CHAPTER 49: Cardiovascular Disorders

As Williams recognized more than a century ago, pregnancy in those with significant heart disease can be extremely hazardous and may lead to decompensation and death. In an analysis of maternal mortality in the United States between 2011 and 2013, the causes previously responsible for most maternal deaths—hemorrhage, hypertensive disorders, and embolism—continued to show declining rates. In contrast, deaths attributable to cardiovascular diseases were responsible for approximately 26 percent of all pregnancy-related deaths (Creanga, 2017). Cardiovascular diseases also account for significant maternal morbidity and are a prominent reason for obstetrical intensive care unit admissions (Small, 2012).

The rising prevalence of cardiovascular diseases complicating pregnancy is likely multifactorial and includes the higher rates of obesity, hypertension, and diabetes (Klingberg, 2017). Indeed, according to the National Center for Health Statistics, almost half of adults aged 20 and older have at least one risk factor for cardiovascular disease (Fryar, 2012). Another related reason is delayed childbearing. Last, as discussed subsequently (Congenital Heart Disease), an increasing number of women with congenital heart disease are now becoming pregnant.

Cardiovascular Physiology

The marked pregnancy-induced anatomical and functional changes in cardiac physiology can have a profound effect on underlying heart disease (Chap. 4, Cardiovascular System). Some of these changes are listed in Table 49-1. Importantly, cardiac output increases approximately 40 percent during pregnancy. Almost half of this total takes place by 8 weeks’ gestation and is maximal by midpregnancy (Capeless, 1989). This early rise stems from augmented stroke volume, which results from lowered vascular resistance. Later in pregnancy, resting pulse and stroke volume are even higher because of greater end-diastolic ventricular volume that results from pregnancy hypervolemia. These changes translate to a cardiac output that enlarges across pregnancy to average 40 percent higher at term. These adaptations are even more profound in multifetal pregnancies (Kametas, 2003; Kuleva, 2011). Importantly, intrinsic left ventricular contractility does not change. Thus, normal left ventricular function is maintained during pregnancy. Namely, pregnancy is not characterized by hyperdynamic function or a high cardiac-output state.

Women with underlying cardiac disease may not always accommodate these changes, and ventricular dysfunction leads to cardiogenic heart failure. A few women with severe cardiac dysfunction can experience evidence of heart failure before midpregnancy. In others, heart failure may develop after 28 weeks’ gestation, when pregnancy-induced hypervolemia and cardiac output reach their maximum. In most, however, heart failure develops peripartum, when labor, delivery, and several common obstetrical conditions add undue cardiac burdens. Some of these include preeclampsia, hemorrhage and anemia, and sepsis.

Ventricular Function in Pregnancy

Ventricular volumes and mass accrue to accommodate pregnancy-induced hypervolemia. This is reflected by greater end-systolic and end-diastolic dimensions. At the same time, however, septal thickness and ejection fraction are unchanged. This is because these alterations are accompanied by substantive ventricular remodeling—plasticity—which is characterized by eccentric expansion of left-ventricular mass that averages 30 to 35 percent near term. All of these adaptations return to prepregnancy values within a few months postpartum.

Certainly for clinical purposes, ventricular function during pregnancy is normal as estimated by the Braunwald ventricular function graph depicted in Figure 4-9. For given filling pressures, there is appropriate cardiac output so that cardiac function during pregnancy is eudynamic. In nonpregnant subjects with a normal heart who sustain a high-output state, the left ventricle undergoes longitudinal remodeling, and echocardiographic functional indices of its deformation provide normal values. In pregnancy, there instead appears to be spherical remodeling, and these calculated indices that measure longitudinal deformation are depressed. Thus, normal nonpregnant indices are likely inaccurate when used to assess function in pregnant women because they do not take into account the spherical remodeling characteristic of normal pregnancy (Savu, 2012; Stewart, 2016).

Adjusting for these geometrical changes, Melchiorre and coworkers (2016) studied normal cardiac echocardiographic findings in 559 nulliparas at four points during pregnancy and again at 1 year postpartum. At term, significant chamber diastolic dysfunction and impaired myocardial relaxation were evident in approximately 18 and 28 percent of the women studied, respectively. Moreover, a significant proportion of women studied demonstrated a drop in stroke volume index and a tendency toward eccentric remodeling. These findings suggest cardiovascular maladaptation to the increased volume demands in a substantial proportion of apparently normal pregnancies. Of note, significant dyspnea at rest was reported by 7.4 percent of the women at term, most of whom had chamber diastolic dysfunction. Cardiac function and all signs of dyspnea fully recovered at 1 year postpartum.

Cardiac magnetic resonance (MR) imaging increasingly is used to evaluate cardiac structure and function. Stewart and associates (2016) performed cardiac MR imaging studies in 23 women longitudinally across pregnancy and at 12 weeks postpartum. Compared with studies performed at 12 to 16 weeks’ gestation, left ventricular mass grew significantly for both normal-weight and overweight women. The calculated geometrical ratio of left ventricular mass to left ventricular end-diastolic volume demonstrated concentric remodeling throughout gestation, which resolved by 12 weeks’ postpartum. The right ventricle also remodels (Martin, 2017). Taken together, these observations likely mean that pregnancy causes a mixture of eccentric and concentric ventricular remodeling.

The physiological adaptations of normal pregnancy can induce symptoms and alter clinical findings that may confound the diagnosis of heart disease. For example, in normal pregnancy, functional systolic heart murmurs are common, respiratory effort is accentuated, edema frequently accrues in lower extremities after midpregnancy, and fatigue and exercise intolerance often develop. Some systolic flow murmurs can be loud, and normal changes in the various heart sounds depicted in Figure 49-1 may erroneously suggest cardiac disease. In contrast, clinical findings that are more likely to suggest heart disease are listed in Table 49-2.

Diagnostic Studies

Noninvasive cardiovascular studies such as electrocardiography, chest radiography, and echocardiography will provide the data necessary for evaluation in most women.

In the electrocardiogram (ECG), an average 15-degree left-axis deviation is found as the diaphragm is elevated in advancing pregnancy. Other findings, depicted in Figure 49-2, include a reduced PR interval, inverted or flattened T waves, and a Q wave in lead D_III (Angeli, 2014). Pregnancy does not alter voltage findings. Atrial and ventricular premature contractions are relatively frequent (Carruth, 1981).

With radiography, anteroposterior (AP) and lateral chest radiographs are useful, and when a lead apron shield is used, fetal radiation exposure is minimal. Gross cardiomegaly can usually be excluded, but slight heart enlargement cannot be detected accurately because the heart silhouette normally is larger in pregnancy. This is accentuated further with a portable AP chest radiograph.

Echocardiography is now widely used and permits accurate diagnosis of most heart diseases during pregnancy. Some normal pregnancy-induced changes include a small increase in the dimensions of all cardiac chambers, a slight but significant growth in left ventricular mass, and greater tricuspid and mitral valve regurgitation (Grewal, 2014). Of note, systolic function normally does not change. Savu (2012) and Vitarelli (2011) and their colleagues have provided normal echocardiographic parameters for pregnancy, which are listed in the Appendix (Maternal Echocardiographic Measurements). In some situations, such as complex congenital heart disease, transesophageal echocardiography may be useful.

Cardiovascular MR imaging, compared with echocardiography, is associated with higher reproducibility and is less hindered by ventricular geometry and body habitus. The right ventricle can also be assessed (Nelson, 2017). Ducas and associates (2014) have published normal reference values for pregnancy.

Of other studies, albumin or red cells tagged with technetium-99m are rarely needed during pregnancy to evaluate ventricular function. That said, the estimated fetal radiation exposure from nuclear medicine studies of myocardial perfusion is negligible. It is safe to perform cardiac catheterization with limited fluoroscopy time. During coronary angiography, the mean radiation exposure to the unshielded abdomen is 1.5 mGy, and less than 20 percent of this reaches the fetus (European Society of Cardiology, 2011). Shortening the fluoroscopic time may help to minimize radiation exposure (Raman, 2015; Tuzcu, 2015). In women with clear indications, any minimal theoretical fetal risk is outweighed by maternal benefits (Chap. 46, X-Ray Dosimetry).

Classification of Functional Heart Disease

No clinically applicable test accurately measures functional cardiac capacity. The clinical classification of the New York Heart Association (NYHA) is based on past and present disability and is uninfluenced by physical signs:

• Class I. Uncompromised—no limitation of physical activity: These women do not have symptoms of cardiac insufficiency or experience anginal pain.

• Class II. Slight limitation of physical activity: These women are comfortable at rest, but if ordinary physical activity is undertaken, discomfort in the form of excessive fatigue, palpitation, dyspnea, or anginal pain results.

• Class III. Marked limitation of physical activity: These women are comfortable at rest, but less than ordinary activity causes excessive fatigue, palpitation, dyspnea, or anginal pain.

• Class IV. Severely compromised—inability to perform any physical activity without discomfort: Symptoms of cardiac insufficiency or angina may develop even at rest. If any physical activity is undertaken, discomfort is increased.

Siu and associates (2001b) expanded the NYHA classification and developed a scoring system for predicting cardiac complications during pregnancy. The system derives from a Canadian prospective analysis of 562 pregnant women with heart disease during 617 pregnancies. Predictors of cardiac complications included: (1) prior heart failure, transient ischemic attack, arrhythmia, or stroke; (2) baseline NYHA class III or IV or cyanosis; (3) left-sided obstruction defined as mitral valve area <2 cm², aortic valve area <1.5 cm², or peak left ventricular outflow tract gradient >30 mm Hg; and (4) ejection fraction <40 percent. The risk of pulmonary edema, sustained arrhythmia, stroke, cardiac arrest, or cardiac death was substantially elevated with one of these factors and even more so with two or more. Khairy and colleagues (2006) reported similar findings.

An even more comprehensive risk stratification system is the modified World Health Organization (WHO) Risk Classification of Cardiovascular Disease and Pregnancy (Table 49-3). It is especially useful for assessing maternal risk and for preconceptional counseling. Lu (2015) and Pijuan-Domènech (2015) and their associates in their analyses concluded that the modified WHO classification provides the greatest predictive accuracy for cardiac complications during pregnancy.

Preconceptional Counseling

Women with severe heart disease will benefit immensely from counseling before pregnancy, and they usually are referred for maternal-fetal medicine or cardiology consultation (Clark, 2012; Seshadri, 2012). Maternal mortality rates generally correlate directly with functional classification, and this relationship may change as pregnancy progresses. From the previously described Canadian study, Siu and colleagues (2001b) observed significant worsening of NYHA class in 4.4 percent of 579 pregnancies in which the baseline class was I or II. As described later, some women have life-threatening cardiac abnormalities that can be reversed by corrective surgery, and subsequent pregnancy becomes less dangerous. In other cases, such as women with mechanical valves taking warfarin, fetal teratogenic concerns predominate. Last, many congenital heart lesions are inherited as polygenic characteristics (Chap. 13, Imprinting). Because of this, some women with congenital heart lesions give birth to similarly affected neonates, and the risk varies widely (Table 49-4).

In most instances, management involves a team approach with an obstetrician, cardiologist, anesthesiologist, and other specialists as needed. With complex lesions or other high-risk cases, evaluation by a multidisciplinary team is recommended early in pregnancy. Within this framework, both prognosis and management are influenced by the type and severity of the specific lesion and by the maternal functional classification. In some, pregnancy termination may be advisable.

With rare exceptions, women in NYHA class I and most in class II negotiate pregnancy without morbidity. Special attention is directed toward both prevention and early recognition of heart failure. Of specific risks, infection with sepsis syndrome can precipitate this. Moreover, bacterial endocarditis is a deadly complication of valvular heart disease (Infective Endocarditis). Each woman is instructed to avoid contact with persons who have respiratory infections, including the common cold, and to report at once any evidence for infection. Pneumococcal and influenza vaccines are recommended (Chap. 9, Immunization).

Cigarette smoking is prohibited. Illicit drug use may be particularly harmful, an example being the cardiovascular effects of cocaine or amphetamines. In addition, intravenous drug use raises the risk of infective endocarditis.

Fortunately, women in NYHA class III and IV are uncommon today. In the prior Canadian study, only 3 percent of the approximately 600 pregnancies were complicated by NYHA class III heart disease, and no women had class IV when first seen (Siu, 2001b). If a woman chooses pregnancy, she must understand the risks and is encouraged to be compliant with planned care. In some women, prolonged hospitalization or bed rest is often necessary.

Labor and Delivery

In general, vaginal delivery is preferred, and labor induction is usually safe (Thurman, 2017). From the large Registry on Pregnancy and Cardiac Disease, Ruys and coworkers (2015) compared pregnancy outcomes between 869 women who had a planned vaginal delivery and 393 gravidas who had a planned cesarean delivery. Planned cesarean delivery conferred no advantage for maternal or neonatal outcome.

Cesarean delivery is usually limited to obstetrical indications, and considerations are given for the specific cardiac lesion, overall maternal condition, and availability of experienced anesthesia personnel and hospital capabilities. Some of these women tolerate major surgical procedures poorly and are best delivered in a unit experienced with management of complicated cardiac disease. Occasionally, pulmonary artery catheterization may be needed for hemodynamic monitoring (Chap. 47, Obstetrical Critical Care). In our experiences, however, invasive monitoring is rarely indicated.

Based on her review, Simpson (2012) recommends cesarean delivery for women with the following: (1) dilated aortic root >4 cm or aortic aneurysm; (2) acute severe congestive heart failure; (3) recent myocardial infarction; (4) severe symptomatic aortic stenosis; (5) warfarin administration within 2 weeks of delivery; and (6) need for emergency valve replacement immediately after delivery. Although we agree with most of these, we have some caveats. For example, we prefer aggressive medical stabilization of pulmonary edema followed by vaginal delivery if possible. Also, warfarin anticoagulation can be reversed with vitamin K, plasma, or prothrombin concentrates.

During labor, the mother with significant heart disease should be kept in a semirecumbent position with a lateral tilt. Vital signs are taken frequently between contractions. Increases in pulse rate much above 100 beats per minute (bpm) or respiratory rate above 24 per minute, particularly when associated with dyspnea, may suggest impending ventricular failure. For evidence of cardiac decompensation, intensive medical management must be instituted immediately. Delivery itself does not necessarily improve the maternal condition and, in fact, may worsen it. Moreover, emergency cesarean delivery may be particularly hazardous. Clearly, both maternal and fetal status must be considered in the decision to hasten delivery under these circumstances.

Analgesia and Anesthesia

Relief from pain and from apprehension is important. Although intravenous analgesics provide satisfactory pain relief for some women, continuous epidural analgesia is recommended for most. The major problem with conduction analgesia is maternal hypotension (Chap. 25, Cesarean Delivery). This is especially dangerous in women with intracardiac shunts in whom flow may be reversed. Hypotension can also be life-threatening if there is pulmonary arterial hypertension or aortic stenosis because ventricular output is dependent on adequate preload. In women with these conditions, narcotic regional analgesia or general anesthesia may be preferable.

For vaginal delivery in women with only mild cardiovascular compromise, epidural analgesia given with intravenous sedation often suffices. This has been shown to minimize intrapartum cardiac output fluctuations and allows forceps or vacuum-assisted delivery. Subarachnoid blockade is not generally recommended in women with significant heart disease due to associated hypotension. For cesarean delivery, epidural analgesia is preferred by most clinicians with caveats for its use with pulmonary arterial hypertension (Cardiomyopathies).

Intrapartum Heart Failure

Cardiovascular decompensation during labor may manifest as pulmonary edema with hypoxia or as hypotension, or both. The proper therapeutic approach depends on the specific hemodynamic status and the underlying cardiac lesion. For example, decompensated mitral stenosis with pulmonary edema due to fluid overload is often best treated with aggressive diuresis. If precipitated by tachycardia, heart rate control with β-blocking agents is preferred. Conversely, the same treatment in a woman suffering decompensation and hypotension due to aortic stenosis could prove fatal. Unless the underlying pathophysiology is understood and the cause of the decompensation is clear, empirical therapy may be hazardous.

Puerperium

Women who have shown little or no evidence of cardiac compromise during pregnancy, labor, or delivery may still decompensate postpartum. Fluid mobilized into the intravascular compartment and reduced peripheral vascular resistance place higher demands on myocardial performance. Therefore, meticulous care is continued into the puerperium (Keizer, 2006; Zeeman, 2006). Postpartum hemorrhage, anemia, infection, and thromboembolism are much more serious complications with heart disease. Indeed, these factors often act in concert to precipitate postpartum heart failure. In addition, sepsis and severe preeclampsia cause or worsen pulmonary edema because of endothelial activation and capillary-alveolar leakage (Chap. 47, Acute Pulmonary Edema).

For puerperal tubal sterilization after vaginal delivery, the procedure can be delayed up to several days to ensure that the mother has normalized hemodynamically and that she is afebrile, not anemic, and ambulating normally. Alternatively, for those desiring future fertility, detailed contraceptive advice is available in the U.S. Medical Eligibility Criteria for Contraceptive Use guidelines (Curtis, 2016).

Most clinically significant congenital heart lesions are repaired during childhood. Examples of those frequently not diagnosed until adulthood include atrial septal defects, pulmonic stenosis, bicuspid aortic valve, and aortic coarctation (Brickner, 2014). In some cases, the defect is mild and surgery is not required. In others, a significant anomaly is amenable to corrective surgery, performed ideally before pregnancy. In rare instances, surgical corrections are necessary during pregnancy.

Valve Replacement before Pregnancy

Numerous reports describe subsequent pregnancy outcomes in women who have a prosthetic mitral or aortic valve. The type of valve, either mechanical or biological, is paramount. From one review, the overall estimated maternal mortality rate was 1.2 percent. The rate was 1.8 percent in the mechanical valve subgroup and 0.7 percent in the bioprosthetic subgroup (Lawley, 2015). Using the Registry of Pregnancy and Cardiac Disease, the maternal mortality rate was 1.4 percent in women with a mechanical heart valve and 1.5 percent in women with a tissue heart valve (van Hagen, 2015). Mechanical heart valve thrombosis complicated 4.7 percent. In total, only 58 percent with a mechanical heart valve had a pregnancy free of serious adverse events compared with 79 percent of patients with a tissue heart valve (Table 49-5). Because of thrombosis risks, anticoagulation may be requisite, but its complications are described in the next section. Thus, pregnancy is undertaken only after serious consideration for women with a prosthetic mechanical valve.

Bouhout and coworkers (2014) reported the outcomes of 27 pregnancies in 14 women who underwent an aortic valve replacement prior to pregnancy. Seven of the 27 pregnancies occurred in five women with a mechanical prosthesis. Complications in this group included two embolic myocardial infarctions and one each of miscarriage, postpartum hemorrhage, placental abruption, and preterm birth. In the bioprosthetic group, nine miscarriages, two hospitalizations for syncope, and one preterm birth were noted.

Porcine tissue valves are safer during pregnancy, primarily because thrombosis is rare and anticoagulation is not required (see Table 49-5). Despite this, valvular dysfunction with cardiac deterioration poses a serious risk. Another drawback is that bioprostheses are less durable than mechanical ones, and valve replacement longevity averages 10 to 15 years. Cleuziou and colleagues (2010) concluded that pregnancy does not accelerate the risk for replacement. But, Nappi and associates (2014) found an association between pregnancy and valve deterioration in women with cryopreserved mitral homograft valves.

Anticoagulation

This is critical for women with mechanical prosthetic valves. Unfortunately, warfarin is the most effective anticoagulant for preventing maternal thromboembolism but causes harmful fetal effects (Chap. 12, Warfarin). Anticoagulation with heparin is less hazardous for the fetus, however, the risk of maternal thromboembolic complications is much higher (McLintock, 2011).

Warfarin is teratogenic and causes miscarriage, stillbirths, and fetal malformations. In one study of 71 women given warfarin throughout pregnancy, the rates of miscarriage were 32 percent; stillbirth, 7 percent; and embryopathy, 6 percent (Cotrufo, 2002). The risk was highest when the mean daily dose of warfarin exceeded 5 mg. Similarly, the American College of Cardiology and the American Heart Association estimate that the risk of embryopathy is dose dependent, with a lower risk—less than 3 percent—if the dose of warfarin is ≤5 mg/d (Nishimura, 2014). If the dosage is >5 mg/d, the risk of embryopathy exceeds 8 percent.

Anticoagulation for mechanical valves using low-dose unfractionated heparin is definitely inadequate and carries a high associated maternal mortality rate (Chan, 2000; Iturbe-Alessio, 1986). Even full anticoagulation with either unfractionated heparin (UFH) or one of the low-molecular-weight heparins (LMWH) is associated with valvular thrombosis (Leyh, 2002, 2003; Rowan, 2001). But, compliance with twice-daily dosing and therapeutic monitoring may have contributed (McLintock, 2014). Thus, if full anticoagulation with dose-adjusted UFH or LMWH is used, meticulous monitoring is recommended. The activated partial thromboplastin time (aPTT) should be at least 2 times control or anti-Xa levels should be 0.8 to 1.2 U/mL at 4 to 6 hours postdose (Nishimura, 2014).

Recommendations for Anticoagulation

Several different treatment options—none of which are completely ideal—are principally based on consensus opinion. Two are from the American College of Chest Physicians and the other jointly from the American College of Cardiology and the American Heart Association (Bates, 2012; Nishimura, 2014). Any of four regimens is recommended. First, adjusted-dose LMWH is given twice daily, with a peak anti-Xa level drawn 4 hours after dosing. In another, adjusted UFH is dosed every 12 hours to keep the midinterval aPTT twice control or anti Xa level between 0.35–0.70 U/mL. As a third option, LMWH or UFH is given as just described until 13 weeks, and then warfarin is substituted until near delivery, at which time it is replaced by LMWH or UFH. Last, in women judged to carry a high risk of thrombosis and for whom the efficacy and safety of heparins are concerns, warfarin is suggested throughout pregnancy. Heparin is then substituted close to delivery. In addition, aspirin, 75 to 100 mg, is given daily.

Heparin is discontinued just before delivery. If delivery supervenes while the anticoagulant is still effective, and extensive bleeding is encountered, then protamine sulfate is given intravenously. Anticoagulant therapy with warfarin or heparin may be restarted 6 hours following vaginal delivery, usually with no problems. Following cesarean delivery, full anticoagulation is withheld, but the optimal duration is not exactly known. The American College of Obstetricians and Gynecologists (2017) advises resuming unfractionated or low-molecular-weight heparin 6 to 12 hours after cesarean delivery. It is our practice, however, to wait at least 24 hours following a major surgical procedure.

Because warfarin, LMWH, and UFH do not accumulate in breast milk, they do not induce an anticoagulant effect in the newborn. These anticoagulants are compatible with breastfeeding (American College of Obstetricians and Gynecologists, 2017).

Cardiac Surgery During Pregnancy

Although usually postponed until after delivery, valve replacement or other cardiac surgery during pregnancy may be lifesaving. Several reviews confirm that such surgery is associated with major maternal and fetal morbidity and mortality. At the Mayo Clinic between 1976 and 2009, 21 pregnant women underwent cardiothoracic surgery requiring cardiopulmonary bypass (John, 2011). The procedures included valve replacements, myxoma excisions, aneurysm repairs, patent foramen ovale closure, prosthetic aortic valve thrombectomy, and septal myectomy. Median cardiopulmonary bypass time was 53 minutes, with a range of 16 to 185 minutes. One woman died 2 days after surgery, three fetuses died, and 52 percent were delivered before 36 weeks’ gestation. Elassy and associates (2014) described 23 women who underwent urgent open cardiac surgery for severe valve malfunction. Two women and 10 fetuses—all at a gestational age below 28 weeks—died before hospital discharge. Only six fetuses were delivered at term. To optimize outcomes, Chandrasekhar and coworkers (2009) recommend that surgery be elective when possible, pump flow rate should remain >2.5 L/min/m², normothermic perfusion pressure should exceed 70 mm Hg, and hematocrit should be kept >28 volumes percent.

Pregnancy after Heart Transplantation

Many successful pregnancies have followed cardiac transplantation (Abdalla, 2014; Vos, 2014). The current recommendations from The International Society of Heart and Lung Transplantation do not discourage pregnancy in stable heart transplant recipients who are more than 1 year posttransplant (Costanzo, 2010). Obviously, a highly specialized level of care with a multidisciplinary team is necessary.

The transplanted heart appears to responds normally to pregnancy-induced alterations (Key, 1989; Kim, 1996). Despite this, complications are common during pregnancy (Dashe, 1998). Of 53 pregnancies in 37 heart recipients, almost half developed hypertension, and 22 percent suffered at least one rejection episode during pregnancy (Armenti, 2002; Miniero, 2004). They were delivered—usually by cesarean—at a mean of 37 to 38 weeks’ gestation. Three fourths of neonates were liveborn. At follow-up, at least five women had died more than 2 years postpartum. Another analysis of 25 such women with 42 pregnancies found no maternal deaths. Major complications included two rejections during the early puerperium, two cases of renal failure, and 11 spontaneous abortions (Estensen, 2011). Five women died 2 to 12 years after delivery. And from the United Kingdom, Mohamed-Ahmed and colleagues (2014) identified 14 women with transplants between 2007 and 2011. Graft rejections occurred in two women, one of whom died.

Rheumatic fever is uncommon in the United States because of less crowded living conditions, penicillin availability, and evolution of nonrheumatogenic streptococcal strains. Still, it remains the chief cause of serious mitral valvular disease in women of childbearing age in the nonindustrialized world (Nanna, 2014; Roeder, 2011).

Mitral Stenosis

Rheumatic endocarditis causes most mitral stenosis lesions. The normal mitral valve surface area is 4.0 cm², and when stenosis narrows this to <2.5 cm², symptoms usually develop (Desai, 2000). The contracted valve impedes blood flow from the left atrium to the ventricle.

With more severe stenosis, the left atrium dilates, left atrial pressure is chronically elevated, and significant passive pulmonary hypertension develops (Table 49-6). These women have a relatively fixed cardiac output, and thus the increased preload of normal pregnancy and other factors that raise cardiac output may cause ventricular failure and pulmonary edema. Indeed, a fourth of women with mitral stenosis have cardiac failure for the first time during pregnancy (Caulin-Glaser, 1999). The resulting pulmonary venous hypertension and pulmonary edema create symptoms of dyspnea, fatigue, palpitations, cough, and hemoptysis. The classic murmur may not be heard in some women, and this clinical picture at term may be confused with idiopathic peripartum cardiomyopathy (Cunningham, 1986, 2012).

Also with significant stenosis, tachycardia shortens ventricular diastolic filling time and elevates the mitral gradient. This too may lead to pulmonary edema. Thus, sinus tachycardia is often treated prophylactically with β-blocking agents. Atrial tachyarrhythmias, including fibrillation, are common in mitral stenosis and are treated aggressively. Atrial fibrillation also predisposes to mural thrombus formation and cerebrovascular embolization that can cause stroke (Chap. 60, Ischemic Stroke). Atrial thrombosis can develop despite a sinus rhythm (Hameed, 2005).

Pregnancy Outcomes

In general, complications are directly associated with the degree of valvular stenosis. Women with a mitral-valve area <2 cm² are at greatest risk (Siu, 2001b). In one study of 46 gravidas with mitral stenosis, 43 percent developed heart failure, and 20 percent developed arrhythmias (Hameed, 2001). Fetal-growth restriction was more common in women with a mitral valve area <1.0 cm².

Prognosis is also related to maternal functional capacity. Among 486 pregnancies complicated by rheumatic heart disease—predominantly mitral stenosis—8 of 10 maternal deaths were in women in NYHA classes III or IV (Sawhney, 2003).

Management

Limited physical activity is generally recommended in women with mitral stenosis. If symptoms of pulmonary congestion develop, activity is further reduced, dietary sodium is restricted, and diuretics are given (Siva, 2005). Also, β-blocker drug therapy slows the ventricular response to activity. If new-onset atrial fibrillation develops, intravenous verapamil, 5 to 10 mg, is given, or electrocardioversion is performed. For chronic fibrillation, digoxin, a β-blocker, or a calcium-channel blocker can slow ventricular response. Therapeutic anticoagulation is indicated with persistent fibrillation, left atrial thrombus, and/or a history of embolism (Nanna, 2014).

Surgical intervention is considered for women with symptomatic severe mitral stenosis and in those with lesser degrees of mitral stenosis—mitral-valve area 1.5 to 2.0 cm²—complicated by recurrent systemic embolization or severe pulmonary hypertension. Balloon valvuloplasty is preferred if the valve is pliable (Bui, 2014). In one review of 71 pregnant women with tight mitral stenosis and heart failure who underwent percutaneous valvuloplasty, 98 percent were either NYHA class I or II at delivery (Esteves, 2006). At a mean of 44 months, the total event-free maternal survival rate was 54 percent. However, eight women required another surgical intervention. All of the 66 newborns who were delivered at term had normal growth and development.

Labor and delivery are particularly stressful for women with symptomatic mitral stenosis (Fig. 49-3). Uterine contractions increase cardiac output by increasing circulating blood volume. Pain, exertion, and anxiety cause tachycardia with possible rate-related heart failure. Epidural analgesia for labor is ideal, but fluid overload is avoided. Abrupt expansion in preload may raise pulmonary capillary wedge pressure and cause pulmonary edema. Wedge pressures rise immediately postpartum. One hypothesis for this suggests that the loss of the low-resistance placental circulation couples with venous “autotransfusion” from a now-empty, contracted uterus and from the lower extremities and pelvis (Clark, 1985).

Most prefer vaginal delivery in women with mitral stenosis. Elective induction is reasonable so that labor and delivery are attended by a scheduled, experienced team. With severe stenosis and chronic heart failure, insertion of a pulmonary artery catheter may help guide management.

Mitral Insufficiency

A trivial degree of mitral insufficiency is found in most normal patients. But if mitral valve leaflets align improperly during systole, abnormal degrees of mitral regurgitation can develop. This is eventually followed by left ventricular dilation and eccentric hypertrophy (see Table 49-6). Acute mitral insufficiency is caused by chordae tendineae rupture, papillary muscle infarction, or leaflet perforation from infective endocarditis. Chronic mitral regurgitation, in contrast, may derive from rheumatic fever, connective tissue diseases, mitral valve prolapse, or left ventricular dilation of any etiology—for example, dilated cardiomyopathy. Less common causes include a calcified mitral annulus, possibly some appetite suppressants, and in older women, ischemic heart disease. Mitral valve vegetations—Libman-Sacks endocarditis—are relatively common in women with antiphospholipid antibodies (Shroff, 2012). These sometimes coexist with systemic lupus erythematosus.

In nonpregnant patients, symptoms from mitral valve insufficiency are rare, and valve replacement is seldom indicated unless infective endocarditis develops. During pregnancy, mitral regurgitation is similarly well tolerated, probably because the lowered systemic vascular resistance yields less regurgitation. Heart failure rarely develops during pregnancy, and occasionally tachyarrhythmias or severely depressed systolic function require treatment.

Mitral Valve Prolapse

This diagnosis implies the presence of a pathological connective tissue disorder—often termed myxomatous degeneration—which may involve the valve leaflets themselves, the annulus, or the chordae tendineae. Mitral insufficiency may develop. Most women with mitral valve prolapse are asymptomatic and are diagnosed during routine examination or echocardiography. The few women with symptoms have anxiety, palpitations, atypical chest pain, dyspnea with exertion, and syncope (Guy, 2012).

Pregnant women with mitral valve prolapse rarely have cardiac complications. Hypervolemia may even improve alignment of the mitral valve, and women without pathological myxomatous degeneration generally have excellent pregnancy outcomes (Leśniak-Sobelga, 2004). For women who are symptomatic, β-blocking drugs diminish sympathetic tone, relieve chest pain and palpitations, and reduce the risk of life-threatening arrhythmias.

Aortic Stenosis

Usually a disease of aging, aortic stenosis in younger women is most likely a congenital lesion. Since the decline in rheumatic disease incidence, aortic stenosis is less common, and the most frequent cause in the United States is a bicuspid valve (Friedman, 2008). A normal aortic valve has an area of 3 to 4 cm², with a pressure gradient <5 mm Hg. If the valve area is <1 cm², there is severe obstruction to flow and a progressive pressure overload on the left ventricle (Roeder, 2011). Concentric left ventricular hypertrophy follows, and if it is severe, end-diastolic pressures become elevated, ejection fraction declines, and cardiac output is reduced (see Table 49-6). Characteristic manifestations develop late and include chest pain, syncope, heart failure, and sudden death from arrhythmias. Life expectancy averages only 5 years after exertional chest pain develops, and valve replacement is indicated for symptomatic patients.

Pregnancy

Clinically significant aortic stenosis is infrequent during pregnancy. Mild-to-moderate degrees of stenosis are well tolerated, however, severe disease is life-threatening. The principal underlying hemodynamic problem is the fixed cardiac output associated with severe stenosis. During pregnancy, several common events acutely lower preload further and thus aggravate the fixed cardiac output. These include vena caval occlusion from the gravid uterus, regional analgesia, and hemorrhage. Importantly, these also decrease cardiac, cerebral, and uterine perfusion. It follows that severe aortic stenosis may be extremely dangerous during pregnancy. From the earlier-cited Canadian study, complication rates were higher if the aortic valve area measured <1.5 cm² (Siu, 2001b). And in the report by Hameed and associates (2001), the maternal mortality rate with aortic stenosis was 8 percent. Women with valve pressure gradients >100 mm Hg appear to be at greatest risk.

Management

For asymptomatic women with aortic stenosis, no treatment except close observation is required. Management of a symptomatic woman includes strict limitation of activity and prompt treatment of infections. If symptoms persist despite bed rest, surgical intervention may be considered. Catheter-based valvuloplasty is associated with risks to both the mother and fetus and is not very effective in the long term (Pessel, 2014; Reich, 2004). The aortic valve can again narrow or new aortic regurgitation may develop. The alternative surgical approach—valve replacement—is associated with significant risk of fetal demise due to the effects of cardiac bypass (Datt, 2010). Accordingly, the American College of Cardiology, the American Heart Association, and the European Society of Cardiology recommend delaying conception until after surgical correction for severe aortic stenosis (Bonow, 2008).

For women with critical aortic stenosis, intensive monitoring during labor is essential. Pulmonary artery catheterization may be helpful because of the narrow margin separating fluid overload from hypovolemia. Women with aortic stenosis are dependent on adequate end-diastolic ventricular filling pressures to maintain cardiac output and systemic perfusion. Abrupt drops in end-diastolic volume may result in hypotension, syncope, myocardial infarction, and sudden death. Thus, avoiding diminished ventricular preload and maintaining cardiac output are key. During labor and delivery, affected women are best managed on the “wet” side. This provides a margin of safety in intravascular volume in anticipation of possible hemorrhage. In women with a competent mitral valve, pulmonary edema is rare.

During labor, narcotic epidural analgesia seems ideal and avoids potentially hazardous hypotension. Easterling and coworkers (1988) studied the effects of epidural analgesia in five women with severe stenosis and demonstrated immediate and profound effects from decreased filling pressures. Xia and associates (2006) emphasize slow administration of dilute local anesthetic agents into the epidural space. In hemodynamically stable women, forceps or vacuum delivery is used for standard obstetrical indications.

Aortic Insufficiency

Aortic valve regurgitation or insufficiency allows diastolic flow of blood from the aorta back into the left ventricle. Frequent causes of abnormal insufficiency are rheumatic fever, connective tissue abnormalities, and congenital lesions. With Marfan syndrome, the aortic root may dilate and create regurgitation (Diseases of the Aorta). Acute insufficiency may also develop with bacterial endocarditis or aortic dissection (Infective Endocarditis and Diseases of the Aorta). Last, aortic and mitral valve insufficiency have both been linked to the appetite suppressants fenfluramine and dexfenfluramine and to the ergot-derived dopamine agonists cabergoline and pergolide (Gardin, 2000; Schade, 2007; Zanettini, 2007). With chronic insufficiency, left ventricular hypertrophy and dilation develop and are followed by slow-onset fatigue, dyspnea, and pulmonary edema, although rapid deterioration usually follows (see Table 49-6).

Aortic insufficiency is generally well tolerated during pregnancy. Like mitral valve insufficiency, diminished vascular resistance is thought to improve hemodynamic function. If symptoms of heart failure develop, diuretics are given and bed rest is encouraged.

Pulmonic Stenosis

This lesion is usually congenital and also may be associated with Fallot tetralogy or Noonan syndrome. The greater hemodynamic burden of pregnancy can precipitate right-sided heart failure or atrial arrhythmias in women with severe stenosis. Surgical correction ideally is done before pregnancy, but if symptoms progress, a balloon valvuloplasty may be necessary antepartum (Galal, 2015; Siu, 2001a).

In studying pregnancy outcomes, Drenthen and colleagues (2006) found infrequent cardiac complications in a group of 81 pregnancies in 51 Dutch women with pulmonic stenosis. The NYHA classification worsened in two women, and nine experienced palpitations or arrhythmias. No changes in pulmonary valvular function or other adverse cardiac events were reported. However, noncardiac complication rates were significant—17 percent had preterm delivery, 15 percent had hypertension, and 4 percent developed thromboembolism.

The incidence of congenital heart disease in the United States approximates 11 per 1000 liveborn neonates (Egbe, 2014). With modern surgeries, approximately 90 percent of those born with congenital heart disease survive to childbearing age, and it is now the most common type of heart disease encountered during pregnancy (Brickner, 2014; Lindley, 2015). Specifically, analysis from the United States Nationwide Inpatient Sample database shows a linear rise in the prevalence of congenital heart disease between 2000 and 2010—from 6.4 to 9.0 per 10,000 women admitted for delivery (Thompson, 2015).

Of pregnancy outcomes in women with congenital heart disease compared with those without, the odds of cardiovascular and obstetrical complications were 10.5 to 35.5 and 1.2 to 2.1 times higher, respectively (Thompson, 2015). Moreover, maternal mortality rates were greater for women with congenital heart disease than for unaffected gravidas—17.8 and 0.7 per 10,000 deliveries, respectively. Opotowsky and coworkers (2012) reported similar risks.

Atrial Septal Defects

Approximately one fourth of all adults has a patent foramen ovale (Miller, 2015). Most atrial septal defects (ASDs) are asymptomatic until the third or fourth decade. The secundum-type defect accounts for 70 percent, and associated mitral valve myxomatous abnormalities with prolapse are common. Most recommend repair if ASD is discovered in adulthood. Pregnancy is well tolerated unless pulmonary hypertension has developed, but this is uncommon (Geva, 2014). Treatment of ASD during pregnancy is indicated for congestive heart failure or an arrhythmia. Based on their review, Aliaga and colleagues (2003) concluded that the risk of endocarditis with an ASD is negligible.

With the potential to shunt blood from right to left, a paradoxical embolism, that is, entry of a venous thrombus through the septal defect and into the systemic arterial circulation, is possible and may cause an embolic stroke (Erkut, 2006; Miller, 2015). In asymptomatic women with ASD, thromboembolism prophylaxis is problematic, and the heterogeneous recommendations have been summarized by Kizer and Devereux (2005). Compression stockings and prophylactic heparin have also been recommended for a pregnant woman with an ASD who is immobile or has another risk factor for thromboembolism (Head, 2005).

Ventricular Septal Defects

These lesions close spontaneously during childhood in 90 percent of cases. Most defects are paramembranous, and the degree of left-to-right shunt and associated physiological derangements are related to lesion size. In general, if the defect measures <1.25 cm², pulmonary hypertension and heart failure do not develop. If the effective defect size exceeds that of the aortic valve orifice, symptoms rapidly develop. For these reasons, most children undergo surgical repair before pulmonary hypertension develops. Adults with unrepaired large defects develop left ventricular failure and pulmonary hypertension and have a high incidence of bacterial endocarditis (Brickner, 2000, 2014).

Pregnancy is well tolerated with small-to-moderate sized shunts. If pulmonary arterial pressures reach systemic levels, however, there is reversal or bidirectional flow—Eisenmenger syndrome (Pulmonary Hypertension). When this develops, the maternal and fetal mortality rates are significantly higher, and thus, pregnancy is not generally advisable. Bacterial endocarditis is more common with unrepaired defects, and antimicrobial prophylaxis is often required (Infective Endocarditis). As shown in Table 49-4, 10 to 16 percent of offspring born to these women also have a ventricular septal defect.

Atrioventricular Septal Defects

These account for approximately 3 percent of all congenital cardiac malformations and are distinct from isolated atrial or ventricular septal defects. An atrioventricular (AV) septal defect is characterized by a common, ovoid AV junction. This defect is associated with aneuploidy, Eisenmenger syndrome, and other malformations (Altin, 2015). Compared with simple septal defects, complications are more frequent during pregnancy. In a review of 48 pregnancies in 29 affected women, complications included persistent deterioration of NYHA class in 23 percent, significant arrhythmias in 19 percent, and heart failure in 2 percent (Drenthen, 2005b). Congenital heart disease was identified in 15 percent of the offspring.

Persistent (Patent) Ductus Arteriosus

The ductus connects the proximal left pulmonary artery to the descending aorta just distal to the left subclavian artery. Functional closure of the ductus from vasoconstriction occurs shortly after term birth. The physiological consequences with its persistence are related to its size. Most significant lesions are repaired in childhood, but for individuals who do not undergo repair, the mortality rate is high after the fifth decade (Brickner, 2014). In some younger women with an unrepaired ductus during pregnancy, however, pulmonary hypertension, heart failure, or cyanosis will develop if systemic blood pressure falls and leads to shunt reversal of blood from the pulmonary artery into the aorta (Vashisht, 2015). A sudden blood pressure decline at delivery—such as with regional analgesia or hemorrhage—may lead to fatal collapse. Accordingly, hypotension is ideally avoided but treated vigorously if it develops. Prophylaxis for bacterial endocarditis is indicated at delivery for unrepaired defects (Infective Endocarditis). As shown in Table 49-4, the incidence of inheritance approximates 4 percent.

Cyanotic Heart Disease

When congenital heart lesions produce right-to-left shunting of blood past the pulmonary capillary bed, cyanosis develops. The classic and most commonly encountered lesion in adults and during pregnancy is the Fallot tetralogy (Lindley, 2015). This is characterized by a large ventricular septal defect, pulmonary stenosis, right ventricular hypertrophy, and an overriding aorta that receives blood from both the right and left ventricles. The magnitude of the shunt varies inversely with systemic vascular resistance. Hence, during pregnancy, when peripheral resistance declines, the shunt increases and cyanosis worsens.

Generally, women with cyanotic heart disease do poorly during pregnancy. With uncorrected Fallot tetralogy, maternal mortality rates approach 10 percent. There is a relationship between chronic hypoxemia, polycythemia, and pregnancy outcomes such as miscarriage and perinatal morbidity. When hypoxemia is intense enough to stimulate a rise in hematocrit above 65 volumes percent, pregnancy wastage is virtually 100 percent.

Although not all cyanotic lesions are repairable, with satisfactory surgical correction before pregnancy, maternal and fetal outcomes are much improved. In a review of 197 pregnancies in 99 women with surgically corrected Fallot tetralogy, pregnancy was usually well tolerated, and no mothers died. Still, almost 9 percent of pregnancies were complicated by adverse cardiac events including new-onset or worsening arrhythmias and heart failure (Balci, 2011; Kamiya, 2012). For women with a pulmonary valve replacement, pregnancy does not adversely affect graft function (Oosterhof, 2006). Prior to or after conception, women with Fallot tetralogy are offered genetic counseling and evaluation for 22q11 deletion syndrome (Lindley, 2015).

Some women with Ebstein anomaly, characterized by a malpositioned and malformed tricuspid valve, may reach reproductive age. Right ventricular failure from volume overload and cyanosis are common during pregnancy. In the absence of cyanosis, heart failure, or significant arrhythmias, affected women usually tolerate pregnancy well (Brickner, 2014).

Pregnancy after Surgical Repair

Transposition of the Great Vessels

Pregnancy following surgical correction of transposition has prominent risks. Canobbio (2006) and Drenthen (2005a), each with their colleagues, described outcomes of 119 pregnancies in 68 women—90 percent had a prior Mustard procedure and 10 percent a previous Senning procedure. During pregnancy, one fourth had arrhythmias, 12 percent developed heart failure, and one subsequently required cardiac transplantation. One woman died suddenly a month after delivery, and another died 4 years later. A third of the newborns were delivered preterm. In another report of 60 pregnancies in 34 women who had undergone transposition repair, approximately a fourth ended in miscarriage or abortion, and another fourth delivered preterm (Trigas, 2014). Deterioration in functional class occurred in seven women, and documented deterioration in systolic function occurred in four women. Finally, two women required resuscitation during delivery, and one experienced supraventricular tachycardia during labor. Of other defects, in women with previously repaired truncus arteriosus and double-outlet right ventricle, successful—although eventful—pregnancies have also been described (Drenthen, 2008; Hoendermis, 2008).

Single Functional Ventricle

With hypoplastic left heart syndrome, almost 70 percent of affected women are now expected to survive into adulthood and frequently become pregnant (Feinstein, 2012). Those who have undergone a Fontan repair are at particularly high risk for complications. In brief, this procedure involves diverting blood via a surgical anastomosis from the vena cava to the pulmonary artery without passing through the right ventricle. Blood flows passively to the pulmonary vasculature. Thus, patients with a Fontan palliation are very preload dependent (Lindley, 2015).

Of outcomes, one review of 14 women conceiving after a Fontan repair found that six spontaneously aborted all pregnancies, and eight others carried 14 pregnancies to viability (Cauldwell, 2016). Cardiac complications included arrhythmias and thromboembolism. Ten newborns delivered preterm, and eight neonates were small for gestational age. Similar complications attend a maternal systemic right ventricle, that is, one in which the right ventricle rather than the left pumps blood to the systemic circulation (Khan, 2015).

Eisenmenger Syndrome

This describes secondary pulmonary hypertension that arises from any cardiac lesion. The syndrome develops when pulmonary vascular resistance exceeds systemic resistance and leads to concomitant right-to-left shunting. The most common underlying defects are atrial or ventricular septal defects and persistent ductus arteriosus (Fig. 49-4). Patients are asymptomatic for years, but eventually pulmonary hypertension becomes severe enough to cause this shunting (Greutmann, 2015).

Pregnant women with Eisenmenger syndrome tolerate hypotension poorly, and death usually is caused by right ventricular failure with cardiogenic shock. In a review of 44 cases through 1978, maternal and perinatal mortality rates approximated 50 percent (Gleicher, 1979). In a later review of 73 pregnancies, Weiss and associates (1998) cited a 36-percent maternal death rate. Three of 26 deaths were antepartum, and the remainder of women died intrapartum or within a month of delivery. In a subsequent study of 13 gravidas, one mother died 17 days after delivery, and there were five perinatal deaths (Wang, 2011). Given such poor outcomes for both mother and fetus, Eisenmenger syndrome is considered to be an absolute contraindication to pregnancy (Brickner, 2014; Lindley, 2015; Meng, 2017; Warnes, 2015). Management of those who do become pregnant has recently been detailed by Broberg (2016) and is discussed in the next section.

Normal resting mean pulmonary artery pressure is 12 to 16 mm Hg. Pulmonary vascular resistance in late pregnancy approximates 80 dyne/sec/cm⁻⁵, which is 34-percent less than the nonpregnant value of 120 dyne/sec/cm⁻⁵ (Clark, 1989). Pulmonary hypertension is defined in nonpregnant individuals as a resting mean pulmonary pressure >25 mm Hg.

The current clinical classification system, shown in Table 49-7, includes five groups of disorders that cause pulmonary hypertension (Galiè, 2016). There are important prognostic and therapeutic distinctions between group 1 pulmonary arterial hypertension and the other groups. Group 1 indicates that a specific disease affects pulmonary arterioles. It includes idiopathic or primary pulmonary arterial hypertension as well as those cases secondary to a known cause such as connective tissue disease. For example, approximately one third of women with scleroderma and 10 percent with systemic lupus erythematosus have pulmonary hypertension (Rich, 2005). Other causes in young women are human immunodeficiency virus (HIV) infection, sickle-cell disease, and thyrotoxicosis (Newman, 2015; Sheffield, 2004).

In pregnant women, group 2 disorders are the most common. These are secondary to pulmonary venous hypertension caused by left-sided atrial, ventricular, or valvular disorders. A typical example is mitral stenosis discussed earlier (Valvular Heart Disease). In contrast, groups 3 through 5 are seen infrequently in young healthy women.

Diagnosis

Symptoms may be vague, and dyspnea with exertion is the most frequent. With group 2 disorders, orthopnea and nocturnal dyspnea are also usually present. Angina and syncope occur when right ventricular output is fixed, and they suggest advanced disease. Chest radiography often shows enlarged pulmonary hilar arteries and attenuated peripheral markings. It also may disclose parenchymal causes of hypertension. Noninvasive echocardiography can provide an estimate of pulmonary artery pressures, although cardiac catheterization remains the standard for measurement. In two studies with a combined 51 pregnant women who underwent both echocardiography and cardiac catheterization, pulmonary artery pressures were significantly overestimated by echocardiography in approximately one third of cases (Penning, 2001; Wylie, 2007).

Prognosis

Regardless of the etiology, the final common pathway of pulmonary hypertension is right heart failure and death. The average survival length after diagnosis is <4 years (Krexi, 2015). That said, longevity depends on the severity and cause of pulmonary hypertension at discovery. As discussed later, some disorders respond to medical interventions, which may improve quality of life. Preconceptional and contraceptive counseling are imperative (Gei, 2014).

Pregnancy

The maternal mortality rate is appreciable in affected women, and this is especially so with idiopathic pulmonary hypertension. In the past, there were frequently poor distinctions in identifying both causes and severity of hypertension. Thus, although most severe cases of idiopathic pulmonary arterial hypertension had the worst prognosis, it was erroneously assumed that all types of pulmonary hypertension were equally dangerous. With widespread use of echocardiography, less-severe lesions with a better prognosis are now discernible. Bédard and coworkers (2009) reported that maternal mortality rate statistics improved during the decade ending in 2007 (25 percent) compared with those for the decade ending in 1996 (38 percent). Importantly, almost 80 percent of the deaths were during the first month postpartum. More recently, Meng and associates (2017) reported mortality rates of 23 percent with group 1 and 5 percent with the other groups. Mortality was related to pulmonary hypertension severity.

As discussed, pregnancy is contraindicated with severe disease, especially in women with pulmonary arterial changes—most cases in group 1. With milder disease from other causes—group 2 being the most common—the prognosis is better (Meng, 2017). With the more frequent use of echocardiography and pulmonary artery catheterization in young women with heart disease, we have identified women with mild-to-moderate pulmonary hypertension who tolerate pregnancy, labor, and delivery well. One example described by Sheffield and Cunningham (2004) is that of pulmonary hypertension that develops with thyrotoxicosis but is reversible with treatment. Similarly, Boggess and colleagues (1995) described nine women with interstitial and restrictive lung disease with varying degrees of pulmonary hypertension, and all tolerated pregnancy reasonably well.

Management

Treatment of symptomatic pregnant women includes activity limitation and avoidance of the supine position later in gestation. Diuretics, supplemental oxygen, and pulmonary vasodilator drugs are standard therapy for symptoms. Some recommend anticoagulation (Hsu, 2011). Several reports describe the successful use of intravenous pulmonary artery vasodilators (Badalian, 2000; Garabedian, 2010; Goya, 2014). Prostacyclin analogues that can be administered parenterally include epoprostenol and treprostinil, whereas iloprost is inhaled. Each has been used in gravidas. Inhaled nitric oxide is an option that has been employed in cases of acute cardiopulmonary decompensation (Lane, 2011). As reviewed by Običan and Cleary (2014), phosphodiesterase-5 inhibitors, such as sildenafil, cause vasodilation of both the pulmonary and systemic vascular beds and have an inotropic effect on the hypertrophic right ventricle. This also has been used to advantage during pregnancy (Goland, 2010; Hsu, 2011; Meng, 2017). Bosentan, an endothelin-receptor antagonist, is teratogenic in mice and contraindicated in pregnancy (Običan, 2014).

During labor and delivery, these women are at greatest risk when venous return and right ventricular filling are diminished. To avoid hypotension, assiduous attention is given to epidural analgesia induction and to blood loss prevention and treatment at delivery (Meng, 2017).

The American Heart Association defines these as a heterogeneous group of myocardial diseases associated with mechanical and/or electrical dysfunction. Affected women usually—but not invariably—have inappropriate ventricular hypertrophy or dilation. Cardiomyopathies stem from varied causes, some of which are genetic (Maron, 2006). Of the two major divisions, primary cardiomyopathies are solely or predominantly confined to heart muscle. Examples are hypertrophic cardiomyopathy, dilated cardiomyopathies, and peripartum cardiomyopathy. Secondary cardiomyopathies result from generalized systemic disorders that produce pathological myocardial involvement. Diabetes, systemic lupus erythematosus, chronic hypertension, and thyroid disorders are representative conditions.

Hypertrophic Cardiomyopathy

Epidemiological studies suggest that this disorder is common, affecting approximately 1 in 500 adults (Herrey, 2014; Maron, 2004). Characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis, the condition is caused by mutations in any one of more than a dozen genes that encode cardiac sarcomere proteins in up to 60 percent of affected patients. In such cases, inheritance is autosomal dominant, and genetic screening is complex (Elliott, 2014). Other genetic and nongenetic causes account for 5 to 10 percent of cases, and the cause is unknown in approximately 25 percent. The myocardial muscle abnormality is typified by left ventricular myocardial hypertrophy with a pressure gradient against left ventricular outflow. Diagnosis is established by echocardiographic identification of a hypertrophied and nondilated left ventricle in the absence of other cardiovascular conditions.

Most affected women are asymptomatic, but dyspnea, anginal or atypical chest pain, syncope, and arrhythmias may develop. Complex arrhythmias may progress to sudden death, which is the most frequent cause of death. Asymptomatic patients with runs of ventricular tachycardia are especially prone to sudden death. Symptoms usually worsen with exercise.

Although limited reports suggest that pregnancy is well tolerated, adverse cardiac events are frequent. In one analysis of 271 pregnancies in 127 affected women, there were no maternal deaths. However, more than a fourth had at least one adverse cardiac symptom—including dyspnea, chest pain, or palpitations (Thaman, 2003). Based on one systematic review that included 237 women with hypertrophic cardiomyopathy who had a combined 408 pregnancies, Schinkel (2014) calculated a maternal mortality rate of 0.5 percent. Worsening of symptoms or other complications occurred in 29 percent, and 26 percent delivered preterm.

Management is similar to that for aortic stenosis. Strenuous exercise is prohibited during pregnancy. Abrupt positional changes are avoided to prevent reflex vasodilation and decreased preload. Likewise, drugs that evoke diuresis or diminish vascular resistance are generally not used. If symptoms develop, especially angina, β-adrenergic or calcium-channel blocking drugs are given. The delivery route of the fetus is determined by obstetrical indications. Choice of anesthesia is controversial, and some authors consider general anesthesia the safest (Pitton, 2007). Neonates rarely demonstrate inherited lesions at birth.

Dilated Cardiomyopathy

This is characterized by left and/or right ventricular enlargement and reduced systolic function in the absence of coronary, valvular, congenital, or systemic disease known to cause myocardial dysfunction. Although there are many known causes of dilated cardiomyopathy—both inherited and acquired, the etiology remains undefined in approximately half of cases (Stergiopoulos, 2011). Some result from viral infections, including myocarditis and HIV (Barbaro, 1998; Felker, 2000). Other causes, which are potentially reversible, include alcoholism, cocaine abuse, and thyroid disease. Watkins and coworkers (2011) reviewed the many complex genetic mutations associated with inherited forms of dilated cardiomyopathy.

Peripartum Cardiomyopathy

This disorder is similar to other forms of nonischemic dilated cardiomyopathy except for its unique relationship with pregnancy (Pyatt, 2011). Indeed, peripartum cardiomyopathy shares a genetic predisposition with both familial and sporadic idiopathic dilated cardiomyopathy (Ware, 2016). Currently, it is a diagnosis of exclusion following a concurrent evaluation for peripartum heart failure.

Although the term peripartum cardiomyopathy has been used widely, at least until recently, little evidence supported a unique pregnancy-induced cardiomyopathy. Pearson (2000) reported findings of a workshop of the National Heart, Lung, and Blood Institute that established the following diagnostic criteria:

1. Development of cardiac failure in the last month of pregnancy or within 5 months after delivery,

2. Absence of an identifiable cause for the cardiac failure,

3. Absence of recognizable heart disease prior to the last month of pregnancy, and

4. Left ventricular systolic dysfunction demonstrated by classic echocardiographic criteria, such as depressed ejection fraction or fractional shortening along with a dilated left ventricle (Fig. 49-5).

The etiology of peripartum cardiomyopathy remains unknown, and proposed causes include viral myocarditis, abnormal immune response to pregnancy, aberrant response to the greater hemodynamic burden of pregnancy, hormonal interactions, malnutrition, inflammation, and apoptosis (Elkayam, 2011). Another suggests that oxidative stress during late pregnancy leads to the proteolytic cleavage of prolactin (Hilfiker-Kleiner, 2014). The resulting 16-kDa prolactin fragment is cardiotoxic and can impair cardiomyocyte metabolism and contractility. Bromocriptine therapy has been suggested because it inhibits prolactin secretion. In one preliminary study, bromocriptine improved recovery of affected women, and a randomized trial is currently recruiting patients (Haghikia, 2015; Sliwa, 2010).

Hypertensive disorders frequently coexist with peripartum cardiomyopathy, and another proposed mechanism links peripartum cardiomyopathy to preeclampsia (Cunningham, 2012; Fong, 2014; Patten, 2012). Antiangiogenic factors—already known to be associated with preeclampsia—can induce peripartum cardiomyopathy in susceptible mice. Thus, cardiomyopathy may be precipitated by antiangiogenic factors in a host made susceptible because of insufficient proangiogenic factors.

Several investigators describe a common pathway linking these suggested etiologies (Arany, 2016; Hilfiker-Kleiner, 2014). Specifically, unbalanced oxidative stress and a high level of prolactin leads to production of the 16-kDa prolactin fragment that seems to both initiate and propagate the disease. The fragment, which mainly affects the endothelium, together with additional antiangiogenic factors might disturb the angiogenic balance during the puerperium and thereby impair cardiac function.

With no proven etiology, the diagnosis of peripartum cardiomyopathy currently requires that other causes of cardiac dysfunction be excluded. Bültmann and coworkers (2005) studied endomyocardial biopsy specimens from 26 women with peripartum cardiomyopathy and reported that more than half had histological evidence of “borderline myocarditis.” They noted viral genomic material for parvovirus B19, human herpesvirus 6, Epstein-Barr virus, and cytomegalovirus. From Parkland Hospital, otherwise “idiopathic” heart failure was found to be caused by hypertensive heart disease, clinically silent mitral stenosis, obesity, or viral myocarditis (Cunningham, 1986). Indeed, 20 percent of women with treated chronic hypertension in pregnancy have concentric hypertrophy (Ambia, 2017).

Ntusi and associates (2015) analyzed the clinical features of 30 women with peripartum cardiomyopathy compared with 53 women with hypertensive heart failure. With cardiomyopathy, the symptoms began postpartum in all women, whereas symptoms began antepartum in 85 percent of women with hypertensive heart failure. Peripartum cardiomyopathy was significantly linked with twin gestation, smoking, and echocardiographic abnormalities. In contrast, hypertensive heart failure patients more often had a family history of hypertension, hypertension and preeclampsia in a prior pregnancy, tachycardia, and left ventricular hypertrophy on echocardiography.

The incidence of peripartum cardiomyopathy varies considerably and depends on the diligence for the search of a cause. In a review of the Nationwide Inpatient Sample database, the incidence rose from 1 in 1181 live births in 2004 to 1 in 849 in 2011 (Kolte, 2014). Two other large population-based studies cite a frequency of 1 in 2000 to 2800 live births (Gunderson, 2011; Harper, 2012). In an earlier study from Parkland Hospital, we identified idiopathic cardiomyopathy in only approximately 1 in 15,000 deliveries—an incidence similar to that of idiopathic cardiomyopathy in young nonpregnant women (Cunningham, 1986).

Prognosis

Approximately half of women suffering from peripartum cardiomyopathy recover baseline ventricular function within 6 months of delivery. But in those with persistent cardiac failure, the mortality rate approaches 85 percent over 5 years (Moioli, 2010). In a group of 100 women with newly diagnosed peripartum cardiomyopathy, 72 percent had a left ventricular ejection fraction ≥50 percent, and 93 percent had event-free survival (McNamara, 2015). However, six women experienced nine major events that included four deaths, four left ventricular assist device implantations, and one heart transplantation. Recovery to a left ventricular ejection fraction ≥50 percent occurred in almost 90 percent of women whose baseline ejection fraction was at least 30 percent. This compared with <40 percent in women whose baseline ventricular ejection fraction was <30 percent. Recovery was also related to the baseline left ventricular end-diastolic diameter. Li and colleagues (2016) also found that a baseline left ventricular ejection fraction <34 percent and a brain natriuretic peptide (BNP) level >1860 pg/mL were associated with an approximately threefold greater risk of persistent left ventricular systolic dysfunction.

Subsequent Pregnancy

From the largest studies on the topic, approximately one third of women with a history of peripartum cardiomyopathy will suffer relapse with worsening of symptoms and deterioration of left ventricular function during another pregnancy (Elkayam, 2014a). The risk of relapse in women with persistent left ventricular dysfunction is substantially higher than in those who have developed normal ventricular function before a subsequent pregnancy (Hilfiker-Kleiner, 2017). But, normalization of left ventricular function does not guarantee an uncomplicated pregnancy, because approximately 20 percent of these women are at risk for deterioration in left ventricular function.

Other Cardiomyopathy Types

Arrhythmogenic right ventricular dysplasia is a unique cardiomyopathy defined histologically by progressive replacement of right ventricular myocardium with adipose and fibrous tissue. It has an estimated population prevalence of 1 in 5000, predisposes to ventricular tachyarrhythmias, and is a cause of sudden death, particularly in younger individuals (Agir, 2014; Elliott, 2008). The additional risk of pregnancy in women with arrhythmogenic right ventricular cardiomyopathy is unknown, however, based on their systematic review, Krul and coworkers (2011) counsel against pregnancy.

Restrictive cardiomyopathy is probably the least common type. This inherited cardiomyopathy is characterized by a ventricular filling pattern in which worsening myocardial stiffness raises ventricular pressure precipitously and allows only a small filling volume (Elliott, 2008). Because of the severe clinical course and poor prognosis in general, pregnancy is not advised (Krul, 2011). Takotsubo cardiomyopathy is a rare form of acute reversible left ventricular apical wall ballooning (Kraft, 2017).

Regardless of the underlying condition that causes cardiac dysfunction, women who develop peripartum heart failure almost always have obstetrical complications that either contribute to or precipitate heart failure. For example, preeclampsia is common and may precipitate afterload failure. Indeed, findings from the Registry on Pregnancy and Cardiac Disease indicate that women with preexisting heart disease who develop preeclampsia have a 30-percent risk of developing heart failure during pregnancy (Ruys, 2014). Moreover, high-output states caused by hemorrhage and acute anemia elevate cardiac workload and magnify the physiological effects of compromised ventricular function. Similarly, infection and sepsis syndrome raise cardiac output and oxygen utilization and depress myocardial function.

In many populations, chronic hypertension with superimposed preeclampsia is the most frequent cause of heart failure in pregnancy. Many of these women have concentric left ventricular hypertrophy (Ambia, 2017). In some, mild antecedent undiagnosed hypertension causes covert cardiomyopathy, and when superimposed preeclampsia develops, together they may cause otherwise inexplicable peripartum heart failure. Obesity is a frequent cofactor with chronic hypertension, and it too is associated with ventricular hypertrophy (Kenchaiah, 2002).

Diagnosis

Congestive heart failure can have a gradual onset or may present as acute “flash” pulmonary edema. Heart failure onset is most likely at the end of the second/beginning of the third trimester and peripartum (Ruys, 2014). Of symptoms, dyspnea is universal and others are orthopnea, palpitations, substernal chest pain, a sudden decline in the ability to complete usual duties, and nocturnal cough. Clinical findings include persistent basilar rales, hemoptysis, progressive edema, tachypnea, and tachycardia (Sheffield, 1999). Hallmark radiographic findings usually are cardiomegaly and pulmonary edema (see Fig. 49-5). Acutely, there is usually systolic failure, and echocardiography shows an ejection fraction <0.45 or a fractional shortening <30 percent, or both, and an end-diastolic dimension >2.7 cm/m² (Hibbard, 1999). Coincidental diastolic failure may also be found, depending on the underlying cause (Redfield, 2016).

Management

Pulmonary edema from heart failure usually responds promptly with diuretic administration to reduce preload. Hypertension is common, and afterload reduction is accomplished with hydralazine or another vasodilator. Because of marked fetal effects, angiotensin-converting enzyme inhibitors are withheld until after delivery. With chronic heart failure, the incidence of associated thromboembolism is high, and thus prophylactic heparin is often recommended.

Left ventricular assist devices are now employed more frequently for acute and chronic heart failure treatment. A few reports describe their use during pregnancy (LaRue, 2011; Sims, 2011). Extracorporeal membrane oxygenation (ECMO) was reported to be lifesaving in a woman with fulminating peripartum cardiomyopathy, and it may be used in women with pulmonary hypertension (Meng, 2017; Smith, 2009).

In the United States, those at greatest risk for endocarditis are those with congenital heart lesions, intravenous drug use, degenerative valve disease, and intracardiac devices (Karchmer, 2015). Subacute bacterial endocarditis usually stems from a low-virulence bacterial infection superimposed on an underlying structural lesion. These are usually native valve infections. Organisms that cause indolent endocarditis are most often viridans-group streptococci or Staphylococcus or Enterococcus species. Among intravenous drug abusers and those with catheter-related infections, Staphylococcus aureus predominates. With prosthetic valve infections, Staphylococcus epidermidis is a frequent cause. Streptococcus pneumoniae and Neisseria gonorrhoeae may occasionally cause acute, fulminating disease. Others have reported Neisseria sicca and N mucosa, group B streptococcus, and Escherichia coli endocarditis during pregnancy or peripartum (Cox, 1988; Deger, 1992; Kangavari, 2000; Kulaš, 2006).

Diagnosis and Management

Infective endocarditis symptoms vary and often develop insidiously. Fever, often with chills, is seen in 80 to 90 percent of cases, a murmur is heard in up to 85 percent, and anorexia, fatigue, and other constitutional symptoms are common (Karchmer, 2015). Clinical clues are anemia, proteinuria, and manifestations of embolic lesions that include petechiae, focal neurological changes, chest or abdominal pain, and ischemia in an extremity. In some cases, heart failure develops. Symptoms may persist for several weeks before the diagnosis is found, and a high index of suspicion is necessary.

Diagnosis is made using the Duke criteria, which include positive blood cultures for typical organisms and evidence of endocardial involvement (Hoen, 2013; Pierce, 2012). Echocardiography may be diagnostic, but lesions <2 mm or those on the tricuspid valve may be missed. If uncertain, transesophageal echocardiography is accurate and informative. Importantly, a negative echocardiographic study does not exclude endocarditis.

Treatment is primarily medical, and ascertainment of the infecting organism and its sensitivities is imperative for antimicrobial selection. Guidelines for appropriate antibiotic treatment are published by professional societies and updated regularly (Habib, 2015; Karchmer, 2015). Recalcitrant bacteremia and heart failure due to valvular dysfunction are but a few reasons that persistent valvular infection may require replacement.

Pregnancy

Infective endocarditis is uncommon during pregnancy and the puerperium. During a 7-year period, the incidence of endocarditis at Parkland Hospital approximated 1 in 16,000 births, and two of seven women died (Cox, 1988). Maternal and fetal mortality rates range from 25 to 35 percent (Habib, 2015; Seaworth, 1986). In a systematic review of infective endocarditis during pregnancy, risk factors were intravenous drug use (14 percent), congenital heart disease (12 percent), and rheumatic heart disease (12 percent) (Kebed, 2014). The most common pathogens were streptococcal (43 percent) and staphylococcal (26 percent) species. Among 51 pregnancies, the maternal mortality rate was 11 percent.

Endocarditis Prophylaxis

For years, patients with heart valve problems were given periprocedural antibiotics for endocarditis prophylaxis. Currently, however, recommendations are more stringent. The American Heart Association recommends prophylaxis for dental procedures in those with: (1) a prosthetic valve or prosthetic material used in a valve repair, (2) prior endocarditis, (3) unrepaired cyanotic heart defect or repaired lesion with residual defect at prosthetic sites, and (4) valvulopathy after heart transplantation (Nishimura, 2017). The American College of Obstetricians and Gynecologists (2016) does not recommend endocarditis prophylaxis for either vaginal or cesarean delivery in the absence of pelvic infection except with the lesions cited above. Women at highest risk for endocarditis are those with cyanotic cardiac disease, prosthetic valves, or both. When indicated, and for women not already receiving intrapartum antimicrobial therapy for another indication that would also provide coverage against endocarditis, prophylactic regimens are shown in Table 49-8. These are administered as close to 30 to 60 minutes before the anticipated delivery time as is feasible.

Both preexisting and new-onset cardiac arrhythmias are often encountered during pregnancy, labor, delivery, and the puerperium (Joglar, 2014; Knotts, 2014). In a study of 73 women with a history of supraventricular tachycardia (SVT), paroxysmal atrial flutter or fibrillation, or ventricular tachycardia, recurrence rates during pregnancy were 50, 52, and 27 percent, respectively (Silversides, 2006). The mechanism(s) responsible for the higher incidence of arrhythmias during pregnancy are not well elucidated. From some studies, estradiol and progesterone are proarrhythmic. Estrogen augments the number of adrenergic receptors in the myocardium, and adrenergic responsiveness seems to be greater in pregnancy (Enriquez, 2014). Perhaps the normal but mild hypokalemia of pregnancy and/or the physiological rise in heart rate serves to induce arrhythmias. Alternatively, detection of arrhythmias may be greater because of the frequent visits typical of routine prenatal care.

Bradyarrhythmias

Slow heart rhythms, including complete heart block, are compatible with a successful pregnancy outcome (Keepanasseril, 2015). Some women with complete heart block have syncope during labor and delivery, and occasionally temporary cardiac pacing is necessary (Hidaka, 2006). In our experiences and from others, women with permanent artificial pacemakers usually tolerate pregnancy well (Hidaka, 2011; Jaffe, 1987). With fixed-rate devices, cardiac output apparently is increased by augmented stroke volume.

Patients with pacemakers or other electrical implants require special precautions during surgery. Stray current may be interpreted as an intracardiac signal by the implanted device and lead to pacing changes. In addition, myocardial burns may result from conduction of current through the pacing electrode rather than through the grounding pad (Pinski, 2002). With these devices, preventive steps include cardiology consultation; bipolar electrosurgery or Harmonic scalpel use rather than monopolar current; if needed, minimal monopolar settings; continuous cardiac and pulse oximetry monitoring; contingency plans for arrhythmias; and close proximity of electrosurgery active and return electrodes (Crossley, 2011).

Supraventricular Tachycardias

The most common arrhythmia seen in reproductive-aged women is paroxysmal SVT. The prevalence during pregnancy is 24 cases per 100,000 hospital admissions, and approximately 20 percent will experience symptomatic exacerbations during pregnancy (Enriquez, 2014). Interestingly, the mean heart rate of pregnant women with paroxysmal SVT is faster compared with nonpregnant women—184 versus 166 bpm, respectively (Yu, 2015). From Hungary, Bánhidy and associates (2015) found that approximately half of women with paroxysmal SVT had an initial onset during pregnancy. Notably, maternal paroxysmal SVT was associated with a twofold greater risk of septal cardiac defects, particularly secundum atrial septal defects, in their offspring.

In contrast, rarely do atrial fibrillation and atrial flutter present for the first time during pregnancy. Indeed, new-onset atrial fibrillation should prompt a search for underlying etiologies that include cardiac anomalies, hyperthyroidism, pulmonary embolism, drug toxicity, and electrolyte disturbances (DiCarlo-Meacham, 2011). Major complications include embolic stroke, and when associated with mitral stenosis, pulmonary edema may develop in later pregnancy if the ventricular rate is increased.

For acute treatment, vagal maneuvers, which include Valsalva maneuver, carotid sinus massage, bearing down, and immersion of the face in ice water, raise vagal tone and block the atrioventricular node (Link, 2012; Page, 2015). Intravenous adenosine is a short-acting endogenous nucleotide that also blocks atrioventricular nodal conduction. Our experiences are similar to those of others in that adenosine is safe and effective for cardioversion in hemodynamically stable gravidas (Page, 2015; Robins, 2004). Transient fetal bradycardia has been described with adenosine (Dunn, 2000).

If pharmacological therapy is ineffective or contraindicated, the American College of Cardiology and the American Heart Association recommend synchronized cardioversion in pregnant women with hemodynamically unstable SVT (Page, 2015). And although electrical cardioversion with standard energy settings is not contraindicated in pregnancy, vigilance is important. Barnes and colleagues (2002) described a case in which direct current cardioversion led directly to a sustained uterine contraction and fetal bradycardia. As an aside, pregnancy has no effect on the operation of implantable cardioverter-defibrillator devices (Boulé, 2014).

If cardioversion fails or is unsafe because of concurrent thrombus, then long-term anticoagulation and heart rate control with medication are necessary (DiCarlo-Meacham, 2011). Other treatment options recommended by the American College of Cardiology and the American Heart Association (Page, 2015) include:

• Intravenous metoprolol or propranolol when adenosine is ineffective or contraindicated

• Intravenous verapamil when adenosine and β-blocking agents are ineffective or contraindicated

• Intravenous procainamide

• Intravenous amiodarone with potentially life-threatening SVT and when other therapies are ineffective or contraindicated.

Pregnancy may predispose otherwise asymptomatic women with Wolff-Parkinson-White (WPW) syndrome to exhibit arrhythmias. In a study of 25 women who had SVT diagnosed before pregnancy, three of 12 women with WPW syndrome and six of 13 without the condition developed SVT during pregnancy (Pappone, 2003). In some patients, accessory pathway ablation may be indicated. Driver and coworkers (2015) have provided a review.

Ventricular Tachycardia

This form of arrhythmia is uncommon in healthy young women without underlying heart disease. Brodsky and associates (1992) described seven pregnant women with new-onset ventricular tachycardia and reviewed 23 reports. Most of these women were not found to have structural heart disease. In 14 cases, tachycardia was precipitated by physical exercise or psychological stress. Abnormalities found included two cases of myocardial infarction, two of prolonged QT interval, and one of anesthesia-provoked tachycardia. They concluded that pregnancy events precipitated the tachycardia and recommended β-blocking agents for control. As previously discussed (Heart Failure), arrhythmogenic right ventricular dysplasia will result occasionally in ventricular tachyarrhythmias (Lee, 2006). If unstable, emergency cardioversion is indicated, and standard adult energy settings are adequate (Jeejeebhoy, 2011; Lin, 2015).

Prolonged QT-Interval

This conduction anomaly may predispose individuals to a potentially fatal ventricular arrhythmia known as torsades de pointes (Roden, 2008). Two studies comprised of 502 pregnant women with long QT syndrome both reported a significant increase in cardiac events postpartum but not during pregnancy (Rashba, 1998; Seth, 2007). The normal rise in heart rate during pregnancy may be partially protective. Paradoxically, β-blocking agents—preferably propranolol—lower the risk of torsades de pointes in patients with long QT syndrome and should be continued throughout pregnancy and the puerperium (Enriquez, 2014; Seth, 2007). Importantly, many medications, including some used during pregnancy such as azithromycin, erythromycin, and clarithromycin, may predispose to QT prolongation (Ray, 2012; Roden, 2004).

Aortic Dissection

Marfan syndrome and coarctation are two aortic diseases that place the pregnant woman at increased risk for aortic dissection (Russo, 2017). Indeed, half of dissection cases in young women are related to pregnancy (O’Gara, 2004). Other risk factors are bicuspid aortic valve and Turner or Noonan syndrome. A high rate of aortic dissection or rupture is also reported in patients with Ehlers-Danlos syndrome (Murray, 2014; Pepin, 2000). Although the mechanism(s) involved are unclear, the initiating event is a tear in the intimal layer of the aorta, followed by hemorrhage into the media, and finally rupture.

In most cases, aortic dissection presents with severe chest pain described as ripping, tearing, or stabbing. Diminution or loss of peripheral pulses coupled with a recently acquired aortic insufficiency murmur is an important physical finding. The differential diagnosis of aortic dissection in pregnancy includes myocardial infarction, pulmonary embolism, pneumothorax, aortic valve rupture, and obstetrical catastrophes, especially placental abruption and uterine rupture.

More than 90 percent of patients with aortic dissection have an abnormal chest radiograph. Aortic angiography is the most definitive method for diagnosis confirmation. However, sonography, computed tomography, and MR imaging are used more frequently depending on the urgency of the clinical situation.

Initial medical treatment is given to lower blood pressure. Proximal dissections most often need to be resected, and the aortic valve replaced if necessary. Distal dissections are more complex, and many may be treated medically. Among nonpregnant patients, survival is not improved by immediate elective repair compared with surveillance and delayed repair of abdominal aortic aneurysms <5.5 cm. But, Karthikesalingam and colleagues (2016) suggest that the size threshold for aneurysm repair should be revisited.

Marfan Syndrome

This autosomal dominant connective tissue disorder has an incidence of 2 to 3 cases per 10,000 individuals and is without racial or ethnic predilection (Ammash, 2008). As discussed in Chapter 59 (Hereditary Connective Tissue Disorders), Marfan syndrome is characterized by generalized tissue weakness that can result in dangerous cardiovascular complications. Because all tissues are involved, other defects are frequent and include joint laxity and scoliosis. Progressive aortic dilation causes aortic valve insufficiency, and there may be infective endocarditis and mitral valve prolapse with insufficiency. Aortic dilation and dissecting aneurysm are the most serious abnormalities. Early death is due either to valvular insufficiency and heart failure or to a dissecting aneurysm.

Pregnancy

Of outcomes, a study using the Nationwide Inpatient Sample from 2003 to 2010 found 339 deliveries in women with Marfan syndrome. There was one maternal death and six (1.8 percent) aortic dissections (Hassan, 2015). Russo and associates (2017) used Texas obstetrical discharge data and found that eight of 47 women with aortic dissection had Marfan syndrome. A study from the United Kingdom reported similar results (Curry, 2014).

The aortic root usually measures approximately 2 cm, and during normal pregnancy, it expands slightly (Easterling, 1991). With Marfan syndrome, aortic root repair is recommended at diameters of 4.0 to 4.5 cm (Smok, 2014). The guidelines of the American College of Cardiology, the American Heart Association, and the American Association of Thoracic Surgeons advise prophylactic aortic repair in women considering pregnancy if the diameter of the ascending aorta exceeds 4 cm (Hiratzka, 2010). The guidelines of the European Society of Cardiology (2011) advise repair of the aorta at diameters ≥4.5 cm. Because shorter patients have dissection at a smaller diameter, surgical repair is also considered using a formula indexed to height (Bradley, 2014; Smok, 2014).

For pregnant women with known thoracic aortic root or ascending aortic dilation, monthly or bimonthly echocardiographic measurements of the ascending aortic dimensions are recommended to detect expansion (Hiratzka, 2010). Prophylactic β-blocking agents have become standard for pregnant women with Marfan syndrome because they reduce hemodynamic stress on the ascending aorta and slow the dilation rate (Simpson, 2012). Ideally, pregnant women with aortic aneurysms are delivered at facilities in which cardiothoracic surgery is available. Vaginal delivery with regional analgesia and an assisted second stage seem safe for women with an aortic root diameter <4 cm.

When the aortic root measures 4 to 5 cm or greater, elective cesarean delivery is recommended with consideration of postpartum replacement of the proximal aorta with a prosthetic graft (Simpson, 2012). Successful aortic root replacement during pregnancy has been described, but the surgery has also been associated with fetal hypoxic-ischemic encephalopathy (Mul, 1998; Seeburger, 2007). Several case reports describe emergency cesarean deliveries in women with acute type A dissections that were repaired successfully at the time of delivery (Guo, 2011; Haas, 2011; Papatsonis, 2009).

To evaluate obstetrical outcomes, investigators for one study of 63 women with Marfan syndrome analyzed their 142 pregnancies. Of 111 pregnancies progressing past 20 weeks’ gestation, 15 percent delivered preterm, and 5 percent had preterm prematurely ruptured membranes (Meijboom, 2006). There were eight perinatal deaths, and half of the neonatal survivors were subsequently diagnosed with Marfan syndrome.

Aortic Coarctation

In this relatively rare lesion, the aorta is abnormally narrowed and is often accompanied by abnormalities of other large arteries. A fourth of affected patients have a bicuspid aortic valve, and another 10 percent have cerebral artery aneurysms. Other associated lesions are persistent ductus arteriosus, septal defects, and Turner syndrome. The collateral circulation arising above the coarctation remodels and expands, often strikingly, to cause localized erosion of rib margins by hypertrophied intercostal arteries. Typical findings include hypertension in the upper extremities but normal or reduced pressures in the lower extremities. Authors have described diagnosis during pregnancy using MR imaging (Sherer, 2002; Zwiers, 2006). Moreover, Jimenez-Juan and associates (2014) found that aortic diameter measured by MR and the risk of adverse events during pregnancy were inversely correlated. Of note, no adverse outcomes occurred if the minimum diameter at the coarctation exceeded 15 mm.

Major complications with aortic coarctation include congestive heart failure after long-standing severe hypertension, bacterial endocarditis of the bicuspid aortic valve, and aortic rupture. Because hypertension may worsen in pregnancy, antihypertensive therapy using β-blocking drugs is usually required. Aortic rupture is more likely late in pregnancy or early puerperium. Cerebral hemorrhage from circle of Willis aneurysms may also occur.

Of outcomes from 188 pregnancies, a third of women had hypertension that was related to significant coarctation gradients, and one woman died from dissection at 36 weeks’ gestation (Beauchesne, 2001). Of nearly 700 deliveries in women with coarctation from the Nationwide Inpatient Sample, hypertensive complications of pregnancy were increased three- to fourfold (Krieger, 2011). Importantly, almost 5 percent of women with coarctation had an adverse cardiovascular outcome—maternal death, heart failure, arrhythmia, cerebrovascular or other embolic event—compared with only 0.3 percent of controls. Of women with coarctation, 41 percent underwent cesarean delivery compared with 26 percent of controls.

Congestive heart failure demands vigorous efforts to improve cardiac function and may warrant pregnancy interruption. Some authors recommend that resection of the coarctation be undertaken during pregnancy to protect against the possibility of a dissecting aneurysm and aortic rupture. This poses significant perfusion risk, especially for the fetus, because all the arterial collaterals must be clamped for variable periods.

Pregnant women with coronary artery disease commonly have the classic risk factors of diabetes, smoking, hypertension, hyperlipidemia, and obesity (James, 2006). Although relatively rare, the risk of acute myocardial infarction is approximately threefold higher in pregnant women compared with nonpregnant women of similar age (Elkayam, 2014b). From more than 50 million hospitalizations in the United States between 1998 and 2009, rates of acute myocardial infarction approximated 2 per 100,000 delivery hospitalizations and 4 per 100,000 postpartum hospitalizations (Callaghan, 2012). Ladner and colleagues (2005) reported a similar rate of 2.7 per 100,000 deliveries.

Myocardial Infarction During Pregnancy

The mortality rate with myocardial infarction in pregnancy is higher compared with age-matched nonpregnant women. In a Nationwide Inpatient Sample study totaling 859 pregnancies complicated by acute infarction, the death rate was 5.1 percent (James, 2006). Women who sustain an infarction <2 weeks before delivery are at especially high risk of death due to the greater myocardial demand of labor and delivery (Esplin, 1999).

In a systematic review of 150 cases, most women developed an acute myocardial infarction (MI) during the third trimester or postpartum (Elkayam, 2014b). Approximately three fourths presented with ST segment-elevation MI (STEMI). The leading mechanisms of acute infarction included spontaneous coronary dissection (43 percent) and atherosclerotic disease (27 percent). Significant complications included heart failure/cardiogenic shock (38 percent), recurrent angina or infarction (19 percent), and ventricular arrhythmias (12 percent). The maternal and fetal mortality rates were 7 and 5 percent, respectively. Of other potential antecedents, coronary artery occlusion in two pregnant smokers with hypercholesterolemia has been described following ergometrine administration (Mousa, 2000; Ramzy, 2015; Sutaria, 2000). Schulte-Sasse (2000) reported myocardial ischemia associated with prostaglandin E₁ vaginal suppositories given for labor induction.

Diagnosis of acute myocardial infarction during pregnancy does not differ from that in nonpregnant patients and is based on clinical presentation, characteristic ECG changes, and evidence of myocardial necrosis reflected by elevated serum troponin levels (Pacheco, 2014). Of note, troponin I levels are undetectable near term in normal pregnancy and do not rise following either vaginal or cesarean delivery (Koscica, 2002; Shivvers, 1999). Importantly, however, troponin I levels are higher in preeclamptic women compared with normotensive controls (Atalay, 2005; Yang, 2006). With spontaneous coronary artery dissection, establishing the diagnosis requires a high index of suspicion in the gravida presenting with chest pain (Codsi, 2016). For this condition, coronary angiography is considered the diagnostic gold standard and should be expediently performed if acute coronary syndrome—defined as myocardial infarction or unstable angina—is present.

Treatment of acute myocardial infarction is similar to that for nonpregnant patients (Pacheco, 2014). An algorithm summarizing one approach to its management during pregnancy is shown in Figure 49-6. Several reports describe successful percutaneous transluminal coronary angioplasty and stent placement during pregnancy (Balmain, 2007; Duarte, 2011; Dwyer, 2005). Cardiopulmonary resuscitation may be required, as described in Chapter 47 (Cardiopulmonary Resuscitation). If the infarct has healed sufficiently, cesarean delivery is reserved for obstetrical indications, and epidural analgesia is ideal for labor (Esplin, 1999).

Pregnancy with Prior Ischemic Heart Disease

The advisability of pregnancy after a myocardial infarction is unclear. Ischemic heart disease is characteristically progressive, and because it is usually associated with hypertension or diabetes, pregnancy in most of these women seems inadvisable. In a review of 30 pregnancies in women who had sustained an infarction remote from pregnancy, none of the women died, four had congestive heart failure, and four had worsening angina during pregnancy (Vinatier, 1994). Pombar and coworkers (1995) evaluated outcomes of women with diabetes-associated ischemic heart disease and infarction. Three had undergone coronary artery bypass grafting before pregnancy. Of 17 women, eight died during pregnancy. Certainly, pregnancy raises cardiac workload, and these investigators concluded that ventricular performance should be assessed using ventriculography, radionuclide studies, echocardiography, or coronary angiography before conception. Without significant ventricular dysfunction, pregnancy will likely be tolerated. For the woman who becomes pregnant before these studies are performed, echocardiography is done. Exercise tolerance testing may be indicated, and radionuclide ventriculography exposes the fetus to minimal radiation.