Echo picture (four-chamber-view) of typical EA with apical displacement of the tricuspid valve
Right atrial and functional right ventricular dilation increases as tricuspid regurgitation worsens. During childhood, already these chambers may be severely dilated giving rise to the term “wall-to-wall” heart.
Increasing degrees of anticlockwise rotation of the tricuspid valve (i.e., greater severity) annulus toward the right ventricular outflow with the fulcrum being the ventriculo-infundibular fold (see Fig. 14.2).
Anatomical and schematic depiction of the tricuspid valve in EA. With the kind permission of Dr. Siew Yen Ho, Cardiac Morphologist, Royal Brompton and Harefield NHS Foundation Trust
Right ventricular cardiomyopathy that includes myofibril loss and discontinuity and scarring of the right ventricular free wall, resulting in right ventricular dilation, thinning, and dysfunction.
Left ventricular cardiomyopathy, occurring in up to 18 % . This cardiomyopathy frequently resembles left ventricular non-compaction and occurs in combination with left heart structural abnormalities such as mitral valve prolapse and dysplasia, ventricular septal defect, and bicuspid aortic valve .
Atrial level shunt, ranging in size and degree as well as direction of shunt.
Bronchopulmonary segmental hypoplasia, particularly in more severe forms, and pulmonary vascular disease.
Altered and eventually diminished right atrial compliance, which dictates physiologic responses to tricuspid regurgitation and right ventricular dysfunction.
EA must be distinguished from other forms of congenital tricuspid regurgitation and/or right ventricular dilatation, such as an endocardial cushion defect, unguarded tricuspid valve, tricuspid valve prolapse, right ventricular dysplasia, or tricuspid valve dysplasia [5, 6].
The clinical presentation depends on the composite interaction of the above pathophysiologic perturbations. Up to half of all affected fetuses die in utero or shortly after birth because of right ventricular dysfunction, while other infants may need early surgery . In milder forms, EA may not present until later life as symptoms may first occur in adult life, mainly due to arrhythmias . Right bundle branch patterns due to infra-Hisian block are most often observed (up to 70 %), and the extent of QRS duration correlates with the amount of right ventricular enlargement . Other electrocardiographic and rhythm abnormalities include accessory atrioventricular or atriofascicular pathways (in 25 %) of patients. These pathways are frequently right sided and multiple. Supraventricular tachyarrhythmias (atrioventricular reciprocating tachycardia, ectopic atrial tachycardia, and atrial fibrillation or flutter) are common and occur in 30–40 % of adults with this anomaly .
220.127.116.11 Atrial Level Shunts in EA
Atrial shunting is present in up to 80–90 % of EA patients . The degree and nature of shunting depends on the relative compliances of the downstream respective ventricles. It plays various roles during the natural history of the disease. During early life, it may help to preserve cardiac output in the face of severe right heart disease. Eventually, it may become the mechanism for symptomatic cyanosis with exercise limitation and may be a vehicle for paradoxical embolism. As tricuspid regurgitation worsens, the right atrium enlarges, and the initial atrial septal defect or patent foramen ovale may be stretched providing a substrate for atrial level shunting. The decision to close the atrial shunt therefore needs to be taken with full appreciation of the potential hemodynamic impact [11, 12]. Atrial shunt closure can result in marked improvement in symptoms and volume unloading of the right ventricle especially in the presence of a predominant left-to-right shunt. In patients with right-to-left shunts, relief of cyanosis is very effective in improving symptoms.
Most cases of EA occur sporadically . Case-control studies have identified reproductive (e.g., maternal age) and environmental risk factors (e.g., maternal exposure to benzodiazepines or lithium therapy) . The genetic basis of isolated EA remains unknown. Studies show that EA is a genetically heterogeneous defect, with sporadic 1p36 and 8p23.1 chromosomal deletions being the most commonly associated imbalances in patients with syndromic EA . Recent investigations have identified mutations in the gene MYH7, which encodes β-myosin heavy chain, in individuals with EA associated with left ventricular non-compaction .
18.104.22.168 Modified History
Medical therapy is used to relieve symptoms of right heart failure or to control arrhythmias, but a substantial proportion of patients will require tricuspid valve repair or replacement during their lifetime. The timing of surgical intervention depends on symptoms, exercise performance, heart size, the occurrence of arrhythmias, or the presence and consequences of interatrial shunting such as paradoxical embolism . Usually, the exercise capacity of adults with EA is moderately impaired, comparable to the exercise capacity of adults with a systemic right ventricle. In a recent single-center study, the mean peak VO2 in a cohort of >300 EA patients with a mean age of 28 years was 22 ml/kg/min or 60 % of predicted .
14.2 Pregnancy Outcomes
The largest study investigating the outcome of pregnancies in mothers with EA included 44 women with 111 pregnancies, resulting in 85 live births (76 %). The majority of women (n = 34) had uncorrected EA. Sixteen women were cyanotic at the time of pregnancy due to interatrial shunting; five women had documented accessory conduction pathways. Twenty-three deliveries were premature, and there were 19 spontaneous miscarriages (17 %), 7 therapeutic abortions, and 2 early neonatal deaths. There were no serious pregnancy-related maternal complications . Patients with mild disease and little to no ventricular dysfunction tolerated pregnancy changes well. Patients with significant preexisting right or left heart dysfunction may experience more overt heart failure symptoms due to an inability to cope with the increased volume and cardiac output demands of pregnancy.
In the EA cohort from the ZAHARA study, 2 of 22 pregnancies were complicated by arrhythmias . In case reports of pregnant women with EA, right heart failure or arrhythmias were the most commonly observed complications [19, 20]. In a recent literature review of pregnancy outcomes in CHD, including 127 completed pregnancies (>20 weeks gestation) in women with EA, arrhythmias complicated 4 % and heart failure 3 % of pregnancies . No pregnancy-related death occurred. Overall, in the absence of maternal cyanosis or symptomatic arrhythmias prior to pregnancy, pregnancy was well tolerated.
Although there is scarce data for women with EA specifically, increased rates of adverse fetal outcomes have been observed in cohorts of women with diverse types of heart disease [21–23]. In a retrospective cohort of 331 women with both congenital and acquired heart disease, Gelson et al. found that low cardiac output and cyanosis are risk factors for adverse fetal outcomes . In a large cohort, pregnancy completion rates in cyanotic women are <50 % . The use of cardiac medications and mechanical prosthetic valve has also been proposed as risk factors for adverse neonatal outcomes . Cyanosis and the need of anticoagulation are not uncommon among EA patients. In the Mayo EA cohort, the mean birth weight of the infants born to cyanotic women was 2.5 kg, compared to 3.1 kg in acyanotic women . There was no difference in late survival between children from mothers with cyanotic or non-cyanotic heart disease.
In a review by Drenthen et al., premature delivery was observed in 22 % of EA pregnancies (vs. 10–12 % expected occurrence), and 12 % of babies were small for gestational age (vs. 10 % of expected occurrence) . None of the studies reported fetal mortality (intrauterine death >20 weeks gestation), but there was a 2 % perinatal mortality (death within the first year of life). Overall, the risk of fetal or perinatal mortality seems to be low.
14.3 Pregnancy Management
14.3.1 Coordinated Care
During pregnancy, EA patients should be evaluated by an ACHD cardiologist, a maternal-fetal medicine specialist and an obstetric and/or cardiac anesthesiologist. Involvement of other consultants may be necessary based on patient’s clinical presentation (i.e., critical care, cardiac surgery, hematology, etc.).
14.3.2 Frequency of Follow-Up
Frequency of follow-up is dictated by maternal cardiac status. Patients who are at low risk (WHO class II) can be seen by a cardiologist every trimester. For women in WHO class III, there is a higher risk of complications, and monthly or bimonthly cardiology follow-up is recommended to assess for changes in their cardiac status . Arrhythmias, most commonly supraventricular tachycardia (SVT), may occur at any point in pregnancy. The patient should be counseled on vagal maneuvers that can potentially interrupt AV node-dependent arrhythmias. EA patients should also look for and report signs of heart failure. Although these are often difficult to distinguish from normal changes of pregnancy, concerning signs include peripheral edema, orthopnea, and rapidly progressive shortness of breath during exertion [24–26].
14.3.3 Fetal Echocardiography
Fetal echocardiography to screen for congenital heart disease is best done between 18 and 22 weeks gestation, when visualization of the heart and outflow tracts is optimal.
14.3.4 Management of Arrhythmias
For acute SVT, the initial recommended interventions in pregnancy are vagal maneuvers and IV adenosine. These are expected to have little effect on the fetus, as adenosine has an extremely short half-life and does not cross the placenta . Additional interventions that may be considered include digoxin, beta-blockers, and verapamil. In the presence of an accessory pathway, SVTs (atrial flutter or atrial fibrillation) can lead to wide-complex tachycardias. In these circumstances, digoxin and calcium channel blockers are contraindicated, since they may increase the ventricular response rate by favoring conduction via the accessory pathway. For patients with an accessory pathway and symptomatic arrhythmias (reentry tachycardias and preexcited atrial fibrillation or atrial flutter), pharmacologic therapy to prevent further arrhythmias and/or slowing the ventricular response rate is necessary. Flecainide and propafenone possess favorable benefit/risk ratio. If the patient is hemodynamically unstable, synchronized cardioversion is recommended. There is no change in the recommended voltage in pregnancy, and the amount of electricity that reaches the fetus is extremely small [24, 27, 28]. Catheter ablation during pregnancy should only be considered for refractory and poorly tolerated cases of arrhythmia . The presence of an atrial arrhythmia longer than 48 h can increase risk for atrial clot, so consideration should be given to anticoagulation in this situation .
14.3.5 Management of Progressive Heart Failure
Heart failure is one of the most common complications for women with heart disease during pregnancy [23, 25, 30, 31]. According to the available published information on EA in pregnancy, overt heart failure occurred in only 3 % of patients . Ruys et al. looked retrospectively at heart failure during pregnancy in women with both congenital and acquired heart disease. They found an overall 13 % incidence of heart failure, the majority of which occurred at the end of the second trimester or in the peripartum period. Several parameters were associated with heart failure, including NYHA class ≥III, WHO pregnancy class ≥III, preexisting cardiomyopathy, preexisting pulmonary hypertension, and preexisting signs of heart failure . Depressed subpulmonary ventricular function has been described as an additional risk factor for heart failure during pregnancy . Measurement of natriuretic peptides (pro-BNP or BNP) can be useful to risk stratify patients. Normal levels of BNP (<100–128 pg/ml) at 20 weeks gestation have been found to have a 96–100 % negative predictive value for heart failure events associated with pregnancy. Patients with elevated BNP at 20 weeks gestation had a higher risk for heart failure [32, 33]. Most available treatment agents for heart failure are acceptable for the use during pregnancy, with the notable exception of ACE inhibitors and aldosterone antagonists. Admission to a tertiary care center may be necessary for careful management and titration of fluid status. In addition to bed rest and supplemental oxygen, furosemide can be used for diuresis, and nitrates or hydralazine can be used for afterload reduction. Inotropes can be considered if needed, although very little is known about the use of these agents during pregnancy [25, 26]. If the patient is placed on bed rest, consideration should be given to thromboembolic prophylaxis, particularly in an EA patient with an interatrial shunt.
14.3.6 Management of Progressive Cyanosis
Patients with cyanosis are at elevated risk for maternal and fetal complications during pregnancy. The management of progressive cyanosis and hypoxemia revolves around maintenance and improvement of oxygenation and oxygen-carrying capacity. Supplemental oxygen may be considered, but, in the presence of an atrial right-to-left shunt, it is unlikely to make a substantial difference . Cardiac output should be maintained by avoiding dehydration, ambulation as tolerated, and compression stockings to optimize venous return. Hematocrit should be maintained in the physiologic range to maximize oxygen-carrying capacity. Low hematocrit may be due to iron deficiency and should be treated with iron supplementation. Elevated hematocrit (>65 %) puts patients at risk of hyperviscosity syndrome, which can decrease oxygen delivery. If signs of hyperviscosity syndrome are seen, such as headache, lethargy, fatigue, dizziness, anorexia, or visual disturbances, hydration or exchange transfusion can be considered as indicated [34, 35]. In severe refractory cases, consideration can be given to percutaneous closure of the atrial septal defect. There are currently no reports in the literature regarding the effects of defect closure on pregnancy outcome in EA patients.
14.3.7 Mode and Timing of Delivery
In patients with EA, the largest available series show vaginal delivery to be safe [17, 20]. However, Caesarean delivery is still preferred for a select group of CHD patients, including cyanotic patients receiving warfarin anticoagulation within 2 weeks of delivery .
Timing of delivery should be discussed as a multidisciplinary group. Women with mild EA can be delivered at early term. In those with more significant complications, such as difficult to control arrhythmia, heart failure, or progressive cyanosis, the decision should be made on an individual basis, weighing the risks of prematurity vs. the risks to the mother of continuing the pregnancy.
14.3.8 Anesthesia Management During Delivery
Anesthetic management during labor and delivery is a vital component to the care of patients with EA. An obstetric anesthesiologist should be involved in the multidisciplinary planning prior to delivery in these patients. For vaginal delivery, early epidural analgesia is typically recommended for patients of all disease severity [24–26, 36]. Slow titration of local anesthetic and judicious fluid boluses before epidural placement can minimize rapid decreases in preload that are often seen with neuraxial anesthesia. For Caesarean section, epidural anesthesia can be slowly titrated to avoid hemodynamic disturbance while providing adequate anesthesia for the procedure. General anesthesia, with careful attention to hemodynamics and oxygenation, is also an option; however, it is generally not preferred in obstetrics .
14.3.9 Monitoring During Labor and Delivery
Patients with EA are at an increased risk for arrhythmia independent of symptoms or associated lesions. Therefore, they should be monitored on continuous telemetry during labor, delivery, and the immediate postpartum period. Hemodynamic monitoring during labor and delivery depends on the current status of each patient. Asymptomatic patients with minor disease and no associated lesions may not need additional hemodynamic monitoring. Patients with significant ventricular dysfunction, severe tricuspid regurgitation, heart failure, or cyanosis should have continuous pulse oximetry throughout labor and delivery. In rare cases, invasive hemodynamic monitoring may give useful additional information. Such monitoring may include invasive blood pressure monitoring, central venous pressure monitoring, minimally invasive cardiac output monitoring, and bioimpedance monitoring [26, 34, 37].
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14.3.10 Specific Recommendations and Pitfalls
Paradoxical embolism: Women with EA and an interatrial shunt are at risk for paradoxical embolus. To help prevent air entrainment into an IV causing a paradoxical embolus, air filters should be placed on all intravenous lines in patients with a known shunt.
Preterm labor: Medications used for premature contractions include tocolytics and drugs given to optimize neonatal outcome if premature labor progresses. The classes of tocolytics currently in use include nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, beta-agonists, and oxytocin antagonist atosiban (Europe only). Beta-agonists, such as terbutaline and hexoprenaline, have significant maternal side effects including tachycardia and an increased propensity for arrhythmias. These drugs should be avoided in EA patients. NSAIDs, such as indomethacin, have few maternal side effects. Commonly reported adverse effects include nausea, heartburn, and platelet inhibition. The platelet inhibition is rarely clinically significant unless there is another underlying bleeding disorder or therapeutic anticoagulation. They should not be used in the cyanotic EA patient. NSAIDs can have significant fetal side effects, including in utero constriction of the ductus arteriosus and oligohydramnios. These drugs are not used beyond 32 weeks of pregnancy and even before only under carefully monitoring of the ductus. Although calcium channel blockers can generally be used safely, they should be used with caution in patients with severe tricuspid regurgitation or other preload-dependent lesions, since the expected vasodilation will decrease preload . Atosiban, an oxytocin receptor antagonist, is approved for use in Europe but not in the USA. It has been reported to cause pulmonary edema, hypotension, and tachycardia/dysrhythmia on rare occasions, but is generally considered safe . Given its limited use, safety in the setting of maternal cardiac disease is unknown. Magnesium sulfate is commonly given in the setting of preterm labor for fetal neuroprotection. It has been shown to decrease the incidence and severity of cerebral palsy in premature infants . At therapeutic levels, it can cause lethargy and hypotonia. Supratherapeutic Mg levels can cause pulmonary edema, cardiac arrhythmias, respiratory depression, and even cardiac arrest. It should be used with extreme caution in EA patients. Corticosteroids, given to improve fetal lung maturity when delivery is anticipated within 2 weeks at gestational ages of less than 34 weeks, can cause fluid retention. They should be used with care in patients with heart failure or depressed ventricular function. Potential fetal benefit of steroid administration should be weighed against maternal risk in individual circumstances.
Induction of labor: Cervical ripening is usually the first step in inducing labor. This is typically accomplished by vaginal application of a prostaglandin analogue, such as misoprostol (prostaglandin E1) and dinoprostone (prostaglandin E2). These agents can generally be used safely, although if there is excessive systemic absorption, they can cause vasodilation, which can lead to hypoxia in patients with a known shunt . Pulse oximetry and blood pressure should be monitored during the use of these medications in these patients. Oxytocin is commonly given to augment uterine contraction strength during labor induction or during spontaneous labor. It is usually given as a continuous infusion at rates starting at 0.5–6 mU/min; a maximum dose has not been published . For patients with heart failure and risk of fluid overload, the preparation can be concentrated to decrease fluid administered. When given with high volumes of fluids, oxytocin can cause fluid retention and hyponatremia due to its structural similarity to vasopressin . Rapidly infused at rates of >2 units/min, oxytocin can cause systemic vasodilation and hypotension. For cyanotic patients with a right-to-left shunt, this may increase the degree of shunting. Although not well studied, oxytocin may increase pulmonary artery pressures [41, 42] and should therefore be used cautiously in patients with right heart dysfunction or existing pulmonary hypertension.
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