PHYSIOLOGICAL CONSIDERATIONS IN PREGNANCY
DIAGNOSIS OF HEART DISEASE
PERIPARTUM MANAGEMENT CONSIDERATIONS
SURGICALLY CORRECTED HEART DISEASE
VALVULAR HEART DISEASE
CONGENITAL HEART DISEASE
DISEASES OF THE AORTA
ISCHEMIC HEART DISEASE
Heart disease complicates more than 1 percent of all pregnancies and is now the leading cause of indirect maternal deaths—accounting for 20 percent of all cases (Simpson, 2012). In an analysis of maternal mortality in the United States between 1987 and 2005, the causes previously responsible for most maternal deaths—hemorrhage and hypertensive disorders—had progressively decreased rates, whereas deaths attributable to cardiovascular diseases had the greatest percentage increase (Berg, 2010). Similarly, in the United Kingdom, the rate of maternal mortality due to cardiac disease increased from 1.65 to 2.31 per 100,000 births between 1997–1999 and 2006–2008 (Centre for Maternal and Child Enquiries, 2011). Cardiovascular diseases also account for significant maternal morbidity and are a leading cause of obstetrical intensive care unit admissions (Small, 2012).
The increasing prevalence of cardiovascular diseases complicating pregnancy is likely due to a number of causes, including higher rates of obesity, hypertension, and diabetes. Indeed, according to the United States National Center for Health Statistics, almost half of adults aged 20 and older have at least one risk factor for cardiovascular disease (Fryar, 2012). And as shown in Figure 49-1, the prevalence of these risk factors among reproductive-aged women is dramatic. Other related factors include delayed childbearing. From 1970 to 2006 the proportion of first births to women aged 35 years or older increased nearly eightfold (Mathews, 2009). Finally, as discussed subsequently, an increasing number of patients with congenital heart disease are now becoming pregnant.
FIGURE 49-1 Prevalence of risk factors for cardiovascular disease among reproductive-aged women. DM = diabetes mellitus. (From Centers for Disease Control and Prevention, 2011.)
PHYSIOLOGICAL CONSIDERATIONS IN PREGNANCY
The marked pregnancy-induced anatomical and functional changes in cardiac physiology can have a profound effect on underlying heart disease (Chap. 4, p. 58). Some of these changes are listed in Table 49-1. Importantly, cardiac output increases approximately 40 percent during pregnancy. Almost half of this total increase takes place by 8 weeks and is maximal by midpregnancy (Capeless, 1989). The early increase stems from augmented stroke volume that results from decreased vascular resistance. Later in pregnancy, resting pulse and stroke volume increase even more because of increased end-diastolic ventricular volume that results from pregnancy hypervolemia. This along with an increase in heart rate translates to increased cardiac output that continues to rise across pregnancy to average 40 percent higher at term. These changes are even more profound in multifetal pregnancy (Kametas, 2003; Kuleva, 2011).
TABLE 49-1. Hemodynamic Changes in 10 Normal Pregnant Women at Term Compared with Repeat Values Obtained 12 Weeks Postpartum
An important study by Clark and colleagues (1989) contributed greatly to the understanding of cardiovascular physiology during pregnancy. Using right-sided heart catheterization, hemodynamic function was measured in 10 healthy primigravid volunteers, and pregnancy values were compared with those measured again at 12 weeks postpartum. As shown in Table 49-1, the cardiac output near term in the lateral recumbent position increased 43 percent. Systemic and pulmonary vascular resistances were concomitantly decreased. Importantly, intrinsic left ventricular contractility did not change. Thus, normal left ventricular function is maintained during pregnancy, that is, 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 may experience evidence of heart failure before midpregnancy. In others, heart failure may develop after 28 weeks when pregnancy-induced hypervolemia and cardiac output reach their maximum. In most, however, heart failure develops peripartum when labor, delivery, and a number of common obstetrical conditions add undue cardiac burdens. Some of these include preeclampsia, hemorrhage and anemia, and sepsis syndrome. In a report of 542 women with heart disease, eight of 10 maternal deaths were during the puerperium (Etheridge, 1977).
Ventricular Function in Pregnancy
Ventricular volumes increase to accommodate pregnancy-induced hypervolemia. This is reflected by increasing end-systolic as well as end-diastolic dimensions. At the same time, however, there is no change in septal thickness or in ejection fraction. This is because these changes 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 (p. 59). For given filling pressures, there is appropriate cardiac output so that cardiac function during pregnancy is eudynamic. Despite these findings, it remains controversial whether myocardial function per se is normal, enhanced, or depressed. Myocardial performance is measured by preload, afterload, contractility, and heart rate. Because these depend on ventricular geometry, they can only be measured indirectly (Savu, 2012). 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, these normal indices are likely inaccurate when used to assess function in pregnant women because they do not take into account the spherical eccentric hypertrophy characteristic of normal pregnancy.
DIAGNOSIS OF HEART DISEASE
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 and at times suggests dyspnea; edema in the lower extremities after midpregnancy is common; and fatigue and exercise intolerance develop in most women. Some systolic flow murmurs may be loud, and normal changes in the various heart sounds depicted in Figure 49-2 may suggest cardiac disease.
FIGURE 49-2 Normal cardiac examination findings in the pregnant woman. S1 = first sound; M1 = mitral first sound; S2 = second sound; P2 = pulmonary second sound. (From Gei, 2001; Hytten, 1991.)
Clinical findings that may suggest heart disease are listed in Table 49-2. Pregnant women with none of these rarely have serious heart disease. As an interesting aside, Melchiorre and associates (2011) found that the prevalence of previously undiagnosed maternal cardiac structural abnormalities is significantly increased in women with high midtrimester uterine artery Doppler resistance indices (Chap. 17, p. 345).
TABLE 49-2. Clinical Indicators of Heart Disease During Pregnancy
Progressive dyspnea or orthopnea
Clubbing of fingers
Persistent neck vein distention
Systolic murmur grade 3/6 or greater
Persistent split second sound
Criteria for pulmonary hypertension
In most women, noninvasive cardiovascular studies such as electrocardiography, chest radiography, and echocardiography will provide data necessary for evaluation. In some situations, such as complex congenital heart disease, transesophageal echocardiography may be useful. Albumin or red cells tagged with technicium-99m are rarely needed during pregnancy to evaluate ventricular function. That said, the estimated fetal radiation exposure from nuclear medicine studies of myocardial perfusion are calculated to range between 5 and 17 mGy depending on the technique employed (Colletti, 2013). If indicated, cardiac catheterization can be performed 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 because of tissue attenuation (European Society of Cardiology, 2011). Shielding the fetus from direct radiation and shortening the fluoroscopic time help to minimize radiation exposure. In women with clear indications, any minimal theoretical fetal risk is outweighed by maternal benefits (Chap. 46, p. 932).
As the diaphragm is elevated in advancing pregnancy, there is an average 15-degree left-axis deviation in the electrocardiogram (ECG), and mild ST changes may be seen in the inferior leads. Atrial and ventricular premature contractions are relatively frequent (Carruth, 1981). Pregnancy does not alter voltage findings.
Anteroposterior (AP) and lateral chest radiographs are useful, and when a lead apron shield is used, fetal radiation exposure is minimal (Chap. 46, p. 931). 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.
Widespread use of echocardiography has allowed accurate diagnosis of most heart diseases during pregnancy. It allows noninvasive evaluation of structural and functional cardiac factors. Some normal pregnancy-induced changes include slightly but significantly increased tricuspid regurgitation, left atrial end-diastolic dimension, and left ventricular mass. Savu (2012) and Vitarelli (2011) and their coworkers have provided normal morphological and functional echocardiographic parameters for pregnancy, which are listed in the Appendix (p. 1293).
Classification of Functional Heart Disease
There is no clinically applicable test for accurately measuring functional cardiac capacity. The clinical classification of the New York Heart Association (NYHA) was first published in 1928, and it was revised for the eighth time in 1979. This classification 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 is based on a prospective analysis of 562 consecutive pregnant women with heart disease during 617 pregnancies in 13 Canadian teaching hospitals. Predictors of cardiac complications included the following: (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 by echocardiography; (4) ejection fraction less than 40 percent. The risk of pulmonary edema, sustained arrhythmia, stroke, cardiac arrest, or cardiac death was substantially increased with one of these factors and even more so with two or more.
At least two studies have been conducted using these latter risk criteria. Khairy and colleagues (2006) reviewed 90 pregnancies in 53 women with congenital heart disease at Brigham and Women’s Hospital. There were no maternal deaths, and heart failure and symptomatic arrhythmias developed in 16.7 and 2.8 percent of the women, respectively. Similar to the Canadian study cited above, the most important predictors of complications were prior congestive heart failure, depressed ejection fraction, and smoking. In a German study that also used these predefined risk predictors, they were found to be accurate in assessing most cardiac outcomes (Stangl, 2008).
Women with severe heart disease will benefit immensely from counseling before undertaking pregnancy, and they usually are referred for maternal-fetal medicine or cardiology consultation (Clark, 2012; Seshadri, 2012).
Maternal mortality rates generally vary directly with functional classification, and this relationship may change as pregnancy progresses. In the 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. Their experiences, however, as well as those of McFaul and coworkers (1988), were that there were no maternal deaths in 1041 women with class I or II disease. 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 considerations predominate.
The World Health Organization Risk Classification of Cardiovascular Disease and Pregnancy is useful for assessing maternal risk associated with various cardiovascular conditions and for preconceptional counseling and planning (Thorne, 2006). Maternal risk is divided among four progressively worsening classes as shown in Table 49-3. Its use has been recommended by the European Society of Cardiology (2011).
TABLE 49-3. World Health Organization (WHO) Risk Classification of Cardiovascular Disease and Pregnancy
Congenital Heart Disease in Offspring
Many congenital heart lesions appear to be inherited as polygenic characteristics, which are discussed in Chapter 13 (p. 274). Because of this, some women with congenital heart lesions give birth to similarly affected infants, the risk of which varies widely as shown in Table 49-4. Environmental factors are also important. One example is a study from Tibet in which the prevalence of fetal heart disease was increased among women living at higher altitudes (> 3600 meters) and was presumably due to lower oxygen concentrations (Chen, 2008).
TABLE 49-4. Risks for Fetal Heart Lesions Related to Affected Family Members
PERIPARTUM MANAGEMENT CONSIDERATIONS
In most instances, management involves a team approach with an obstetrician, cardiologist, anesthesiologist, and other specialists as needed. With complex lesions or with women who are especially at risk, evaluation by a multidisciplinary team is recommended early in pregnancy. During consultation, cardiovascular changes likely to be poorly tolerated by an individual woman are identified, and plans are formulated to minimize these. In some, pregnancy termination may be advisable. Maxwell (2010) has provided an in-depth checklist that considers detailed management options. The four changes that affect management that are emphasized by the American College of Obstetricians and Gynecologists (1992) include decreased vascular resistance, increased blood volume and cardiac output and their fluctuations peripartum, and hypercoagulability. Within this framework, both prognosis and management are influenced by the type and severity of the specific lesion and by the patient’s functional classification.
With rare exceptions, women in NYHA class I and most in class II negotiate pregnancy without morbidity. Special attention should be directed toward both prevention and early recognition of heart failure as discussed on page 990. Infection with sepsis syndrome is an important factor in precipitating cardiac failure. Moreover, bacterial endocarditis is a deadly complication of valvular heart disease (p. 990). Each woman should receive instructions 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.
Cigarette smoking is prohibited, because of both its cardiac effects and its propensity to cause upper respiratory infections. Illicit drug use may be particularly harmful, an example being the cardiovascular effects of cocaine or amphetamines. In addition, intravenous drug use increases the risk of infective endocarditis.
Fortunately, cases of NYHA class III and IV are uncommon today. In the Canadian study, only 3 percent of approximately 600 pregnancies were complicated by NYHA class III heart disease, and no women had class IV when first seen (Siu, 2001b). In a Turkish study, 8 percent of pregnancies in women with cardiac diseases were NYHA class III or IV (Madazli, 2010). An important question in these women is whether pregnancy should be undertaken. If women make that choice, they must understand the risks, and they are encouraged to be compliant with planned care. In some, prolonged hospitalization or bed rest is often necessary with continued pregnancy.
Labor and Delivery
In general, vaginal delivery is preferred, and labor induction is usually safe (Oron, 2004). Cesarean delivery is limited to obstetrical indications, and considerations are given for the specific cardiac lesion, overall maternal condition, and availability of experienced anesthesia personnel and general support facilities. Some of these women tolerate major surgical procedures poorly and are best delivered in a unit experienced with management of complicated cardiac disease. In some women, pulmonary artery catheterization may be indicated for hemodynamic monitoring (Chap. 47, p. 941). 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 lateral tilt. Vital signs are taken frequently between contractions. Increases in pulse rate much above 100 bpm or respiratory rate above 24 per minute, particularly when associated with dyspnea, may suggest impending ventricular failure. If there is any evidence of cardiac decompensation, intensive medical management must be instituted immediately. It is essential to remember that delivery itself does not necessarily improve the maternal condition and in fact, may worsen it. Moreover, emergency operative 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 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, p. 514). This is especially dangerous in women with intracardiac shunts in whom flow may be reversed. Blood passes from right to left within the heart or aorta and thereby bypasses the lungs. 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 conduction 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. For cesarean delivery, epidural analgesia is preferred by most clinicians with caveats for its use with pulmonary arterial hypertension (p. 987). Finally, general endotracheal anesthesia with thiopental, succinylcholine, nitrous oxide, and at least 30-percent oxygen has also proved satisfactory.
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 approached 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. Heart failure is discussed in more detail on page 990.
Women who have shown little or no evidence of cardiac compromise during pregnancy, labor, or delivery may still decompensate postpartum when fluid mobilization into the intravascular compartment and reduction of peripheral vascular resistance place higher demands on myocardial performance. Therefore, it is important that meticulous care be 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 (Cunningham, 1986). In addition to increased cardiac work, many of these—for example, sepsis and severe preeclampsia—cause or worsen pulmonary edema because of endothelial activation and capillary-alveolar leakage (Chap. 47, p. 947).
Sterilization and Contraception
If indicated, tubal sterilization is performed at cesarean delivery. If it is to be performed after vaginal delivery, the procedure can be delayed up to several days to ensure that the mother has become hemodynamically near normal and that she is afebrile, not anemic, and ambulating normally. Other women are given detailed contraceptive advice. Special considerations for contraception in women with various cardiac disorders are discussed in some of the following sections and in Table 38-3 (p. 698).
SURGICALLY CORRECTED HEART DISEASE
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, 2000). In some cases, the defect is mild and surgery is not required. In others, a significant structural anomaly is amenable to surgical correction. With successful repair, many women attempt pregnancy. In some instances, surgical corrections have been performed 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 is paramount, and pregnancy is undertaken only after serious consideration in women with a prosthetic mechanical valve. This is because anticoagulation is requisite, and at least when not pregnant, warfarin is necessary. As shown in Table 49-5, a number of serious complications can develop with mechanical valves. Both thromboembolisms involving the prosthesis and hemorrhage from anticoagulation are of extreme concern. This is in addition to deterioration in cardiac function. Overall, the maternal mortality rate is 3 to 4 percent with mechanical valves, and fetal loss is common.
TABLE 49-5. Outcomes Reported Since 1990 in Pregnancies Complicated by a Heart-Valve Replacement
Porcine tissue valves are much safer during pregnancy, primarily because thrombosis is rare and anticoagulation is not required (see Table 49-5). Despite this, valvular dysfunction with cardiac deterioration or failure is common and develops in 5 to 25 percent of involved pregnancies. Another drawback is that bioprostheses are not as durable as mechanical ones, and valve replacement longevity averages 10 to 15 years. Based on their longitudinal study of 100 reproductive-aged women with a biological heart valve prosthesis, Cleuziou and colleagues (2010) concluded that pregnancy does not accelerate the risk for replacement.
This is critical for women with mechanical prosthetic valves. Unfortunately, warfarin is the most effective anticoagulant for preventing maternal thromboembolic complications but causes significant fetal morbidity and mortality. Anticoagulation with heparin is less hazardous for the fetus, however, the risk of maternal thromboembolic complications is much higher (McLintock, 2011).
As noted, warfarin, despite its effective anticoagulation, is teratogenic and causes miscarriage, stillbirths, and fetal malformations (Chap. 12, p. 252). In one study of 71 pregnancies in 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. From a systematic review, Chan and coworkers (2000) concluded that the best maternal outcomes were achieved with warfarin anticoagulation but with a 6.4-percent embryopathy rate. And although heparin substituted before 12 weeks’ gestation eliminated embryopathy, thromboembolic complications during that time were increased significantly.
In examining heparin, anticoagulation for mechanical valves using low-dose unfractionated heparin is definitely inadequate and has a high associated maternal mortality rate (Chan, 2000; Iturbe-Alessio, 1986). Even fullanticoagulation with either unfractionated heparin (UFH) or one of the low-molecular-weight heparins (LMWH) is associated with valvular thrombosis (Leyh, 2002, 2003; Rowan, 2001). Thus, many authorities recommend warfarin. However, the American College of Chest Physicians has recommended use of any of several regimens that include adjusted-dose UFH or LMWH heparin given throughout pregnancy as subsequently discussed (Bates, 2012).
Recommendations for Anticoagulation. A number of different treatment options—none of which are completely ideal—have been proposed and are principally based on consensus opinion. For this reason, they differ and allow more than one scheme. For example, and as shown in Table 49-6, the most recent guidelines of the American College of Chest Physicians for the management of pregnant women with mechanical prosthetic valves offer several different treatment options.
TABLE 49-6. American College of Chest Physicians Guidelines for Anticoagulation of Pregnant Women with Mechanical Prosthetic Valves
Any one of the following anticoagulant regimens is recommended:
Adjusted-dose LMWH twice daily throughout pregnancy. The doses should be adjusted to achieve the manufacturer’s peak anti-Xa level 4 hours after subcutaneous injection
Adjusted-dose UFH administered every 12 hours throughout pregnancy. The doses should be adjusted to keep the midinterval aPTT at least twice control or attain an anti-Xa level of 0.35 to 0.70 U/mL
LMWH or UFH as above until 13 weeks’ gestation, then warfarin substitution until close to delivery when LMWH or UFH is resumed
In women judged to be at very high risk of thromboembolism and in whom concerns exist about the efficacy and safety of LMWH or UFH as dosed above—some examples include older-generation prosthesis in the mitral position or history of thromboembolism—warfarin treatment is suggested throughout pregnancy with replacement by UFH or LMWH (as above) close to delivery. In addition, low-dose aspirin—75 to 100 mg daily—should be orally administered
aPTT = activated partial thromboplastin time; LMWH = low-molecular-weight heparin; UFH = unfractionated heparin. Adapted from Bates, 2012.
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 duration is not exactly known. The American College of Obstetricians and Gynecologists (2011b) 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, and preferably 48 hours, following a major surgical procedure.
Because warfarin, low-molecular-weight heparin, and unfractionated heparin do not accumulate in breast milk, they do not induce an anticoagulant effect in the infant. Therefore, these anticoagulants are compatible with breast feeding (American College of Obstetricians and Gynecologists, 2011b).
Because of their possible thrombogenic action, estrogen-progestin oral contraceptives are relatively contraindicated in women with prosthetic valves. Because these women are generally fully anticoagulated, however, any increased risk is speculative. Contraceptive options are discussed in Chapters 38 and 39. Sterilization should be considered because of the serious pregnancy risks faced by women with significant heart disease.
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. Sutton and associates (2005) found that maternal mortality rates with cardiopulmonary bypass are between 1.5 and 5 percent. Although these are similar to those for nonpregnant women, the fetal mortality rate approaches 20 percent. In a longitudinal study from the Mayo Clinic, John and coworkers (2011) reported the outcomes of 21 pregnant women who underwent cardiothoracic surgery requiring cardiopulmonary bypass between 1976 and 2009. The procedures included eight aortic valve replacements, six mitral valve repairs or replacements, two myxoma excisions, two aortic aneurysm repairs, one patent foramen ovale closure, one prosthetic aortic valve thrombectomy, and one septal myectomy. Median cardiopulmonary bypass time was 53 minutes, with a range of 16 to 185 minutes. One woman died two days after surgery, and three other deaths occurred 2, 10, and 19 years postoperatively. Three fetuses died, and 52 percent delivered before 36 weeks. To optimize outcomes, Chandrasekhar and coworkers (2009) recommend the following: surgery done electively when possible, pump flow rate maintained > 2.5 L/min/m2, normothermic perfusion pressure > 70 mm Hg, pulsatile flow used, and hematocrit kept > 28 percent.
Mitral Valvotomy During Pregnancy
Tight mitral stenosis that requires intervention during pregnancy was previously treated by closed mitral valvotomy (Pavankumar, 1988). More recently, however, percutaneous transcatheter balloon dilatation of the mitral valve has largely replaced surgical valvotomy during pregnancy (Fawzy, 2007). Rahimtoola (2006) summarized outcomes of 36 women—25 of whom were NYHA class III or IV—who underwent balloon commissurotomy at an average gestational age of 26 weeks. Surgery was successful in 35 women, and left atrial and pulmonary artery pressures were reduced as the mitral valve area was increased from 0.74 to 1.59 cm2. Esteves and associates (2006) described similarly good outcomes in 71 pregnant women with tight mitral stenosis and heart failure who underwent percutaneous valvuloplasty. At delivery, 98 percent were either NYHA class I or II. At a mean of 44 months, the total event-free maternal survival rate was 54 percent, however, eight women required another surgical intervention. The 66 infants who were delivered at term all had normal growth and development.
Pregnancy after Heart Transplantation
The first successful pregnancy in a heart-transplant recipient was reported 25 years ago by Löwenstein and associates (1988). Since that time, more than 50 pregnancies in heart-transplant recipients have been described. Key (1989) and Kim (1996) and their colleagues provide detailed data to show that the transplanted heart responds normally to pregnancy-induced changes. Despite this, complications are common during pregnancy (Dashe, 1998).
Armenti (2002) from the National Transplantation Pregnancy Registry and Miniero (2004), each with their coworkers, described outcomes of 53 pregnancies in 37 heart recipients. Almost half developed hypertension, and 22 percent suffered at least one rejection episode during pregnancy. They were delivered—usually by cesarean—at a mean of 37 to 38 weeks. Three fourths of infants were liveborn. At follow-up, at least five women had died more than 2 years postpartum. From Scandinavia, Estensen and associates (2011) detailed the outcomes of 19 women who had received a heart transplant and six who received both a heart and lung transplant. These 25 women had 42 pregnancies, and there were no maternal deaths. Major complications included two rejections during the early puerperium, two cases of renal failure, and 11 spontaneous abortions. Five women died 2 to 12 years after delivery. Ethical considerations of counseling and caring for such women related to pregnancy were summarized by Ross (2006).
VALVULAR HEART DISEASE
Rheumatic fever is uncommon in the United States because of less crowded living conditions, availability of penicillin, and evolution of nonrheumatogenic streptococcal strains. Still, it remains the chief cause of serious mitral valvular disease (Roeder, 2011).
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. The most prominent complaint is dyspnea due to pulmonary venous hypertension and edema. Fatigue, palpitations, cough, and hemoptysis are also common.
With more severe stenosis, the left atrium dilates, left atrial pressure is chronically elevated, and significant passive pulmonary hypertension develops (Table 49-7). These women have a relatively fixed cardiac output, and thus the increased preload of normal pregnancy, as well as other factors that increase 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). Because the murmur may not be heard in some women, this clinical picture at term may be confused with idiopathic peripartum cardiomyopathy (Cunningham, 1986, 2012).
TABLE 49-7. Major Cardiac Valve Disorders
Also with significant stenosis, tachycardia shortens ventricular diastolic filling time and increases the mitral gradient. This raises left atrial as well as pulmonary venous and capillary pressures and may result in 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, p. 1192). Atrial thrombosis can develop despite a sinus rhythm, and Hameed (2005) reported three such women. One suffered an embolic stroke, and another had pulmonary edema causing maternal hypoxemia leading to fetal encephalopathy.
In general, complications are directly associated with the degree of valvular stenosis. Recall that investigators from the large Canadian study found that women with a mitral-valve area < 2 cm2 were at greatest risk. In another study, Hameed (2001) described 46 pregnant women with mitral stenosis—43 percent developed heart failure and 20 percent developed arrhythmias. Fetal-growth restriction was more common in those 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—Sawhney (2003) reported that eight of 10 maternal deaths were in women in NYHA classes III or IV.
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). A β-blocker drug is usually given to slow the ventricular response to activity (Maxwell, 2010). 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 is given to slow ventricular response. Therapeutic anticoagulation with heparin is indicated with persistent fibrillation. Some recommend heparin anticoagulation for those with severe stenosis even if there is a sinus rhythm (Hameed, 2005).
Labor and delivery are particularly stressful for women with symptomatic mitral stenosis. 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 with strict attention to avoid fluid overload. Abrupt increases in preload may increase pulmonary capillary wedge pressure and cause pulmonary edema. The effects of labor on pulmonary pressures in women with mitral stenosis are shown in Figure 49-3. Wedge pressures increase most immediately postpartum. Clark and colleagues (1985) hypothesize that this is likely due to loss of the low-resistance placental circulation along with the venous “autotransfusion” from a now-empty uterus and from the lower extremities and pelvis.
FIGURE 49-3 Mean pulmonary capillary wedge pressure measurements (red graph line) in eight women with mitral valve stenosis. Shaded yellow and blue boxes are mean (± 1 SD) pressures in nonlaboring normal women at term. A. First-stage labor. B. Second-stage labor 15 to 30 minutes before delivery. C. Postpartum 5 to 15 minutes. D. Postpartum 4 to 6 hours. E. Postpartum 18 to 24 hours. (Data from Clark, 1985, 1989.)
Most consider vaginal delivery to be preferable 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.
A trivial degree of mitral insufficiency is found in most normal patients (Maxwell, 2010). But if there is improper coaptation of mitral valve leaflets during systole, abnormal degrees of mitral regurgitation may develop. This is eventually followed by left ventricular dilatation and eccentric hypertrophy (see Table 49-7). Chronic mitral regurgitation has a number of causes, including rheumatic fever, mitral valve prolapse, or left ventricular dilatation 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 (Roldan, 1996; Shroff, 2012). These sometimes coexist with systemic lupus erythematosus (Chap. 59, p. 1170). In contrast, acute mitral insufficiency is caused by chordae tendineae rupture, papillary muscle infarction, or leaflet perforation from infective endocarditis.
In nonpregnant patients, symptoms from mitral valve incompetence are rare, and valve replacement is seldom indicated unless infective endocarditis develops. Likewise, mitral regurgitation is well tolerated during pregnancy, probably because decreased systemic vascular resistance results in less regurgitation. Heart failure only rarely develops during pregnancy, and occasionally tachyarrhythmias 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 by routine examination or while undergoing echocardiography. The small percentage of 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 change generally have excellent pregnancy outcomes (Leśniak-Sobelga, 2004; Rayburn, 1987). In a study of 3100 women in the Taiwanese Birth Registry with mitral valve prolapse, however, the preterm birth rate was 1.2 times higher than among controls (Chen, 2011).
For women who are symptomatic, β-blocking drugs are given to decrease sympathetic tone, relieve chest pain and palpitations, and reduce the risk of life-threatening arrhythmias. According to the American College of Obstetricians and Gynecologists (2011a), mitral valve prolapse is not considered an indication for infective endocarditis prophylaxis.
Usually a disease of aging, aortic stenosis in women younger than 30 years is most likely due to a congenital lesion. This stenosis is less common since the decline in incidences of rheumatic diseases, and the most frequent cause in this country is a bicuspid valve (Friedman, 2008). A normal aortic valve has an area of 3 to 4 cm2, with a pressure gradient of less than 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 (Carabello, 2002; Roeder, 2011). Concentric left ventricular hypertrophy follows, and if severe, end-diastolic pressures become elevated, ejection fraction declines, and cardiac output is reduced (see Table 49-7). Characteristic clinical 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.
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, a number of events acutely decrease preload further and thus aggravate the fixed cardiac output. These include vena caval occlusion, 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 large Canadian multicenter study cited above, there were increased complications if the aortic valve area was < 1.5 cm2 (Siu, 2001b). And in the report by Hameed and associates (2001) described earlier, the maternal mortality rate with aortic stenosis was 8 percent. Women with valve gradients exceeding 100 mm Hg appear to be at greatest risk.
For the asymptomatic woman with aortic stenosis, no treatment except close observation is required. Management of the symptomatic woman includes strict limitation of activity and prompt treatment of infections. If symptoms persist despite bed rest, valve replacement or valvotomy using cardiopulmonary bypass must be considered. In general, balloon valvotomy for aortic valve disease is avoided because of serious complications, which exceed 10 percent. These include stroke, aortic rupture, aortic valve insufficiency, and death (Reich, 2004). In rare cases, it may be preferable to perform valve replacement during pregnancy (Datt, 2010).
For women with critical aortic stenosis, intensive monitoring during labor is important. 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 decreases in end-diastolic volume may result in hypotension, syncope, myocardial infarction, and sudden death. Thus, the management key is avoidance of decreased ventricular preload and the maintenance of cardiac output. During labor and delivery, such women should be managed on the “wet” side, maintaining a margin of safety in intravascular volume in anticipation of possible hemorrhage. In women with a competent mitral valve, pulmonary edema is rare, even with moderate volume overload.
During labor, narcotic epidural analgesia seems ideal, thus avoiding potentially hazardous hypotension, which may be encountered with standard conduction analgesia techniques. Easterling and coworkers (1988) studied the effects of epidural analgesia in five women with severe stenosis and demonstrated immediate and profound effects of decreased filling pressures. Xia and associates (2006) emphasize slow administration of dilute local anesthetic agents into the epidural space. Forceps or vacuum delivery is used for standard obstetrical indications in hemodynamically stable women. Late cardiac events include pulmonary edema, arrhythmias, cardiac interventions, and death, which were identified within 1 year of delivery in 70 pregnancies (Tzemos, 2009).
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, resulting in regurgitation. Acute insufficiency may develop with bacterial endocarditis or aortic dissection. Aortic and mitral valve insufficiency have 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 dilatation develop and are followed by slow-onset fatigue, dyspnea, and edema, although rapid deterioration usually follows (see Table 49-7).
Aortic insufficiency is generally well tolerated during pregnancy. Like mitral valve incompetence, diminished vascular resistance is thought to improve hemodynamic function. If symptoms of heart failure develop, diuretics are given and bed rest is encouraged.
The pulmonary valve is affected by rheumatic fever far less often than the other valves. Instead, pulmonic stenosis is usually congenital and also may be associated with Fallot tetralogy or Noonan syndrome. The clinical diagnosis is typically identified by auscultating a systolic ejection murmur over the pulmonary area that is louder during inspiration.
Increased hemodynamic burdens 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 angioplasty may be necessary antepartum (Maxwell, 2010; Siu, 2001a). In a study of 81 pregnancies in 51 Dutch women with pulmonic stenosis, cardiac complications were infrequent (Drenthen, 2006). 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 complications were increased—17 percent had preterm delivery; 15 percent had hypertension; and 4 percent developed thromboembolism. Interestingly, two of the offspring were diagnosed with pulmonic stenosis, and another had complete transposition and anencephaly.
CONGENITAL HEART DISEASE
The incidence of congenital heart disease in the United States is approximately 8 per 1000 liveborn infants. Approximately a third of these have critical disease that requires cardiac catheterization or surgery during the first year of life. Others require surgery in childhood, and it is currently estimated that there are nearly 1 million adults in this country with congenital heart disease (Bashore, 2007).
According to an analysis from the Nationwide Inpatient Sample discharge database, more than 30,000 women admitted for delivery between 1998 and 2007 had congenital heart disease—a rate of 71.6 per 100,000 deliveries (Opotowsky, 2012). After statistical adjustments, women with congenital heart disease were found to be eight times more likely to sustain an adverse cardiovascular event that included death, heart failure, arrhythmia, and cerebrovascular or embolic event. Of these, arrhythmia was the most common, and the rate of maternal death was approximately 1.5 per 1000. Thompson and coworkers (2014) found similar risks.
Atrial Septal Defects
After bicuspid aortic valve, these are the most frequently encountered adult congenital cardiac lesions. Indeed, a fourth of all adults have a patent foramen ovale (Kizer, 2005). Most 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 discovered in adulthood. Pregnancy is well tolerated unless pulmonary hypertension has developed, but this is uncommon (Maxwell, 2010; Zuber, 1999). Treatment is indicated for congestive heart failure or an arrhythmia. Based on their review, Aliaga and associates (2003) concluded that the risk of endocarditis with an atrial septal defect 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 (Chap. 60, p. 1192). Erkut and associates (2006) described a woman who developed an entrapped thrombus in a patent foramen ovale postpartum. In asymptomatic women, thromboembolism prophylaxis is problematic, and recommendations include either observation or antiplatelet therapy such as low-dose aspirin (Kizer, 2005; Maxwell, 2010). Compression stockings and prophylactic heparin for a pregnant woman with a septal defect and concurrent immobility or other risk factors for thromboembolism have also been recommended (Head, 2005).
Ventricular Septal Defects
These lesions close spontaneously during childhood in 90 percent of cases. Most defects are paramembranous, and physiological derangements are related to lesion size. In general, if the defect is less than 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; Maxwell, 2010).
Pregnancy is well tolerated with small to moderate left-to-right shunts. If pulmonary arterial pressures reach systemic levels, however, there is reversal or bidirectional flow—Eisenmenger syndrome (p. 985). When this develops, the maternal mortality rate is significantly increased, and thus, pregnancy is not generally advisable. Bacterial endocarditis is more common with unrepaired defects, and antimicrobial prophylaxis is often required (p. 991). As shown in Table 49-4, up to 15 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, but still, some of these women become pregnant. Compared with simple septal defects, complications are more frequent during pregnancy. In a review of 48 pregnancies in 29 such 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 (Akintunde, 2011). The physiological consequences of persistence of this structure 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, 2000). 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 (Maxwell, 2010). A sudden blood pressure decline at delivery—such as with conduction analgesia or hemorrhage—may lead to fatal collapse. Therefore, hypotension should be avoided whenever possible and treated vigorously if it develops. Prophylaxis for bacterial endocarditis may be indicated at delivery for unrepaired defects (p. 991). As shown in Table 49-4, the incidence of inheritance is approximately 4 percent.
Cyanotic Heart Disease
When congenital heart lesions are associated with 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 (Maxwell, 2010). It 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 decreases, the shunt increases and cyanosis worsens. Women who have undergone repair and who do not have a recurrence of cyanosis do well in pregnancy.
Some women with Ebstein anomaly with a malpositioned, malformed tricuspid valve may reach reproductive age. Right ventricular failure from volume overload and appearance or worsening of cyanosis are common during pregnancy. In the absence of cyanosis, these women usually tolerate pregnancy well.
Women with cyanotic heart disease generally do poorly during pregnancy. With uncorrected Fallot tetralogy, for example, maternal mortality rates approach 10 percent. Moreover, any disease complicated by severe maternal hypoxemia is likely to lead to miscarriage, preterm delivery, or fetal death. There is a relationship between chronic hypoxemia, polycythemia, and pregnancy outcome. When hypoxemia is intense enough to stimulate a rise in hematocrit above 65 percent, pregnancy wastage is virtually 100 percent.
Pregnancy after Surgical Repair
Some of the more complex lesions cannot be successfully repaired. But with satisfactory surgical correction of cyanotic lesions before pregnancy, maternal and fetal outcomes are much improved (Maxwell, 2010).
Fallot Tetralogy. Balci (2011) and Kamiya (2012) and their associates described a total of 197 pregnancies in 99 women with surgically corrected Fallot tetralogy. Pregnancy was usually well tolerated, and there were no maternal deaths. Still, almost 9 percent of pregnancies were complicated by adverse cardiac events including new onset or worsening of arrhythmias and heart failure. For women with a pulmonary valve replacement, Oosterhof and coworkers (2006) reported that pregnancy did not adversely affect graft function.
Transposition of the Great Vessels. Pregnancy following surgical correction of transposition also has risks. Canobbio (2006) and Drenthen (2005a), each with their colleagues, described outcomes of 119 pregnancies in 68 women—90 percent had a Mustard procedure and 10 percent a Senning procedure. During pregnancy, a fourth had arrhythmias. Twelve percent developed heart failure, and one of these patients 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, but no infant had heart disease. In a more recent study, Metz and associates (2011) reported that five of 14 pregnancies resulting in live births were complicated by symptomatic intracardiac baffle obstruction, which required postpartum stenting. In review, baffles are surgically constructed conduits that redirect anomalous cardiac blood flow and are integral to initial transposition correction.
Successful—although eventful—pregnancies in women with previously repaired truncus arteriosus and double-outlet right ventricle have also been described (Drenthen, 2008; Hoendermis, 2008).
Single Functional Ventricle. Feinstein and associates (2012) recently reviewed the remarkably improved treatments for patients with hypoplastic left heart syndrome. Almost 70 percent of these women are now expected to survive into adulthood and frequently become pregnant. Those who have undergone a Fontan repair are at particularly high risk for complications, which include atrial arrhythmias and peripartum heart failure (Nitsche, 2009). In a report of four pregnancies post-Fontan repair, there were no maternal deaths, but complications were frequent (Hoare, 2001). All were delivered preterm, two had supraventricular arrhythmias, and two developed ventricular failure. Similarly high complication rates were described by Jain and coworkers (2011) in 15 women with a systemic right ventricle, that is, one in which the right ventricle rather than the left pumps blood to the support systemic circulation.
This describes secondary pulmonary hypertension that develops 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 right-to-left shunting, and few persons survive into the fifth decade (Makaryus, 2006; Maxwell, 2010).
FIGURE 49-4 Eisenmenger syndrome due to a ventricular septal defect (VSD). A. Substantial left-to-right shunting through the VSD leads to morphological changes in the smaller pulmonary arteries and arterioles. Specifically, medial hypertrophy, intimal cellular proliferations, and fibrosis lead to narrowing or closure of the vessel lumen. These vascular changes create pulmonary hypertension and a resultant reversal of the intracardiac shunt (B). With sustained pulmonary hypertension, extensive atherosclerosis and calcification often develop in the large pulmonary arteries. Although a VSD is shown here, Eisenmenger syndrome may also develop in association with a large atrial septal defect or patent ductus arteriosus.
The prognosis for pregnancy depends on the severity of pulmonary hypertension but survival has improved during the past 50 years. Women with Eisenmenger syndrome tolerate hypotension poorly, and the cause of death usually is right ventricular failure with cardiogenic shock. Management is discussed subsequently. 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 coworkers (1998) cited a 36-percent maternal death rate. Three of 26 deaths were antepartum, and the remainder died intrapartum or within a month of delivery. In a more recent study of 13 pregnant women, there was one maternal death 17 days after delivery, and there were five perinatal deaths (Wang, 2011).
Normal resting mean pulmonary artery pressure is 12 to 16 mm Hg. In the study by Clark and colleagues (1989), pulmonary vascular resistance in late pregnancy was approximately 80 dyn/sec/cm−5, which was 34-percent less than the nonpregnant value of 120 dyne/sec/cm−5. Pulmonary hypertension is a hemodynamic observation and not a diagnosis and is defined in nonpregnant individuals as a mean pulmonary pressure > 25 mm Hg.
The World Health Organization classification shown in Table 49-8 has been adopted by the American College of Cardiology and the American Heart Association (McLaughlin, 2009). There are important prognostic and therapeutic distinctions between group I pulmonary hypertension and the other groups. Group I 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. Approximately a third of women with scleroderma and 10 percent with systemic lupus erythematosus have pulmonary hypertension (Rich, 2005). Other causes in young women are sickle-cell disease and thyrotoxicosis (Sheffield, 2004). Another is plexogenic pulmonary arteriopathy associated with cirrhosis and portal hypertension, and this has been reported to cause a maternal death (Sigel, 2007).
TABLE 49-8. World Health Organization Classification of Some Causes of Pulmonary Hypertension
I Pulmonary arterial hypertension
Idiopathic—previously “primary” pulmonary hypertension
Familial—chromosome 2 gene in TGF superfamily
Associated with: collagen-vascular disorders, congenital left-to-right cardiac shunts, HIV infection, thyrotoxicosis, sickle hemoglobinopathies, antiphospholipid antibody syndrome, diet drugs, portal hypertension
Persistent pulmonary hypertension of the newborn
II Pulmonary hypertension with left-sided heart disease
Left-sided atrial or ventricular disease
Left-sided valvular disease
III Pulmonary hypertension associated with lung disease
Chronic obstructive pulmonary disease
Interstitial lung disease
IV Pulmonary hypertension due to chronic thromboembolic disease
HIV = human immunodeficiency virus; TGF = transforming growth factor.
Adapted from Simmoneau, 2004.
Group II disorders are the most commonly encountered in pregnant women. These are secondary to pulmonary venous hypertension caused by left-sided atrial, ventricular, or valvular disorders. A typical example is mitral stenosis discussed on page 981. In contrast, groups III through V are seen infrequently in young otherwise healthy women.
Symptoms may be vague, and dyspnea with exertion is the most common. With group II 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 commonly shows enlarged pulmonary hilar arteries and attenuated peripheral markings. It also may disclose parenchymal causes of hypertension. Although cardiac catheterization remains the standard criterion for the measurement of pulmonary artery pressures, noninvasive echocardiography is often used to provide an estimate. In 33 pregnant women who underwent both echocardiography and cardiac catheterization, pulmonary artery pressures were significantly overestimated by echocardiography in a third of cases (Penning, 2001).
Longevity depends on the severity and cause of pulmonary hypertension at discovery. For example, although invariably fatal, idiopathic pulmonary hypertension has a 3-year survival rate of 60 percent, whereas that due to collagen-vascular diseases has only a 35-percent rate (McLaughlin, 2004). Some disorders respond to pulmonary vasodilators, calcium-channel blockers, prostacyclin analogues, or endothelin-receptor blockers, all which may improve quality of life. The prostacyclin analogues epoprostenol and treprostinil significantly lower pulmonary vascular resistance but must be given parenterally (Humbert, 2004; Roeleveld, 2004). Preconceptional counseling is imperative as emphasized by Easterling and associates (1999).
Pulmonary Hypertension and Pregnancy
The maternal mortality rate is appreciable, but 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 separable. Curry (2012) and Weiss (1998) and their colleagues reviewed 36 cases of pulmonary hypertension in pregnancy and found an approximate 30-percent mortality rate. Bédard and coworkers (2009) reported that mortality statistics improved during the decade ending in 2007 compared with those for the decade ending in 1996. Mortality rates were 25 and 38 percent, respectively. Importantly, almost 80 percent of the deaths were during the first month postpartum.
Pregnancy is contraindicated with severe disease, especially those with pulmonary arterial changes—most cases in group I. With milder disease from other causes—group II being the most common—the prognosis is much better. 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 (Chap. 58, p. 1151). 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.
Treatment of symptomatic pregnant women includes activity limitation and avoidance of the supine position in late pregnancy. Diuretics, supplemental oxygen, and vasodilator drugs are standard therapy for symptoms. Some recommend anticoagulation (Hsu, 2011; Larson, 2010). In addition, there are many reports describing the successful use of intravenous pulmonary artery vasodilators in both singleton and twin gestations (Badalian, 2000; Easterling, 1999; Garabedian, 2010). Prostacyclin analogues that can be administered parenterally include epoprostenol and treprostinil, whereas iloprost is inhaled. There are reports of successful use of each in pregnant women, but data are insufficient to prefer one over another. Inhaled nitric oxide is also an option that has been employed in cases of acute cardiopulmonary decompensation during pregnancy or the puerperium (Lane, 2011).
Labor and Delivery
These women are at greatest risk during labor and delivery when there is diminished venous return and decreased right ventricular filling—both associated with most maternal deaths. To avoid hypotension, assiduous attention is given to epidural analgesia induction and to blood loss prevention and treatment at delivery. Parneix and coworkers (2009) describe low-dose spinal-epidural analgesia for cesarean delivery. Women with group I severe hypertension have been delivered successfully while using either inhaled nitric oxide or iloprost (Lam, 2001; Weiss, 2000).
The American Heart Association defines cardiomyopathies 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 dilatation. Cardiomyopathies are due to various causes that frequently are genetic (Maron, 2006). In general, and as shown in Table 49-9, cardiomyopathies may be divided into two major groups:
• Primary—cardiomyopathies solely or predominantly confined to heart muscle—examples include hypertrophic cardiomyopathy, dilated cardiomyopathies, and peripartum cardiomyopathy.
• Secondary—cardiomyopathies due to generalized systemic disorders that produce pathological myocardial involvement—examples are diabetes, lupus, and thyroid disorders.
TABLE 49-9. Some Primary and Secondary Causes of Cardiomyopathy
Genetic—hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, left ventricular noncompaction, glycogen storage diseases, conduction system disease, mitochondrial myopathies, ion-channelopathies
Mixed—predominantly nongenetic—dilated and restrictive cardiomyopathy
Acquired—myocarditis, stress (takotsubo), peripartum cardiomyopathy
Infiltrative—amyloidosis, Gaucher disease, Hurler and Hunter diseases
Toxicity—drugs, heavy metals
Endocrine—diabetes mellitus, thyroid dysfunction
Neuromuscular/neurological—Friedrich ataxia, neurofibromatosis
Autoimmune—systemic lupus erythematosus, scleroderma
Adapted from Maron, 2006.
Epidemiological studies suggest that the disorder is common, affecting approximately 1 in 500 adults (Maron, 2004). The condition—characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis—is caused by mutations in any one of more than a dozen genes that encode cardiac sarcomere proteins. Inheritance is autosomal dominant, and genetic screening is complex and not currently clinically available (Osio, 2007; Spirito, 2006). The myocardial muscle abnormality is characterized by left ventricular myocardial hypertrophy with a pressure gradient to 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 common form of death. Asymptomatic patients with runs of ventricular tachycardia are especially prone to sudden death. Symptoms are usually worsened by exercise.
Although limited reports suggest that pregnancy is well tolerated, adverse cardiac events are common. Thaman and coworkers (2003) reviewed 271 pregnancies in 127 affected women. Although there were no maternal deaths, more than a fourth had at least one adverse cardiac symptom—including dyspnea, chest pain, or palpitations. Singla and associates (2011) described a pregnant patient with undiagnosed hypertrophic cardiomyopathy who presented with preeclampsia and an acute myocardial infarction.
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 is determined by obstetrical indications. Choice of anesthesia is controversial, and in the opinion of some authors, general anesthesia is considered safest (Pitton, 2007). Infants rarely demonstrate inherited lesions at birth.
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 cases are result from viral infections, including myocarditis and human immunodeficiency virus (Barbaro, 1998; Felker, 2000). Other causes, which are potentially reversible, include alcoholism, cocaine abuse, and thyroid disease. Watkins and colleagues (2011) reviewed the many complex genetic mutations associated with inherited forms of dilated cardiomyopathy.
This disorder is very similar to other forms of nonischemic dilated cardiomyopathy except for its unique relationship with pregnancy (Pyatt, 2011). 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, there was little evidence to support a unique pregnancy-induced cardiomyopathy. Pearson (2000) reported findings of a workshop of the National Heart, Lung, and Blood Institute and the Office of Rare Diseases 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).
FIGURE 49-5 Peripartum cardiomyopathy with mild pulmonary edema. Anterior-posterior projection chest radiograph of a woman with an abnormally enlarged heart and mild perihilar opacification consistent with dilated cardiomyopathy.
The etiology of peripartum cardiomyopathy remains unknown, and many potential causes—including viral myocarditis, abnormal immune response to pregnancy, abnormal response to the increased hemodynamic burden of pregnancy, hormonal interactions, malnutrition, inflammation, and apoptosis—have been proposed but not proven (Elkayam, 2011). Another theory suggests that oxidative stress during late pregnancy leads to the proteolytic cleavage of prolactin (Hilfiker-Kleiner, 2007). The resulting 16-kDa prolactin fragment has been found to be cardiotoxic and can impair the metabolism and contractility of cardiomyocytes. Based on this proposed mechanism, bromocriptine therapy has been suggested because it inhibits prolactin secretion (Chap. 36, p. 673). Indeed, there has been at least one preliminary study in which bromocriptine improved recovery of affected women (Sliwa, 2010).
Another intriguing mechanism to explain the etiology of peripartum cardiomyopathy was described by Patten (2012). It links peripartum cardiomyopathy to preeclampsia syndrome. This is biologically plausible given that hypertensive disorders frequently coexist with peripartum cardiomyopathy (Cunningham, 2012; Fong, 2014; Gunderson, 2011). These investigators showed that antiangiogenic factors—already known to be associated with preeclampsia—can induce peripartum cardiomyopathy in susceptible mice. Thus, they posit peripartum cardiomyopathy to be a vascular disease precipitated by antiangiogenic factors that act in a host made susceptible because of insufficient proangiogenic factors.
In the absence of a 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. They attributed these findings to reactivation of latent viral infection that triggered an autoimmune response. Another report described 28 women at Parkland Hospital who had peripartum heart failure of obscure etiology who were initially thought to have idiopathic peripartum cardiomyopathy (Cunningham, 1986). In 21 of these, heart failure was found to be caused by hypertensive heart disease, clinically silent mitral stenosis, obesity, or viral myocarditis. Particularly important were the silent cardiomyopathic effects that even intermediate-duration chronic hypertension may have on ventricular function.
After exclusion of an underlying cause for heart failure, the default diagnosis is idiopathic or peripartum cardiomyopathy. Thus, its incidence is highly dependent on the diligence of the search for a cause. Because of this, the cited incidence varies from approximately 1 in 2500 to 1 in 15,000 births. In a review of the National Hospital Discharge Survey database of 3.6 million births, a prevalence of 1 in 3200 births was computed (Mielniczuk, 2006). Two other large population-based studies cited a frequency of 1 in 2000 to 2800 (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. The distinction between heart failure from an identifiable cause and peripartum cardiomyopathy is of obstetrical importance. Women with a true cardiomyopathy do not fare well overall as a group, and their immediate and 1-year mortality rate is 2 to 15 percent (Harper, 2012; Mielniczuk, 2006). Approximately 50 percent 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).
A study from India described the outcomes of 36 women with peripartum cardiomyopathy (Mandal, 2011). Five women died either from heart failure or cerebrovascular accident. Of six women who had a subsequent pregnancy, one woman died and two developed heart failure. In a follow-up study from Haiti, Fett and coworkers (2009) performed echocardiography every 6 months in 116 women with peripartum cardiomyopathy. Only 28 percent of these women recovered a left ventricular ejection fraction > 0.51, and in three fourths of these, this level was not attained until after a year. With a mean follow-up of 39 months, de Souza and colleagues (2001) reported that 18 percent of 44 such women had died from end-stage heart failure. Similar long-term outcomes were assessed by a survey of members of the American College of Cardiology (Elkayam, 2001). Respondents reported that a return to normal ventricular function does not guarantee a problem-free pregnancy, and that if another pregnancy is undertaken in women with an ejection fraction persistently < 0.5, it should be with great trepidation.
Other Primary Causes of Cardiomyopathy
Arrhythmogenic Right Ventricular Dysplasia
This unique cardiomyopathy is defined histologically by progressive replacement of right ventricular myocardium with adipose and fibrous tissue. As described on page 992, this disorder predisposes to ventricular tachyarrhythmias. It has an estimated prevalence is 1 in 5000 and is a cause of sudden death, particularly in younger people (Elliott, 2008). The additional risk of pregnancy in women with arrhythmogenic right ventricular cardiomyopathy is unknown. However, based on a systematic review, Krul and associates (2011) advise against pregnancy.
This inherited cardiomyopathy is probably the least common type. It is characterized by a ventricular filling pattern in which increased myocardial stiffness causes ventricular pressure to rise precipitously with only a small increase in volume (Elliott, 2008). Due to the severe clinical course in nonpregnant patients and the poor prognosis in general, pregnancy is not advised (Krul, 2011).
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. High-output states caused by hemorrhage and acute anemia increase cardiac workload and magnify the physiological effects of compromised ventricular function. Similarly, infection and sepsis syndrome increase cardiac output and oxygen utilization tremendously, and sepsis can depress myocardial function (Chap. 47, p. 948).
As described in Chapter 50 (p. 1003), in many populations, chronic hypertension with superimposed preeclampsia is the most frequent cause of heart failure in pregnant women. Many of these women have concentric left ventricular hypertrophy. In some, mild antecedent undiagnosed hypertension causes covert cardiomyopathy, and when superimposed preeclampsia develops, together they may cause otherwise inexplicable peripartum heart failure. As discussed throughout Chapter 48 (p. 963), obesity is a common cofactor with chronic hypertension, and it leads to eccentric ventricular hypertrophy. In the Framingham Heart Study, obesity alone was associated with a doubling of the heart failure risk in nonpregnant individuals (Kenchaiah, 2002).
Congestive heart failure can have a gradual onset or may present as acute “flash” pulmonary edema. The first warning sign is likely to be persistent basilar rales, frequently accompanied by a nocturnal cough (Jessup, 2003). A sudden decline in the ability to complete usual duties, increased dyspnea on exertion, and/or attacks of smothering with cough are symptoms of serious heart failure. Clinical findings may include hemoptysis, progressive edema, tachypnea, and tachycardia. Dyspnea is universal, and other symptoms include orthopnea, palpitations, and substernal chest pain (Sheffield, 1999). Hallmark findings usually include cardiomegaly and pulmonary edema (see Fig. 49-5). Acutely, there is usually systolic failure, and echocardiographic findings include 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.
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 the woman is delivered (Chap. 12, p. 247). With chronic heart failure, there is a high incidence of associated thromboembolism, and thus prophylactic heparin is often recommended.
Left ventricular assist devices (LVADs) are employed more frequently for acute and chronic heart failure treatment. However, there are only a few reports describing their use during pregnancy (LaRue, 2011; Sims, 2011). Extracorporeal membrane oxygenation (ECMO) was reported to be lifesaving in a woman with fulminating cardiomyopathy (Smith, 2009).
Bacterial infection of a heart valve involves cardiac endothelium and usually results in valvular vegetations. In this country, those at greatest risk are women with congenital heart lesions, intravenous drug use, degenerative valve disease, and intracardiac devices (Karchmer, 2012). Subacute bacterial endocarditis usually is due to 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 is the predominant organism. Staphylococcus epidermidis frequently causes prosthetic valve infections. Streptococcus pneumoniae and Neisseria gonorrhoeae may occasionally cause acute, fulminating disease. Antepartum endocarditis has also been described with Neisseria sicca and Neisseria mucosa, the latter causing maternal death (Cox, 1988; Deger, 1992). Only a few cases of group B streptococcal endocarditis have been described (Kangavari, 2000). Endocarditis due to Escherichia coli following cesarean delivery was described in an otherwise healthy young woman (Kulaš, 2006).
Endocarditis symptoms are variable and often develop insidiously. Fever, often with chills, is seen in 80 to 90 percent of cases, a murmur is heard in 80 to 85 percent, and anorexia, fatigue, and other constitutional symptoms are common. The illness is frequently described as “flulike” (Karchmer, 2012). Other findings are anemia, proteinuria, and manifestations of embolic lesions, including petechiae, focal neurological manifestations, 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 in diameter or those on the tricuspid valve may be missed. If uncertain, transesophageal echocardiography (TEE) is accurate and informative. Importantly, a negative echocardiographic study does not exclude endocarditis.
Treatment is primarily medical with appropriate timing of surgical intervention if necessary. Knowledge of the infecting organism and its sensitivities is imperative for sensible antimicrobial selection. Guidelines for appropriate antibiotic treatment are published by professional societies and are updated regularly (Hoen, 2013). Most streptococci are sensitive to penicillin G, ceftriaxone, or vancomycin given intravenously for 4 to 6 weeks, along with gentamicin for 2 to 4 weeks. Complicated infections are treated longer, and women allergic to penicillin are either desensitized or given intravenous ceftriaxone or vancomycin for 4 weeks. Staphylococci, enterococci, and other organisms are treated according to microbial sensitivity for 4 to 6 weeks (Darouiche, 2004; Karchmer, 2012). Prosthetic valve infections are usually treated for 6 weeks. Recalcitrant bacteremia and heart failure due to valvular dysfunction are but a few reasons that persistent valvular infection may require replacement.
Endocarditis in Pregnancy
Infective endocarditis is uncommon during pregnancy and the puerperium. Treatment is the same as that described above. During a 7-year period, the incidence of endocarditis at Parkland Hospital was approximately 1 in 16,000 births, and two of seven women died (Cox, 1988). From their reviews, Seaworth (1986) and Cox (1989) cited a maternal mortality rate of 25 to 35 percent.
For years, patients with real or imagined heart valve problems were given periprocedural antibiotic prophylaxis for endocarditis. This was despite the questioned efficacy of antimicrobial prophylaxis. Currently, however, recommendations are more stringent. The American Heart Association recommends prophylaxis for dental procedures in those with prosthetic valves; prior endocarditis; unrepaired or incompletely repaired cyanotic heart defects or during the 6 months following complete repair; and valvulopathy after heart transplantation (Wilson, 2007). In agreement with this, the American College of Obstetricians and Gynecologists (2011a) does not recommend endocarditis prophylaxis for either vaginal or cesarean delivery in the absence of pelvic infection. Exceptions are the small subset of patients 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 49-10. These are administered as close to 30 to 60 minutes before the anticipated delivery time as is feasible. Despite these new recommendations, prophylaxis is still overused, likely because of prior liberal recommendations. In a study from one institution, only six of 50 women who received antibiotics for endocarditis prophylaxis were judged to have an appropriate indication (Pocock, 2006).
TABLE 49-10. Antibiotic Prophylaxis for Infective Endocarditis in High-Risk Patients
Standard (IV): ampicillin 2 g or cefazolin or ceftriaxone 1 g
Penicillin-allergic (IV): cefazolin or ceftriaxone 1 g or clindamycin 600 mg
Oral: amoxicillin 2 g
American Heart Association (Wilson, 2007):
Standard: ampicillin 2 g IV or IM or amoxicillin 2 g PO
Penicillin-allergic: clarithromycin or azithromycin 500 mg PO; cephalexin 500 mg PO; clindamycin 600 mg PO, IV, or IM; or cefazolin or ceftriaxone 1 g IV or IM
ACOG = American College of Obstetricians and Gynecologists; IM = intramuscular; IV = intravenous; PO = orally.
Both preexisting and new-onset cardiac arrhythmias are often encountered during pregnancy, labor, delivery, and the puerperium (Gowda, 2003). In a study of 73 women with a history of supraventricular tachycardia, 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 increased incidence of arrhythmias during pregnancy are not well elucidated. According to Eghbali and associates (2006), adaptive electric cardiac remodeling of potassium-channel genes may be important. Perhaps the normal but mild hypokalemia of pregnancy and/or the physiological increase in heart rate serves to induce arrhythmias (Chap. 4, p. 58). Alternatively, detection of arrhythmias may be increased because of the frequent visits typical of normal prenatal care.
Slow heart rhythms, including complete heart block, are compatible with a successful pregnancy outcome. Some women with complete heart block have syncope during labor and delivery, and occasionally temporary cardiac pacing is necessary (Hidaka, 2006). In our experiences, as well as those of Hidaka (2011) and Jaffe (1987) and their associates, women with permanent artificial pacemakers usually tolerate pregnancy well. With fixed-rate devices, cardiac output apparently is increased by augmented stroke volume.
The most common arrhythmia seen in reproductive-aged women is paroxysmal supraventricular tachycardia (Robins, 2004). If diagnosed when nonpregnant, approximately a third of women have an occurrence during pregnancy (Maxwell, 2010). Conversely, 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 including 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.
Treatment of supraventricular tachycardias include vagal maneuvers—Valsalva, carotid sinus massage, bearing down, and immersion of the face in ice water—which serve to increase vagal tone and block the atrioventricular node (Link, 2012). Intravenous adenosine is a very 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 pregnant women (Maxwell, 2010; Robins, 2004). Transient fetal bradycardia has been described with adenosine (Dunn, 2000).
Electrical cardioversion with standard energy settings is not contraindicated in pregnancy, but vigilance is important. Barnes and associates (2002) described a case in which direct current cardioversion led directly to a sustained uterine contraction and fetal bradycardia. 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).
Pregnancy may predispose otherwise asymptomatic women with Wolff-Parkinson-White (WPW) syndrome to exhibit arrhythmias (Maxwell, 2010). In a study of 25 women who had supraventricular tachycardia diagnosed before pregnancy, three of 12 women with WPW syndrome and six of 13 without the condition developed supraventricular tachycardia during pregnancy. In some patients, accessory pathway ablation may be indicated (Pappone, 2003). For this, the typical fluoroscopic procedure-related fetal radiation dose is < 1 cGy (Damilakis, 2001).
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 anesthesia-provoked tachycardia in another. They concluded that pregnancy events precipitated the tachycardia and recommended β-blocker therapy for control. As previously discussed, 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; Nanson, 2001).
This conduction anomaly may predispose individuals to a potentially fatal ventricular arrhythmia known as torsades de pointes (Roden, 2008). Two studies involving a combined total of 502 pregnant women with long QT syndromeboth reported a significant increase in cardiac events postpartum but not during pregnancy (Rashba, 1998; Seth, 2007). It was hypothesized that the normal increase in heart rate during pregnancy may be partially protective. Paradoxically, β-blocker therapy has been shown to decrease the risk of torsades de pointes in patients with long QT syndrome and should be continued during pregnancy and postpartum (Gowda, 2003; Seth, 2007). Importantly, many medications, including some used during pregnancy such as azithromycin, erythromycin, and clarithromycin, may predispose to QT prolongation (Al-Khatib, 2003; Ray, 2012; Roden, 2004).
DISEASES OF THE AORTA
Marfan syndrome and coarctation are two aortic diseases that place the pregnant woman at increased risk for aortic dissection. Indeed, half of cases in young women are related to pregnancy (O’Gara, 2004). Other risk factors are bicuspid aortic valve and Turner or Noonan syndrome. Pepin and colleagues (2000) also reported a high rate of aortic dissection or rupture in patients with Ehlers-Danlos syndrome (Chap. 59, p. 1181). Although the mechanism(s) involved are unclear, the initiating event is a tear in the aorta’s intima layer, followed by hemorrhage into the media layer, 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 in conjunction with a recently acquired aortic insufficiency murmur is an important physical finding. The differential diagnosis of aortic dissection includes myocardial infarction, pulmonary embolism, pneumothorax, and aortic valve rupture as well as obstetrical catastrophes, especially placental abruption and uterine rupture (Lang, 1991).
More than 90 percent of patients with aortic dissection have an abnormal chest radiograph. Aortic angiography is the most definitive method for confirming the diagnosis. However, noninvasive imaging—sonography, computed tomography, and magnetic resonance (MR) imaging—is used more frequently. The urgency of the clinical situation frequently dictates which procedure is best.
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. Survival in nonpregnant patients is not improved by elective repair of abdominal aortic aneurysms smaller than 5.5 cm (Lederle, 2002).
This autosomal dominant disorder has a high degree of penetrance. The incidence is 2 to 3 per 10,000 individuals and is without racial or ethnic predilection (Ammash, 2008). Prenatal diagnosis is usually possible using linkage analysis (Chap. 13, p. 277). The syndrome is due to abnormal fibrillin—a constituent of elastin—caused by any of dozens of mutations in the FBN1 gene located on chromosome 15q21 (Biggin, 2004). Thus, Marfan syndrome is a connective-tissue disorder 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 dilatation causes aortic valve insufficiency, and there may be infective endocarditis and mitral valve prolapse with insufficiency. Aortic dilatation and dissecting aneurysm are the most serious abnormalities. Early death is due either to valvular insufficiency and heart failure or to a dissecting aneurysm.
Effect of Pregnancy on Marfan Syndrome
In the past, case reports reflected biased outcomes, and the maternal mortality rate was inaccurately magnified (Elkayam, 1995). In a prospective evaluation of 21 women during 45 pregnancies cared for at the Johns Hopkins Hospital, only two had dissection, and one died postpartum from graft infection (Rossiter, 1995). Although there were no maternal deaths among 14 women followed by Rahman and coworkers (2003), two required surgical correction of an aortic aneurysm. These investigators concluded that aortic dilatation > 40 mm or mitral valve dysfunction are high-risk factors for life-threatening cardiovascular complications during pregnancy. Conversely, women with minimal or no dilatation, and those with normal cardiac function by echocardiography, are counseled regarding the small but serious potential risk of aortic dissection.
The aortic root usually measures approximately 2 cm, and during normal pregnancy, it increases slightly (Easterling, 1991). With Marfan syndrome, if aortic root dilatation reaches 4 cm, then dissection is more likely. If dilatation reaches 5 to 6 cm, then elective surgery should be considered before pregnancy (Gott, 1999; Williams, 2002). Prophylactic β-blocker therapy has become the standard medical approach for pregnant women with Marfan syndrome because it reduces hemodynamic stress on the ascending aorta and slows the rate of dilation (Simpson, 2012). 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 cerebral damage (Mul, 1998; Seeburger, 2007). There are a number of case reports describing emergency cesarean deliveries in women with acute type A dissection that was repaired successfully at the time of delivery (Guo, 2011; Haas, 2011; Papatsonis, 2009).
Obstetrical outcomes of 63 women with Marfan syndrome with a total of 142 pregnancies were reviewed by Meijboom and coworkers (2006). Of 111 women delivered after 20 weeks, 15 percent had preterm delivery, and 5 percent had preterm prematurely ruptured membranes. There were eight perinatal deaths, and half of the neonate survivors were subsequently diagnosed with Marfan syndrome.
This is a relatively rare lesion 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 to a striking extent, 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. Several authors have described diagnosis during pregnancy using MR imaging (Dizon-Townson, 1995; Sherer, 2002; Zwiers, 2006).
Effect of Pregnancy on Coarctation
Major complications include congestive heart failure after longstanding 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 postpartum. Cerebral hemorrhage from circle of Willis aneurysms may also develop. Beauchesne and associates (2001) described the outcomes of 188 pregnancies from the Mayo Clinic. A third had hypertension that was related to significant coarctation gradients, and one woman died from dissection at 36 weeks. Using the United States Nationwide Inpatient Sample between 1998 and 2007, Krieger and colleagues (2011) studied nearly 700 deliveries among women with coarctation. Hypertensive complications of pregnancy were increased three- to fourfold in women with coarctation. 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 0.3 percent of controls. A total of 41 percent of women with coarctation 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 have recommended that resection of the coarctation be undertaken during pregnancy to protect against the possibility of a dissecting aneurysm and aortic rupture. This poses significant risk, especially for the fetus, because all the collaterals must be clamped for variable periods.
Some authors recommend cesarean delivery to prevent transient blood pressure elevations that might lead to rupture of the aorta or coexisting cerebral aneurysms. Available evidence, however, suggests that cesarean delivery should be limited to obstetrical indications.
ISCHEMIC HEART DISEASE
United States statistics indicate that the mortality rate from coronary heart disease among all women aged 35 to 44 years has been increasing by an average of 1.3 percent per year since 1997 (Ford, 2007). Still, coronary artery disease and myocardial infarction are rare complications of pregnancy. In a review of California hospital discharge records between 1991 and 2000, Ladner and associates (2005) reported myocardial infarction in 2.7 per 100,000 deliveries. James and coworkers (2006) used the Nationwide Inpatient Sample database and reported acute myocardial infarction in 6.2 per 100,000 deliveries. In Canadian hospitals between 1970 and 1998, MacArthur and colleagues (2006) reported the incidence of peripartum myocardial ischemia to be 1.1 per 100,000 deliveries.
Pregnant women with coronary artery disease commonly have classic risk factors such as diabetes, smoking, hypertension, hyperlipidemia, and obesity (James, 2006). As an aside, a large, prospective population-based study from Germany found that women who had experienced recurrent spontaneous abortions or stillbirths were also at a substantially higher risk of myocardial infarction later in life (Kharazmi, 2011). Although the reason(s) for this association were not specifically studied, there are a number of conditions—such as certain thrombophilias—which are associated with both (Chap. 59, p. 1173).
Bagg and colleagues (1999) reviewed the course of 22 diabetic pregnant women with White class H ischemic heart disease (Chap. 57, p. 1126). These and other authors documented unusually high mortality rates in those who suffered myocardial infarction (Pombar, 1995; Reece, 1986). Coronary artery occlusion in two pregnant smokers with hypercholesterolemia has been described following a routine intramuscular injection of 0.5-mg ergometrine (Mousa, 2000; Sutaria, 2000). Finally, Schulte-Sasse (2000) described myocardial ischemia associated with prostaglandin E1 vaginal suppositories for labor induction.
Diagnosis during pregnancy is not different from the nonpregnant patient. Measurement of serum levels of the cardiac-specific contractile protein troponin I provides an accurate diagnosis (Shade, 2002). Troponin I was reported by Shivvers and colleagues (1999) to be undetectable near term (Appendix, p. 1291). Koscica and colleagues (2002) found that levels do not increase following either vaginal or cesarean delivery. Importantly, however, levels of troponin I are higher in preeclamptic women than in normotensive controls (Atalay, 2005; Yang, 2006).
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. Vinatier and associates (1994) reviewed 30 pregnancies in women who had sustained an infarction remote from pregnancy. Although none of these women died, four had congestive heart failure and four had worsening angina during pregnancy. Pombar and coworkers (1995) reviewed 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 increases cardiac workload, and all of these investigators concluded that ventricular performance should be assessed using ventriculography, radionuclide studies, echocardiography, or coronary angiography before conception. If there is no significant ventricular dysfunction, pregnancy will likely be tolerated.
For the woman who becomes pregnant before these studies are performed, echocardiography should be done. Exercise tolerance testing may be indicated, and radionuclide ventriculography results in minimal radiation exposure for the fetus (Chap. 46, p. 932). Zaidi and associates (2008) described the use of serial T2-weighted cardiovascular MR imaging in a woman who suffered a myocardial infarction during the first trimester to better define the extent and severity of infarction.
Myocardial Infarction During Pregnancy
The mortality rate with myocardial infarction in pregnancy is increased compared with age-matched nonpregnant women. Hankins and coworkers (1985) reviewed 68 cases and reported an overall maternal mortality rate of approximately 35 percent. Hands and colleagues (1990) found an overall mortality rate of 30 percent, and this was highest in the third trimester. Later studies are more reassuring. In a Nationwide Inpatient Sample study totaling 859 pregnancies complicated by acute infarction during 2000 to 2002, there was a 5.1-percent death rate (James, 2006). Women who sustain an infarction less than 2 weeks before delivery are at especially high risk of death due to the increased myocardial demand during labor or delivery (Esplin, 1999).
Treatment is similar to that for nonpregnant patients (Maxwell, 2010; Roth, 2008). Acute management includes administration of oxygen, nitroglycerin, low-dose aspirin, heparin, and β-blocking drugs with close blood pressure monitoring. Lidocaine is used to suppress malignant arrhythmias and calcium-channel blockers or β-blockers are given if indicated. Tissue plasminogen activator has been used in pregnant women, but only those remote from delivery because of hemorrhage. In some women, invasive or surgical procedures may be indicated because of acute or unrelenting disease. A number of reports describe successful percutaneous transluminal coronary angioplasty and stent placement during pregnancy (Balmain, 2007; Duarte, 2011; Dwyer, 2005). Cardiopulmonary resuscitation may be required, and maternal and perinatal effects are discussed in Chapter 47 (p. 956).
If the infarct has healed sufficiently, cesarean delivery is reserved for obstetrical indications, and epidural analgesia is ideal for labor (Esplin, 1999).
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