Chapter 33. Cardiovascular Disease in Pregnancy

• Pregnancy.
• History of heart disease.
• Symptoms and signs of heart disease.
• Echocardiographic or other objective evidence of heart disease.

Cardiovascular disease occurs in up to 4% of pregnancies, but the incidence is increasing due to improved prognosis of women with congenital heart disease and a trend toward older maternal age. The unique hemodynamic changes associated with pregnancy make diagnosis and management of heart disease in pregnant patients a challenge to the physicians, who must consider not only the patient but also the risks to the fetus.

In general, the normal hemodynamic changes associated with pregnancy are well tolerated by those who have a normal cardiovascular system, valvular regurgitation, and left-to-right intracardiac shunts. On the other hand, the highest maternal and fetal morbidity and mortality is seen with severe obstructive valvular lesions, severe aortic disease (dilated thoracic aorta or uncorrected coarctation), New York Heart Association (NYHA) class III or IV heart failure, uncontrolled hypertension, and cyanotic congenital heart disease. As a rule, spontaneous vaginal delivery, often with use of vacuum extraction or forceps to facilitate stage 2 of labor to avoid the hemodynamic stress associated with pushing, is preferred. Cesarean section, with few exceptions, should be reserved for obstetric indications.

Normal pregnancy is accompanied by significant physiologic changes, although the specific mechanisms remain virtually unknown (Table 33–1). This increased hemodynamic burden of pregnancy may unmask previously unrecognized heart disease. The normal signs and symptoms associated with pregnancy, such as shortness of breath, fatigue, and exercise intolerance, may obscure the diagnosis of heart disease. The clinician must, therefore, have a thorough knowledge of these normal changes and the aspects of the history and physical examination that suggest the presence of heart disease.

Blood Volume

The increase in maternal blood volume begins as early as the sixth week of pregnancy, peaks at approximately 32 weeks of gestation, and stays at that level (40–50% higher than pregestational levels) until delivery. A rapid rise in blood volume is typically noted until mid-pregnancy, after which the rise is slower. The plasma volume shows a more rapid and significant rise than the red blood cell mass, accounting for the appearance of physiologic anemia during pregnancy. The levels of hemoglobin and hematocrit may be as low as 11 g/dL and 33%, respectively. Iron supplementation may mitigate the drop in hemoglobin. The increased blood volume is maintained until after delivery, when a spontaneous diuresis occurs. At the same time, there is an increased venous return due to the relief of vena caval compression after delivery. These rapid postpartum changes in blood volume are critical for patients with underlying heart disease.

Cardiac Output

One of the most significant changes during pregnancy is the increase in cardiac output, which begins to rise during the first trimester and peaks around the 25th week of gestation and then levels off. Total cardiac output increases up to 50% over pregestational levels. Cardiac output is the product of stroke volume and heart rate. During the early part of pregnancy, the increase in cardiac output is predominantly the result of an increase in stroke volume, augmented by increased intrinsic myocardial contractility. Numerous studies have shown a gradual increase in left ventricular systolic function attributed to left ventricular afterload reduction due to the low-resistance runoff of the placenta. The rise in left ventricular systolic function begins in early pregnancy, peaks in the 20th week, and then remains constant until delivery. As pregnancy advances, heart rate increases and stroke volume mildly decreases. The increased cardiac output in late pregnancy is maintained because of the increased heart rate. The heart rate increase typically peaks around 32 weeks gestation, reaching 15–20 bpm above the prepregnancy heart rate. There is a significantly greater increase in cardiac output in twin gestations compared with singletons.

A unique aspect of pregnancy is the hemodynamic changes induced by a change in a patient's position. When the patient is in the supine position, the gravid uterus induces profound mechanical compression of the inferior vena cava, decreasing venous return to the heart, and thus, cardiac output. A change from the supine to the left lateral position results in a 25–30% increase in cardiac output because of an increase in stroke volume.

Blood Pressure and Vascular Resistance

Systolic and diastolic pressures drop during pregnancy. A small decrease in systolic blood pressure begins in the first trimester, peaks at midgestation, and returns to or exceeds prepregnancy levels at term. The diastolic blood pressure decreases more than the systolic blood pressure, due to a significant fall in systemic vascular resistance, and results in a wider pulse pressure. The systemic blood pressure increases during pregnancy with the patient's age and parity. It also varies with the patient's position. The highest levels are recorded early in the pregnancy when the patient is upright, and the lowest levels occur when she is supine. During the latter part of pregnancy, the effect of position on systemic blood pressure depends on the relative degrees of inferior vena cava and aortic compression. It is recommended to use automated cuff measurements as there may be absence of the fifth Korotkoff sound in some pregnant women. Total vascular resistance, including both the systemic and the pulmonary, decrease during pregnancy. The mechanism for the fall in resistances is poorly understood but is attributed to the low-resistance circulation of the pregnant uterus and to hormonal changes (progesterone and prostaglandin among many) associated with pregnancy. The systemic vascular resistance (SVR) drops approximately 10% in the first trimester and reaches nadir around 20 weeks of gestation with SVR around 35% less than baseline. There is a small increase in SVR toward the end of pregnancy.

Congenital Heart Disease

Because the medical and surgical treatment of uncorrected or surgically corrected congenital heart diseases (CHD) has improved, more women are surviving into adulthood and may become pregnant. It is recommended that patients with CHD consult with a cardiologist experienced in adult CHD and a maternal-fetal specialist before conception. The prevalence of cardiac complications greatly depends on the type of congenital lesion; regurgitant lesions are typically tolerated well, while stenotic lesions carry a higher risk. The risk for all-comers is estimated to be up to 13%, with the predominant symptoms being congestive heart failure/pulmonary edema and arrhythmias. Maternal mortality primarily occurs in women with Eisenmenger syndrome. Obstetric complications are not increased, except in cases of hypertension and thromboembolic disease (2%). Premature delivery occurs in about 16%, and children small for gestational age are also common. Overall, offspring mortality is around 4%. The risk of recurrence of congenital malformations in the offspring depends on the type and ranges from 0.6% to 10%.

Only a few conditions place a patient at a high risk to advise against pregnancy (Table 33–2). High-risk patients with severe cyanotic CHD, marked decreased functional capacity, symptomatic severe obstructive lesions, or Eisenmenger syndrome should be advised against pregnancy.

Acyanotic Heart Disease

Atrial Septal Defect

Secundum atrial septal defect is the most common congenital cardiac abnormality encountered during pregnancy. Patients with uncomplicated atrial septal defects usually tolerate pregnancy with little problem. Patients may not be able to tolerate the acute blood loss that can occur at the time of delivery because of increased shunting from left to right caused by systemic vasoconstriction associated with hypotension. Patients with symptomatic or hemodynamically significant lesions should have these closed percutaneously or surgically prior to pregnancy to decrease the incidence of thromboembolism and arrhythmias. Percutaneous closure can be performed during pregnancy but is reserved for decompensated patients. The incidence of supraventricular arrhythmias may increase in older pregnant patients, which may result in right ventricular failure and venous stasis leading to paradoxical emboli. Low-dose aspirin, once daily after the first trimester until delivery, may help prevent clot formation. Patients should use compressive stockings, and all intravenous lines should have air filters. Pulmonary hypertension from an atrial septal defect usually occurs late in life, past the childbearing years. However, if there is severe pulmonary hypertension (Eisenmenger syndrome), pregnancy should be avoided. Bacterial endocarditis prophylaxis is not recommended. Vaginal delivery is preferred over cesarean section. Risk of CHD in the offspring is estimated to be 8–10%.

Ventricular Septal Defect

Most isolated ventricular septal defects have closed by adulthood. Women with ventricular septal defects generally fare well in pregnancy if the defect is small and pulmonary artery pressure is normal. Congestive heart failure and arrhythmia are reported only in patients with decreased left ventricular systolic function prior to pregnancy. Endocarditis prophylaxis during delivery is not recommended. Air filters should be used on intravenous lines to avoid paradoxic embolism. Large ventricular septal defects with pulmonary hypertension are a contraindication to pregnancy.

Atrioventricular Septal Defect (Endocardial Cushion Defect)

This defect includes a large central defect that may lie above the valve (atrial septal defect) or may extend to variable degrees above and below the atrioventricular valve. The defect can therefore be small or large. Many of these are repaired in childhood. While most complete atrioventricular canal defects are seen in Down syndrome, most partial defects are seen in non–Down syndrome patients. Adult patients without repair may be asymptomatic or may have symptoms of congestive heart failure, arrhythmias, and pulmonary hypertension with cyanosis. The key to good pregnancy outcome is exclusion of hemodynamically significant residual lesions, pulmonary hypertension, and cyanosis prior to conception. Trisomy 21 patients have a 50% risk of transmitting trisomy 21 and other genetic defects to their offspring.

Congenital Aortic Stenosis

This is most commonly caused by a congenital bicuspid aortic valve. The prevalence in the general population is 1–2% but may be as high as 9–21% in some families, where the condition appears to be autosomal dominant with reduced penetrance. The condition is usually more common in men (2:1 ratio). In patients with congenital aortic stenosis, the outcome during pregnancy depends on the severity of the obstruction. Pregnancy is usually well tolerated in mild-to-moderate aortic stenosis (aortic valve area [AVA] 1.0–2.0 cm2). Patients with severe aortic stenosis with a valve area of < 1.0 cm2 and mean transvalvular gradients greater than 40 mm Hg may experience an increased risk of complications (from 10–44%), although death is very rare, and fetal morbidity is increased. The increased cardiac output and decreased SVR of pregnancy creates an additional hemodynamic burden in these patients. Syncope, cerebral symptoms, dyspnea, angina pectoris, and even heart failure may occur for the first time during pregnancy. Ideally valve replacement should be performed before pregnancy in symptomatic patients with severe aortic stenosis or if the left ventricular ejection fraction is below 50%. Valvuloplasty, if needed, is preferred over surgery during pregnancy. As part of the bicuspid aortic valve syndrome, the aortic root often will be dilated, evidence that the condition is not only a disease of the valve but of the connective tissue as well. When the aortic root is dilated, there is an increased risk of aortic dissection during pregnancy, and such events have been reported when the aorta is greater than 40 mm, although the true incidence is unknown. The risk of aortic dissection is higher than in the general population but not as high as in Marfan syndrome. Current guidelines would advise counseling and consideration for prophylactic aortic root repair if the aorta exceeds 45 mm. Obtaining serial echocardiograms at least every 3 months to monitor progression of root dilatation appears prudent. Hemodynamic monitoring during labor and delivery should be performed in patients with moderate-to-severe aortic stenosis. Endocarditis prophylaxis is not recommended for vaginal delivery. Cesarean section is recommended in the presence of critical aortic stenosis, aortic aneurysm, or dissection. The risk for the condition in the offspring is variable but at least 4%.

Pulmonic Stenosis

The natural history of pulmonic stenosis favors survival into adulthood even with severe obstruction to right ventricular outflow. Mild-to-moderate pulmonic stenosis (mean gradient < 40 mm Hg) usually presents no increased risk during pregnancy. Patients with severe pulmonic stenosis may occasionally tolerate pregnancy without the development of congestive heart failure. Vaginal delivery is tolerated well. Ideal treatment consisting of balloon valvuloplasty should be performed before conception but may be performed safely during pregnancy if necessary. The risk in the offspring is about 3.5%.

Coarctation of the Aorta

In uncomplicated coarctation of the aorta, pregnancy is usually safe for the mother but may be associated with fetal underdevelopment because of the diminished uterine blood flow. The blood pressure may decrease slightly, as during normal pregnancy, but still remains elevated. Maternal deaths in these patients are usually the result of aortic rupture or cerebral hemorrhage from an associated berry aneurysm of the circle of Willis. Patients with the greatest risk during pregnancy are those with severe hypertension or associated cardiac abnormalities, such as bicuspid aortic valves. Treatment consists of limitation of physical activity and maintenance of systolic blood pressure around 140 mm Hg for fetal circulation; β-blockers are preferred and should be continued through delivery. Generally, vaginal deliveries are recommended unless there are obstetric indications for a cesarean delivery. Good pain management for labor and delivery is very important in order to minimize maternal cardiac stress and help to control blood pressure. In cases of severe gradient across the coarctation or associated bicuspid valve with dilated aorta, cesarean section should be considered. Surgical treatment should be reserved for patients in whom complications develop (eg, aortic dissection, uncontrollable hypertension, and refractory heart failure).

Patent Ductus Arteriosus

Most patients with a patent ductus arteriosus undergo repair in childhood. A normal pregnancy can be expected in patients with small-to-moderate shunts and no evidence of pulmonary hypertension. Patients with a large patent ductus arteriosus, elevated pulmonary vascular resistance, and a reversed shunt are at greatest risk for complications during pregnancy. The decreased SVR associated with pregnancy increases the right-to-left shunt and may cause intrauterine oxygen desaturation. Patients in whom heart failure develops are treated with digoxin and diuretics. Closure of the patent ductus arteriosus may be done safely during pregnancy using a percutaneous ductal occluder device. The preferred mode of delivery is vaginal in most patients, with hemodynamic monitoring considered at the time of delivery. The risk of patent ductus arteriosus occurring in an offspring is about 4%.

Cyanotic Heart Disease

Tetralogy of Fallot

This is the most common cyanotic CHD found in pregnant patients. The syndrome consists of pulmonary stenosis, right ventricular hypertrophy, an overriding aorta, and a ventricular septal defect. The decrease in SVR, the increased cardiac output, and the increased venous return to the right heart augment the amount of right-to-left shunt and further decrease the systemic arterial saturation. Acute blood loss during postpartum hemorrhage is particularly dangerous because venous return to the right heart is impaired. The labile hemodynamics during labor and the peripartum period may precipitate cyanosis, syncope, and even death in surgically untreated women. Patients with uncorrected or partially corrected tetralogy of Fallot are advised against becoming pregnant because they have a high rate of miscarriages (12–40%) as well as a high risk of heart failure (15–25%), arrhythmias (5%) and stroke, myocardial infarction (MI), or death (4–34%). Patients who have had good surgical repair with no important hemodynamic residual lesions and good functional capacity may anticipate successful pregnancies, although the risk of arrhythmias may be increased. Pregnancy is usually well tolerated even in the setting of severe pulmonary regurgitation, as long as right ventricular function is no more than mildly depressed and sinus rhythm is maintained. Antibiotic prophylaxis is recommended for patients with uncorrected tetralogy of Fallot and those in whom prosthetic material has been placed within 6 months. Screening for 22q11.2 microdeletion should be considered in patients with conotruncal abnormalities before pregnancy to provide appropriate genetic counseling. In the absence of a 22q11 deletion, the risk of a fetus having CHD is approximately 4–6%. Fetal echocardiography should be offered to the mother in the second trimester.

Transposition of the Great Arteries (TGA)

TGA implies that each great artery arises from the wrong ventricle. TGA is atrioventricular concordance with ventriculoarterial discordance, and the aorta arises from the systemic right ventricle while the pulmonary artery arises from the nonsystemic left ventricle. Most adults born with TGA will have had one or more operations in childhood. Comprehensive evaluation is recommended before pregnancy in all patients with TGA and prior repair. The risk of pregnancy depends on the type(s) of repair. For patients after atrial baffle, major prepregnancy concerns include ventricular function assessment, systemic atrioventricular regurgitation, and atrial arrhythmias. The physiologic stresses of pregnancy, although clinically well tolerated late after an atrial baffle procedure, carry an increased risk of right ventricular dysfunction that may be irreversible. Isolated reports are available on the outcome of pregnancy after the arterial switch procedure: In the absence of important cardiovascular residua, pregnancy is well tolerated. A comprehensive anatomic and functional assessment, including assessment of coronary artery anatomy, is recommended before a patient proceeds with pregnancy. Patients who had the atrial baffle should have antibiotic prophylaxis before vaginal delivery.

Eisenmenger Syndrome

This syndrome may occur due to several types of CHD and is characterized by systemic-level pulmonary hypertension with right-to-left or bidirectional shunt with deoxygenation. The right-to-left shunt and deoxygenation will increase with the decrease in SVR occurring with pregnancy. The risk of maternal and fetal morbidity and mortality is so high that patients are advised against becoming pregnant. There is a 35% chance of death in the mother and 15–30% chance of offspring mortality.

Surgically Corrected Congenital Heart Disease

The obstetric care of patients who have had surgical correction of a CHD requires an understanding of the type of surgical procedure, the sequelae, and the hemodynamic consequences. Although atrial flutter may occasionally develop following surgical closure, the successful closure of an uncomplicated atrial septal defect results in no increased maternal risk during pregnancy. Surgical closure of a patent ductus arteriosus that is not associated with pulmonary hypertension is also not associated with maternal complications during pregnancy. In pulmonary hypertension that develops before surgical closure, the decrease in the pulmonary vascular resistance may not be complete, and complications during pregnancy will depend on its severity. Correction of congenital pulmonary stenosis with either surgery or balloon dilatation that leaves little or no transvalvular gradient presents no difficulty to pregnant patients. Surgical correction of coarctation of the aorta with complete relief of the obstruction decreases the development of associated hypertension and the risk of aortic rupture during pregnancy. Successful repair of tetralogy of Fallot with little residual gradient across the pulmonary outflow tract and relief of the cyanosis should result, with careful management, in a normal pregnancy. Pregnancy after repair of complex CHD is increasingly encountered. In such patients, the outcome depends on the mother's functional status, the type of repair, the sequelae, and the cardiovascular response to an increase in stress.

Valvular Heart Disease

No randomized controlled trial data are available to guide decision making for pregnant women with valvular heart disease. However, many patients with valvular heart disease can be treated successfully through their pregnancy with conservative medical treatment, focusing on optimization of intravascular volume and systemic load. Ideally, symptomatic patients should be treated before conception. Drugs, in general, should be avoided whenever possible. Antibiotics for infective endocarditis prophylaxis for uncomplicated vaginal delivery are not indicated, unless a prosthetic valve was placed within 6 months. Although there are few supportive data, antibiotic prophylaxis is often given for complicated vaginal deliveries.

Mitral Valve Disease

Mitral Stenosis

Mitral stenosis is the most commonly encountered acquired valvular lesion in pregnancy and is almost always caused by rheumatic heart disease. Mitral stenosis may be first diagnosed during pregnancy and is the valvular disorder most likely to develop serious complications during pregnancy. Increased left atrial pressure and even pulmonary edema due to a decrease in diastolic filling time during the tachycardia of pregnancy may develop in women who were previously asymptomatic. In critical mitral stenosis, due to a large diastolic gradient (even at rest), any demand of increased cardiac output results in a significant elevation in the left atrial pressure and pulmonary edema. The most common symptoms include dyspnea, fatigue, orthopnea, and dizziness or syncope, symptoms that may be difficult to distinguish from normal effects of pregnancy. Signs and symptoms of mitral stenosis may develop for the first time during pregnancy. The greatest danger is in late pregnancy and labor due to increased heart rate and cardiac output, blood volume expansion, and intensified oxygen demand. Pulmonary edema may occur immediately after delivery even after uncomplicated labor when the blood returns from the decompressed inferior vena cava. Mild-to-moderate mitral stenosis (mean diastolic pressure gradient < 10 mm Hg) may be managed safely with the use of diuretics to relieve pulmonary and systemic congestion and β-blockers to prevent tachycardia to optimize diastolic filling. If diuretics are needed before the third trimester, then there is a high chance that additional measures such as balloon dilatation, commissurotomy, or early delivery may be needed, and close follow-up is needed. Diuretics, β-blockers, digoxin, or direct-current cardioversion for atrial fibrillation should be instituted in cases of hemodynamic compromise, taking into consideration maternal safety. Refractory cases and patients with severe mitral stenosis with heart failure and those with significant pulmonary hypertension prompt mechanical relief, either by percutaneous balloon valvuloplasty or surgery, preferably before conception. Patients with a history of acute rheumatic fever and carditis should continue receiving penicillin prophylaxis.

Mitral Regurgitation

Mitral regurgitation (most commonly due to mitral valve prolapse) in the absence of NYHA class III or IV heart failure symptoms is generally tolerated well during pregnancy, even if severe. The decrease in systemic blood pressure in pregnancy may reduce the amount of mitral regurgitation. Left ventricular dysfunction, if severe, may precipitate heart failure. Medical management includes use of diuretics; in rare instances, surgical management is necessary, preferably mitral valve repair, which is indicated for severe, acute regurgitation or ruptured chordae and uncontrollable heart failure symptoms. In the future, percutaneous mitral valve repair may be an option for severe, symptomatic mitral regurgitation during pregnancy.

Mitral Valve Prolapse

Mitral valve prolapse is the most common heart disease encountered in pregnancy. Patients without comorbidity, such as a connective tissue, skeletal, or other cardiovascular disorders, tolerate pregnancy. The click and murmur become less prominent during pregnancy. No special precautions for isolated mitral valve prolapse are required. Antibiotic prophylaxis is not recommended. The incidence of complications of the mitral valve prolapse (3%) is similar in pregnant and nonpregnant patients.

Aortic Valve Disease

Aortic Stenosis

Aortic stenosis in pregnancy is most commonly caused by a congenital bicuspid aortic valve (see previous section).

Aortic Regurgitation

Isolated chronic aortic regurgitation without left ventricular dysfunction is usually tolerated well. Even if patients are symptomatic, they can often be treated medically with salt restriction, diuretics, and vasodilators. The most common causes are rheumatic disease, bicuspid aortic valve, endocarditis, and a dilated aortic root. Surgery is only indicated for patients with refractory (NYHA class III or IV) symptoms. Acute aortic regurgitation, as in nonpregnancy, is not well tolerated and should be regarded as a surgical emergency.

Pulmonic and Tricuspid Valve Disease

Pulmonic Valve Regurgitation

Pulmonic valve regurgitation may occur in isolation or in combination with other heart lesions. Isolated pulmonic regurgitation can be managed conservatively.

Tricuspid Valve Disease

Tricuspid valve disease may be congenital or acquired. Isolated tricuspid valve disease can be managed successfully with diuretics. Special care should be given to diuretic-induced hypoperfusion.

Prosthetic Heart Valves

Females with a prosthetic heart valve can usually tolerate the hemodynamic burden of pregnancy without difficulty. The function of the prosthesis can be evaluated and monitored throughout the pregnancy with noninvasive Doppler echocardiography. Two types of heart valves are available with their own distinct risks and advantages: tissue valves and mechanical prostheses. The main differences between the types are durability, risk of thromboembolism, valve hemodynamics, and effect on fetal outcome.

Tissue valves (bioprostheses) may be selected for a pregnant patient to avoid anticoagulation and risk of thromboembolism and should be considered in women of childbearing age who desire a pregnancy if there are no other indications for anticoagulation and if the patient accepts the eventual need for replacement of the prosthesis. Bioprostheses in young women in general are associated with an increased risk of structural valve deterioration. Recent data suggest that this risk is not further increased with pregnancy. The risk of failure is estimated to be at least 50% in 10 years and higher if in the mitral position. Therefore, most women of childbearing age will need reoperation, and the risk of a second open-heart surgery should be considered when discussing the risk with the patient. The newer pericardial bioprostheses may offer better durability, but not enough data are available at the moment to make an estimate of the risk. Homografts appear to have a very low risk of failure even in younger patients and also offer superior hemodynamic profiles over other valves and should therefore be considered when possible.

Mechanical valves are indicated in pregnant patients with other coexisting heart disorders requiring anticoagulation (eg, atrial fibrillation, apical thrombus, or history of thromboembolism). Maternal thromboembolism complicates 4–14% of pregnancies in women with mechanical valves despite a therapeutic international normalized ratio (INR), with a reported mortality of 1–4%. This complication is more likely in patients with the older generation valves (caged-ball, tilting disk) in the mitral position but is also reported in the newer bileaflet valves. The choice of prosthetic valve and the safe method of anticoagulation are, therefore, still of concern in pregnant patients and need further study.

Unfortunately, significant maternal and fetal risk of either hemorrhage or thrombosis with the accompanying use of warfarin or heparin remains a major problem. The decision on the choice of anticoagulation should therefore be made with both the patient and the physician after full discussion of potential risks and benefits, and the risk of pregnancy in patients with prosthetic heart valves should be discussed in detail with the patient and the family prior to conception.

The incidence of warfarin embryopathy (nasal hypoplasia, hypoplasia of extremities, and mental retardation) is estimated to be 5–30% when the fetus is exposed during the critical period of organogenesis between the fourth and eighth gestational weeks. The risk of miscarriage and still birth is estimated to be 15–56%, depending on the series. Some studies indicate that the risk may be very low if the woman can be controlled on 5 mg or less of warfarin, and the earlier studies reporting a very high incidence of adverse effects may have been with the use of higher doses. Unfractionated heparin, which does not cross the placenta, is believed to be safe for use during pregnancy; however, due to increase in plasma volume and increased renal excretion, the drug needs to be administered in higher doses and with increased frequency. There is a small risk of osteopenia resulting in fractures and in heparin-induced thrombocytopenia. Low-molecular-weight heparin (LMWH) may provide an advantage in terms of less bleeding and a more predictable response. There is increasing evidence that LMWH can be used for prevention of mechanical valve thrombosis during pregnancy. To adequately prevent thrombosis and prevent bleeding, both peak and trough anti-Xa levels should be measured (Table 33–3), and compliance with dosing is of utmost importance. In almost every instance of reported valve thrombosis with LMWH, subtherapeutic anti-Xa levels were found. Anti-Xa activity should be measured once weekly for the first 4 weeks and later at least once every 2 weeks. High-risk cases may benefit from addition of low-dose aspirin. Table 33–3 shows a recommended regimen for anticoagulation in mechanical prosthetic heart valves taking into account the risk of the patient as well as the risk of side effects from the drugs. Patients with prosthetic heart valves should be managed by cardiologists and obstetricians experienced with this high-risk group.

Infective Endocarditis

Underlying structural abnormalities of the heart predispose patients to the development of infective endocarditis. The most common cause is rheumatic heart disease, with others being mitral valve prolapse, injecting drug abuse, and iatrogenic procedures. The estimated incidence of infective endocarditis during pregnancy is 0.005–1.0% of all pregnancies. Although it is rare, the development of infective endocarditis during pregnancy can have devastating consequences, with maternal and fetal mortality rates estimated to be 22% and 15%, respectively. The clinical diagnosis and the management of infective endocarditis in pregnancy are the same as for nonpregnant patients (see Chapter 22); however, special consideration must be given to the diagnostic and therapeutic approaches during pregnancy to reduce the risk to the fetus.

Rheumatic Heart Disease

Despite an overall decline in the incidence of rheumatic heart disease in Europe and North America, rheumatic valvular disease remains common in women of childbearing age.

The cardiac involvement in acute rheumatic fever is a pancarditis involving the endocardium, myocardium, and pericardium. It is the involvement of the endocardium, including the valvular and the subvalvular apparatus, that gives rise to the acute manifestations as well as causes the development of chronic rheumatic valvular heart disease. The specific valvular conditions are described in previous sections. The mitral valve is most commonly affected, followed by the aortic valve, and less frequently the tricuspid and pulmonic valves.

Mild rheumatic fever may be difficult to diagnose in pregnancy due to tachycardia, functional murmur, and anemia. The management of acute rheumatic fever is similar in pregnant and nonpregnant patients and consists of bed rest, anemia correction, and penicillin. In severe cases, vasodilators, positive inotropes, or even surgery may be required. Echocardiography can be performed safely during pregnancy to delineate myocardial and heart valve function.

Myocarditis

This inflammatory process is either focal or diffuse and involves the heart musculature. Of all the infectious and noninfectious causes, viral infection with enterovirus, most commonly coxsackie B virus, accounts for most of the cases, but adenovirus, parvovirus B19, cytomegalovirus, Herpesviridae family, and more lately H1/N1 influenza virus have been implicated. Acute rheumatic fever is discussed in the previous section. Other important causes include acquired immunodeficiency syndrome (AIDS) and Chagas disease due to Trypanosoma cruzi, which is the most common cause in South and Central America. Only a few cases of myocarditis have been reported in pregnancy. Clinical manifestations range from incidental finding of silent myocarditis to overt heart failure with hemodynamic collapse. In the acute stage, the electrocardiogram (ECG) is almost always abnormal, showing Q waves with ST- and T-wave changes, which may mimic acute MI. The erythrocyte sedimentation rate (ESR) and cardiac enzymes are usually elevated. Viral cultures may or may not be helpful. Noninvasive imaging studies may reveal regional wall motion abnormalities. Although endomyocardial biopsy is the gold standard for the diagnosis of myocarditis, a negative result does not rule it out, and rarely does the biopsy aid in diagnosing the etiology or guide management. Therefore, endomyocardial biopsy is not routinely recommended. All pregnant women in whom myocarditis is suspected should be hospitalized. Therapy is supportive, with bed rest; avoidance of strenuous activity; and treatment of heart failure with digoxin, diuretics, and vasodilators. Angiotensin-converting enzyme (ACE) inhibitors should be avoided because of the risk of fetal anomalies. Administration of corticosteroids and immunosuppressive therapy has been controversial and has demonstrated no proven benefit. Potential complications of myocarditis include arrhythmia, heart blocks, and cardiogenic shock. Anticoagulation should be seriously considered, especially for patients with severe left ventricular dysfunction.

Cardiomyopathy

Peripartum Cardiomyopathy (PPCM)

This rare but distinct form of heart failure with left ventricular dysfunction occurs during pregnancy or postpartum. Classically, it is described as occurring between the last month of pregnancy and 5 months postpartum, but cases that do not appear different have been reported from week 17 of pregnancy to 6 months postpartum. PPCM remains a diagnosis of exclusion. The prevalence appears to be increasing, but this is most likely due to increased diagnosis with the common use of echocardiography. Its estimated incidence in the United States is 1 in 2000–4000 deliveries and is higher in other countries such as South Africa (1 in 1000) and Haiti (1 in 300). Its cause is unknown but is probably multifactorial. Risk factors include age greater than 30 years, patients with history of hypertension and preeclampsia, twin (or greater) pregnancies, and African American women in the United States. Histopathology reveals a dilated heart with pale myocardium, but myocardial biopsy is of little value. Because signs and symptoms of normal pregnancy resemble heart failure, PPCM is easily missed or diagnosed late in the course. PPCM usually presents with dyspnea, cough, orthopnea, paroxysmal nocturnal dyspnea, fatigue, palpitations, and chest pain. Echocardiography is central to diagnosis. The echocardiogram demonstrates dilated left ventricle with marked overall impairment of systolic function. Pulmonary artery catheter placement should be considered for optimized treatment of these patients. Medical therapy is essentially supportive and similar to that for other forms of heart failure and includes salt restriction, diuretics, digoxin, and afterload reduction with hydralazine (the drug of choice). ACE inhibitors are contraindicated during pregnancy because of associated fetal central nervous system anomalies but can be used after delivery. There is no good evidence for the use of immunoglobulin, although it has been tried in some small trials. A possible promising specific treatment is the use of bromocriptine, a prolactin antagonist. It is believed that the increased oxidative stress as seen with PPCM transforms prolactin to an antiangiogenic and proapoptotic protein with harmful effect on the microvasculature. A small South African study demonstrated improved outcome, and it is expected this may be followed by larger trials in other geographic locations. Heparin should seriously be considered for treating possible thromboembolic phenomena in pregnant patients with very low left ventricular ejection fraction (< 35%). In cases refractory to medical therapy, use of an intra-aortic balloon pump for temporary stabilization and left ventricular assist device as a bridge to transplant is indicated.

Most patients recover partially or even completely, typically within 2–6 months after delivery. There is distinct geographical variation in the rate of recovery, which appears to be at least 50% in the United States but no more than 20–40% in other countries and in women of African American descent. Mortality rates also vary, and recent data from the United States estimate a mortality rate of 0–19%. Mortality in other regions appears higher (15–40%). There is an increased risk of death with increasing age, multiparity, and African American ethnicity and when diagnosis is delayed. Women with a history of PPCM have a significant risk of deleterious fetal and maternal outcome in subsequent pregnancies, even if their left ventricular function has returned to normal. The risk in subsequent pregnancies is around 20% if left ventricular systolic function is normal and around 45% if function has not recovered. Patients who have had fulminant courses and whose left ventricular function has remained depressed should be advised against becoming pregnant again. Women with severe symptoms refractory to medical therapy should terminate the pregnancy as this often results in improvement of symptoms and cardiac function. Recovery of left ventricular function may continue beyond 6 months, and repeat echocardiograms are recommended.

Hypertrophic Cardiomyopathy

This primary myocardial disease shows a characteristic hypertrophy of the left or right ventricular myocardium. The hypertrophy is asymmetric and most commonly involves the intraventricular septum (asymmetric septal hypertrophy). Pathophysiologic mechanisms include presence of a hyperdynamic left ventricle, obstruction of left ventricular outflow tract, mitral regurgitation, and myocardial ischemia. Prevalence in the young population (age 23–35 years) is 2 per 1000. A large number of patients are asymptomatic. Severe illness is manifested by poor functional capacity, heart failure, and sudden death.

Dyspnea is the most common symptom, with others being chest pain (which may be postprandial), dizziness, syncope, and palpitations. In younger patients, sudden death may be the first manifestation, with an annual incidence in the population being 6%. Physical examination varies from normal to characteristic findings in patients with high gradients. The auscultatory hallmark is a diamond-shaped, grade 3–4/6 systolic murmur, heard best at apex radiating to the left sternal border. The murmur increases in intensity during the strain phase of the Valsalva maneuver. Electrocardiogram shows ventricular hypertrophy, ST and T changes, and Q waves in inferolateral leads. Ventricular arrhythmias are commonly seen on Holter monitoring. Echocardiography diagnostically demonstrates asymmetric septal hypertrophy (with a ratio of septum to posterior wall thickening exceeding 1.5) and decreased septal motion.

Most patients do well during pregnancy. High-risk pregnant patients with a higher likelihood of worsening symptoms during pregnancy include those who were symptomatic prior to pregnancy and asymptomatic patients with left ventricular dysfunction. Increased incidence of supraventricular as well as ventricular arrhythmia in pregnancy has been reported. Maternal hypertrophic cardiomyopathy does not influence fetal outcome, although in about half of the patients, it is familial with autosomal dominant inheritance and confers a 50% risk for affecting the child. Genetic counseling is therefore recommended, and a detailed discussion regarding risks and a thorough evaluation of the patient are required prior to conception.

In asymptomatic patients, outcome is usually good, but close monitoring is recommended. Therapy needs to be individualized in symptomatic patients. β-Blockers have been used most frequently and relatively safely in symptomatic patients but are not recommended for routine use. Of the calcium channel blockers, verapamil has been used sporadically in pregnant patients. Dual-chamber pacing for arrhythmia has been shown to be beneficial but is reserved for severely symptomatic cases refractory to medical therapy. Surgical myectomy has not yet been reported in pregnancy. Atrial fibrillation occurs in 10% of the patients, leading to an increased risk of systemic emboli and hemodynamic worsening. Sotalol, procainamide, and direct-current cardioversion have all been used to treat pregnant patients. Prophylactic placement of an implantable cardioverter-defibrillator should be considered in patients with high-risk features similar to nonpregnant patients. Alcohol septal ablation may reduce symptoms but does not alter prognosis. Hemodynamic monitoring with a pulmonary catheter is recommended for clinical deterioration encountered during labor and delivery and should be considered even in asymptomatic patients. Fortunately, the strain of vaginal delivery is well tolerated in women with hypertrophic cardiomyopathy. Cesarean section is reserved for obstetric indications. Epidural anesthesia should be avoided. Magnesium should be used for tocolysis if needed.

Coronary Artery Disease

Coronary artery disease is a leading cause of death in women in the United States. Coronary artery disease kills more women than the next 16 leading causes of death combined. The incidence of MI during pregnancy and postpartum is estimated to be 3–7 in 100,000 and predominantly antepartum or intrapartum. Because of a trend toward older childbearing age, the incidence of coronary artery disease may be increasing. Earlier studies reported a mortality rate of 37–50% due to MI during pregnancy. However, recent data suggest the rate is much lower at 5–11%, possibly due to improved diagnosis and use of percutaneous coronary intervention in acute coronary syndromes during pregnancy. It is not clear if pregnancy itself increased the risk of MI. The known risk factors include age (30-fold increased if older than 40 years compared with younger than 20 years), hypertension, diabetes mellitus, smoking, and thrombophilia (Table 33–4). The causes of MI in pregnancy include atherosclerosis, congenital lesions (anomalous origin of coronary artery), inflammatory diseases of coronary arteries (Kawasaki disease), connective tissue (eg, Ehlers-Danlos) or vasospastic disorders, and spontaneous coronary artery dissection, which may account for up to 30% of cases. Only around 40% of the women who undergo coronary angiography will have atherosclerotic lesions as a cause of the MI. Coronary artery dissections may be seen at any time during the pregnancy but are much more common in the peripartum period (50%) or postpartum (34%). Most MIs that occur during pregnancy are anterior and transmural, involving the left anterior descending artery. Successful treatment of acute MI during pregnancy with thrombolytic therapy has been reported, but given the risk of placental and fetal bleeding, percutaneous coronary intervention is the preferred treatment for acute ST elevation MI in pregnancy. When percutaneous coronary intervention is indicated, bare-metal stents should be used. β-Blockers are the mainstay of medical therapy. Non-ST elevation acute coronary syndromes should be managed conservatively unless there are high-risk features where angiography may be considered. While coronary artery bypass grafting carries similar risk for the woman as in nonpregnancy, there is an increased risk of fetal mortality (10–19%). The most common presentation is angina pectoris. Patients with a high index of suspicion should undergo a stress test for risk stratification. Due to risk to the fetus, submaximal exercise at 70% of maximum predicted heart rate is recommended, preferably with fetal monitoring. Left ventricular function needs to be assessed to determine the choice of therapy and predict likelihood of survival. The normal physiologic changes of pregnancy may precipitate myocardial ischemia and heart failure in women with left ventricular impairment caused by an infarct. Troponin I remains the most useful marker for monitoring pregnant women for a myocardial injury because it is undetectable during normal labor and delivery, although women with preeclampsia and gestational hypertension may have mildly elevated levels. Lipid-lowering drugs of the statin type are contraindicated during pregnancy due to reported teratogenicity, and the risk clearly outweighs the potential benefit. Efforts should be made to limit myocardial oxygen consumption, particularly during late pregnancy and delivery, in women with known coronary artery disease.

Arrhythmias

Most arrhythmias occurring during pregnancy are benign. Sinus tachycardia, sinus arrhythmia, sinus bradycardia, atrial premature beats, and ventricular premature beats are very common during pregnancy. These are easily diagnosed using standard diagnostic tools such as 12-lead ECG and Holter monitoring. These arrhythmias are hemodynamically insignificant and require no treatment, and the patient can be reassured of their innocence. The occurrence of more complex arrhythmias should, however, raise the suspicion of underlying cardiac disease. Symptomatic arrhythmias, which are rare during pregnancy, may develop during an otherwise uncomplicated pregnancy or in association with underlying cardiac disease. In fact, cardiac arrhythmias may be the first manifestation of cardiac disease during pregnancy.

Supraventricular Arrhythmias

Paroxysmal Supraventricular Tachycardia

The most common arrhythmia encountered during pregnancy is paroxysmal supraventricular tachycardia (PSVT), either atrioventricular nodal reentry tachycardia or resulting from an accessory pathway (see below); it has been estimated to occur in approximately 3% of pregnant patients. In patients with a previous history of PSVT, the frequency and severity of the episodes may increase during pregnancy. The symptoms of PSVT are dyspnea, lightheadedness, and anxiety in patients without underlying cardiac disease. In patients with underlying cardiac abnormalities, angina, heart failure, and syncope may occur as a result of myocardial ischemia and decreased cardiac output. Although there is concern about the effects of hypotension on the fetus during these episodes, women with PSVT do not have an increase in perinatal complications. Patients should have an echocardiogram to excluded structural heart disease. The Valsalva maneuver and carotid massage are less effective in pregnant women as compared with nonpregnant women. Intravenous adenosine, verapamil, or metoprolol are all effective in terminating the tachycardia. Maintenance therapy should only be considered if the arrhythmia is recurrent, and then verapamil or metoprolol may be a good choice. Ablation procedures should be avoided during pregnancy due to the radiation risk on the fetus.

Atrial Flutter and Atrial Fibrillation

Atrial flutter, which is uncommon during pregnancy, and atrial fibrillation are usually found in patients with underlying cardiac disease. The hemodynamic consequences and the associated symptoms depend on the underlying cardiac status and the ventricular rate during the tachycardia. During pregnancy, atrial fibrillation is most commonly found in association with mitral stenosis. The development of this arrhythmia in these patients may precipitate congestive heart failure and embolic events. Consideration should be given to anticoagulation therapy if persistent. β-Blockers, verapamil, and digoxin are preferred for long-term rate control, whereas verapamil, metoprolol, or diltiazem usually will slow the heart rate acutely.

Wolff-Parkinson-White Syndrome

This preexcitation syndrome usually occurs in patients without underlying cardiac disease. Patients with Wolff-Parkinson-White (WPW) syndrome may have recurrent arrhythmias—most commonly, atrioventricular reentry tachycardia, atrial fibrillation, or atrial flutter. The hemodynamic effects of the associated arrhythmias are related to the type of arrhythmia and the ventricular rate. Many patients with WPW syndrome are asymptomatic, but pregnancy is associated with an increased incidence of arrhythmias in women with this syndrome. WPW may present with an irregular wide complex tachycardia, which is best treated with procainamide.

Ventricular Arrhythmias

Premature Ventricular Complexes

Premature ventricular complexes (PVCs) are relatively common in pregnant women and may be associated with complaints of palpitations. Pregnant women with PVCs and no underlying cardiac disease have an excellent prognosis and require no treatment. Reassurance to the patient is frequently all that is required, along with avoidance of such aggravating factors as smoking and stimulants.

Ventricular Tachycardia

Defined as the occurrence of three or more consecutive ventricular complexes, ventricular tachycardia is a serious cardiac arrhythmia that, if sustained, can lead to death. Ventricular tachycardia is rare during pregnancy, but when it occurs, it is usually associated with underlying cardiac disease. The most common cardiac abnormalities associated with ventricular tachycardia are mitral valve prolapse, valvular disease, and cardiomyopathy. The prognosis for patients with nonsustained ventricular tachycardia (< 30 seconds in duration) and no underlying cardiac disease is excellent. In such patients, the ventricular tachycardia is catecholamine-sensitive, and extreme exercise should be avoided. In some patients, therapy with β-adrenergic blocking drugs may be indicated. Sustained ventricular tachycardia (> 30 seconds in duration) or hemodynamically significant ventricular tachycardia is usually associated with underlying cardiac disease, and therapy with antiarrhythmics is usually indicated. Such patients should also undergo evaluation for such precipitating factors as myocardial ischemia, electrolyte imbalance, congestive heart failure, digitalis intoxication, stimulants, and hypoxia. Drugs that can be used are procainamide, lidocaine, or sotalol. Amiodarone should be avoided. In hemodynamically unstable patients, immediate direct-current cardioversion should be performed. Patients with aborted sudden death, syncopal ventricular tachycardia, or ventricular fibrillation or flutter should have an implantable cardioverter-defibrillator implanted, preferably under echocardiographic guidance.

Heart Blocks

First-degree heart block is evident as PR prolongation on the ECG and results from an increased time of conduction through the atrioventricular junction. First-degree heart block is primarily associated with rheumatic heart disease or digitalis therapy and does not usually require therapy. Second-degree heart block can be divided into two types: Mobitz type I (Wenckebach) and Mobitz type II. Mobitz type I is characterized by progressive lengthening of the PR interval until an impulse is blocked. It is a relatively benign disorder and occurs when vagal tone is increased. Treatment is seldom indicated. Mobitz type II is a sudden block of conduction without previous prolongation of the PR interval. It often precedes the development of complete heart block. It is rare during pregnancy but may occur in association with rheumatic heart disease or infections. If the ventricular rate is slow and the patient is symptomatic, treatment with permanent pacing is indicated.

Complete heart block can be congenital or acquired. Its onset is usually prior to the pregnancy, and it rarely progresses. Approximately half the cases of complete heart block occurring during pregnancy have an associated ventricular septal defect. Other causes include ischemic heart disease, myocarditis, and rheumatic heart disease. The need for pacemaker therapy depends on the ventricular escape rate. Symptoms are rare at a rate of 50–60 bpm; if the rate suddenly slows, however, syncope may develop. Permanent pacing is indicated in such patients.

Pericardial Diseases

Pericarditis is usually a mild, self-limited disease. Its incidence, diagnosis, and treatment are similar in pregnant and nonpregnant patients. Most pregnancies, even the complicated ones, may safely reach full term. Idiopathic pericarditis is the most common cause of pericardial disease, others being trauma, infections (viral, bacterial, fungal, tuberculosis), radiation, and collagen vascular diseases.

Sharp, stabbing chest pain that is exacerbated in the supine position and relieved by leaning forward is the most common complaint. Pathognomonic finding of pericardial friction rub is best heard with the diaphragm of the stethoscope over the second and fourth intercostal spaces in midclavicular line or the left sternal border, with the patient leaning forward and inspiring deeply. Characteristic ST-segment elevations with upward concavity and upright T waves have been reported in 80% of patients with acute pericarditis. Echocardiography is an important diagnostic modality and may reveal thickened pericardium, pericardial effusion, and, most importantly, cardiac tamponade.

Pregnant patients in whom pericarditis is suspected who present with ECG changes, tachycardia, and ill appearance should be hospitalized for complete bed rest. Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and indomethacin are effective analgesics that may be used safely before 20 weeks gestation. After 20 weeks gestation, prednisone not to exceed 25 mg/day is the preferred drug. Colchicine should be avoided. Corticosteroids should be avoided in tuberculosis. Pericardiectomy is reserved for severe, relapsing pericarditis, refractory to medical treatment. Symptoms of a complicating pericardial effusion with cardiac tamponade mimic the symptoms of pregnancy and include shortness of breath, dyspnea on exertion, and fatigue. Echocardiogram will quickly establish the diagnosis. Treatment for symptomatic cardiac tamponade is percutaneous drainage with surgical pericardial window reserved for refractory cases.

Asymptomatic pericardial effusion is frequently encountered in all trimesters, most commonly in the third (up to 40%), but resolves postpartum. Pericardial constriction has been rarely reported in pregnancy, although it could occur as a pericarditis sequel. Most patients have dyspnea, marked edema, and ascites in the latter half of pregnancy. Diuretics, corticosteroids, and pericardiectomy (reserved for refractory cases and associated with reasonable maternal and fetal risk) have all been used to treat pericardial constriction in pregnant patients. Preterm delivery and fetal death have been reported.

Pulmonary Hypertension

Pulmonary Arterial Hypertension (World Health Organization Class I)

This entity is defined as mean pulmonary artery pressure by right heart catheter of more than 25 mm Hg at rest, a pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mm Hg, and pulmonary vascular resistance > 3 Wood units. Within this class is primary pulmonary hypertension, which poses a significant risk to pregnant women, with mortality approaching 40%, warranting prevention of pregnancy or early therapeutic abortion (see Table 33–2). However, should these women become pregnant, several options are available. The most common presenting symptoms are dyspnea, fatigue, chest pain, palpitations, syncope or near-syncope, and Raynaud phenomenon. Characteristic physical findings are a result of markedly increased pulmonary pressures, leading to right ventricular hypertrophy and failure with decreased cardiac output. The echocardiogram reveals elevated pulmonary artery pressures, right atrial enlargement, right ventricular hypertrophy, and tricuspid regurgitation. A new onset or worsening of symptoms is commonly seen in the second and third trimesters.

Treatment options include inhaled nitric oxide, calcium channel blockers, sildenafil, epoprostenol (class B), and iloprost (class C). Incidents of premature labor and delivery are high. Patients should lie in the left lateral decubitus position to improve cardiac output. Planned vaginal delivery seems to be safe in stable patients. Epidural anesthesia has been used in most reported cases. Patients should be monitored for 7–10 days postpartum prior to discharge to ensure stability. Patients with primary pulmonary hypertension should be considered for anticoagulation treatment with low-molecular-weight heparin.

Thromboembolic Disease

Venous thromboembolic disease is a leading cause of morbidity and mortality during pregnancy and postpartum and accounts for 20% of maternal deaths in the United States. Venous thromboembolism affects pregnant women five times more frequently than nonpregnant women. It is estimated to complicate 2 in 1000 pregnancies. The diagnosis is complicated by symptoms similar to usual pregnancy symptoms such as shortness of breath, tachycardia, and leg swelling. As many as up to 33% of deep venous thrombosis cases may occur in the first trimester, although the risk is highest postpartum (five times higher than during the pregnancy). The immediate postpartum period risk for pulmonary embolism is 15 times greater than during the pregnancy. Risk factors for venous thromboembolism include age > 35 years, body mass index > 30 kg/m2, a family or personal history of deep venous thrombosis or pulmonary embolism, varicose veins, smoking, or any known hypercoagulable state, as well as multiple previous pregnancies. Pulmonary embolism will occur in 15–24% of patients with untreated deep venous thrombosis and may be fatal in 15%. Diagnosis of deep venous thrombosis should be made with compression ultrasound or impedance plethysmography. Magnetic resonance imaging (MRI) can be performed to diagnose iliac thrombosis. The diagnosis of pulmonary embolism is complicated by the similarities of deep venous thrombosis and pulmonary embolism symptoms with the normal pregnancy symptoms (leg swelling and dyspnea) and the need to avoid radiation in the pregnant patient. The American Thoracic Society recommends initial screening chest x-ray and, if normal, to proceed to a ventilation-perfusion scan, which is considered safe throughout pregnancy. To further decrease radiation, consideration should be given to performing perfusion scan alone, or one may use dose-reduction techniques and use xenon-133 over technetium-99m. If there is no defect, then pulmonary embolism would be very unlikely. If the chest x-ray is abnormal, the test of choice would be a pulmonary angiogram. Except in the first trimester, pulmonary angiogram exposes the fetus to less radiation than a helical computed tomography (CT) scan, and the theoretical risk of exposing the fetus to iodine has not manifested in current studies. An echocardiogram may support the diagnosis of acute embolus by demonstrating right heart enlargement without hypertrophy and elevated pulmonary artery pressure. Hypokinesis with relative sparing of the right ventricular apex may be seen.

The main treatment for deep venous thrombosis during pregnancy consists of heparin, although warfarin can be given after the first trimester until 35 weeks gestation. If unfractionated heparin is used, a target activated partial prothrombin time should be 2.0–2.5. If an LMWH is used, the patient should be monitored with anti-Xa levels. Pulmonary embolism, if stable, should be treated with intravenous heparin for at least 5 days. Oral anticoagulation should be continued for 6 months thereafter. In unstable pulmonary embolism, consideration to thrombolysis and embolectomy should be given. An inferior vena caval filter may also be needed.

Diseases of the Aorta

Marfan Syndrome

Marfan syndrome is an inheritable autosomal dominant connective tissue disorder of the fibrillin gene on chromosome 15 with a prevalence of 1 in 3000–5000 individuals. It involves the ocular, skeletal, and cardiovascular systems. Patients are predisposed to aortic dissection or actual rupture of the aorta most commonly originating in the ascending portion during pregnancy, most likely in the third trimester. High-risk patients have significant associated cardiac abnormalities, such as mitral valve prolapse, mitral and aortic regurgitation, and an aortic root greater than 4.0 cm in diameter. All women with Marfan syndrome planning to become pregnant should undergo a screening transthoracic echocardiogram. High-risk patients (aortic root > 4.0 mm or rapidly progressive dilatation) should have elective surgery before conception, preferably with valve-sparing surgery if no significant aortic regurgitation is present. If the diagnosis is made during pregnancy, β-blockers are strongly recommended, with some authorities advocating prompt termination of pregnancy with aortic repair. Close follow-up with echocardiography should be performed. Women at increased risk for complications during pregnancy should be advised against attempting a pregnancy that may be associated with a 50% maternal mortality rate (see Table 33–2). Patients with no dissection or aortic root enlargement can deliver vaginally with epidural anesthesia and facilitated stage 2 of labor. However, if there is aortic root enlargement, aortic regurgitation, or rapid progression of the aorta size, cesarean delivery is recommended. The risk of the offspring inheriting the disorder is 50%.

Loeys-Dietz Syndrome

This syndrome is caused by genetic mutation in transforming growth factor (TGF)-β with autosomal dominant inheritance with variable clinical expression. The most common manifestations are aortic aneurysms with a high risk of dissection, hypertelorism, bifid uvula or cleft palate, generalized arterial tortuosity, and aneurysms throughout the arterial tree. Loeys-Dietz syndrome may be misdiagnosed as Marfan syndrome, but patients with Loeys-Dietz syndrome will have normal fibrillin gene. Women with this syndrome should be advised against pregnancy due to the risk of aortic dissection with normal aortic diameter and a risk for uterine rupture during pregnancy.

Hypertension

Hypertension affects 12% of pregnancies and is responsible for 18% of maternal deaths in the United States, but may be on the rise. Risk factors include African American ethnicity, age greater than 45 years, and women with diabetes. Hypertension in pregnancy causes increased rates of intracerebral hemorrhage, placental abruption, intrauterine growth retardation, prematurity, and intrauterine death. Hypertensive disorders in pregnancy can be divided into four groups: (1) chronic, persistent hypertension (blood pressure ≥ 140/90 mm Hg before pregnancy or before the 20th gestational week, or persisting beyond the forty-second postpartum day); (2) gestational hypertension (hypertension developing beyond the 20th gestational week, not associated with preeclampsia or eclampsia and resolving within 42 days postpartum); (3) preeclampsia/eclampsia (hypertension beyond the 20th gestational week with > 300 mg protein/24 hours or > 30 mmol/L in spot urine sample; eclampsia includes presence of seizures); (4) preeclampsia superimposed on chronic hypertension (onset of preeclampsia symptoms in woman with chronic hypertension beyond 20 weeks gestation). Elevated measurements should be confirmed on two occasions, and the patient should be supine in the left lateral position and having rested for at least 10 minutes. The degree of blood pressure elevation does not correlate with risk for eclamptic seizures. Ambulatory blood pressure monitoring may be of value and improve risk prediction. The drug treatment of choice for mild hypertension is methyldopa. Treatment should be initiated if blood pressure is > 150/100 mm Hg. For severe hypertension, drugs such as hydralazine, labetalol, and nifedipine can be used. Target diastolic blood pressure is 80–105 mm Hg depending on the risk.

History

The evaluation of heart disease in pregnancy is difficult due to the normal anatomic and physiologic changes of pregnancy. Therefore, taking a careful history is very important and should include a history of rheumatic fever, valvular disorder, arrhythmia, CHD, coronary risk factors or established coronary artery disease, and cardiac surgery.

Symptoms & Signs

Reduced exercise tolerance and fatigue are the most common symptoms reported in pregnant women, probably due to increased body weight and anemia. Dizziness, light-headedness, or even syncopal episodes may occur during the latter part of pregnancy because mechanical compression of the uterus on the inferior vena cava decreases venous return and thus the cardiac output. Palpitations are also a frequent complaint but usually are not associated with a significant arrhythmia. Dyspnea and orthopnea, probably due to hyperventilation, are also reported.

Physical Examination

The physical examination of pregnant patients with normal cardiovascular systems changes because of the increased hemodynamic burden. The evaluation of patients with suspected heart disease during pregnancy requires a thorough knowledge of the normal physiologic changes (see Table 33–1).

A normal pregnant patient has a slightly fast resting heart rate, large pulse, slightly widened pulse pressure, and warm extremities. Jugular venous distention is seen starting at the 20th week. Edema of the ankles and legs is commonly encountered in late pregnancy. A prominent but unsustained left ventricular impulse may be palpated in late pregnancy and may simulate the volume overload seen in aortic or mitral regurgitation. The auscultatory findings of normal pregnancy begin late in the first trimester and usually disappear 2–4 weeks after delivery. During cardiac auscultation, the first heart sound is loud and exhibits an exaggerated splitting. The second heart sound during late pregnancy is often increased and may exhibit persistent expiratory splitting, especially with the patient in the left lateral position. A third heart sound has been reported to be frequent in late pregnancy. However, because of its association with heart failure, the presence of a third heart sound should lead to further investigation of underlying heart disease, especially in women with symptoms and other signs suggestive of heart disease. A fourth heart sound is rarely heard during a normal pregnancy and may indicate hypertensive heart disease or presence of ischemia.

Systolic murmurs are common during pregnancy and result from the increased blood volume and hyperkinetic state. Most frequently, they are innocent early systolic murmurs, grade 1–2/6, that are best heard at the lower left sternal border and over the pulmonary area, radiating to the suprasternal notch or to the left of the neck. They usually represent vibrations created by ejection of blood into the pulmonary trunk. A cervical venous hum or mammary souffle heard best in the right supraclavicular area in a supine position is a benign systolic, or a continuous, murmur occurring in late pregnancy (Table 33–5). Diastolic heart murmurs are unusual and usually represent valvular abnormalities.

Diagnostic Difficulties

Although systolic murmurs are common, the finding of a diastolic murmur is rare during a normal pregnancy and should warrant further diagnostic evaluation. Both systolic and diastolic murmurs associated with cardiac disease can increase or decrease in intensity during pregnancy. Innocent flow murmurs and benign vascular murmurs usually decrease in the sitting position. The systolic murmurs of aortic or pulmonic stenosis usually increase in intensity because of the increased cardiac output and blood volume. The diastolic murmur of mitral stenosis is also increased and may even be first detected during pregnancy. The augmented blood volume and the increased heart rate of pregnancy shorten the diastolic filling period and increase the rate of blood flow across the mitral valve. In contrast, murmurs of mitral or aortic regurgitation may soften or even disappear during pregnancy as a result of the decrease in peripheral vascular resistance. The circulatory changes of pregnancy also affect the auscultatory findings in cardiac abnormalities, such as mitral valve prolapse and hypertrophic cardiomyopathy, which are dependent on volume. The increase in left ventricular volume during pregnancy may attenuate or abolish the click and late systolic murmur typical of mitral valve prolapse. The systolic murmur of hypertrophic obstructive cardiomyopathy may also decrease or disappear as the left ventricular volume increases during pregnancy.

Diagnostic Studies

Electrocardiography

The ECG is an important diagnostic technique that can indicate the presence of underlying cardiac abnormalities. Cardiac chamber hypertrophy, myocardial ischemia and infarction, pericarditis, myocarditis, conduction abnormalities, and the presence of atrial and ventricular arrhythmias may be detected by ECG. In patients with suspected cardiac arrhythmias, ambulatory Holter monitoring may be indicated. During normal pregnancy, sinus tachycardia, a shift of the axis to the left or right, may be observed, and transient ST abnormalities are common.

Echocardiography

Transthoracic echocardiography is an important diagnostic noninvasive study that can be performed safely in pregnancy. The intracardiac structures can be evaluated for abnormalities of the great vessels, cardiac chambers, and heart valves. Chamber sizes and ventricular function can also be measured.

During the echocardiographic examination, the normal physiologic changes that occur with pregnancy should be kept in mind. When the patient is evaluated in the left lateral position, an increase in the diastolic dimensions of the right and left ventricles is common because of volume increases that occur with a normal pregnancy. Because of the increase in the left ventricular dimensions, mitral valve prolapse may improve or disappear during pregnancy. Right and left atrial dimensions may also increase slightly; these changes increase as the pregnancy progresses. Small pericardial effusions are common throughout pregnancy in healthy women, but with highest incidence in the last trimester.

Doppler echocardiography provides reliable quantitative and qualitative information regarding the presence and severity of valvular stenosis and regurgitation. Doppler echocardiography can measure the valve area and gradients across stenotic valves. Small degrees of pulmonary, tricuspid, and mitral regurgitation have frequently been found in normal individuals, whether pregnant or not. In patients with CHD (corrected or uncorrected), Doppler echocardiography can detect the presence of intracardiac shunts and estimate the shunt ratios by determining the right and left cardiac outputs. It can measure pulmonary artery systolic pressure to assess the effects of the valvular lesions and intracardiac shunts on the pulmonary circulation.

Transesophageal echocardiography (TEE) provides superior images of the intracardiac structures and great vessels, providing the same detailed analysis of cardiac structure, function, and hemodynamic assessment possible with transthoracic echocardiography. TEE can be used for patients in whom the transthoracic examination is technically suboptimal and for those with suspected prosthetic or native valve dysfunction, infective endocarditis, CHD, or aortic dissection. Although experience with TEE during pregnancy has been limited, the procedure should be considered in pregnant patients for whom the risks are less than the possible benefit. The procedure should be performed by an experienced echocardiographer, and fetal monitoring, in addition to the routine monitoring of the patient, should be available (Table 33–6).

Exercise Tolerance Test

Little is known about the safety of an exercise test to establish ischemic heart disease in pregnancy. Fetal bradycardia, marked hypoxia, acidosis, and severe hypothermia at peak exercise have been reported. In light of these facts, the use of a submaximal stress test (approximately 70% of the maximal predicted heart rate) with close fetal monitoring is recommended, until more information regarding its safety is available. Maximal oxygen consumption, unchanged in pregnancy, could be used for the assessment of the functional status in cardiac patients during pregnancy.

Chest Radiography

The usefulness of chest films during pregnancy is limited because of the potential hazard to the fetus from radiation exposure. Whenever a chest film is believed necessary, the abdominopelvic area should be shielded with lead to minimize exposure. The normal cardiac changes of pregnancy, such as chamber enlargement and the horizontal position of the heart because of the elevation of the diaphragm, should not be misinterpreted as cardiac disease. Newer and more accurate techniques such as Doppler echocardiography have largely replaced chest films in the evaluation of cardiac structure and function. Chest x-rays are recommended as part of the evaluation of the pregnant patient suspected of having acute pulmonary embolism.

Radionuclide Studies

Myocardial perfusion scans and radionuclide ventriculography should be avoided, if possible, especially in the first trimester of pregnancy because of the risk of rare but possible fetal malformations. Also, in women of childbearing age, the incidence of coronary heart disease is low, and other noninvasive techniques, such as exercise echocardiography, can be used to assess coronary artery disease. In cases of suspected pulmonary embolism, a limited ventilation-perfusion scan (only performing the perfusion phase) may be performed weighing out the risks and the benefits. The minimal dose of isotope possible should be used, and xenon-133 is preferred over technetium-99m.

Computed Tomography

CT scanning imposes ionizing radiation to the mother and in part to the fetus and should only be used if no other imaging modalities can provide the diagnostic information. Using specific low-dose protocols, the amount of radiation with a CT scan may be less than that of a radionuclide scan. For certain studies, iodine contrast is used, which may carry a small risk for hypothyroidism in the fetus, although newer studies have not been able to detect this. At present, it appears the only time CT angiography benefit may outweigh the risk is in pregnant women suspected of pulmonary embolism. Aortic dissections should be evaluated by TEE or MRI.

Magnetic Resonance Imaging

MRI provides multiplanar images of the body with excellent soft-tissue contrast without the use of ionizing radiation. MRI is, in general, regarded as safe in pregnancy. However, safety data are limited. Therefore, MRI should be limited to cases where ultrasonography is inconclusive and where patient care depends on further imaging. Gadolinium contrast should be avoided.

Pulmonary Artery Catheterization

Bedside hemodynamic monitoring can be performed with a balloon-tipped pulmonary artery catheter. In most patients, inflating the balloon permits flotation of the catheter through the right heart without the need for fluoroscopy. With the catheter in the pulmonary artery, the balloon is inflated until it occludes a small vessel; the pulmonary artery wedge pressure obtained reflects the left ventricular end-diastolic pressure. Pulmonary artery pressures and cardiac output can also be measured. The placement of a balloon flotation catheter should be considered during the early stages of labor in any patient with cardiac disease who has been symptomatic during the pregnancy. Furthermore, because of postpartum hemodynamic changes, hemodynamic monitoring should be continued for up to 48 hours following delivery.

Cardiac Catheterization

In some patients with cardiac disease who decompensate during pregnancy, complete diagnostic information cannot be obtained by noninvasive methods alone. This is particularly important when surgical intervention is contemplated. Cardiac catheterization in these patients may need to be performed during pregnancy. Because the radiation required for the performance of this technique has potentially adverse effects on the fetus, cardiac catheterization should be performed only if the needed information cannot be obtained by any other means. Whenever possible, cardiac catheterization should be performed after major organogenesis has occurred (> 12 weeks after the last menses). The radial approach is the preferred method to minimize the risk of radiation exposure to the abdomen, which should be lead shielded. The exposure to x-rays should be reduced to a minimum; catheter position can be guided in some cases by Doppler and contrast echocardiography.

Pharmacologic Treatment

Treatment of the pregnant patient with cardiac disease requires the collaborative consultation of the obstetrician and cardiologist at regular intervals during gestation and careful planning for delivery with the anesthesiologist. All cardiovascular drugs during pregnancy should be avoided, if possible, especially in the first trimester. Most cardiovascular drugs cross the placenta and are secreted into the breast milk, mandating a detailed evaluation of risk-to-benefit ratio (Table 33–7).

Heart Failure

Treatment of heart failure is more challenging in pregnant patients than in nonpregnant women. Salt restriction and activity limitation are extremely important. In patients with pulmonary congestion, medical therapy should begin with digoxin. Although digoxin has been safely used during pregnancy for many years, blood levels should be monitored to avoid toxicity. Diuretics, although not teratogenic, may cause impaired uterine blood flow and placental perfusion, and hence should only be used in severely symptomatic patients. Thiazide diuretics have been associated with neonatal thrombocytopenia, jaundice, hyponatremia, and bradycardia, and loop diuretic are preferred.

Afterload is already reduced during pregnancy; hence, further reduction in afterload may only be beneficial in selected cases. Hydralazine, the most frequently used afterload-reducing agent during pregnancy, is a direct arteriolar dilator and has not been associated with adverse fetal effects. ACE inhibitors are contraindicated in pregnancy due to their associated increased risk of premature delivery, low birth weight, fetal hypotension, renal failure, bony malformations, persistent patent ductus arteriosus, respiratory distress syndrome, and even death. Angiotensin II receptor blockers have similar adverse reactions and are thus rendered unsafe. Data on nitrates are limited and require further evaluation. β-Blockers may be used safely, although atenolol should be avoided.

Arrhythmias

During pregnancy, any precipitating factors of arrhythmia should be avoided or corrected. In general, conservative treatment of cardiac arrhythmias is indicated. Direct-current cardioversion is the treatment of choice in patients with hemodynamic compromise due to arrhythmia. Although no antiarrhythmic is completely safe during pregnancy, most are tolerated well and are relatively safe. Drugs with the longest record of safety should be used as first-line therapy. Digoxin, although one of the safest drugs for treating arrhythmia during gestation, may cause increased risk of prematurity and intrauterine growth retardation. Adenosine has been reported safe and successful in terminating supraventricular tachycardias during pregnancy.

Quinidine, with minimal fetal risk, has the longest record of being used safely and effectively in the treatment of both atrial and ventricular tachycardia during pregnancy. When quinidine is indicated during pregnancy, blood levels should be closely monitored because drug interactions with warfarin may develop excessively prolonged prothrombin time, with the potential for hemorrhage. Procainamide has also been used safely and is the drug of choice in the treatment of wide-complex tachycardias.

Amiodarone is associated with fetal hypothyroidism, smaller size at birth for date of gestation, and prematurity, and is also secreted in breast milk. Amiodarone is thus reserved only for treating life-threatening arrhythmias or those refractory to other medical therapy. Verapamil, although used during pregnancy, should be discontinued at the onset of labor to avoid dysfunctional labor and postpartum hemorrhage.

β-Adrenergic blocking agents are relatively safe and have frequently been used in pregnant patients to treat arrhythmia, hypertrophic cardiomyopathy, and hyperthyroidism. Propranolol is a nonselective β-blocker that has been used frequently during pregnancy. Fetal and newborn heart rate, blood glucose levels, and respiratory status should be monitored closely.

Lidocaine may be used for ventricular tachycardia, especially in the setting of an acute MI, but it requires close monitoring of blood levels.

Thrombosis and Thromboembolism

Even though increased concentrations of clotting factors and platelet adhesiveness and decreased fibrinolysis in pregnancy result in an overall increased risk of thrombosis and embolism, the actual incidence of venous thromboembolism during pregnancy is lower than previously reported. The gestational age at presentation appears to be equally distributed. Pulmonary embolism cases are reported to occur most commonly in the postpartum period and are strongly associated with a cesarean section. About 40% of asymptomatic patients with deep venous thrombosis may indeed have a pulmonary embolism.

The major indications for anticoagulants during pregnancy include the presence of mechanical heart valves and prophylaxis for recurrent pulmonary thromboembolism. Some patients with rheumatic heart disease with atrial fibrillation and cardiomyopathies may also be candidates for anticoagulation during pregnancy. The best method of anticoagulation in a pregnant patient is still controversial. A recommended regimen is suggested in Table 33–3.

Warfarin has been associated with fetal wastage due to spontaneous abortion and stillbirths, optic nerve atrophy and blindness, microcephaly, mental retardation, and even death due to intracranial hemorrhage. Its use in the first trimester is associated with warfarin embryopathy in 5–30% of newborns, a syndrome comprising nasal bone hypoplasia and epiphyseal stippling. The risk may be less if the patient can be controlled on a daily dose of 5 mg or less. Warfarin poses significant risks to both the mother and the fetus during labor and delivery; however, breastfeeding women can be prescribed warfarin because it is not secreted in the breast milk. In the second trimester, warfarin is the treatment of choice, with INR monitoring. Therefore, warfarin should be given only after the 12th gestational week and should be stopped before delivery around 35th week.

Heparin is generally the drug of choice for anticoagulation in pregnant patients, unless there is a very high risk for thromboembolism (see section on prosthetic heart valves). As soon as pregnancy is diagnosed, oral anticoagulants should be discontinued, and subcutaneous heparin, with a goal partial thromboplastin time (PTT) of 2–2.5 times normal, should be initiated. If LMWH is used, anti-Xa levels (peak and trough) should be monitored. Complications of unfractionated heparin administration include thrombocytopenia, alopecia, and osteoporosis. At the 36th week of gestation, subcutaneous heparin should be switched to intravenous route. To avoid the risk of bleeding during labor and delivery, heparin should be discontinued 24 hours prior. Anticoagulation should then be resumed 4 hours after delivery if no bleeding complications.

Low-dose aspirin has been safely used in pregnancy. Dipyridamole should not be used in a pregnant patient. Thrombolytic therapy has been used safely and effectively but should be avoided whenever possible.

Endocarditis Prophylaxis

The American Heart Association does not recommend prophylaxis for infective endocarditis in pregnant patients. However, many obstetrician do decide to administer antibiotics in high-risk patients at time of rupture of the membranes in patients undergoing vaginal delivery. The patients considered highest risk are those with mechanical prosthetic heart valves, those with a history of infective endocarditis, and those with uncorrected or recently corrected cyanotic CHDs or with residual defects. In addition, patients with a known infection should be treated.

Surgical Treatment

Ideally, most cardiac diseases requiring surgical correction are diagnosed and treated before the patient becomes pregnant, so the data are anecdotal. In general, cardiac surgery in pregnant patients is not associated with significant maternal risk but may cause fetal wastage. Fetal risk has been reported to be as high as 33%. Pregnant women requiring cardiac surgery need utmost care, adequate valve selection, and anticoagulation to ensure a good outcome.

Surgery should be reserved for severely symptomatic patients and those who are refractory to medical therapy, and it should be avoided in the first trimester, if possible. Procedures not involving cardiopulmonary bypass are preferred because of associated risks of fetal bradycardia and hypoperfusion.

Labor & Delivery

Labor and delivery are periods of maximal hemodynamic stress during pregnancy. Pain, anxiety, and uterine contractions all contribute to altered hemodynamics. Oxygen consumption is higher, and cardiac output is increased up to 50%. Both systolic and diastolic pressures are increased significantly during uterine contractions, especially in the second stage. Anesthesia and analgesia during labor and delivery may affect oxygen consumption, but they do not reduce increased cardiac output secondary to uterine contractions.

Acute decompensation may develop in patients with preexisting cardiac disease. This increase in preload and cardiac output can be devastating in a patient with limited cardiac reserve or an obstructive valvular lesion. Patients at greatest risk for complications during labor and delivery include those with significant pulmonary hypertension and those in NYHA functional class III or IV.

The preferred method of delivery is vaginal, with careful attention paid to pain control by regional anesthesia to avoid tachycardia. Postpartum hemorrhage and excessive fluid intake should be prevented. Invasive hemodynamic monitoring may be needed in some cases to guide treatment rapidly during labor and delivery. In these patients, the monitoring should be continued for at least 24–48 hours after delivery or until hemodynamic stability is ensured. Cesarean section, with few exceptions, should be performed only for obstetric indications because it can also create blood loss and fluid shifts. Regardless of the delivery method, however, effective pain control is absolutely essential.

Maternal mortality and morbidity rates during pregnancy depend on the underlying cardiac lesion and the functional status of the patient (see Table 33–2). The greatest risk of maternal mortality (25–50%) is for patients with pulmonary hypertension, Eisenmenger syndrome, NYHA class III and IV, and Marfan syndrome with a dilated aorta. Pulmonary vascular disease prevents the adaptive mechanisms of normal pregnancy and makes labor, delivery, and the early postpartum period particularly problematic. Moderate-to-severe mitral stenosis, aortic stenosis, the presence of mechanical prosthetic valves, uncomplicated coarctation of the aorta, uncorrected CHDs (without Eisenmenger syndrome), and Marfan syndrome with a normal aorta are associated with a 5–10% mortality rate. Left-to-right shunts, pulmonary valve disease, corrected CHD, bioprosthetic valves, and mild-to-moderate mitral stenosis have a mortality rate of less than 1%.

The functional status of a patient should be classified according to the NYHA classification system. Patients in class I or II can be expected to undergo pregnancy with a less than 0.5% risk of death.