8 Dawn L. Adamson1 and Catherine Nelson‐Piercy2 1 Department of Cardiology, University Hospital of Coventry and Warwickshire NHS Trust, Coventry, UK 2 Guy’s and St Thomas’ Foundation Trust, Imperial College Health Care Trust, London, UK Although pregnancies complicated by significant heart disease are rare in the UK, Europe and the developed world, cardiac disease remains the leading cause of maternal death in the UK [1]. There were 49 indirect deaths attributed to cardiac disease in 2011–2013, giving a death rate of 2.1 per 100 000 maternities [1]. The maternal mortality rate from cardiac disease has continued to rise since the early 1980s though may now be stabilizing. The major causes of cardiac deaths over the last 15 years are cardiomyopathy (predominantly peripartum), myocardial infarction and ischaemic heart disease, dissection of the thoracic aorta and sudden adult death syndrome [2]. In the UK, rheumatic heart disease is now extremely rare in women of childbearing age and mostly confined to migrants. Women with congenital heart disease who have undergone corrective or palliative surgery in childhood and who have survived into adulthood are encountered more frequently. These women may have complicated pregnancies yet mortality remains low, probably due to extensive multidisciplanary pre‐pregnancy counselling and clear pathways of care for those with adult congenital heart disease. Women with metal prosthetic valves face difficult decisions regarding anticoagulation in pregnancy and have a greatly increased risk of haemorrhage, valve failure and fetal loss. Because of significant physiological changes in pregnancy, symptoms such as palpitations, fatigue and shortness of breath are very common and innocent findings. Not all women with significant heart disease are able to meet these increased physiological demands. The significance of orthopnoea and paroxysmal nocturnal dyspnoea as symptoms of pulmonary oedema may not be appreciated by maternity staff. The care of the pregnant and parturient woman with heart disease requires a multidisciplinary approach involving obstetricians, cardiologists, anaesthetists and specialist midwives, preferably in a dedicated antenatal cardiac clinic. This allows formulation of an agreed and documented management plan encompassing management of both planned and emergency delivery. The most common and important cardiac conditions encountered in pregnancy are discussed in this chapter. Blood volume starts to rise by the fifth week after conception secondary to oestrogen‐ and prostaglandin‐induced relaxation of smooth muscle that increases the capacitance of the venous bed. Plasma volume increases and red cell mass rises but to a lesser degree, thus explaining the physiological anaemia of pregnancy. Relaxation of smooth muscle on the arterial side results in a profound fall in systemic vascular resistance and together with the increase in blood volume determines the early increase in cardiac output. Blood pressure falls slightly, but by term has usually returned to the pre‐pregnancy value. The increased cardiac output is achieved by an increase in stroke volume and a lesser increase in resting heart rate of 10–20 bpm. By the end of the second trimester the blood volume and stroke volume have risen by between 30 and 50%. This increase correlates with the size and weight of the products of conception and is therefore considerably greater in multiple pregnancies as is the risk of heart failure in women with concomitant heart disease [3]. Although there is no increase in pulmonary capillary wedge pressure, serum colloid osmotic pressure is reduced. The gradient between colloid oncotic pressure and pulmonary capillary wedge pressure is reduced by 28%, making pregnant women particularly susceptible to pulmonary oedema. Pulmonary oedema will be precipitated if there is an increase in cardiac preload (such as infusion of fluids), increased pulmonary capillary permeability (such as in pre‐eclampsia), or both. In late pregnancy in the supine position, pressure of the gravid uterus on the inferior vena cava (IVC) causes a reduction in venous return to the heart and a consequent fall in stroke volume and cardiac output. Turning from the lateral to the supine position may result in a 25% reduction in cardiac output. Pregnant women should therefore be nursed in the left or right lateral position wherever possible. If the mother has to be kept on her back, the pelvis should be rotated so that the uterus drops forward and cardiac output as well as uteroplacental blood flow is optimized. Reduced cardiac output is associated with reduction in uterine blood flow and therefore placental perfusion; this can compromise the fetus. Labour is associated with further increases in cardiac output (15% in the first stage and 50% in the second stage). Uterine contractions lead to autotransfusion of 300–500 mL of blood back into the circulation and the sympathetic response to pain and anxiety further elevate heart rate and blood pressure. Cardiac output is increased more during contractions but also between contractions. The rise in stroke volume with each contraction is attenuated by good pain relief and further reduced by epidural analgesia and the supine position. Epidural analgesia or anaesthesia causes arterial vasodilatation and a fall in blood pressure [4]. General anaesthesia is associated with a rise in blood pressure and heart rate during induction but cardiovascular stability thereafter. Prostaglandins given to induce labour have little effect on haemodynamics but ergometrine causes vasoconstriction and Syntocinon can cause vasodilation and fluid retention. In the third stage up to 1 L of blood may be returned to the circulation due to the relief of IVC obstruction and contraction of the uterus. The intrathoracic and cardiac blood volumes rise, and cardiac output increases by 60–80% followed by a rapid decline to pre‐labour values within about 1 hour of delivery. Transfer of fluid from the extravascular space increases venous return and stroke volume further. Those women with cardiovascular compromise are therefore most at risk of pulmonary oedema during the third stage of labour and the immediate postpartum period. All the changes revert quite rapidly during the first week and more slowly over the following 6 weeks, but even at 1 year significant changes still persist and are enhanced by a subsequent pregnancy [5]. These may include a loud first heart sound with exaggerated splitting of the second heart sound and a physiological third heart sound at the apex. A systolic ejection murmur at the left sternal edge is heard in nearly all women and may be remarkably loud and be audible all over the precordium. It varies with posture and if unaccompanied by any other abnormality reflects the increased stroke output. However, diastolic murmurs are virtually always pathological. Venous hums and mammary souffles may be heard. Because of the peripheral vasodilatation the pulse may be bounding and in addition ectopic beats are very common in pregnancy. Ankle swelling is common in the normal pregnant woman but if accompanied by hypertension consider pre‐eclampsia. The ECG axis shifts slightly to the left (superiorly) in late pregnancy due to a more horizontal position of the heart. Small Q waves and T‐wave inversion in the inferior leads are not uncommon. Atrial and ventricular ectopics are both common. Troponin is not affected by pregnancy and remains a valid test for myocardial ischaemia. The amount of radiation received by the fetus during a maternal chest X‐ray (CXR) is negligible and CXR should never be withheld if clinically indicated in pregnancy. Transthoracic echocardiography is the investigation of choice for excluding, confirming or monitoring structural heart disease in pregnancy. Transoesophageal echocardiography is also safe with the usual precautions to avoid aspiration. Magnetic resonance imaging (MRI) and chest computed tomography (CT) are safe in pregnancy. Routine investigation with electrophysiological studies are normally postponed until after pregnancy but angiography should not be withheld in, for example, acute coronary syndromes. The outcome and safety of pregnancy are related to: Most women with pre‐existing cardiac disease tolerate pregnancy well if they are asymptomatic or only mildly symptomatic (NYHA class II or less) before the pregnancy, but important exceptions are pulmonary hypertension, Marfan’s syndrome with a dilated aortic root, and some women with mitral or aortic stenosis. Women with cyanosis (oxygen saturation below 80–85%) have an increased risk of fetal growth restriction, fetal loss, and thromboembolism secondary to the reactive polycythaemia. Their chance of a live birth in one study was less than 20% [7]. A number of scores have been developed to predict cardiac events. The CARPREG score identified an increased risk of cardiac events if the woman was classified as above NYHA class II, had cyanosis, had a left ventricular ejection fraction less than 40%, or had signficant left heart obstruction [8]. The total score predicted the risk of events such as stroke, arrhythmia, pulmonary oedema and death complicating pregnancies in women with structural heart disease. This was followed by the Zahara I score which included the first three parameters but added the presence of valvular regurgitation, mechanical valve prosthesis, cyanotic heart disease and cardiac medication required before pregnancy [9]. Finally, the simple modified World Health Organization (WHO) criteria were developed and when tested in a clinical cohort of pregnant women [10] appeared to predict risk better than the former two scoring systems [11]. Whichever score is used, all risk estimations show increased risk for the women with increasing class, risk score or number of predictors. The presence of these identified factors therefore also act as reasons to refer to specialist centres for counselling and management of the pregnancy. Women with the above risk factors for adverse cardiac or obstetric events should be managed and counselled by a multidisciplinary team including cardiologists with expertise in pregnancy, obstetricians with expertise in cardiac disease, fetal medicine specialists and paediatricians. There should be early involvement of obstetric anaesthetists and a carefully documented plan for delivery. Asymptomatic acyanotic women with simple defects usually tolerate pregnancy well. Many defects will have been treated surgically or by the interventional paediatric cardiologist but others are first discovered during pregnancy. Women with congenital heart disease are at increased risk of having a baby with congenital heart disease and should therefore be offered genetic counselling if possible before pregnancy [12] and detailed scanning for fetal cardiac anomalies with fetal echocardiography by 18–20 weeks’ gestation. The risk of congenital heart disease in the child is higher with left‐sided lesions such as coarctation of the aorta and is 50% in women with Marfan’s syndrome. Those lesions associated with a reduced cardiac output are associated with an increased risk of fetal growth restriction. After bicuspid aortic valve, secundum atrial septal defect (ASD) is the commonest congenital cardiac defect in adults. Paradoxical embolism is rare and arrhythmias do not usually develop until middle age. Mitral regurgitation caused by mitral leaflet prolapse develops in up to 15% of uncorrected ASDs. Pulmonary hypertension is rare. No problems are anticipated during pregnancy but acute blood loss is poorly tolerated. It can cause massive increase in left‐to‐right shunting and a precipitous fall in left ventricular output, blood pressure and coronary blood flow and even lead to cardiac arrest. Like regurgitant valve disease, these defects, which increase the volume load of the right ventricle, are well tolerated in pregnancy unless the defects are large and complicated by pulmonary vascular disease. Pulmonary stenosis does not usually give rise to symptoms during pregnancy. However, when severe and causing right ventricular failure, balloon pulmonary valvotomy has been successfully carried out during pregnancy. The procedure is best performed during the second trimester. Left ventricular outflow tract obstruction at any level can cause problems during pregnancy. Pre‐pregnancy assessment is the ideal. Significant obstruction results if aortic valve area is less than 1 cm2 or if the non‐pregnant mean gradient across the valve is above 50 mmHg. Indications that pregnancy will be high risk include failure to achieve a normal rise in blood pressure without the development of ST‐ or T‐wave changes during exercise, impaired left ventricular function, and symptoms including chest pain, syncope or pre‐syncope. The ECG will normally show left ventricular hypertrophy and the Doppler transaortic valve velocity will rise during pregnancy if the stroke volume increases in normal fashion. Therefore the measured gradients in pregnancy will increase and should always be compared to pre‐pregnancy where possible. If left ventricular systolic function is impaired, the left ventricle may not be capable of generating a high gradient across the valve, and a low gradient may therefore be falsely reassuring. Any patient who develops angina, dyspnoea or resting tachycardia should be admitted to hospital for rest. Administration of a β‐adrenergic blocking drug will increase diastolic coronary flow time and left ventricular filling with resultant improvement in angina and left ventricular function. If despite these measures angina, pulmonary congestion and left ventricular failure persist or progress, balloon aortic valvotomy needs to be considered [13]. These valves are intrinsically not ideal and severe aortic regurgitation may be created, but if successful the procedure may buy time and allow completion of the pregnancy. Most cases encountered will already have been surgically corrected, although residual narrowing is not uncommon and may not have been identified before pregnancy if the woman has not had regular follow‐up. Ideally, any narrowing or pre‐ or post‐stenotic dilatation or aneurysm formation should be assessed with MRI prior to pregnancy. Aortic coarctation may first be diagnosed during pregnancy and should always be considered when raised blood pressure is recorded at booking, especially if investigation for secondary causes of pre‐existing hypertension has not previously been undertaken. Although the blood pressure can be lowered, adequate control cannot be maintained during exercise, which increases the risk of cerebral haemorrhage or aortic dissection [14]. Women with uncorrected coarctation should therefore be advised to rest and avoid exertion. The risk of dissection is increased in patients with pre‐existing aortic abnormality associated with coarctation, Marfan’s syndrome or other inherited connective tissue disorders. Hypertension should be aggressively treated, and to minimize the risk of rupture and dissection beta‐blockers are the ideal agents. Left ventricular failure is unlikely in the absence of an associated stenotic bicuspid aortic valve or endocardial fibroelastosis with impaired left ventricular function. Normal delivery is usually possible, although severe coarctation would indicate a shortened second stage. The majority (80%) of patients with Marfan’s syndrome have some cardiac involvement, most commonly mitral valve prolapse and regurgitation. Pregnancy increases the risk of aortic rupture or dissection, usually in the third trimester or early after birth. The risk of type A aortic dissection in pregnant women with Marfan’s syndrome is around 1%, even in the absence of a dilated aortic root [6]. Progressive aortic root dilatation and an aortic root dimension above 4 cm are associated with increased risk (10%) [15]. Women with aortic roots greater than 4.6 cm should be advised to delay pregnancy until after aortic root repair or root replacement with resuspension of the aortic valve [16]. Conversely, in women with minimal cardiac involvement and an aortic root of less than 4 cm pregnancy outcome is usually good, although those with a family history of aortic dissection or sudden death are also at increased risk, since in some families aortic root dissection occurs in the absence of preliminary aortic dilatation [6]. Management should include counselling regarding the dominant inheritance of the condition, echocardiography every 4–6 weeks to assess the aortic root in those with cardiac involvement, and beta‐blockers for those with hypertension or aortic root dilatation. Vaginal delivery for those with stable aortic root measurements is possible but elective caesarean section with regional anaesthesia is recommended if there is an enlarged or dilating aortic root. Cyanotic congenital heart disease in the adult is usually associated with either pulmonary hypertension (as in Eisenmenger’s syndrome) or pulmonary stenosis (as in tetralogy of Fallot). Patients with single ventricle, transposition of the great arteries and complex pulmonary atresias with systemic blood supply to the lungs may all survive to adult life with or without previous palliative surgery. Tetralogy of Fallot is the association of severe right ventricular outflow tract obstruction with a large subaortic ventricular septal defect (VSD) and overriding aorta causing right ventricular hypertrophy and right‐to‐left shunting with cyanosis. Pregnancy is tolerated well but fetal growth is poor with a high rate of miscarriage, prematurity and small‐for‐dates babies. The haematocrit tends to rise during pregnancy in cyanosed women because systemic vasodilatation leads to an increase in right‐to‐left shunting. Women with a resting arterial saturation of 85% or more, haemoglobin below 18 g/dL and haematocrit below 55% have a reasonable chance of a successful outcome. Arterial saturation falls markedly on effort so rest is prescribed to optimize fetal growth but subcutaneous low‐molecular‐weight heparin (LMWH) should be given to prevent venous thrombosis and paradoxical embolism. Most women will have had previous surgical correction of tetralogy of Fallot and do well in pregnancy providing they have no signficant pulmonary stenosis or right ventricular failure [17]. Survivors of neonatal palliative surgery for complex congenital heart disease need individual assessment. Echocardiography by a paediatric or adult congenital cardiologist enables a detailed assessment to be made. Following the Fontan operation for tricuspid atresia or transposition with pulmonary stenosis, the right ventricle is bypassed and the left ventricle provides the pump for both the systemic and pulmonary circulations. Increases in venous pressure can lead to hepatic congestion and gross oedema but pregnancy can be successful. It is important that women with a Fontan circulation are kept well filled peripartum as without optimal preload the left ventricle cannot adequately drive the pulmonary circulation. These women are usually anticoagulated with warfarin outside pregnancy and LMWH in pregnancy. Pulmonary vascular disease, whether secondary to a reversed large left‐to‐right shunt such as a VSD (Eisenmenger’s syndrome) or to lung or connective tissue disease (e.g. scleroderma) or due to idiopathic arterial pulmonary hypertension, is extremely dangerous in pregnancy and women known to have significant pulmonary vascular disease should be advised from an early age to avoid pregnancy and be given appropriate contraceptive advice [10]. Maternal mortality was around 25–40% [18], but with a highly specialized team managing these women with aggressive drug regimens, the reported mortality rate has fallen to around 17% [19]. This mortality rate is still high and therefore the advice to these women not to undergo a pregnancy still stands. The danger relates to fixed pulmonary vascular resistance that cannot fall in response to pregnancy, and a consequent inability to increase pulmonary blood flow with refractory hypoxaemia. Pulmonary hypertension is defined as a non‐pregnant elevation of mean (not systolic) pulmonary artery pressure of 25 mmHg or more at rest or 30 mmHg on exercise in the absence of a left‐to‐right shunt. Pulmonary artery systolic (not mean) pressure is usually estimated using Doppler ultrasound to measure the regurgitant jet velocity across the tricuspid valve. This should be considered a screening test. There is no agreed relation between the mean pulmonary pressure and the estimated systolic pulmonary pressure. If the systolic pulmonary pressure estimated by Doppler is thought to indicate pulmonary hypertension, a specialist cardiac opinion is recommended. If there is pulmonary hypertension in the presence of a left‐to‐right shunt, the diagnosis of pulmonary vascular disease is particularly difficult and further investigation including cardiac catheterization to calculate pulmonary vascular resistance is likely to be necessary. Pulmonary hypertension as defined by Doppler studies may also occur in mitral stenosis and with large left‐to‐right shunts that have not reversed. Women with pulmonary hypertension who still have predominant left‐to‐right shunts are at lesser risk and may do well during pregnancy, but although such women may not have pulmonary vascular disease and a fixed pulmonary vascular resistance (or this may not have been established prior to pregnancy), they have the potential to develop it and require very careful monitoring. Modern management of pulmonary hypertension includes drugs such as sildenafil/tadalfil and bosentan/macitentan. With such therapies, pulmonary pressures can be reduced to within the normal range, and therefore pregnancy may be safely negotiated. Although bosentan is teratogenic in animals, the benefit of continuing therapy in pregnancy probably outweighs this risk. In the event of unplanned pregnancy a therapeutic termination should be offered. Elective termination carries a 7% risk of mortality, hence the importance of avoiding pregnancy if possible. If such advice is declined, multidisciplinary care, elective admission for bed rest, oxygen and thromboprophylaxis with LMWH are recommended [20]. Fetal growth should be carefully monitored. Most fatalities occur during delivery or the first week after birth. There is no evidence that monitoring the pulmonary artery pressure before or during delivery improves outcome; indeed insertion of a pulmonary artery catheter increases the risk of thrombosis, which may be fatal in such women. Vasodilators given to reduce pulmonary artery pressure will (with the exception of inhaled nitric oxide and prostacyclin) inevitably result in a concomitant lowering of the systemic pressure, exacerbating hypoxaemia. There is no evidence that abdominal or vaginal delivery or regional versus general anaesthesia improve outcome in pregnant women with pulmonary hypertension. Great care must be taken to avoid systemic vasodilatation. The patient should be nursed in an intensive care unit after delivery. Nebulized prostacyclin can be used to try to prevent pulmonary vasoconstriction. When sudden deterioration occurs (usually in the postpartum period) resuscitation is rarely successful and no additional cause is found at post‐mortem, although there may be concomitant thromboembolism, hypovolaemia or pre‐eclampsia. Death is usually preceded by vagal slowing, a fall in blood pressure and oxygen saturation, followed by ventricular fibrillation. This common condition may also be called ‘floppy mitral valve’ and may be sporadic or inherited as a dominant condition in some families with variants of Marfan’s syndrome. Pregnancy is well tolerated and for women with isolated mitral valve prolapse there are no implications for the mother or fetus in pregnancy. Worldwide, mitral stenosis remains the most common potentially lethal pre‐existing heart condition in pregnancy. There are many pitfalls because (i) an asymptomatic patient may deteriorate in pregnancy, (ii) mitral stenosis may have increased in severity since a previous uncomplicated pregnancy, (iii) stenosis can recur or worsen after valvuloplasty or valvotomy, and (iv) mitral stenosis that may previously not have been recognized may be missed during routine antenatal examination because the murmur is low‐pitched, usually quiet, diastolic and submammary. Women may deteriorate secondary to tachycardia (related to pain, anxiety, exercise or intercurrent infection), arrhythmias or the increased cardiac output of pregnancy. Sinus tachycardia at rest should prompt concern. Tachycardia is the reflex response to failure to increase stroke volume and it reduces the time for left atrial emptying during diastole so that left ventricular stroke volume falls, the reflex sinus tachycardia accelerates and left atrial pressure climbs. This creates a vicious circle of increasing heart rate and left atrial pressure and can precipitate pulmonary oedema. The anxiety caused by the dyspnoea increases the tachycardia and exacerbates the problem (Fig. 8.1). Pulmonary oedema may also be precipitated by increased volume (such as occurs during the third stage of labour or following injudicious intravenous fluid therapy) [21]. The risks are increased with severe mitral stenosis (mitral valve area <1 cm2), moderate or severe symptoms prior to pregnancy, and in those diagnosed late in pregnancy. Fig. 8.1 Mitral stenosis. The ECG in mitral stenosis shows left atrial P waves and right axis deviation. The CXR shows a small heart but with prominence of the left atrial appendage and left atrium and pulmonary congestion or oedema. The diagnosis is confirmed with transthoracic echocardiography. Women with severe mitral stenosis should be advised to delay pregnancy until after balloon, open or closed mitral valvotomy, or if the valve is not amenable to valvotomy until after mitral valve replacement. Beta‐blockers decrease heart rate, increase diastolic filling time and decrease the risk of pulmonary oedema [21] and should be given in pregnancy to maintain a heart rate of under 90 bpm. Diuretics should be commenced or continued if indicated. It is also important that the woman does not over‐exert herself. In the event of pulmonary oedema, the patient should be sat up, oxygen should be given and the heart rate slowed by relief of anxiety with diamorphine, and intravenous furosemide 20 mg administered. Digoxin should only be used if atrial fibrillation occurs as it does not slow the heart in sinus rhythm (because increased sympathetic drive easily overcomes its mild vagotonic effect). If medical therapy fails or for those with severe mitral stenosis, balloon mitral valvotomy may be safely and successfully used in pregnancy if the valve is suitable [22], although this will require transfer to a hospital with major cardiac facilities. Percutaneous balloon valvotomy carries a risk of major complications of about 1%, whereas for surgical valvotomy the risks are as follows. If an open operation on the mitral valve is likely to be required, this should be deferred if possible until after delivery. Women with mitral stenosis should avoid the supine and lithotomy positions as much as possible for labour and delivery. Fluid overload must be avoided; even in the presence of oliguria, without significant blood loss, the temptation to give intravenous colloid must be resisted. Cautious epidural analgesia or anaesthesia is suitable for the patient with mitral stenosis as is vaginal delivery but limitation of maternal effort with an instrumental delivery may be indicated. Patients with regurgitant valve disease, either mitral or aortic, tolerate pregnancy much better than patients with valvular stenosis. The systemic vasodilatation in pregnancy reduces regurgitant flow as does tachycardia in patients with aortic regurgitation. When the valve disease is of rheumatic origin the advent of sudden atrial fibrillation may precipitate pulmonary oedema. Similarly, monitoring of left ventricular function is important in those with severe mitral or aortic regurgitation. Most women with prosthetic heart valves have sufficient cardiovascular reserve to accomplish pregnancy safely. The optimal strategy for anticoagulation in women with metal heart valve replacements in pregnancy is controversial since the interests of the mother and the fetus are in conflict. These women require lifelong anticoagulation and this must be continued in pregnancy because of the increased risk of thrombosis. However, warfarin is associated with warfarin embryopathy (chondrodysplasia punctata) if given during the period of organogenesis (6–12 weeks’ gestation) [23] and with fetal intracerebral haemorrhage in the second and third trimesters. Despite a maternal international normalized ratio (INR) within the therapeutic range, there is a greater anticoagulant effect on the fetus than on the mother because the immature fetal liver produces only low levels of vitamin K‐dependent clotting factors and maternal procoagulants do not cross the placenta due to their large molecular size. The fetal risk from warfarin is dose dependent. Women requiring more than 5 mg daily are at increased risk of teratogenesis, miscarriage and stillbirth [24,25]. Heparin and LMWH do not cross the placenta and are therefore an attractive option. However, even in full anticoagulant doses, they are associated with an increased risk of valve thrombosis and embolic events [23,24,26]. Heparins can also cause retroplacental haemorrhage so the risk of fetal loss is not eliminated. Further disadvantages of unfractionated heparin include a need for parenteral administration, powerful but short duration of action, narrow therapeutic index, a steep dose–response curve, increasing dose requirement during pregnancy, and lack of agreed optimal test or target for safe and effective activity. Overshooting with incremental dosage brings a risk of bleeding. High doses of unfractionated heparin long term may also cause osteoporosis. LMWHs have a better safety profile in pregnancy and provided there is close monitoring of anti‐Xa levels with appropriate dose adjustments and good compliance with twice‐daily injections, recent data would suggest a lower risk of thrombotic events [26,27]. Most clinicians use concomitant low‐dose aspirin and many women need an increase in the LMWH dose in order to maintain peak anti‐Xa levels of 0.8–1.2 IU/mL [27]. There are three basic options for anticoagulation management. Whilst the registry of pregnancy and cardiac disease (ROPAC) found a high rate of pregnancy loss in women using vitamin K antagonsists in the entire first trimester, no specific regimen turned out to be clearly safest [28]. Currently, therefore, the choice of regimen depends on several factors. If warfarin is used in pregnancy, serial fetal scans are indicated to detect embryopathy and intracerebral haemorrhage. Warfarin should be discontinued and substituted for LMWH for 10 days prior to delivery to allow clearance of warfarin from the fetal circulation. For delivery itself, LMWH therapy is interrupted. Conversion from LMWH back to warfarin should be delayed for at least 5 days after delivery to minimize the risk of obstetric haemorrhage. There is a high risk of antenatal but particularly postpartum bleeding in women with mechanical valves [27]. In the event of bleeding or the need for urgent delivery in a fully anticoagulated patient, warfarin may be reversed with recombinant human factor VIIa, fresh frozen plasma and vitamin K, and heparin with protamine sulfate. High doses of vitamin K should be avoided if possible since it renders the woman extremely difficult to anticoagulate with warfarin after delivery. Thrombolytic treatment can be used for prosthetic valve thrombosis during pregnancy, and although it may cause embolism or bleeding or placental separation, the risks are lower than those of cardiothoracic surgery. Myocardial infarction and ischaemic heart disease are now seen more commonly in pregnant and postpartum women and pregnancy increases the risk of myocardial infarction [29]. When myocardial infarction occurs in pregnancy it often develops without a preceding history of typical angina. Pregnant women may present with atypical features as they often do outside of pregnancy. These include epigastric pain, nausea or dizziness as well as with more classical chest, neck and left arm pain. In pregnancy the underlying cause may be due to non‐atherosclerotic conditions and thus can occur in a young individual without risk factors. These include spontaneous coronary artery dissection and coronary artery thrombosis, both of which are more common in pregnancy [2,30]. Most occur during late pregnancy or around or after delivery. Coronary ischaemia may also be associated with drug abuse from crack cocaine. Where there is thrombus on a normal coronary artery, embolic occlusion should always be considered and an embolic source such as mitral stenosis or infective endocarditis sought. The risk factors for ischaemic heart disease in pregnancy are the same as those for the non‐pregnant woman. The risk is increased in older multigravid women and in those who smoke and those with diabetes, obesity, hypertension, hypercholesterolaemia or a family history of coronary artery disease [29,31]. There should be a low threshold for investigating chest pain and other symptoms that could be due to acute coronary syndrome particularly in women with risk factors. Troponin is not affected by pregnancy and this should be requested along with serial ECGs in women in whom acute coronary syndrome is suspected. A raised troponin should therefore raise concern regarding an acute coronary syndrome and investigated appropriately. The management of acute myocardial infarction and acute coronary syndrome is as for the non‐pregnant woman. Coronary angiography should be undertaken without hesitation in order to define the pathology and determine management. Intravenous and intracoronary thrombolysis and percutaneous coronary intervention (PCI) and stenting have all been successfully performed in pregnancy. PCI is preferred as it has clinical superiority over thrombolysis outside of pregnancy but also coronary artery dissection is probably best treated with PCI. Both aspirin and beta‐blockers are safe in pregnancy. Clopidogrel also appears to be safe but no data exist for the newer agents such as prasugrel or ticagrelor. The data for glycoprotein IIb/IIIa inhibitors are limited to case reports and these drugs are normally avoided where possible. It was thought statins should be discontinued for the duration of pregnancy as they are associated with an increased risk of malformations [32]. However, new safety data seem to be reassuring, but until we have more robust evidence, suspension of treatment is still advisable [33]. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by hypertrophy of the undilated left ventricle in the absence of an abnormal haemodynamic load and with underlying myocyte and myofibrillar disarray. Family studies, now sometimes aided by genetic identification of a responsible mutant gene, have indicated the broad spectrum of phenotypic abnormality that exists not only between individuals at different ages but within families. Patient series previously described from specialist centres represented a highly skewed population of high‐risk patients referred because of disabling symptoms or a malignant family history. In the years before echocardiography only gross examples of the disorder could be identified but these patients formed the basis of many of the published natural history studies. HCM is not infrequently first diagnosed in pregnancy when a systolic murmur leads to an ECG and echocardiographic study. Most patients are asymptomatic and do well. HCM used to be regarded as a rare disease with a high risk of sudden death but is now recognized to be relatively common, being found in 1 in 500 young adults in a recent study and in most patients the disorder is benign. Patients with HCM respond well to pregnancy by a useful increase in their normally reduced left ventricular cavity size and stroke volume. The danger relates to left ventricular outflow tract obstruction that may be precipitated by hypotension or hypovolaemia. Symptoms of shortness of breath, chest pain, dizziness or syncope indicate the need for a beta‐blocker [34]. Ventricular arrhythmias are commoner in older patients but uncommon in the young. Sudden death has only very rarely been reported during pregnancy. It is most important in all patients to avoid vasodilatation during labour and delivery and during regional anaesthesia/analgesia. Any hypovolaemia will have the same effect and should be rapidly and adequately corrected. Equally, some HCM patients have a stiff ventricle and can therefore develop pulmonary oedema if they receive large volume loads. It is most unusual to find hypertrophy in the infants of mothers with HCM. This pregnancy‐specific condition is defined as the development of cardiac dysfunction towards the end of pregnancy or in the months following delivery, in the absence of an identifiable cause or recognizable heart disease prior to the last month of pregnancy, and left ventricular systolic dysfunction demonstrated by echocardiographic criteria [35]. The left ventricle may not be dilated but left ventricular ejection fraction is nearly always reduced (<45%). Echocardiography may show dilatation that usually involves all four chambers but is dominated by left ventricular hypokinesia, which may be global or most marked in a particular territory. The condition is rare but the true incidence is unknown as mild cases undoubtedly go unrecognized. Recognized risk factors include multiple pregnancy, hypertension (pre‐existing or related to pregnancy or pre‐eclampsia), multiparity, increased age and Afro‐Caribbean race. Peripartum cardiomyopathy does not differ clinically from dilated cardiomyopathy except in its temporal relationship to pregnancy. The severity varies from catastrophic to subclinical, when it may be discovered only fortuitously through echocardiography. Diagnosis should be suspected in the peripartum patient with breathlessness, tachycardia or signs of heart failure. Pulmonary oedema is often a major feature and may be precipitated by the use of Syntocinon or by fluids given to maintain cardiac output during spinal anaesthesia for delivery. The CXR shows an enlarged heart with pulmonary congestion or oedema and often bilateral pleural effusions. Systemic embolism from mural thrombus may herald the onset of ventricular arrhythmias or precede the development of clinical heart failure and pulmonary embolism may further complicate the clinical picture. The differential diagnosis includes pre‐existing but undiagnosed dilated cardiomyopathy, pulmonary thromboembolism, amniotic fluid embolism, myocardial infarction and pulmonary oedema related to pre‐eclampsia or β2‐agonist therapy for preterm labour. Echocardiography immediately implicates the left ventricle and excludes pulmonary embolism as the cause. Pre‐eclampsia may rarely cause transient impairment of left ventricular function but this normally recovers rapidly after delivery. Management is as for other causes of heart failure, with oxygen, diuretics, vasodilators and angiotensin‐converting enzyme (ACE) inhibitors if post partum. Thromboprophylaxis is imperative. The cautious addition of a cardioselective β‐adrenergic blocking drug may be helpful if tachycardia persists, particularly if the cardiac output is well preserved. The most gravely ill patients will need intubation, ventilation and monitoring with use of inotropes and sometimes temporary support from an intra‐aortic balloon pump, ECMO (extracorporeal membrane oxygenation) or ventricular assist device. Heart transplantation may be the only chance of survival in severe cases. More recently, the role of bromocriptine in peripartum cardiomyopathy has been investigated. Animal studies have suggested that oxidative stress raises the 16‐kDa cleaved form of prolactin, which is angiostatic and pro‐apoptotic, thus providing a plausible aetiology for the condition. A proof of concept pilot study was then undertaken which concluded that the addition of bromocriptine to standard heart failure treatment appeared to improve left ventricular ejection fraction and we now await a larger randomized trial [36]. Currently, about 50% of women make a spontaneous and full recovery. Most case fatalities occur close to presentation and cardiomyopathy is the cause of almost one‐quarter of maternal cardiac deaths [2]. Recent data show a 5‐year survival of 94% [37]. Patients should remain on an ACE inhibitor for as long as left ventricular function remains abnormal. Prognosis and recurrence depend on the normalization of left ventricular size, which may continue to improve for several years after delivery [38,39]. Those women with severe myocardial dysfunction (defined as left ventricular end‐diastolic dimension ≥6 cm and fractional shortening ≤21%) are unlikely to regain normal cardiac function on follow‐up [40]. Those whose left ventricular function and size do not return to normal within 6 months and prior to a subsequent pregnancy are at significant risk of worsening heart failure (50%) and death (25%) or recurrent peripartum cardiomyopathy in the next pregnancy. They should therefore be advised against pregnancy [38]. Women who have recovered normal left ventricular size and function should have their functional reserve assessed using stress (exercise) echocardiography. Even if this is normal there is a risk of recurrent heart failure in subsequent pregnancies [34]. Atrial and ventricular premature complexes are common in pregnancy. Many pregnant women are symptomatic from forceful heart beats that occur following a compensatory pause after a ventricular premature complex. Most women with symptomatic episodes of dizziness, syncope and palpitations do not have arrhythmias [41]. A sinus tachycardia requires investigation for possible underlying pathology such as blood loss, infection, heart failure, thyrotoxicosis or pulmonary embolus. The commonest arrhythmia encountered in pregnancy is supraventricular tachycardia (SVT). First onset of SVT (both accessory pathway mediated and atrioventricular nodal re‐entrant) is rare in pregnancy but exacerbation of symptoms is common in pregnancy [41]. Half of SVTs do not respond to vagal manoeuvres. Propranolol, verapamil and adenosine have Food and Drug Administration approval for acute termination of SVT. Adenosine has advantages over verapamil, including probable lack of placental transfer, and may be safely used in pregnancy for SVTs that do not respond to vagal stimulation [42]. For prevention of SVTs, beta‐blockers or verapamil may be used. Flecainide is safe and is used in the treatment of fetal tachycardias. Propafenone and amiodarone should be avoided [43], the latter because of interference with fetal thyroid function [44]. Temporary and permanent pacing, cardioversion and automatic implantable defibrillators are also safe in pregnancy. Care is needed when bipolar diathermy is used at caesarean section since this may be misinterpreted by the implantable defibrillator as venticular fibrillation leading to deployment of a shock. The device is therefore usually inactivated during caesarean section. This should be managed according to the same protocols as used in the non‐pregnant woman. Pregnant women (especially those in advanced pregnancy) should be ‘wedged’ to relieve any obstruction to venous return from pressure of the gravid uterus on the IVC. This can be most rapidly achieved by turning the patient into the left lateral position. If cardiopulmonary resuscitation is required, then the pelvis can be tilted while keeping the torso flat to allow external chest compressions. Emergency caesarean section may be required to aid maternal resuscitation. Infective endocarditis (IE) is rare in pregnancy but threatens the life of both mother and child. Fatal cases of endocarditis in pregnancy have occurred antenatally, rather than as a consequence of infection acquired at the time of delivery [2]. Treatment is essentially the same as outside pregnancy, with emergency valve replacement if indicated. As always, the baby should be delivered if viable before the maternal operation. The current UK recommendations from the National Institute for Health and Care Excellence [45] are that antibiotic prophylaxis against IE is not required for childbirth. The British Society for Antimicrobial Chemotherapy [46] and the American Heart Association have recommended cover only for patients deemed to be at high risk of developing IE (such as women with previous IE) and for those who have the poorest outcome if they develop IE (such as those with cyanotic congenital heart disease). If antibiotic prophylaxis is used it should be with amoxicillin 2 g i.v. plus gentamicin 120 mg i.v. at the onset of labour or ruptured membranes or prior to caesarean section, followed by amoxicillin 500 mg orally (or i.m/i.v. depending on the patient’s condition) 6 hours later. For women who are allergic to penicillin, vancomycin 1 g i.v. or teicoplanin 400 mg i.v. may be used instead of amoxicillin.
Heart Disease in Pregnancy
Physiological adaptations to pregnancy, labour and delivery
Normal findings on examination of the cardiovascular system in pregnancy
Cardiac investigations in pregnancy
General considerations in pregnant women with heart disease
Specific cardiac conditions
Congenital heart disease
Acyanotic congenital heart disease
Atrial septal defect
Ventricular septal defect and patent ductus
Pulmonary stenosis
Aortic stenosis
Coarctation of the aorta
Marfan’s syndrome
Cyanotic congenital heart disease
Tetralogy of Fallot
Postoperative congenital heart disease
Eisenmenger’s syndrome and pulmonary hypertension
Acquired valve disease
Mitral valve prolapse
Rheumatic heart disease
Mitral stenosis
Regurgitant valve disease
Mechanical heart valves
Coronary artery disease
Hypertrophic cardiomyopathy
Peripartum cardiomyopathy
Arrhythmias
Cardiac arrest
Endocarditis prophylaxis
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