The successes of paediatric cardiology and cardiac surgery have enabled a new cohort of women, born with congenitally malformed hearts, to reach adulthood. Many of these women differ both anatomically and physiologically from any who have considered pregnancy in the past. Most women in this new cohort can anticipate safe and successful pregnancies. Pregnancy, however, imparts additional haemodynamic loads, changes in mechanisms of clotting, and increased propensity to arrhythmias, all of which increase the risk of adverse maternal cardiac events during pregnancy. In addition, there may be risks for adverse fetal and neonatal events. The recognition and appropriate management of such risks, when present, should optimise outcomes, while the recognition in other cases that a woman with a congenitally malformed heart is not at high risk allows reassurance.
IMPACT OF PREGNANCY ON THE CARDIOVASCULAR SYSTEM
Haemodynamic Changes during Pregnancy
The maternal volume of blood increases by approximately 50%, beginning during the first trimester, and peaking in the third trimester. 1,2 There is also an increase of up to 40% in the mass of erythrocytes. 3 The average heart rate increases by 10 to 20 beats per minute. Beginning early in the first trimester, the systemic vascular resistance and systemic arterial pressure begin to decrease owing to the low-resistance circuit in the uterus and to the effects of endogenous vasodilators. The systemic vascular resistance decreases until mid pregnancy, plateaus, and then rises toward the levels existing prior to pregnancy. 4,5 Systemic arterial pressure also begins to return toward pre-pregnancy levels in the third trimester. The changes in blood volume, vascular resistance, and heart rate all contribute to an increase in cardiac output, which begins early in the first trimester, continues to increase until approximately the end of the second trimester, rising to between one-third and one-half of the levels existing prior to pregnancy, 4,6–11 and then plateaus until term. Cardiac output is affected by position, and is highest when the mother is lying on her left side. The supine gravid uterus can compress the inferior caval vein, which limits venous return, and may lead to a substantial reduction in cardiac output. Women with cardiac disease have been shown to have lower cardiac output during pregnancy when compared to women without such disease. 12 The increased blood volume and systemic vasodilation also affect the flow of blood to other organs, including the skin, uterus, and kidneys. In the kidney, the result is an increase in the effective renal flow of plasma, and a 50% increase in the rate of glomerular filtration. 13
Labour is associated with a further increase by approximately 10% in basal cardiac output, augmented by an additional surge of up to one-sixth with each uterine contraction. 14 Anxiety, pain, tachycardia, and hypertension or hypotension also contribute to cardiac complications at the time of labour and delivery. Following delivery, there is a further increase in cardiac output due to relief of compression on the inferior caval vein, and auto-transfusion from the now fully contracted uterus. Rapid mobilisation of interstitial fluid in the immediate period following pregnancy may have a significant negative impact on a woman with already compromised cardiac function. Although many of the described changes regress within the first few days after delivery, complete resolution of pregnancy-induced effects on cardiac function may not occur until 6 months after delivery. 15
Cardiac Symptoms and Signs in Normal Pregnancy
During pregnancy, women often experience fatigue, dyspnea, tachypnoea, palpitations, presyncope, and decreased exercise tolerance. Such symptoms can be identical to those of cardiac decompensation, and clinicians must be careful to differentiate this possibility. Blood pressure decreases during the first part of pregnancy, and then during the last 6 weeks reaches or exceeds pre-pregnancy levels. Blood pressure should be taken when the mother is sitting or lying on her left side to avoid a falsely low reading caused by supine caval venous compression limiting venous return. The diastolic blood pressure falls more than the systolic pressure, resulting in a wide pulse pressure. The heart rate increases. Warm, erythematous hands and feet, nasal congestion, and breast engorgement are due to increased blood flow. Peripheral oedema may be noted. There may be a laterally displaced apical impulse due to modest increase in cardiac size, as well as upward displacement of the heart by the gravid uterus. There is often prominence of the jugular venous pulsation. There may be wide splitting of the first and second heart sounds. The continuous murmur of a venous hum in the right supraclavicular fossa, or a mammary souffle over an engorged breast, can become apparent during pregnancy. A systolic flow murmur is common, secondary to the hyperdynamic circulation, and is best heard at the left lower sternal border.
IMPACT OF PREGNANCY ON COMMON CARDIAC DIAGNOSTIC TESTS
The surface electrocardiogram may show a sinus tachycardia. Because of the change in position of the heart, the electrocardiogram may show a shift in the frontal plane axis, or inversion of the T waves in the inferior leads. The chest radiograph may show a more horizontal cardiac shadow because of elevation of the diaphragm, and an enlarged cardiac silhouette. The pulmonary vascular markings may become more prominent due to increased blood flow, simulating the vascularity produced by a systemic-to-pulmonary shunt. Echocardiographically, the increase in blood volume manifests as mild increases in the dimensions of the atriums and ventricles. The left ventricular mass increases. 7,15,16 The increased cardiac output is associated with increases in velocities of flow across all cardiac valves. Mitral regurgitation may either improve or worsen, according to the relative impact of the fall in systemic vascular resistance versus the change in geometry of the mitral valvar apparatus associated with increasing chamber size. Mild depression of left ventricular contractility has been demonstrated, 11 but left ventricular systolic performance is thought generally to be preserved. 8,10,11
PRECONCEPTION COUNSELING AND CONTRACEPTION
All women with congenitally malformed hearts should have age-appropriate counseling prior to potential conception, beginning in adolescence. 17 This responsibility often falls to the specialist in congenital cardiac disease caring for the woman at the time, and his or her team, as the patient will often not have access to any others qualified to offer knowledgeable advice. Counseling should address:
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The diagnosis and long-term prognosis for the mother
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The maternal risk of pregnancy
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The risk to the fetus and neonate, including the risk of transmission of congenital cardiac disease to offspring
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Safe and unsafe options for contraception
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The need for high-risk obstetrical and multi-disciplinary care during pregnancy, if appropriate
It is common that information regarding diagnosis, previous procedures, and prognosis are not known to, or are misunderstood by, the patient. Clarification of diagnosis and functional capacity are fundamental to effective preconception counseling. The specialist in congenital cardiac disease is well suited to this task and also to ensuring that this information is provided to, and understood by, other caregivers involved in the management of the pregnancy. Discussion of long-term prognosis of the mother may be straightforward, or very complex and sensitive, depending on the underlying cardiac lesion, the types of surgical interventions, the residual lesions, and co-morbid medical conditions. Because maternal cardiac status can change over time, women with congenitally malformed hearts should be advised to ensure regular follow-up, and in particular to obtain a contemporaneous updated assessment prior to finalizing a decision to pursue pregnancy. 17 We discuss general and lesion-specific maternal and fetal risks associated with pregnancy in the later sections of this chapter.
Family planning needs are often poorly addressed in women with congenitally malformed hearts. 18 The safety and efficacy of various types of contraception need to be considered, but this has not been studied in women with congenitally malformed hearts. Recommendations regarding proper use of contraceptives have been extrapolated from studies in women without cardiac disease, and are based on expert opinion. 19–22 Options include:
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Barrier methods
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Combined oral contraceptives containing oestrogen and progestin
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Oral contraception with progestin alone
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Intra-uterine devices
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Sterilisation
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Emergency contraception
Barrier methods do not pose a health risk to the mother, but are associated with high rates of failure. Up to one-third of women using this technique will have an unintended pregnancy within the first year of use. Barrier methods, therefore, should not be recommended to women in whom there is a significant maternal risk of pregnancy.
Combined oral contraceptives have good efficacy, but the oestrogen component is associated with a risk of both arterial 23,24 and venous 25 thrombosis, which limits their use in women with cyanotic cardiac disease, the Fontan circulation, significant systemic ventricular dysfunction, sustained arrhythmias, mechanical valves, or prior thromboembolic events ( Table 60-1 ). Other forms of combined contraception such as skin patches containing ethinyl estradiol and norelgestromin, and vaginal rings containing ethinyl estradiol and etonogestrel, are also associated with a thrombotic risk. The risk of stroke in association with combined oral contraceptives is further increased if a woman has a history of hypertension, diabetes, obesity, smoking, or migraine headaches. 24 Both oestrogens and progestins can interfere with the metabolism of warfarin, and international normalised ratios need to be monitored more closely in women using these forms of contraception.
| Class 1: Always Usable | Class 2: Broadly Usable | Class 3: Caution in Use | Class 4: Do Not Use | ||
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Oral contraception using progestin alone is not associated with a risk of arterial or venous thrombosis, 26 but those using these agents suffer higher rates of failure compared to those using combined oestrogens and progestin. Such higher rates of failure are particularly seen with older pills containing only progestin, the so-called mini-pills, which should not be used in women with cardiac disease who face substantial risk of pregnancy. 20 A newer form of pill containing desogestrel is associated with lower rates of failure. 27 Pills containing only progesterone are associated with higher rates of vaginal breakthrough bleeding, and may thus be unacceptable to some patients. Bosentan can reduce the efficacy of pills containing exclusively progestin, so these should not be used alone in patients with pulmonary arterial hypertension undergoing medication with bosentan, in whom the maternal risk associated with pregnancy is substantial. Other forms of contraception using progestin alone include injectable medroxyprogesterone acetate, subcutaneous implants containing etonogestrel, and intra-uterine systems impregnated with levonorgestrel. Depo-Provera, the injectable form of medroxyprogesterone, is given by deep intramuscular injection, and can result in haematomas, a problem for women taking anticoagulants. Implanon, containing etonogestrel, is a subdermal implant that carries less risk of producing haematomas than is seen with intramuscular injection.
Insertion of intra-uterine devices can be associated with bacteraemia. As a result, such devices are contra-indicated in women at high risk for endocarditis, such as those who have suffered previous endocarditis, or those with mechanical heart valves. In approximately one-twentieth of women, a vasovagal reaction will occur when the cervix is instrumented for placement of a device. This can be particularly hazardous in women with pulmonary hypertension and those with the Fontan circulation.
Sterilisation should be considered for women in whom pregnancy carries a very high risk. This process has a number of limitations, including late rates of failure estimated as high as 1 in 200, 28 though bilateral fimbriectomy is associated with a much lower rate of failure. Further limitations are the associated maternal risks of general anaesthetics or abdominal insufflation with carbon dioxide, poorly tolerated in women with the Fontan circulation, for example, and the psychological impact on the patient. A new alternative utilises hysteroscopic insertion of intratubal stents under oral analgesia. 29 This method may prove useful for women at high risk with other techniques of sterilisation. Vasectomy may not be an ideal solution because a male partner may outlive his spouse and may wish to father children with a new partner.
Emergency contraception, the so-called morning-after pill, available in forms containing oestrogen and progestin, or progestin only, is safe for women with congenitally malformed hearts, and its availability should be made known. 19,30 Termination may be the most appropriate response to pregnancy in infrequent cases, and the possibility should be explored when indicated.
When pregnancy is actively considered, or when the woman presents in a gravid condition, the assessment must incorporate advice about the proper level of obstetric and multi-disciplinary care during pregnancy. Most women with congenitally malformed hearts will benefit from an initial cardiac and high-risk obstetrical consultation. Those with minor lesions and their caregivers can be reassured regarding the low risk of adverse events and the appropriateness of standard obstetrical care. Women at higher risk can be referred appropriately to high-risk obstetrical units, where they will have access to specialists with experience in managing complex cardiac disease through pregnancy. 31
GLOBAL AND LESION SPECIFIC RISKS AND OUTCOMES
Global Assessment of Maternal and Fetal or Neonatal Risks
Maternal cardiac disease is a risk factor for adverse maternal and fetal events. When evaluating pregnant women with cardiac disease, a global assessment is made of the risk of adverse maternal cardiac events, with fetal and neonatal risks considered separately. This should be supplemented with weighing of lesion-specific risks when these are known.
A Canadian consortium prospectively developed and validated a global risk index for pregnant women with heart disease. A poor functional state defined as New York Heart Association functional class three or four, or cyanosis, systemic ventricular systolic dysfunction, obstruction in the left heart, and history of prior cardiac events such as arrhythmia, stroke, and cardiac failure, were all predictors of adverse maternal cardiac events during pregnancy. 32 A point-score system assigned one point to each of these predictors. Patients with no predictors were at low risk, having a chance of adverse events in only one-twentieth of pregnancies, whereas those with one predictor were at intermediate risk, adverse effects being anticipated in one-quarter of pregnancies, and those with more than one predictor were at very high risk, with adverse events anticipated in three-quarters of pregnancies ( Table 60-2 and Fig. 60-1 ). When applying the global score for risk, it should be borne in mind that patients previously known to be at high risk, such as those with Eisenmenger’s syndrome, pulmonary hypertension, the Fontan circulation, or Marfan syndrome with a dilated aortic root, were not represented or else under-represented in the populations studied. These previously known markers of high risk, therefore, are not reflected in the global score, and must be separately considered through application of a parallel lesion-specific evaluation of risk. In a recent study, dysfunction of the subpulmonary ventricle and severe pulmonary regurgitation were shown to be additional predictors for adverse maternal cardiac events. 33 Other factors that increase maternal cardiac risk during pregnancy include prosthetic valves, anticoagulant therapy, and co-morbid medical conditions such as diabetes and hypertension.
| 1.1 Adverse Event | 1.2 Risk Factor | 1.3 Adverse Event | 1.4 Risk Factor |
|---|---|---|---|
| Maternal cardiac adverse event ∗ | General risks
| Neonatal adverse event † |
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∗ Maternal cardiac adverse events include: pulmonary oedema, arrhythmia, stroke and death. The general risk factors can be used to constitute a risk index: the risk of a maternal cardiac adverse event with no risk factors present is <5%, with one risk factor present is 25%, and with more than one risk factor present is 75%. Data from Siu SC, Sermer M, Colman JM, et al: Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515–521.
† Neonatal adverse event include premature birth, small-for-gestational age birth weight, respiratory distress syndrome, intraventricular haemorrhage, and fetal or neonatal death. Data from Siu SC, Sermer M, Colman JM, et al: Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515–521.
‡ History of premature delivery or rupture of membranes, incompetent cervix, or caesarean section; or intra-uterine growth retardation, antepartum bleeding >12 weeks of gestation, febrile illness, or uterine/placental abnormalities during present pregnancy.
A British working group has also created a classification of risk for women with cardiac conditions undergoing pregnancy. This categorises the risk during pregnancy using global and lesion-specific elements 19 ( Table 60-3 ). According to these recommendations, pregnancy is contraindicated in women with cardiac lesions associated with extremely high risks of maternal morbidity and mortality. These lesions include systemic ventricular dysfunction producing New York Heart Association functional class, three or four symptoms, an ejection fraction of less than 30%, peripartum cardiomyopathy with any residual left ventricular dysfunction, severe obstruction of the left ventricular outflow tract, Marfan syndrome with an aortic root diameter of greater than 40 mm, and pulmonary arterial hypertension.
| Class 1: No Risk | Class 2: Small Increased Risk | Class 2–3: Depending on the Individual | Class 3: Significant Risk | Class 4: Pregnancy Contra-indicated |
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∗ Risk assessment should be individualized for patients with more complex cardiac anatomy.
General and lesion-specific recommendations for evaluation and management of pregnancy have also been published by the European Society of Cardiology 34 and the Canadian Cardiovascular Society. 35–37 In addition, there are excellent texts available devoted to pregnancy in women with cardiac disease. 38–40
Although the risks of adverse maternal events during pregnancy and the early peripartal period are reasonably well described, little data is available concerning late maternal outcomes in women with congenitally malformed hearts. 41,42
Women with cardiac disease also have an increased risk of adverse fetal and neonatal events. In a prospective study, 43 we showed that the risk of neonatal complications, such as premature birth, weight at birth small for gestational age, respiratory distress syndrome, intraventricular haemorrhage, and fetal or neonatal death, is higher in women with cardiac disease, amplified by specific maternal cardiac risk factors, and further amplified by concomitant maternal non-cardiac risk factors for adverse fetal and neonatal outcomes ( Fig. 60-2 ; see also Table 60-2 ).
The risk related to inheritance merits separate discussion. Baseline probability of a congenitally malformed heart in the absence of an affected relative is from 0.4% to 0.6%, but increases about 10-fold when a parent is affected, 44 with some studies suggesting a higher rate of transmission when the mother is the affected parent. 44,45 With certain lesions, the likelihood of transmission is higher. In those with atrioventricular septal defects, the maternal transmission is reported to be 11.6%. 45 In autosomal dominant syndromes such as Noonan’s syndrome, 46 Holt-Oram syndrome, 47 Williams syndrome, 48 Marfan syndrome, and the 22q11 deletion syndromes, the risk is 50%, though penetration and phenotypic expression may vary. Because of successful management of patients with congenitally malformed hearts, there is an expanding pool of potential parents who carry higher genetic risk for transmission to offspring. The impact that this will have on rates of congenital cardiac disease in newborns is offset to an unknown extent by advances in diagnosis during early pregnancy through fetal screening that may lead to termination of some affected pregnancies. 49 In our experience, the result of fetal echocardiography in a woman with a known increased risk of carrying a fetus with a congenitally malformed heart is infrequently used to support termination, but rather is applied to facilitate peripartal planning and neonatal management.
We have shown that a careful assessment at least 2 weeks after delivery, supplemented by clinically guided use of echocardiography, can identify additional cases of congenital cardiac disease in offspring of women with congenitally malformed hearts that were not identified by fetal echocardiography. 50
Lesion-specific Risks, Outcomes, and Strategies for Management
Left-to-right Shunts
Simple left-to-right shunts, including those produced by interatrial communications, ventricular septal defect, and patency of the arterial duct, are generally well tolerated during pregnancy. The increase in volume load is counteracted to some extent by the fall in peripheral vascular resistance, and complications are rare. 51–53 Potential complications include arrhythmias, deterioration in functional class, cardiac failure, and paradoxical embolism. Arrhythmias were reported in only 1 of 123 pregnancies in women with atrial septal defects, and in no pregnancies in women with ventricular septal defects. None of the patients developed cardiac failure during pregnancy. 54
Atrioventricular septal defects are more complex, and are associated with regurgitation across both the right and left sides of the common atrioventricular junction. Compared to women with simple lesions, those with atrioventricular septal defect are more likely to experience cardiac complications. 53,55 When intracardiac shunts are associated with pulmonary hypertension, the risk again is high, and mainly attributable to the pulmonary hypertension, discussed separately below.
Transposition
Atrial redirection procedures such as the Mustard or Senning operations were the original techniques used to repair patients with transposition, albeit now superseded in most instances by the arterial switch operation (see Chapter 38 ). Women with arterial switch operations have only recently begun to reach childbearing age, and only limited outcome data is available. 56 Most women with transposition now of childbearing age, therefore, will have had an atrial repair in infancy, and as a consequence will have the morphologically right ventricle and tricuspid valve supporting the systemic circulation. This is associated with variable degrees of systemic ventricular dysfunction and systemic atrioventricular valvar regurgitation. Additional sequels that may impact on pregnancy include atrial arrhythmias, sinus nodal dysfunction, and obstruction or leak across the atrial baffle. Cardiac failure, functional deterioration, and arrhythmias are the main complications reported during pregnancy. 57–64 In addition, obstetric complications, such as premature rupture of membranes, premature labour, premature delivery, and thromboembolic complications, were frequent. 61 Those studying the late effects of pregnancy on the systemic right ventricle found late echocardiographic evidence of systemic ventricular dilation in almost one-third of the women, and deterioration in the function of the systemic ventricle in one-quarter. 63 Premature delivery is reported in one-third of pregnancies, with one-fifth of babies born small for gestational age. 54
Congenitally Corrected Transposition
Congenitally corrected transposition is also associated with a morphologically right ventricle supporting the systemic circulation. It is also frequent to find regurgitation of the abnormal systemic atrioventricular valve, ventricular septal defect and pulmonary stenosis, and disturbances of atrioventricular conduction (see Chapter 39 ). Although maternal deaths have not been reported, cardiac failure, arrhythmias, endocarditis, myocardial infarction, and stroke have been described as complications of pregnancy. 65,66
Those with Functionally Univentricular Hearts and the Fontan Circulation
The Fontan procedure, initially developed as a palliation to improve haemodynamics in patients with tricuspid atresia, has been extended to provide palliation for those with other complex congenital cardiac lesions not amenable to biventricular repair. Despite overall benefit, patients remain with functionally univentricular physiology, and have limited ability to increase cardiac output. Late complications in patients with the Fontan circulation include elevated right atrial and systemic venous pressures, arrhythmias, ventricular dysfunction, protein-losing enteropathy, and thromboembolic events (see Chapter 31 ). All these problems can be provoked or aggravated by the additional haemodynamic load of pregnancy. Therefore, women with the Fontan circulation need to be educated about the potential maternal risks of pregnancy. If they choose to become pregnant, they must be monitored closely. In one retrospective report on 33 pregnancies including 15 live births, supraventricular tachycardia occurred in one woman. 67 In the same series, two-fifths of women had spontaneous abortions. Others have suggested that maternal cardiac and non-cardiac complications are common, 68,69 with one study reporting miscarriage in half of those becoming pregnant, with amenorrhoea in two-fifths. 69
Obstruction of the Left Ventricular Outflow Tract
A bifoliate aortic valve (see Chapter 44 ) is the most common cause of an obstructed left ventricular outflow tract in women of childbearing age. A smaller number of cases are due to subvalvar or supravalvar stenosis, or other abnormalities at the valvar level. Severe obstruction may not be well tolerated during pregnancy because the increased blood volume and stroke volume may provoke left ventricular failure. Furthermore, abrupt changes in preload may be poorly tolerated by the hypertrophied ventricle, so haemorrhage, or the effects of general or regional anaesthetic agents, can lead to profound haemodynamic embarrassment. During pregnancy, women with severe obstruction are at risk for the development of angina, functional deterioration, cardiac failure and arrhythmias, as well as sudden death, though adverse maternal cardiac events are not as common as described in early reports. 70 Our group found adverse maternal cardiac events in around one-twentieth of women during or immediately after pregnancy, 70,71 with similar observations reported by others. 72,73 Our patients frequently required intervention within a few years after pregnancy, up to two-fifths of those with severe stenosis, so this possibility should be addressed during pre-pregnancy counseling. 71 Balloon aortic valvoplasty and aortic valvar surgery have been performed successfully during pregnancy. 74 Because of the risk to the fetus, such interventions should only be performed if there are no other alternatives. Despite relatively reassuring maternal outcomes, fetal, neonatal, and obstetric complications are common in women with aortic stenosis. 71 Aortic insufficiency, on the other hand, is generally well tolerated unless severe and associated with depressed left ventricular function.
Aortic Coarctation
Most women with coarctation of the aorta have had some type of repair (see Chapter 46 ). Repair may be associated with sequels, in particular development of aneurysms when Dacron has been used for a patch, or pseudoaneurysms. 75 Thus, imaging of the site of repair, optimally by magnetic resonance imaging, is optimal prior to conception. 76 Patients with unrepaired coarctation, or those with repaired coarctation and residual or recurrent obstruction, are subject to upper body hypertension. Antihypertensive treatment directed at the upper body may exacerbate hypotension distal to the coarctation, and thus compromise placental perfusion. This may explain the increased incidence of intra-uterine restriction of growth and prematurity seen in the offspring of such patients. 77 In contemporary studies, maternal mortality in women with repaired coarctation is rare, but women are at increased risk for pregnancy-induced hypertension, pre-eclampsia, and complications related to the associated bifoliate aortic valve. 32,76–78 Dissection of the aorta has been reported.
Marfan Syndrome and Other Aortopathies
Pregnancy-related haemodynamic and hormonal changes impact the structure of the aortic wall, and increase the risk of dilation and dissection. This phenomenon manifests as an increased risk of spontaneous dissection, even in women with no known or diagnosable aortopathy. 79 This is very low in otherwise normal women. Dissection has best been described in those with Marfan syndrome, but women with other aortopathies that have genetic and/or pathologic similarities, such as familial thoracic aortic aneurysm and dissection syndrome, Loeys-Dietz syndrome, the aortopathy associated with the bicuspid aortic valve, Turner’s syndrome, and vascular Ehlers-Danlos syndrome, are also at increased risk of aortic complications. 80,81
In a seminal prospective study of women with Marfan syndrome followed through 45 pregnancies, no significant change was found in the size of the aortic root in those initially having roots of normal size, but one-third of women with dilated roots or those having prior surgery suffered either aortic dissection or progressive aortic dilation. 82 In a recent prospective study, favourable outcomes were reported with no significant changes in aortic root diameter during or following pregnancy when compared to a matched group of childless women. Those with diameters of the root between 40 and 45 mm, however, had a mildly increased rate of growth compared to women with aortic root diameters less than 40 mm. 83 Although there are no trials demonstrating benefit of β-blockade during pregnancy in women with aortopathy, we do recommend such treatment during and after pregnancy in women with Marfan syndrome, coarctation of the aorta, and other aortopathies, in the hope that this may attenuate the risk of aortic dilation or dissection.
Pulmonary Valvar Stenosis
Women with pulmonary valvar stenosis have been reported to tolerate pregnancy well, in spite of the pregnancy-associated increase in preload, 32,72,84 albeit that the risk of hypertensive and neonatal complications may be underappreciated. 85
Tetralogy of Fallot
Most patients with tetralogy of Fallot will have undergone an intracardiac repair, and many repaired patients will have pulmonary regurgitation and/or right heart dilation and dysfunction in late follow-up. Other potential late complications include surgical scars and patches that can act as a substrate for arrhythmia, residual shunts, and left ventricular dysfunction. One recent study reported adverse cardiac events, including cardiac failure and arrhythmias, in one-eighth of patients. 86 Another study, including 20 pregnancies in women with unrepaired tetralogy of Fallot, reported adverse events such as arrhythmias, cardiac failure, and progressive right ventricular dilation in one-sixth. 87 The presence of severe pulmonic regurgitation and/or a dysfunctional subpulmonary right ventricle is known to be associated with worse maternal outcome during pregnancy. 33 The late effects of pregnancy on the dilated, dysfunctional right ventricle, however, are unknown.
Ebstein’s Malformation
Ebstein’s malformation can manifest a broad spectrum of severity. Those with severe forms of the disease may present early in life with cyanosis or right-sided cardiac failure, whereas those with mild forms may first be detected incidentally in adulthood (see Chapter 34 ). The ability of the heart to tolerate the increased demands of pregnancy is dependent on the size and function of the functional right ventricle, the degree of tricuspid regurgitation, and the propensity to arrhythmias. Women with interatrial shunts are at risk for reversal of the flow if they are unable to adapt to the increased preload, and women who enter pregnancy with any degree of right-to-left shunting at the atrial level are likely to demonstrate worsening hypoxaemia and cyanosis as pregnancy proceeds. Despite these potential problems, reported pregnancy outcomes have been favourable. 88,89
Cyanotic Cardiac Disease
Cyanosis is the visible manifestation of maternal hypoxaemia. In a woman with manifest or potential hypoxemia due to right-to-left shunting, it should be established whether the shunt is due to pulmonary hypertension, in other words, Eisenmenger’s syndrome, or another cause, since pulmonary hypertension itself imparts an extremely high risk to pregnancy, as discussed below.
In the absence of pulmonary hypertension, women with cyanotic disease are at risk for adverse maternal cardiac events during pregnancy, in particular cardiac failure, arrhythmias, thrombosis, embolism, and endocarditis, though death is rare. 90–92 The pregnancy-induced fall in systemic vascular resistance will facilitate right-to-left shunting, especially when the shunt is at the level of the ventricles or great arteries. Fetal outcomes are poor. Infants are born small for gestational age. 91 Live births are compromised, and prematurity is common. 90 If maternal saturation of oxygen is less than 0.85, only one-eighth of fetuses progress to be born alive. 90,93
Pulmonary Hypertension
In spite of advances in treatment, pulmonary hypertension continues to provide a very high risk for pregnancy. When associated with a right-to-left shunt, in other words, Eisenmenger’s syndrome, the effects of maternal hypoxaemia and cyanosis play a major additional role. 94 The increased volume load directed through the high-resistance pulmonary circuit will provoke elevations in subpulmonary ventricular pressure, potentially causing subpulmonary ventricular failure, and will augment the right-to-left shunt if present, thereby worsening hypoxaemia. Hypoxaemia acts as a pulmonary vasoconstrictor, thus constituting a vicious cycle. As well, pulmonary thrombosis and pulmonary emboluses are more likely during pregnancy, and may further increase pulmonary vascular resistance. Challenges at delivery, including loss of blood, epidural anesthesia, and vagal responses associated with expulsive efforts of the mother in the second stage of labour, may further facilitate right-to-left shunting, leading to a potential spiral of hypoxaemic pulmonary vasoconstriction, hypotension, and death.
The high mortality of pregnancy in Eisenmenger’s syndrome 95 has remained in the range of 30%, even in more recent reports. 96 Outcomes may be better with early diagnosis and comprehensive management. 96,97 In addition, targeted advanced pulmonary vascular therapies applied in specialised centres are likely to provide better outcomes, 94 though reports of such improved outcomes are sparse at the time of writing, and the risk remains high. As a consequence, the widely held consensus is to advise against pregnancy in women with significant pulmonary hypertension of any cause and, in the event of unexpected pregnancy, to offer termination as the safest option. 94,97,98
Prosthetic Heart Valves
Women with any type of artificial heart valve are at increased risk for complications during pregnancy. Bioprosthetic and mechanical valves each have advantages and disadvantages. Careful consideration of the risks and benefits of each is required prior to selection of the type of prosthetic valve in a woman of childbearing age. During pregnancy, normally functioning bioprosthetic valves are safer than mechanical valves because they are less thrombogenic and do not require ongoing anti-coagulation. Bioprosthetic valves, nonetheless, have limited durability, and women with these valves will generally require repeated surgery in the future. 99,100 Although some studies have suggested that pregnancy accelerates the degeneration of bioprosthetic valves, other studies have not demonstrated this finding. 99,101,102 Less information is available on the safety of homografts during pregnancy, albeit that one study found no valve-related complications occurring during pregnancy. 103
Mechanical valves have better durability than bioprosthetic ones, but are associated with significantly greater maternal and fetal risks during pregnancy. Because pregnancy is a hypercoagulable state, and because anti-coagulation can be difficult to manage with changing body weight during pregnancy, there is an increased risk of maternal thromboembolic events, occurring on average in one-sixth of pregnancies, of which approximately half is valvar thrombosis. 104–108 Valves in the mitral position give higher thrombotic risks than those in the aortic position, as do early models of mechanical valves, such as those with balls in cages, or the first generation of those with tilting discs. Anti-coagulant therapy is complicated by a risk of bleeding. 109 Specific thrombotic risks are dependent on the type of anti-coagulation used.
Options for anti-coagulants include unfractionated heparin, low-molecular-weight heparin, and oral anti-coagulants such as warfarin and adjunctive aspirin. Heparin does not cross the placenta and therefore is a safer alternative for the fetus. Heparin given subcutaneously, nonetheless, is difficult to manage, and is a less effective anti-coagulant, with higher maternal thrombosis rates than warfarin. Valvar thrombosis, which can be fatal, is less common in pregnancy when oral anti-coagulants are used throughout, when compared to oral anti-coagulants with unfractionated heparin substituted between 6 to 12 weeks of gestation, or heparin is given throughout pregnancy. 109 Heparin may also cause maternal thrombocytopenia and osteoporosis. Warfarin crosses the placenta and is associated with warfarin embryopathy in first trimester use and fetal intracranial bleeding, which is a risk throughout pregnancy. 109 The risk of warfarin embryopathy has been shown to be less if heparin is substituted from 6 until 12 weeks of gestation and also in women whose therapeutic dose of warfarin is less than 5 mg per day. 110,111 Because intracranial bleeding can occur during vaginal delivery in a fetus exposed to maternal warfarin, heparin should be substituted at least 2 weeks prior to delivery, or the fetus must be delivered by caesarean section. Low-molecular-weight heparin is easier to use than unfractionated heparin, and has better bioavailability. It also does not cross the placenta and therefore is safe for the fetus. Initial reports of valvar thrombosis and maternal deaths could have been due to bias in reporting, and to inadequate dosing and monitoring. Recent guidelines suggest that, if low-molecular-weight heparin is used during pregnancy, dosing by weight is not adequate, and careful monitoring of anti-Xa levels is required. 112 Low-dose aspirin is safe and may enhance the effectiveness of heparin in pregnant women with mechanical valves. 112 Both heparin and warfarin are safe in the breastfeeding mother. 112
There is no consensus on optimal regimes for anti-coagulation in pregnant women with mechanical valves, so the choice should be tailored to the individual after risk and benefits are discussed in detail. No randomised trials are available. Guidelines, predominantly based on expert opinion, have been published by the American Heart Association/American College of Cardiology 112 ( Table 60-4 ), the American College of Chest Physicians 113 ( Table 60-5 ), and the European Society of Cardiology. 34 An alternative approach that incorporates additional risk factors, including the types of valve and their thrombotic potential, was recently recommended. 108
