maternal morbidity including heart failure, arrhythmia and syncope [40]. Women who are symptomatic or who have severe stenosis (peak outflow gradient >80 mmHg) or left ventricular dysfunction are advised to delay conception until after surgical correction. If a pregnant woman becomes symptomatic or is so at the time of pregnancy, diagnosis then bed rest should be advised and a full assessment carried out. Although valve replacement can be considered, wherever possible open heart surgery, with the need for cardiac bypass, should be avoided as it carries a 1.5–5% risk of maternal mortality and a 16–33% risk of fetal mortality, independent of gestational age [41]. Fetal mortality can, however, be reduced to 10% by avoiding hypothermia and maintaining perfusion pressures. Aortic balloon valvuloplasty may be used as a palliative procedure, allowing deferral of valve replacement until after birth [42].

Aortic regurgitation

Aortic regurgitation in young women is usually due to congenital bicuspid valve, rheumatic heart disease, endocarditis or dilated aortic annulus. In the absence of left ventricular dysfunction, aortic regurgitation is usually well tolerated during pregnancy [39]. This is due to the combination of a fall in systemic vascular resistance and an increase in heart rate, which shortens diastole and thus the degree of regurgitation.

Prosthetic heart valves

Bioprosthetic heart valves in the presence of a normally functioning left ventricle and the absence of pulmonary hypertension are not associated with increased risk during pregnancy. Some reports have suggested that pregnancy accelerates structural degeneration of bioprosthetic valves [43, 44]. However, several recent large series have failed to confirm this [45–47].

Patients with mechanical heart valves require lifelong anticoagulation to reduce the risk of thrombotic events. During pregnancy, the risk of thrombosis increases further owing to the hypercoaguable state. As such, pregnancy in women with mechanical valve replacement is associated with marked maternal morbidity and potential mortality with a 25% incidence of thrombotic episodes (stroke, valve thrombosis and myocardial infarction) and a maternal mortality rate of 1–4% [48]. Effective anticoagulation is critical and the risk to the mother and fetus need to be carefully balanced. Controversy still exists regarding the safest and most efficient anticoagulant regime to use. The types of anticoagulation that can be used during pregnancy include warfarin, unfractionated heparin and low-molecular-weight heparin. Warfarin is the best therapeutic option for the mother but it carries a risk of warfarin embryopathy and fetal loss. Heparin does not cross the placenta and as such does not affect the fetus. It is, however, associated with an increased risk of thrombotic events compared with warfarin. Unfractionated heparin can be used during pregnancy but is problematic, with an attenuated response of activated thromboplastin time (aPTT), variable sensitivities of aPTT reagents and wide peaks or troughs with the use of subcutaneous unfractionated heparin. The long half-life of low-molecular-weight heparin allows better control of anticoagulation than unfractionated heparin provided that anti-Xa concentrations are closely monitored, maintaining values greater than 1. A recent study by McLintock et al. reports on 34 pregnancies in women with mechanical heart valves treated with predominantly low-molecular-weight heparin [49]. Thrombotic complications occurred in 10.6% of pregnancies. Noncompliance or subtherapeutic anti-Xa levels contributed in each case, suggesting that therapeutic doses of low-molecular-weight heparin are associated with a low risk of thrombosis. The available regimes and risk of maternal and fetal complications are listed in Table 2. Warfarin is stopped at week 36 to allow the fetus to metabolize it before delivery, thereby reducing the risk of hemorrhage.

Aortopathies

Pregnancy has been associated with an increased risk of aortic dissection in the general population [50]. This is probably due to the combination of an increased cardiac output and blood volume and hormonal changes that weaken the aortic wall. Women with known aortopathy are at increased risk, particularly near term or postnatally.

Marfan syndrome

Marfan syndrome is an inherited disorder of connective tissue. A total of 80% of Marfan patients have some cardiac involvement, usually MVP, mitral regurgitation, aortic root dilatation and/or aortic incompetence. In women with Marfan syndrome, pregnancy increases the risk of thoracic aortic aneurysm leading to aortic dissection, rupture, or both. The risk appears to be dependent on aortic root diameter. With an aortic root less than 4 cm, the overall maternal mortality during pregnancy is 1%. This increases to as much as 25% as the aortic root diameter expands beyond 4 cm [51]. In this situation, pregnancy should be postponed until after aortic arch replacement [52]. In the event of an unplanned pregnancy, the option of termination of pregnancy should be discussed. Aortic root diameter should be monitored throughout pregnancy with serial echocardiograms and if aortic root dilatation occurs, prophylactic β-blockade is advised. Hypertension should be treated aggressively.

Coarctation of the aorta

Coarctation of the aorta occurs in 6–8% of patients with congenital heart disease. The majority of cases are diagnosed in infancy or childhood and are either surgically corrected or treated by balloon dilatation or stent implantation. Women with repaired coarctation of the aorta are expected to reach childbearing age. By contrast, native coarctation is encountered much less frequently. Pregnancy is usually well tolerated in adequately repaired coarctation [53]. It is essential to assess cardiac status prior to conception, excluding and appropriately managing complications such as re-coarctation, aneurysm at the site of repair, an associated bicuspid aortic valve or systemic hypertension. In both corrected and native coarctation, pregnancy poses the risk of aortic dissection and rupture, and resistant hypertension. Poorly controlled hypertension may lead to pre-eclampsia, hypertensive crisis and rupture of an intracranial aneurysm and, as such, needs to be tightly controlled with β-blockers as the first-line agent.

Bicuspid aortic valve disease

The presence of a bicuspid aortic valve is associated with proximal aortic aortopathy. This can occur in the presence of coarctation of the aorta and/or AS. This form of aortic root dilatation during pregnancy is predisposed to aortic dissection, particularly in the third trimester [54]. If the aortic root is dilated at diagnosis then it should be closely monitored with monthly echocardiograms. Where the aortic root diameter is less than 4 cm it should be monitored with echocardiograms in each trimester. Symptoms of dissection should be promptly investigated with echocardiogram and computed tomography, accepting that there is a risk of radiation exposure.

Cyanotic heart disease

Cyanotic heart disease without pulmonary hypertension is caused by persistent truncus arteriosus, uncorrected TOF with pulmonary stenosis/atresia, univentricular heart, tricuspid atresia and Ebstein’s anomaly with ASD. During pregnancy the fall in systemic vascular resistance and rise in cardiac output exacerbates any right-to-left shunting worsening pre-existing cyanosis and hypoxia. Maternal complications depend mainly on ventricular function and include hemorrhage, thromboembolism (owing to polycythemia secondary to hypoxia) and heart failure [55].

Pulmonary hypertension

Pregnancy in the presence of pulmonary hypertension of any cause remains high risk. Fixed pulmonary vascular resistance prevents any increase in pulmonary blood flow to match the increased cardiac output. Pregnancy is poorly tolerated with a risk of worsening cyanosis and hypoxia, arrhythmias, heart failure and death. The majority of complications occur at term or during the first postpartum week. Maternal mortality depends on the underlying cause, with mortality rates of 36% in Eisenmenger’s syndrome, 30% in primary pulmonary hypertension and 56% in secondary pulmonary hypertension reported [56]. Patients should be advised of these risks when contemplating pregnancy. Anticoagulation, oxygen therapy and pulmonary vasodilators (sildenafil, nitric oxide or prostacyclin [endothelin antagonists are contraindicated in pregnancy]) may improve outcome [57]. The postpartum period is particularly high risk for maternal mortality and, as such, high-dependency care should continue for several days postdelivery.

Ischemic heart disease

Acute myocardial infarction is relatively rare during pregnancy and the puerperium. However, the risk of mortality is high at 5–20% for the mother and 9–19% for the baby [8–10]. Pregnancy itself has been identified as a risk factor for acute myocardial infarction owing to the increased blood volume, altered hemodynamics and hypercoaguable state [8]. There is a high incidence of known risk factors for atherosclerosis in pregnant patients who suffer an acute myocardial infarction during pregnancy and the postpartum period [9]. Hyperlipidemia, hypertension and diabetes have the potential to be better controlled preconception, and smoking cessation and avoidance of excessive weight gain can be strongly encouraged. To reduce maternal morbidity and mortality, prompt diagnosis and treatment is essential. Once myocardial infarction is diagnosed, acute phase intervention should not be withheld. The treatment of choice is percutaneous coronary catheterization. If this is not available, thrombolysis should be considered.

Cardiac arrhythmias

Pregnancy increases the incidence of cardiac arrhythmia. The risk of both new onset and exacerbation of supraventricular tachycardia (SVT) is increased during pregnancy [58]. Atrial fibrillation and atrial flutter are rare and may be caused by pre-existing congenital or valvular heart disease, thyrotoxicosis or electrolyte imbalance. Owing to the risk of thromboembolism and the potential detrimental effect on the fetus, early treatment is important either with conversion to sinus rhythm or ventricular rate control. Other causes of SVT encountered in pregnancy are re-entrant tachycardia, for example Wolf–Parkinson–White syndrome and Lown–Levine–Ganong syndrome. Initial treatment in the hemodynamically stable patient to terminate an SVT should involve the vagal maneuver. If this fails, intravenous adenosine may be safely used. Second-line treatments include digoxin, β-blockers and calcium-channel blockers. Ventricular tachycardia is uncommon in pregnancy. It is usually associated with underlying heart disease, but new onset of ventricular tachycardia without structural heart disease has been reported [59]. Initial therapy with lidocaine or procainamide should be considered in hemodynamically stable patients. Amiodarone is relatively contraindicated, as it is associated with fetal hypothyroidism, growth retardation and prematurity, although it has been recently used to control fetal tachyarrhythmias. β-blockers and sotalol are used prophylactically. Electrical cardioversion is safe in pregnancy and necessary in all patients with tachyarrhythmias who are hemodynamically unstable [59]. Attention should be paid to airway management to reduce the risk of aspiration/regurgitation of gastric content and care should be taken to avoid the supine position and thus aortocaval compression.

Cardiomyopathy

Dilated cardiomyopathy

Increased intravascular volume and cardiac output during pregnancy is poorly tolerated in patients with dilated cardiomyopathy, potentially leading to cardiac decompensation. Moderate/severe left-ventricular dysfunction and NYHA class greater than II are predictive of adverse cardiac events [60]. Patients should be advised of these risks when contemplating pregnancy. In the event of an unplanned pregnancy a termination of pregnancy should be offered.

Hypertrophic cardiomyopathy

Clinical and genetic screening of families with hypertrophic cardiomyopathy and the widespread use of echocardiography has led to the identification of increasing numbers of women with hypertrophic cardiomyopathy who would have previously been unaware of their condition. Pregnancy in asymptomatic women is usually well tolerated [61]. However, in those women with heart failure or severe symptoms prior to pregnancy, there is a risk of symptomatic progression, atrial fibrillation, syncope and maternal death [62].

Peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is thought to be caused by the interaction of several factors, including hemodynamic stress, genetics, immune dysregulation and fetal microchimerism. The severity of symptoms varies from catastrophic to subclinical. Recent mortality rates of approximately 30% have been reported [63, 64], with 50% of women recovering normal left-ventricular function [65]. Adequate treatment with β-blockers, diuretics, hydralazine and digoxin reduce mortality rates and improve overall prognosis. Subsequent pregnancy after a diagnosis of PPCM carries higher risk of relapse if left-ventricular systolic function is not fully recovered first; and even with full recovery, some additional risk of relapse remains [66]. Recent data suggested a role for prolactin in the pathophysiology of PPCM and a proof-of-concept study has shown that bromocriptine may be of benefit [67].

Effect of heart disease on pregnancy outcomes

Obstetric complications

The presence of heart disease does appear to increase the risk of obstetric complication. In a retrospective study of 112 pregnancies in women with congenital heart disease, Ouyang et al. report a 32.6% rate of adverse obstetric outcomes [68]. Preterm delivery and postpartum hemorrhage were the most frequent complications seen. Preterm delivery was due to preterm premature rupture of membranes and indicated deliveries. The increased rate of postpartum hemorrhage is probably due to an increased rate of planned assisted delivery. However, the use of anticoagulation in the peripartum period and cyanosis are independent predictors of postpartum hemorrhage [6]. The only cardiac lesion with specific increased risks is coarctation of the aorta, which is associated with an increased risk of pregnancy-induced hypertension [6].

If obstetric complications do occur, this can have significant impact on the outcomes of pregnancy. For example, pre-eclampsia increases the risk of cardiac decompensation and death and postpartum hemorrhage can lead to hypovolemic shock, which is often poorly tolerated. The relative immunocompromise of pregnancy increases the risk of infection (e.g., urinary tract infection). This can increase the heart rate, potentially worsening cardiac function.

Fetal & neonatal outcomes

The presence of maternal heart disease impacts on the fetus in a number of ways. First, the risk of spontaneous miscarriage and therapeutic abortion is increased in women with heart disease [7]. The offspring of a mother with congenital heart disease are also at increased risk of inheriting a congenital heart disease. The overall risk of the offspring inheriting polygenic cardiac disease is quoted at 3–5%, compared with a 1% risk in the general population [69]. The risk is, in fact, dependent on the affected parent’s condition and there is an increased risk if a previous sibling has been affected (Table 3)[70]. Certain cardiac medications can adversely affect the fetus (e.g., ACE inhibitors, warfarin and statins). ACE inhibitors are known to have teratogenic effects in the first trimester and should therefore be avoided during this period [71]. Exposure in the second and third trimester can lead to marked fetal hypotension and decreased (fetal) renal blood. Where ACE inhibitors must be continued, the lowest possible dose should be used and amniotic fluid levels and fetal growth should be monitored carefully. Statins have been identified as potential teratogens on the basis of theoretical considerations. However, epidemiological data suggest that statins are not major teratogens. Given the scarcity of available data, it is still advisable to avoid statins during the first trimester [72].

The rate of neonatal complication is significantly increased in women with heart disease. Siu et al. in their prospective longitudinal study of pregnancy outcomes in women with heart disease reported neonatal outcomes in 302 pregnancies [7]. Neonatal complications occurred in 18% of pregnancies. Preterm delivery occurred in 15%, fetal growth restriction in 4%, respiratory distress syndrome or intraventricular hemorrhage in 2% and neonatal death in 3% of pregnancies. Predictors of adverse neonatal outcomes were NYHA class greater than II, cyanosis, maternal left-ventricular obstruction, maternal smoking, maternal age under 20 years or over 35 years, multiple gestation and anticoagulation during pregnancy.

Neonatal complications are particularly high in women with cyanotic heart disease and in women with a Fontan repair [73]. Pregnancy is associated with a high incidence of fetal loss, stillbirth, fetal growth restriction and preterm delivery [74]. In cyanotic heart disease, the risk increases significantly when maternal oxygen saturations fall below 85% (Table 4). This should be discussed prepregnancy and the fetus should be monitored carefully throughout pregnancy.

Long-term effects of pregnancy

There are limited data on the effects of pregnancy on long-term outcomes in women with heart disease. Most data focus on maternal outcomes during pregnancy, but the impact of the hemodynamic burden of pregnancy (whether positive or negative) beyond the pueperium is not clear. There are some published data for some lesions. In women with Marfan syndrome a prospective study of aortic root growth during pregnancy compared mean aortic root size in 23 women undergoing pregnancy with 22 women who did not become pregnant. There was no difference in the rate of aortic expansion during a 6.4-year follow-up [75]. In women with AS, pregnancy has been shown to have an adverse effect on the heart, with higher rates of cardiac intervention and late cardiac events seen in women who have undergone pregnancy compared with matched controls who have not been pregnant [76]. Data also suggest that pregnancy has an irreversible deleterious effect on ventricular function in women with TOF [25], peripartum cardiomyopathy and a systemic right ventricle [29].

Management principles

Although strict protocols for the management of heart disease in pregnancy do not exist, a number of basic principles can be applied.

Prepregnancy counseling

The management of women with heart disease should ideally take place before conception. In women with congenital lesions this process should begin during adolescence with discussions about family planning, contraception and pregnancy.

Women with heart disease contemplating pregnancy should be assessed in a multidisciplinary prepregnancy clinic (staffed by an obstetrician, cardiologist, anesthetist and midwife). A full cardiac assessment should be performed. The history should focus on the patients’ exercise capacity and past cardiac events. Echocardiography should assess cardiac hemodynamics including valve areas and pulmonary pressures. In patients with impaired functional capacity an exercise test with maximum oxygen uptake refines risk stratification for pregnancy. These risks should be discussed with the woman and her family and a risk of maternal morbidity and mortality quoted.

Patients should be assessed and counseled regarding their need for any medical, interventional or surgical treatment prior to conception. Avoidance of pregnancy should be advised for patients with pulmonary hypertension, Eisenmenger’s syndrome or Marfan’s syndrome with an aortic root diameter greater than 4 cm. Contraception should also be discussed as a means of delaying or preventing pregnancy [77]. A sensitive yet important issue that should be addressed with the mother and her family is her capacity to care for a child and her overall life expectancy. The risk of recurrence of heart disease in the offspring should also be considered.

Antenatal care

Once pregnant, women should be cared for by medical personnel who are experienced in the management of pregnant patients with heart disease. A multidisciplinary approach should be applied including obstetricians, cardiologists, anesthetists and neonatologists. Regular antenatal checks are advised throughout pregnancy. The purpose of antenatal care is to ensure the continued wellbeing of the mother and fetus. Prompt treatment of anemia, urinary tract infection and arrhythmias are important; intervention before major cardiac decompensation and the early diagnosis and management of preeclampsia can prevent significant problems. Medication should be reviewed and teratogenic drugs stopped and an alternative used where possible. In general, warfarin should be changed for low-molecular-weight heparin for the duration of pregnancy, except in the case of metallic heart valves. In certain circumstances, specific therapy is required, including avoidance of vasodilators to maintain preload, empirical β-blockers in Marfan’s syndrome and prophylactic heparin in pregnancy complicated by pulmonary hypertension. Admission for bed rest and monitoring may be required and is advised with a NYHA class greater than III.

As there is an association between increased nuchal thickness and cardiac defects in both chromosomally abnormal and normal fetuses, fetal assessment should involve a nuchal translucency scan early in pregnancy. A fetal echogram should be performed between 18 and 22 weeks with a routine anomaly scan at 20 weeks. The assessment of fetal growth with serial ultrasound scans is essential in women with heart disease, especially if this is in the form of cyanotic heart lesions.

Labor & delivery

The appropriate timing for delivery is crucial to balance both maternal and neonatal mortality and morbidity. Labor and delivery require careful planning. Vaginal delivery is recommended in most women with heart disease. There is no direct evidence to link mode of delivery with outcome; however, it is known to be associated with a smaller shift in blood volume, hemorrhage, clotting and infection. In the absence of infection, infective endocarditis prophylaxis is not recommended except in high-risk patients.

Labor and delivery are an additional burden on the maternal cardiovascular system and requires continuous monitoring of both mother and fetus. Maternal preload, blood pressure and blood loss should be monitored carefully throughout, with invasive monitoring occasionally required. Low-dose epidural with adequate volume loading does not decrease systemic vascular resistance and is thus the analgesia of choice. The length of the second stage may be shortened by elective assisted delivery to avoid excessive maternal effort. During the third stage of labor bolus doses of oxytocin should be avoided as they result in an initial fall in arterial blood pressure followed by an increase in cardiac output. Oxytocin also has a direct effect on the heart, causing decreased cardiac contractility and heart rate. If oxytocin is to be used, it should be given by slow intravenous infusion. Ergometrine should also be avoided in most cases as it can cause acute hypertension. The safety of misoprostol is yet to be determined. Mechanical maneuvers to reduce postpartum hemorrhage (bimanual compression, uterine compression sutures, intrauterine balloons) are useful alternatives. Careful hemodynamic monitoring postpartum is typically required for 24–72 h, but this should be extended to 10–14 days in cases of pulmonary hypertension. Multidisciplinary follow-up should take place 6 weeks after delivery.

Expert commentary

The increase in maternal mortality associated with heart disease in the UK is of obvious concern. Only by identifying why we are seeing this rapid change in mortality rate will we be able to reverse it. We must learn from the recent confidential enquiry. Of the maternal deaths associated with heart disease two-thirds of the women were overweight or obese. Care was considered substandard in nearly half of the cases, to the degree that in two-thirds of these cases the assessor thought that different care may have prevented death. Increasing numbers of deaths are occurring in women with acquired heart disease, not diagnosed prior to pregnancy but with know risk factors. The presence of these risk factors must be highlighted in the antenatal clinic. The occurrence of cardiac symptoms (palpitations, chest pain, severe shortness of breath) in these women should prompt early referral for investigation (ECG and echocardiography), promoting the timely diagnosis of unsuspected cardiac disease in pregnant women. Women with pre-existing heart disease should be assessed preconceptually and risk factors for cardiac complications should be identified (prior cardiac event, baseline NYHA class greater than II, cyanosis, left-heart obstruction, reduced systemic left-ventricular function and significant pulmonary regurgitation) [6], and used to guide the intensity of antenatal and postnatal care.

Five-year view

With initiatives such as the European Registry on Pregnancy and Heart Disease and the UK obstetric surveillance system (UKOSS), the next 5 years are likely to bring an improved knowledge of the potential complications experienced by women during pregnancy with pre-existing heart disease and their prognosis. Improvement in the management of pregnancy complications will only be possible with our research efforts focused on understanding how heart disease impacts on the cardiovascular physiological adaptations to pregnancy and what the impact of pregnancy is on the natural history of the underlying heart condition. Combining the information from the registry with the results of the basic physiological studies will allow us to develop appropriate interventions, the benefit of which can be tested in multicenter studies. Ultimately, we should be capable of improving pregnancy outcomes for those with pre-existing and acquired heart disease. Until then we must concentrate on raising the profession’s awareness of the possibility of heart disease in pregnant women and promote management protocols based on the best evidence currently available to us.

Table 1. Right-sided heart lesions.

Volume overload	Pressure overload
Pulmonary regurgitation	Pulmonary stenosis
Ebsteins anomaly of the tricuspid valve	l-TGA
Repaired TOF	d-TGA after atrial switch

d-TGA: Dextro-TGA; l-TGA: Levo-TGA; TGA: Transposition of the great arteries; TOF: Tetralogy of Fallot.

Table 2. Anticoagulation regimes in pregnancy for women with mechanical heart valves.

Regime	Maternal complication			Fetal complications
	Thrombotic events (%)	Death (%)		Fetal anomalies (%)	Fetal wastage (%)
Warfarin until week 35, then heparin until delivery	3.9	1.8		6.4	33.6
Unfractionated heparin until week 13, then warfarin until week 35, then heparin until delivery	9.2	4.2		3.4	26.5
Low-molecular-weight heparin throughout pregnancy	10.6	0		NA	4
Unfractionated heparin throughout pregnancy	33.3	15		0	42.9

With any of the above regimes, consider adjunctive antiplatelet therapy in the second and third trimester.

NA: Not available.

Data taken from [48,49].

Table 3. Risk of congenital heart disease in the offspring of women with heart disease.

Cardiac lesion	Risk of CHD in fetus (%)
	Previous sibling affected	Father affected	Mother affected
Marfan syndrome	–	50	50
Aortic stenosis	2	3	15–17.9
Pulmonary stenosis	2	2	6.5
VSD	3	2	9.5–15.6
ASD	2.5	1.5	4.6–11
PDA	3	2.5	4.1
COA	–	–	14.1
TOF	2.5	1.5	2.6

ASD: Atrial septal defect; CHD: Congenital heart disease; COA: Coarctation of the aorta; PDA: Patent ductur arteriosus; TOF: Tetralogy of Fallot; VSD: Ventricular septal defect.

Data taken from [69,70].

Table 4. Chance of live birth in women with cyanotic heart disease.

Factor	Chance of live birth (%)
Maternal SaO2 (%)
>90	92
85–90	45
<85	12
Maternal Hb (g/dl)
<16	71
17–19	45
>20	8

Hb: Hemoglobin.

Data from[74].

Box 1. Physiological changes in normal pregnancy.

• • Decreased systemic and pulmonary vascular resistance

• • Increased blood volume

• • Initial fall in blood pressure to 20 weeks followed by an increase until term

• • Increased heart rate

• • Increased stroke volume

• • Increased cardiac output

• • Physiological cardiac hypertrophy

• • Pulmonary capillary wedge pressure unchanged

Box 2. Predictors of adverse maternal outcomes.

• • Prior cardiac event (heart failure, transient ischemic attack or stroke) or arrhythmia

• • Baseline New York Heart Association class greater than II or cyanosis

• • Left heart obstruction (mitral valve area <2 cm², aortic valve area <1.5 cm², or peak ventricular outflow tract gradient >30 mmHg by echocardiography)

• • Reduced systemic left-ventricular function (ejection fraction <40%)

Key issues

• • Heart disease is the leading cause of maternal mortality in the UK.

• • Ischemic heart disease is rapidly increasing in the pregnant population and is now the most common cause of cardiac death in pregnancy in the UK.

• • The congenital cardiac conditions of highest risk during pregnancy are pulmonary vascular disease, Marfan syndrome with a dilated aortic root, left-sided obstructive lesions and a dilated poorly functioning left ventricle.

• • Women with heart disease contemplating pregnancy should be assessed in a multidisciplinary prepregnancy clinic (staffed by an obstetrician, cardiologist, anesthetist and midwife).

• • Multidisciplinary input is required throughout the management of pregnancy.

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Effect of maternal heart disease on pregnancy outcomes

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Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

1.A 27-year-old woman from the UK with congenital heart disease is considering a first pregnancy. Which of the following is the most accurate description of her potential risks associated with pregnancy?

• □ A Heart disease is the second leading cause of maternal mortality in the UK

• □ B The incidence of heart disease during pregnancy has increased since 1990

• □ C The severity of heart disease during pregnancy has increased since 1990

• □ D Acquired heart disease is more common than congenital heart disease in pregnant women

2. Which of the following is the most common cause of cardiac death during pregnancy in the UK?

• □ A Ischemic heart disease

• □ B Congestive heart failure

• □ C Arrhythmias

• □ D Dilated cardiomyopathy

3. A 34-year-old woman with congenital heart disease is pregnant and has prior heart failure. She is a baseline New York Heart Association class II patient – with reduced systemic left ventricular function and an ejection fraction of 35%. How many high risk factors for maternal morbidity and mortality is she likely to have?

• □ A One

• □ B Two

• □ C Three

• □ D Four

4. A 32-year-old woman considering pregnancy has a mechanical heart valve. Which of the following regimens for anticoagulation is likely to be associated with the combination of lowest maternal and fetal complications?

• □ A Warfarin until week 35, then heparin until delivery

• □ B Unfractionated heparin until week 13, then warfarin until week 35, then heparin until delivery

• □ C Low-molecular-weight heparin throughout pregnancy

• □ D Unfractionated heparin throughout pregnancy

5. A 28-year-old woman with heart disease is contemplating pregnancy. Which of the following is likely to pose the highest mortality risk to her fetus?

• □ A Use of statins during the third trimester

• □ B Oxygen saturation below 85%

• □ C Use of low-molecular-weight heparin during pregnancy

• □ D Maternal hemoglobin of 17 g/dl

Notes

Data from [6].