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Diagnosis of Heart Disease in PregnancyPregnant women with heart disease are at higher risk for cardiovascu-lar complications during pregnancy and also have a higher incidence of neonatal complications.1 However, the signifi cant hemodynamic changes that accompany pregnancy make the diagnosis of certain forms of cardiovascular disease diffi cult. During normal pregnancies, women frequently experience dyspnea, orthopnea, easy fatigability, dizzy spells, and, occasionally, even syncope. On physical examination, dependent edema, rales in the lower lung fi elds, visible neck veins, and cardiomegaly are commonly found. Systolic murmurs occur in more than 95% of pregnant women, and internal mammary fl ow murmurs and venous hums are common. A third heart sound (S3 gallop) is often present.2 Nevertheless, certain fi ndings indicate heart disease in preg-nancy and should suggest the presence of a signifi cant cardiovascular abnormality. These symptoms include severe dyspnea, syncope with exertion, hemoptysis, paroxysmal nocturnal dyspnea, and chest pain related to exertion. Physical signs of organic heart disease include a fourth heart sound (S4 gallop), cyanosis, clubbing, diastolic murmurs, sustained cardiac arrhythmias, and loud, harsh systolic murmurs.3

If there is a strong suspicion of heart disease during pregnancy, confi rmatory diagnostic tests should be initiated. The changes of normal pregnancy must be recognized so that the fi ndings are not misinterpreted. For example, nonspecifi c ST segment and T-wave abnormalities and shifts in the electrical axis can occur.4 Pregnancy also produces changes in the echocardiogram, including alterations in cardiac dimensions and performance. The internal dimensions of all the cardiac chambers are increased, and slight regurgitation through the four valves is frequently observed. The ejection fraction (EF) and stroke volume are concomitantly larger, and the cardiac output is increased.5 A small pericardial effusion can be a normal fi nding in pregnant women.6 Both radiographic and radionuclide diagnostic pro-cedures should be avoided during pregnancy unless the procedure is deemed essential for the health and safety of the mother.

Pre-Conception CounselingIf a woman plans to become pregnant but knows that she has heart disease, she and her physicians must be fully aware of several funda-mental principles. The cardiovascular system undergoes specifi c adap-tations to meet the increased demands of the mother and fetus during

pregnancy. The most important of these are increases in blood volume, cardiac output, and heart rate. These adaptations exacerbate the symp-toms and clinical signs of heart disease and may necessitate signifi cant escalation in treatment.

Cardiac risk varies among the specifi c forms of heart disease and also with severity. During prepregnancy counseling, the physician should describe the nature of the heart disease in terms comprehensi-ble to the prospective parents. The risk to the woman, which can vary from negligible to prohibitive, should be spelled out as clearly as pos-sible.7 On this basis, the patient may be advised either that the con-templated pregnancy is safe, will be uncomfortable and will necessitate treatment, carries a signifi cantly increased risk, or would be extremely dangerous and should not be undertaken.

In the case of certain cardiac conditions, the patient should be strongly advised to undergo the necessary treatment before pregnancy and to allow several months to elapse before becoming pregnant. Examples in this category include the following:

� Large intracardiac shunt (atrial or ventricular septal defect) with mild to moderate pulmonary hypertension

� Patent ductus arteriosus (PDA) with mild to moderate pulmonary hypertension

� Severe coarctation of the aorta� Severe mitral stenosis or regurgitation� Severe aortic stenosis or regurgitation� Tetralogy of Fallot� Various congenital malformations and acquired heart diseases

Again, it is imperative that the palliative procedure be carried out before pregnancy is undertaken and that a year or so elapse before pregnancy occurs. Flexibility in clinical judgment is necessary, however. A woman with moderately severe valvular disease may require a pros-thetic valve in the future. In such a case, the patient should be advised to have her family before valve replacement—with its associated anti-coagulant risk—is required8 (see Pregnancy in Patients with Artifi cial Heart Valves, later). The valvular heart lesions associated with high and low maternal and fetal risk during pregnancy are listed in Tables 39-1 and 39-2.

As previously noted, some cardiac disorders are so serious in nature that the physiologic changes of a superimposed pregnancy pose pro-hibitive risks to the mother; they carry such a high maternal mortality risk that pregnancy is contraindicated. In such circumstances, patients must be strongly cautioned against becoming pregnant. If such a patient is seen for the fi rst time when she is already pregnant, termina-tion of the pregnancy is recommended. The most serious of the cardiac

Chapter 39

Cardiac DiseasesDaniel G. Blanchard, MD, and Ralph Shabetai, MD

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798 CHAPTER 39 Cardiac Diseases

disorders are those involving pulmonary hypertension, particularly those associated with a right-to-left shunt in cardiac blood fl ow (Eisenmenger syndrome). Low cardiac output states and entities in which there is an increased risk of aortic dissection (Marfan syndrome) also represent an extraordinarily high risk of maternal mortality. These high-risk maternal cardiovascular disorders are listed in Table 39-3.

In some women with specifi c dangerous cardiovascular diseases, pregnancy is contraindicated because of the substantial risk of mater-nal death.9 Examples include the following:

� Dilated cardiomyopathy or left ventricular dysfunction (EF < 40%) of any cause

� Severe pulmonary hypertension of any cause� Marfan syndrome, especially with aortic root dilation (diameter

> 4 cm)

If a patient with one of these disorders presents when she is already pregnant, she should be strongly urged to consider early termina-tion. A carefully planned suction curettage before 13 weeks’ gestation would place such a patient at minimal risk. Termination of pregnancy beyond 13 weeks increases the risk to the mother, because many of the cardiovascular alterations that occur in pregnancy have taken place.

Infective endocarditis often causes rapid and serious deterioration of the cardiac status, posing a major threat to the life and health of the mother and, therefore, of the fetus as well. Scrupulous attention to prophylaxis against endocarditis is critical during pregnancy. Pregnant women must pay meticulous attention to their dental health; if they have cardiac lesions susceptible to infective endocarditis, neglect of antibacterial prophylaxis could have dire consequences. In general, women with valvular heart disease should have antibiotic prophylaxis at the time of delivery.10,11

The prospective parents will want to know not only about the risk to the health and life of the future mother but also about the fetal risks. One of the most important questions is whether the mother’s heart disease is hereditary and, if so, what is the risk that the infant will be born with the same defect. A detailed family cardiac history must be obtained before pregnancy, especially if the prospective mother has heart disease.

Some of the cardiomyopathies, especially hypertrophic forms, may be inherited in a mendelian manner.12 Familial dilated cardiomyopathy has also been described. Approximately 20% of idiopathic dilated car-diomyopathy is inherited.13 There is a strong familial tendency in certain congenital malformations, such as PDA and arterial septal defect (ASD). Additionally, mothers with congenital heart disease may have children with unrelated congenital malformations: this risk appears to be approximately 5%.3,14 Also, pregnant women with advanced heart disease, especially those with low cardiac output or severe hypoxia, experience a greatly increased incidence of spontane-ous abortion, stillbirths, and small or deformed children.9 For most pregnant women with heart disease, vaginal delivery (with a low threshold for forceps or vacuum assistance) is recommended. Elective cesarean section is recommended in cases of Marfan syndrome or aortic aneurysm of any cause.3

Today’s prospective mother wants to know about the risks to her fetus of drugs, other therapies, and diagnostic tests that are used to treat heart disease. Echocardiography poses no threat to the fetus, but radiation incurred with radionuclide angiography, cardiac catheteriza-tion with contrast angiography, or computed tomography pose a potential hazard to the fetus. If these studies are required, they should be performed before pregnancy occurs; they should be repeated there-after only if mandated for the safety of the mother, and pelvic shielding should be used.

TABLE 39-1 VALVULAR HEART LESIONS ASSOCIATED WITH HIGH MATERNAL AND/OR FETAL RISK DURING PREGNANCY

Severe AS with or without symptomsAR with NYHA functional class III-IV symptomsMS with NYHA functional class II-IV symptomsMR with NYHA functional class III-IV symptomsAortic and/or mitral valve disease resulting in severe pulmonary

hypertension (pulmonary pressure greater than 75% of systemic pressures)

Aortic and/or mitral valve disease with signifi cant LV dysfunction (EF < 40%)

Mechanical prosthetic valve requiring anticoagulationMarfan syndrome with or without AR

AR, aortic regurgitation; AS, aortic stenosis; EF, ejection fraction; LV,

left ventricular; MR, mitral regurgitation; MS, mitral stenosis; NYHA,

New York Heart Association.

Reproduced with permission from Bonow RO, Carabello B, DeLeon AC,

et al: ACC/AHA 2006 guidelines for the management of patients with

valvular heart disease. Circulation 114:84, 2006.

TABLE 39-2 VALVULAR HEART LESIONS ASSOCIATED WITH LOW MATERNAL AND FETAL RISK DURING PREGNANCY

Asymptomatic AS with low mean gradient (<25 mm Hg and aortic valve area >1.5 cm2) in the presence of normal LV systolic function (EF > 50%)

NYHA functional class I or II AR with normal LV systolic functionNYHA functional class I or II MR with normal LV systolic functionMVP with no MR or mild to moderate MR with normal LV systolic

functionMild MS (mitral valve area >1.5 cm2, gradient <5 mm Hg) without

severe pulmonary hypertensionMild to moderate pulmonary valve stenosis

AR, aortic regurgitation; AS, aortic stenosis; EF, ejection fraction; LV,

left ventricular; MR, mitral regurgitation; MS, mitral stenosis; MVP,

mitral valve prolapse; NYHA, New York Heart Association.

Reproduced with permission from Bonow RO, Carabello B, DeLeon AC,

et al: ACC/AHA 2006 guidelines for the management of patients with

valvular heart disease. Circulation 114:84, 2006.

TABLE 39-3 HIGH-RISK MATERNAL CARDIOVASCULAR DISORDERS

Disorder

Estimated Maternal

Mortality Rate (%)

Aortic valve stenosis 10-20Coarctation of the aorta 5Marfan syndrome 10-20Peripartum cardiomyopathy 15-60Severe pulmonary hypertension 50Tetralogy of Fallot 10

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799CHAPTER 39 Cardiac Diseases

Maternal infection with the virus that causes German measles (rubella) is associated with a high risk of congenital malformation of the fetal heart as well as PDA. If the patient has not had German measles as a child and has never been inoculated against it and her antibody titer confi rms the absence of immunity, she should be vacci-nated some months before becoming pregnant.

Every pregnant woman who is known or thought to have heart disease should, at a minimum, be evaluated once by a cardiologist who understands the cardiovascular adaptations to pregnancy. The cardi-ologist will prescribe necessary diagnostic studies and treatments and, of equal importance, will not allow unnecessary ones. The effects of heart disease can often be ameliorated by correcting coexisting medical problems, such as anemia, chronic infection, anxiety, thyroid dysfunc-tion, hypertension, and arrhythmia.

Cardiovascular Adaptations to PregnancyIncreased Blood VolumeThe cardiovascular alterations observed in pregnancy are discussed in detail in Chapter 7 but are reviewed here briefl y. It is worthwhile to reconsider and emphasize some of the most important cardiovascular changes that occur during pregnancy, because they may signifi cantly alter the course of cardiac disease or may themselves be infl uenced by a specifi c disorder.

Blood volume and cardiac output increase during pregnancy.15 The uterus hypertrophies, endometrial vascularization is greatly increased, and the placenta becomes a highly vascular structure that functions to some extent as an arteriovenous shunt. In addition, generalized arte-riolar dilation develops, mediated most probably by estrogen. These mechanisms combine to lower systemic vascular resistance and increase the pulse pressure. The total blood volume rises steadily during the fi rst trimester and is increased by almost 50% by the 30th week, remaining more or less constant thereafter.16 Several mechanisms are responsible for increasing blood volume in pregnancy, including steroid hormones of pregnancy, elevated plasma renin activity, and elevated plasma aldosterone levels. Human placental lactogen, atrial natriuretic factor, and other peptides may also play signifi cant roles in governing changes of blood volume in pregnancy. Hypervolemia also occurs with trophoblastic disease, indicating that a fetus is not essential for its development. Heart rate increases by 10 to 20 beats/min. In a normal pregnancy, blood pressure does not increase, because the increased intravascular volume is balanced by decreased peripheral vascular resistance mediated by the placenta. Plasma volume tends to increase more than the red blood cell mass, accounting for a “physio-logic anemia” that is common in pregnancy. Treatment with iron cor-rects the anemia which, if left untreated, may become signifi cant (hematocrit as low as 33% and hemoglobin 11 g/dL).

Cardiac OutputCardiac output rises during the fi rst few weeks of pregnancy and is 30% to 45% above the nonpregnant level by the 20th week, remaining there until term.15 The increase in cardiac output in the fi rst trimester begins rapidly and peaks between the 20th and 26th week. Early in pregnancy, the dominant factor is elevated stroke volume; later, increased heart rate predominates.17 In late pregnancy, the enlarged uterus partially impedes venous return by compressing the inferior

vena cava, accounting for lower cardiac output. This is one reason why some obstetricians prefer to manage labor with the patient in the left decubitus position.

Cardiac PerformanceEchocardiographic studies have shown increases in the left ventricular fi ber shortening velocity and in EF. These changes do not necessarily indicate increased myocardial contractility but may simply be the result of decreased peripheral vascular resistance and increased preload. In any case, stroke volume is increased, and cardiac output is further augmented by the 10% to 15% increase in heart rate that characterizes normal pregnancy.18

Demands on the cardiovascular system increase signifi cantly during labor and delivery. Pain increases sympathetic tone, and uterine contractions induce wide swings in the systemic venous return. With placental separation, autotransfusion of at least 500 mL takes place, placing an acute load on the diseased heart, unless offset by blood loss. These large shifts in blood volume can precipitate, on the one hand, shock, and on the other, pulmonary edema in women with severe heart disease.

If a chest radiograph is obtained in a pregnant woman, the cardiac silhouette often appears slightly enlarged owing to the combined effects of volume overload and elevation of the diaphragm. Routine echocardiographic studies have demonstrated that a small, silent peri-cardial effusion is quite common.6

Electrocardiographic ChangesThe mean QRS axis may shift to the left19 as a result of the elevated diaphragm. In later pregnancy, the axis may shift to the right when the fetus descends into the pelvis. Minor ST segment and T-wave changes may be observed, usually in lead III but sometimes aVF as well. Less often, T inversions may appear transiently in the left precordial leads. Occasionally, small Q waves may accompany T-wave inversion in leads III and aVF. These changes are seldom of suffi cient magnitude to raise the question of ischemic heart disease, which in any case is relatively uncommon in pregnancy, especially if the mother is young and free from symptoms. Extrasystoles and supraventricular tachycardia are more common during pregnancy. Symptoms of palpitations are common during pregnancy but only rarely signify the presence of organic heart disease.

General Guidelines for ManagementDuring treatment of all pregnant patients with heart disease, priority must be given to maternal health, but all possible therapeutic measures should also be taken to protect the developing fetus. The aspects of management are outlined in Table 39-4.

Because pregnancy increases the demands on the heart, physical exertion frequently must be restricted, especially if it causes symptoms. Some women with certain forms of cardiac disease, such as signifi cant mitral stenosis and cardiomyopathy, tolerate pregnancy poorly and cannot endure physical exertion. They may require strict bed rest for the duration of the pregnancy, particularly during the last trimester. Women with heart disease have a limited ability to increase cardiac output to meet increased metabolic demands and should minimize the demands placed on the heart from physical activity.

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Cardiovascular DrugsSome of the drugs commonly used in the management of cardiovas-cular disease have potentially harmful effects on the developing embryo and fetus. For example, there is no question that oral anticoagulants are potential teratogens when administered in the fi rst trimester (see Chapter 20 and later discussion in this chapter). The “warfarin embry-opathy syndrome,” consisting of nasal hypoplasia, optic atrophy, digital abnormalities, and mental impairment, occurs in a minority of cases. The actual risk of warfarin embryopathy is diffi cult to estimate and has ranged from 4% to 67% in various reports.20,21 A risk of 4% to 10% seems more reasonable.22 There is some evidence that embryopathy is less likely if the warfarin dose is 5 mg/day or less.23 The fetal risks continue beyond the fi rst trimester, because warfarin increases the possibility of both fetal and intrauterine bleeding.

Anticoagulation presents a signifi cant practical problem in the management of atrial fi brillation, systemic or pulmonary embolism, thrombophlebitis, and pulmonary hypertension in pregnancy. The most vexing problem arises in the setting of prosthetic heart valves10,11 (dis-cussed later). In the case of mechanical valve prostheses, warfarin appears to be superior to heparin in preventing valvular thrombosis. Although heparin is safer for the fetus, there is probably an increased risk for the mother.20,24 This is a complex medical issue, and no random-ized trial to determine the optimal anticoagulant therapy for women with a prosthetic valve has been conducted. Therefore, recommenda-tions are based on smaller studies and on clinical judgment.10,11 No single regimen is likely to be applicable to all such cases, because the issue is complicated by the type and generation of the prosthetic valve, the cardiac rhythm, and the size and contractility of the cardiac chambers.

β-Adrenergic blocking agents, used for the treatment of hyper-tension and tachyarrhythmia, have been associated with neonatal respiratory depression, sustained bradycardia, and hypoglycemia when administered late in pregnancy or just before delivery. However, if they are used judiciously in selected cases (e.g., in women with cardiomy-opathy and heart failure), β-blockers are usually well tolerated.

The thiazide diuretics are another class of drugs that can produce harmful effects on the fetus—especially if they are used in the third trimester or for extended periods—and may impair normal expansion of plasma volume. Rarely, severe neonatal electrolyte imbalance, jaundice, thrombocytopenia, liver damage, and even death have been reported.

There have been numerous reports of fetal and neonatal renal complications after the use of angiotensin-converting enzyme (ACE)

inhibitors during pregnancy.25,26 These complications suggest a pro-found and deleterious effect on fetal renal function, leading to decreased renal function and oligohydramnios, as well as neonatal renal failure. ACE inhibitors are absolutely contraindicated during pregnancy. Another class of antihypertensive drugs, the angiotensin receptor blockers, also may affect fetal renal function and are likewise absolutely contraindicated in pregnancy.

The indications and possible adverse effects of commonly pre-scribed cardioactive drugs during pregnancy are summarized in Table 39-5.

Team Approach to Medical CareMedical care for pregnant women with heart disease is best provided through the cooperative efforts of a cardiologist who is familiar with the hemodynamic changes of pregnancy and an obstetrician. Frequent visits to both specialists, along with open consultations, can provide the patient with consistent advice and reassurance and can circumvent the worry and anxiety created by confusing and confl icting informa-tion. In addition, the anesthesiologist needs to be consulted during the antepartum period to outline the anticipated approach to intra-partum management, a time of maximum risk for most of these women. The role of the anesthesiologist and the approach to women with pregnancies complicated by cardiac disease are summarized in Chapter 56.

Congenital Heart DiseaseA number of simple congenital malformations are compatible with a normal or nearly normal pregnancy. Congenital malformations previ-ously associated with high maternal morbidity and mortality and fetal wastage now frequently end with a satisfactory outcome because of palliative or corrective surgery. Despite recent advances, however, women with congenital heart disease who become pregnant still have a signifi cant risk of miscarriage, cardiac complications, and premature delivery.27

The care of adults with congenital heart malformation is an impor-tant and growing branch of cardiology7,28,29 that requires the coopera-tive efforts of medical and pediatric cardiologists, cardiac surgeons, and, in the case of pregnancy, obstetricians and anesthesiologists.30,31

Left-to-Right Shunt

Atrial Septal DefectASD may be undiscovered before pregnancy, because symptoms are often absent and the physical fi ndings are not blatant. Other causes of left-to-right shunt, such as PDA and ventricular septal defect (VSD), are more likely to be discovered and treated in infancy or childhood. Physicians should be alert to the higher possibility of uncorrected defects in women who have immigrated from an undeveloped country.

Closure of uncomplicated large ostium secundum ASD is straight-forward and safe and usually is curative. Therefore, the procedure should be done before pregnancy. Many ASDs can now be closed per-cutaneously, using a “clamshell” or “umbrella” device inserted via a transvenous catheter.32 If the patient is unwilling to undergo ASD closure, she can be advised that the lesion is unlikely to complicate pregnancy and labor, provided that pulmonary hypertension is not present.3

TABLE 39-4 CARDIAC DISEASE IN PREGNANCY: ASPECTS OF MANAGEMENT

Activity restrictionDiet modifi cationTeam approach for medical careInfection controlImmunizationsProphylaxis against bacterial endocarditisProphylaxis against rheumatic feverInterruption of pregnancyCounselingContraception or sterilizationCardiovascular surgeryCardiovascular drugs

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TABLE 39-5 INDICATIONS FOR AND POSSIBLE ADVERSE EFFECTS OF COMMONLY PRESCRIBED CARDIOACTIVE DRUGS ON MOTHER AND FETUS

Drug Use in Pregnancy Potential Side Effects Breastfeeding Risk Category*

Adenosine Maternal and fetal arrhythmias No side effects reported; data on use during fi rst trimester are limited

Data NA C

Amiodarone Maternal arrhythmias IUGR, prematurity, congenital goiter, hypothyroidism and hyperthyroidism, transient bradycardia, prolonged QT in the newborn

Not recommended

C

ACEIs and angiotensin receptor blockers

Hypertension Oligohydramnios, IUGR, prematurity, neonatal hypotension, renal failure, anemia, death, skull ossifi cation defect, limb contractures, patent ductus arteriosus

Compatible X

β-Blockers Hypertension, maternal arrhythmias, myocardial ischemia, mitral stenosis, hypertrophic cardiomyopathy, hyperthyroidism, Marfan syndrome

Fetal bradycardia, low placental weight, possible IUGR, hypoglycemia; no information on carvedilol

Compatible; monitoring of infant’s heart rate recommended

Acebutolol: BLabetalol: CMetoprolol: CPropranolol: CAtenolol: D

Digoxin Maternal and fetal arrhythmias, heart failure

No evidence for unfavorable side effects on the fetus

Compatible C

Diltiazem Myocardial ischemia, tocolysis Limited data; increased incidence of major birth defects

Compatible C

Disopyramide Maternal arrhythmias Limited data; may induce uterine contraction and premature delivery

Compatible C

Diuretics Hypertension, congestive heart failure

Hypovolemia leads to reduced uteroplacental perfusion, fetal hypoglycemia, thrombocytopenia, hyponatremia, hypokalemia; thiazide diuretics can inhibit labor and suppress lactation

Compatible C

Flecainide Maternal and fetal arrhythmias Limited data; 2 cases of fetal death after successful treatment of fetal SVT reported, but relation to fl ecainide uncertain

Compatible C

Heparin Anticoagulation None reported Compatible CHydralazine Hypertension None reported Compatible CLidocaine Local anesthesia, maternal

arrhythmiasNo evidence for unfavorable fetal effects; high

serum levels may cause CNS depression at birth

Compatible C

Nifedipine Hypertension, tocolysis Fetal distress related to maternal hypotension reported

Compatible C

Nitrates Myocardial infarction and ischemia, hypertension, pulmonary edema, tocolysis

Limited data; use is generally safe; few cases of fetal heart rate deceleration and bradycardia have been reported

Data NA C

Procainamide Maternal and fetal arrhythmias Limited data; no fetal side effects reported Compatible CPropafenone Fetal arrhythmias Limited data; fetal death reported after direct

intrauterine administration in fetuses with fetal hydrops

Data NA C

Quinidine Maternal and fetal arrhythmias Minimal oxytocic effect, high doses may cause premature labor or abortion; transient neonatal thrombocytopenia and damage to eighth nerve reported

Compatible C

Sodium nitroprusside

Hypertension, aortic dissection Limited data; potential thiocyanate fetal toxicity, fetal mortality reported in animals

Data NA C

Sotalol Maternal arrhythmias, hypertension, fetal tachycardia

Limited data; 2 cases of fetal death and 2 cases of signifi cant neurologic morbidity in newborns reported, as well as bradycardia in newborns

Compatible; monitoring of infant’s heart rate recommended

B

Verapamil Maternal and fetal arrhythmias, hypertension, tocolysis

Limited data; other than 1 case of fetal death of uncertain cause, no adverse fetal or newborn effects reported

Compatible C

Warfarin Anticoagulation Crosses placental barrier; fetal hemorrhage in utero, embryopathy, CNS abnormalities

Compatible X

ACE, angiotensin-converting enzyme inhibitor; CNS, central nervous system; IUGR, intrauterine growth retardation; NA, not available; SVT, supraventricular tachycardia.*U.S. Food and Drug Administration classifi cation of drug risk. B: Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal reproduction studies have shown an adverse effect that was not confi rmed in controlled studies in women. C: Either studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drug should be given only if the potential benefi ts justify the potential risks to the fetus. D: There is positive evidence of human fetal risk, but the benefi ts from use in pregnant women may be acceptable despite the risk. X: Studies in animals or human beings have demonstrated fetal abnormalities. The risk of the use of the drug in pregnant women clearly outweighs any possible benefi t. The drug is contraindicated in women who are or may become pregnant.Source: Drug Information for the Health Care Professional (USDPI Vol 1). Micromedex, 23rd ed, January 1, 2003. (Adapted and modifi ed from Elkayam U. Pregnancy and cardiovascular disease. In Zipes DP, Libby P, Bonow RO, Braunwald E (eds): Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005, p 1965.)

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Metcalfe and colleagues33 reported one maternal death among 219 pregnancies in 113 women with ASD. Peripheral vasodilation, if any-thing, reduces the left-to-right shunt.17 Because ASD in young women is not associated with heart failure, diuretics and extreme limitation of intravenous infusion are not warranted. A small percentage of patients with ASD have atrial fl utter or fi brillation, which usually is paroxysmal. This arrhythmia can be managed along conventional lines, often with digoxin if necessary. The prospective mother should be informed that closure of the defect does not prevent atrial fi brillation once the arrhythmia has occurred.

ASD can be diffi cult to diagnose during pregnancy. The murmur associated with ASD may be inconspicuous, being a pulmonary ejec-tion systolic murmur and therefore not unlike the physiologic murmur of pregnancy. However, the second heart sound is widely split and may be fi xed throughout the respiratory cycle, a distinctly abnormal fi nding. The electrocardiogram (ECG) shows incomplete right bundle branch block and, in the case of the much more common ostium secundum defect, right axis deviation. In the less common ostium primum defect, marked left axis deviation accompanies incomplete right bundle branch block. The chest radiograph shows right atrial and right ven-tricular enlargement, prominent pulmonary arteries, and plethoric lung fi elds. Echocardiography establishes or confi rms the diagnosis (Fig. 39-1), obviating the need for cardiac catheterization in many cases.

Complicated Atrial Septal DefectIf atrial arrhythmias recur frequently—and especially if the heart rate is diffi cult to control—catheter ablation is successful in restoring normal sinus rhythm without the need for antiarrhythmic drugs. In most cases, this procedure should not be done until after delivery because of the extensive radiation exposure that is needed. In rare instances, pregnancy and labor may be associated with a paradoxical systemic embolus resulting from a thrombus migrating from the infe-rior vena cava across the ASD into the left atrium.

In the uncommon event that the patient is more than 35 years old and has an uncorrected large ASD, the likelihood of chronic atrial fi brillation, right ventricular dysfunction, and pulmonary hyperten-sion rises signifi cantly. Pregnancy is not advised if any of these sequelae is present. If the patient insists on going through with the pregnancy, prolonged bed rest will be required, and vigorous treatment of heart failure may be needed. The maternal risk is increased, and there is sig-nifi cant risk of fetal loss. Although warfarin is generally recommended for chronic atrial fi brillation, its use is best avoided (especially in the fi rst trimester); aspirin would be a reasonable compromise. Severe pulmonary hypertension is an uncommon feature of an ostium secun-dum ASD but is a contraindication to pregnancy. The ostium primum ASD, which is associated with Down syndrome and poses a risk of endocarditis, is more often associated with severe pulmonary hyper-tension. Infective endocarditis rarely, if ever, complicates a simple ostium secundum ASD; therefore, prophylaxis during labor is not warranted.

Ventricular Septal DefectThe clinical spectrum and risk of VSD may range from so mild that it has little or no effect on pregnancy to so high that maternal or fetal death can occur. Small defects in the muscular ventricular septum frequently close spontaneously during childhood. However, these defects occasionally persist, allowing a small left-to-right shunt, mani-fested by a loud pansystolic murmur along the left sternal border accompanied by a coarse thrill. The chest radiograph is often normal, as is the ECG. The echocardiogram is usually diagnostic (Fig. 39-2).

These fi ndings constitute the maladie de Roger. Prophylaxis against infective endocarditis is indicated, but otherwise this lesion has no effect on pregnancy or labor.

When the defect is in the membranous septum, spontaneous closure is rare. In the absence of signifi cant pulmonary vascular disease, the same pansystolic murmur and thrill are found. If the shunt is large, however, the lung fi elds are plethoric on chest radiography, and the heart and pulmonary arteries are enlarged. The classic ECG shows a pattern of biventricular hypertrophy. In such cases, fl ow through the pulmonary vascular bed is usually at least twice the systemic cardiac output. Patients with a relatively large, uncomplicated left-to-right shunt through a VSD tolerate pregnancy well and, in this respect, are comparable to patients with ASD. However, prophylaxis against endo-carditis is essential in cases of VSD.

Here it is appropriate to detour from clinical description to pathophysiology. Pulmonary vascular resistance is calculated as the pressure drop across the pulmonary vascular bed divided by the fl ow through it:

LA

RV

RA

LA

RV

RA

FIGURE 39-1 Transesophageal echocardiographic image of atrial septal defect (ostium secundum). In the upper panel, a large defect in the interatrial septum is present. In the lower panel, the blue/yellow color represents blood fl ow from the left atrium (LA) into the right atrium (RA). RV, right ventricle.

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R = (MPAP − MPCWP)/Qpulm

where R is pulmonary vascular resistance in Wood units; MPAP and MPCWP (in mm Hg) are the mean pulmonary arterial and capillary wedge pressures, respectively; and Qpulm is total fl ow through the right heart and pulmonary circulation (i.e., cardiac output plus left-to-right shunt) in liters per minute.

Resistance can be described in Wood units or in dyne·s/cm5. The Wood unit has the merit of simplicity and is derived from clinical units of pressure and fl ow. The more fundamental but less friendly dyne·s/cm5 can be obtained by multiplying Wood units by 80. Normal pul-monary vascular resistance is 0.5 to 1.5 units. When a clinician is faced with a pregnant woman with pulmonary hypertension, the key to her risk during pregnancy lies in the pulmonary vascular resistance. High fl ow, by itself, can be the mechanism for pulmonary hypertension without dangerous elevation in the resistance. This mechanism can be appreciated by rewriting the resistance equation to read

P = Q · R

where P is the pressure drop and Q is the fl ow across the pulmonary vascular bed.

A patient at one extreme may have a large shunt with pulmonary fl ow of 20 L/min and an R of 3 units, yielding an MPAP of 55 mm Hg (assuming a normal MPCWP of 5 mm Hg). At the other extreme, a patient with pulmonary vascular disease may have a pulmonary blood fl ow of 7 L/min and an R of 7 units, yielding an MPAP of 44 mm Hg. The higher the pulmonary vascular resistance (R), the greater the maternal risk. The risk is prohibitive when R reaches the systemic level (approximately 15 Wood units). In borderline cases (e.g., patients with R between 5 and 8 units), a pulmonary arteriolar vasodilating agent is sometimes administered to determine whether the increased resistance is partially reversible or completely irreversible. An increase in pulmo-nary vascular resistance of 3 to 4 units is considered mild, 5 to 7 units is moderate, and more than 8 units is severe.

VSD may be associated with considerable increase in pulmonary vascular resistance, refl ecting occlusive disease of the small pulmonary arteries and arterioles. This development, if it is to occur, usually does so in childhood; unless corrected, it leads to the Eisenmenger syn-drome (discussed later). However, a small number of adults may survive with VSD and pulmonary vascular resistance that is signifi -cantly elevated but falls short of the Eisenmenger syndrome. Such patients are at high risk for death during pregnancy or labor, and there is a high risk of fetal impairment or loss. The patient should be told that early therapeutic abortion would be the safest option, and that later pregnancy would be hazardous and would require intensive care, with physical exercise strictly curtailed and prolonged bed rest enforced. The combination of decreased physical activity, pulmonary hyperten-sion, and pulmonary vascular disease would constitute a sound ratio-nale for instituting anticoagulation, which is another reason why pregnancy is better avoided or terminated.

Some authorities strongly advise that delivery be effected prema-turely by means of cesarean section and urge sterilization at the same operation. The dangers must be thoroughly understood by women in this category who insist on continuing pregnancy.

Patent Ductus ArteriosusThe loud, continuous or machinery murmur of typical PDA with a large left-to-right shunt and no pulmonary vascular disease is so striking that the lesion is almost invariably detected and corrected in infancy or childhood. Occasionally, however, women of childbearing age or pregnant women from underdeveloped countries may present with a PDA. If the left-to-right shunt is large, the circulation is hyper-dynamic, with a wide arterial pulse pressure, low arterial diastolic pressure, and hyperactive precordium. The heart may be somewhat enlarged to clinical and radiologic examination, and the ECG may show left ventricular hypertrophy. The echocardiogram is useful for demonstrating a shunt between the two great vessels (Fig. 39-3). The signs of hyperdynamic circulation resulting from the PDA are exaggerated by pregnancy.

Because the murmur of PDA is systolic-diastolic, it is commonly referred to as a “continuous” murmur, although it usually peaks late in systole. Because of its characteristics, the murmur is also referred to as a “machinery” murmur. It is maximal in the left infraclavicular region. It must be distinguished from a venous hum, which is loudest in the neck rather than the infraclavicular area. Venous hum is common in pregnant women, and it changes dramatically with changes in the position of the head.

Division or occlusion of the PDA should be accomplished before pregnancy is undertaken. Currently, most PDAs can be closed by the insertion of an occluder device delivered via a percutaneous intravas-

rv lv

ra

la

rvlv

FIGURE 39-2 Transesophageal echocardiographic image of a small muscular ventricular septal defect. In the upper panel, a small communication is seen (arrow) between the right ventricle (rv) and left ventricle (lv). In the lower panel, color imaging confi rms blood fl ow between the two chambers. la, left atrium; ra, right atrium.

Ch039-X4224.indd 803 8/26/2008 4:07:25 PM


cular catheter.34 If a patient does become pregnant before PDA occlu-sion, an uncomplicated left-to-right shunt can be managed safely. Endocarditis is a risk in patients with PDA, and antibiotic prophylaxis is required. Embolic complications of infective endocarditis and end-arteritis secondary to PDA may take the form of infected pulmonary emboli. The patient becomes febrile with respiratory symptoms, and the chest radiograph shows multiple opacities and infi ltrates.

The leading cause of Eisenmenger syndrome is a large VSD, fol-lowed in prevalence by a large PDA. As with VSD, individuals with PDA may sustain severe increases in pulmonary vascular resistance with the corresponding pulmonary hypertension and right ventricular hyper-trophy, yet fall short of Eisenmenger physiology. The maternal risk during pregnancy is high in this situation, similar to that encountered in VSD with equivalent pathology. Treatment is the same as in VSD with Eisenmenger syndrome. When the pulmonary pressure rises, the aortopulmonary shunt decreases, and the murmur becomes progres-sively quieter and shorter, until it fi nally disappears.

In general, the woman with uncomplicated PDA tolerates preg-nancy well. If pulmonary hypertension supervenes, the risk to the mother becomes signifi cant. Therefore, if pulmonary hypertension is suspected and documented, termination of pregnancy is strongly recommended.

Eisenmenger SyndromeEisenmenger syndrome is characterized by a congenital communica-tion between the systemic and pulmonary circulations and increased pulmonary vascular resistance, either to systemic level (so that there is no shunt across the defect) or exceeding systemic (allowing right-to-left shunting). As mentioned, the most common underlying defect is a large VSD, followed in prevalence by a large PDA. Eisenmenger pathophysiology is less common in ASD. Occasionally, this type of pathophysiology develops in other, less common defects. By the time the syndrome is fully developed, it is often diffi cult clinically to diag-nose the underlying defect. For this discussion, the VSD serves as a good model (Fig. 39-4).

Eisenmenger pathophysiology develops only if the defect is large and is not restrictive, resulting in equal systolic pressure in the two

ventricles. It is more common in girls and develops at a young age. Therefore, when increased pulmonary vascular resistance is detected in a child with a large VSD, operative closure must be done as soon as possible to prevent the development of Eisenmenger pathophysiology. Once this has appeared, pulmonary hypertension is irreversible, and the VSD is consequently inoperable (unless lung transplantation is performed as well).

The major clues that pulmonary vascular resistance is increasing are (1) diminution of evidence of a left-to-right shunt and (2) the appearance of progressively severe pulmonary hypertension. The pan-systolic murmur of VSD or the continuous murmur of PDA is replaced by a short ejection systolic murmur. The lungs are no longer plethoric

PA

AO

FIGURE 39-3 Transesophageal echocardiographic image of a patent ductus arteriosus. A communication is present between the proximal portion of the descending aorta (AO) and the pulmonary artery (PA). Color imaging (arrow) confi rms blood fl ow from the aorta into the PA.

Head andupper extremities

Trunk andlower extremities

Arterial blood(fully saturated)

Small admixture ofvenous bloodNo visible cyanosis

Venous and arterialbloodCyanosis visible

Venous blood

Descendingaorta

LV

LA

RA

RV

IVC

SVC

PV

PV

PA

PA

AortaPA

Rightlung Left

lung

FIGURE 39-4 Eisenmenger complex. Here the cause of right-to-left shunt across the ventricular septal defect is increased pulmonary vascular resistance arising in the small pulmonary arteries and arterioles. IVC, inferior vena cava; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RV, right ventricle; SVC, superior vena cava. (Reprinted by permission of the publisher. From Taussig HB: Congenital Malformations of the Heart. Cambridge, Mass, Harvard University Press, 1960. Copyright © 1960 by the Commonwealth Fund by the President and Fellows of Harvard College.)

Ch039-X4224.indd 804 8/26/2008 4:07:27 PM


but show large central pulmonary arteries and small peripheral arteries characteristic of severe pulmonary hypertension. Because the shunt has disappeared, the radiographic cardiothoracic ratio returns to normal but the main pulmonary segment is prominent. There is usually a striking right ventricular heave, a loud and palpable pulmo-nary valve closure sound, and an ejection sound in early systole. When concentric ventricular hypertrophy gives way to dilatation and right-sided heart failure, evidence of tricuspid regurgitation appears. Until then, the mean venous pressure is normal but the amplitude of the a wave may be increased, refl ecting decreased right ventricular diastolic compliance.

If pulmonary vascular resistance is signifi cantly higher than sys-temic levels, right-to-left shunting of blood occurs and causes cyanosis and clubbing of the fi ngers and toes. This shunting of deoxygenated blood into the systemic circulation leads to hypoxemia and triggers a reactive erythrocytosis as the system attempts to increase peripheral oxygen delivery. This increases blood viscosity and can cause sludging and decreased fl ow of blood, especially in small vessels. A high hemat-ocrit value, however, is not an automatic indication for serial phle-botomy, because this approach can lead to iron defi ciency and microcytosis. Tissue hypoxia may then actually worsen, a particularly undesirable result in pregnancy. Phlebotomy is reserved for patients without evidence of iron defi ciency on laboratory testing who have symptoms of hyperviscosity, including headache, dizziness, visual dis-turbance, myalgia, and bleeding diathesis. Quantitative volume replace-ment is necessary during phlebotomy.

Attempted surgical correction of a congenital cardiac shunt after Eisenmenger syndrome is present usually results in the death of the patient.35 Many patients ultimately die of right-sided heart failure, pulmonary hypertension, or pulmonary hemorrhage.36

The woman with Eisenmenger syndrome must be informed that pregnancy carries a mortality risk of about 50%.37 Even if the mother survives, the outcome for the fetus is likely to be poor, because the fetal mortality rate exceeds 50% in cyanotic women with Eisenmenger syn-drome.36 Sudden death may occur at any time, but labor, delivery, and particularly the early puerperium seem to be the most dangerous periods.38 Any signifi cant fall in venous return, regardless of cause, impairs the ability of the right heart to pump blood through the high, fi xed pulmonary vascular resistance. Hypotension and shock can occur quickly and are often unresponsive to medical therapy.

The major physiologic diffi culty in pulmonary hypertension is maintenance of adequate pulmonary blood fl ow. Any event or condi-tion that decreases venous return, such as vasodilation on the systemic side of the circulation from epidural anesthesia or pooling of blood in the lower extremities from vena caval compression, decreases preload to the right ventricle and pulmonary blood fl ow. Therefore, manage-ment during pregnancy centers on the maintenance of pulmonary blood fl ow. If the patient insists on continuing her pregnancy, limita-tion of physical activity is essential, as is the use of pressure-graded elastic support hose, low-fl ow home oxygen therapy, and monthly monitoring of blood and platelet counts. Because of the precarious physiologic balance, a planned delivery should be performed with intensive care monitoring, including a Swan-Ganz catheter and provi-sions for skilled obstetric anesthesia care. Anesthetic considerations for this entity are discussed in Chapter 56.

On a more optimistic note, a report published in 1995 described 13 pregnancies in 12 women with Eisenmenger syndrome who elected not to accept advice to terminate pregnancy.39 Mean systolic pulmo-nary arterial pressure was 113 mm Hg. Three spontaneous abortions, one premature labor, and two maternal deaths occurred. The seven patients who reached the end of the second trimester were hospitalized

until term, treated with oxygen and heparin, and delivered by cesarean section. One patient died a month after delivery. Most of the infants were small, and one died. Despite this better-than-average outcome, pregnancy should not be encouraged in women with Eisenmenger syndrome or in those with a systemic level of pulmonary hypertension of any cause.

Primary Pulmonary HypertensionSevere idiopathic (“primary”) pulmonary hypertension, like the Eisenmenger syndrome, carries a high risk in pregnancy, and the same principles apply to its management. Pregnancy is not advised in women with this condition, because the mortality rate approaches 50%.40

Severe pulmonary hypertension can result from taking appetite-suppressing drugs. The fenfl uramine-phentermine regimen (“fen-phen”) was a notorious culprit41 and was withdrawn from the market. Treatment strategies include vasodilators, sometimes by chronic intra-venous infusion, and nitric oxide inhalation. In some 25% of cases, pulmonary arterial pressure is lowered by prostacyclin infusion.42 This response predicts a favorable response to chronic oral nifedipine administration and a good prognosis. Balloon atrial septostomy,43,44 through the foramen ovale or via transseptal puncture, can be used, in extreme cases of pulmonary hypertension, to relieve right heart pres-sure, usually as a bridge to transplantation.

Congenital Obstructive LesionsSome congenital cardiac malformations are characterized by obstruc-tion to left or right ventricular outfl ow. The more common examples include pulmonary stenosis, aortic stenosis, and coarctation of the aorta. The hypoplastic left heart syndrome seldom allows survival to childbearing age, and those who do survive usually have undergone a major palliative procedure, such as construction of a ventriculoaortic conduit with a prosthetic valve, that would constitute a strong contra-indication to pregnancy.

Mitral StenosisCongenital mitral stenosis is a rare malformation. When it is associated with an ASD, it constitutes the Lutembacher syndrome. Survival to childbearing age is usual. Both lesions tend to promote atrial fi brilla-tion. Ideally, the mitral valve and the atrial defect should be repaired before pregnancy.

Aortic Stenosis(see also the later section on aortic stenosis under Aortic Valve Disease)

Bicuspid aortic valve is one of the more common congenital malfor-mations that may lead to aortic stenosis, regurgitation, or both (Fig. 39-5). Often, aortic stenosis is not present during early life but pro-gresses over time because of valve calcifi cation and gradual restriction in leafl et motion. The bicuspid valve may occur as an isolated defect or in combination with other congenital anomalies, most commonly aortic coarctation. Congenital aortic stenosis, on the other hand, can be severe at birth and may cause severe left ventricular hypertrophy

Ch039-X4224.indd 805 8/26/2008 4:07:28 PM


that limits the ability of the heart to respond to demands for increased cardiac output.

In the syndrome of severe congenital aortic stenosis, the pulses are of slow upstroke and diminished amplitude. Unlike adults with acquired aortic stenosis, children and young adults with congenital aortic stenosis have an abnormally loud aortic valve closure sound. Left ventricular ejection is prolonged, so that the aortic valve closure sound may occur after the pulmonary valve closure sound. Therefore, split-ting of the second heart sound is paradoxical and is heard in expiration instead of inspiration. Often a loud ejection sound is heard in early systole. The duration of the ejection murmur and the time to its peak intensity increase with worsening severity of aortic stenosis.

The ECG shows severe left ventricular hypertrophy. The chest radiograph is characterized by poststenotic dilatation of the aorta. Although some patients complain of dyspnea, chest pain, and syncope, others remain asymptomatic. The lesion can be recognized and its severity assessed by Doppler echocardiography.

Critical calcifi c aortic stenosis is usually treated by aortic valve replacement in older patients, but aortic valve repair is often possible in younger women of childbearing age with congenital aortic stenosis. If aortic stenosis is severe—and especially if it is symptomatic—the woman should be advised against becoming pregnant. She should be advised that, if the aortic valve must be replaced, pregnancy and labor would be diffi cult and dangerous because of the need for anticoagulant treatment after a mechanical prosthesis is implanted. Maternal mortal-ity rates as high as 17% have been reported,45 although more recent data have suggested a somewhat lower risk. However, these studies also emphasize the adverse effects of severe maternal aortic stenosis on fetal outcomes, including increased rates of preterm delivery and intrauter-ine growth restriction.46 If aortic stenosis is moderate in severity, the patient should be advised to complete her pregnancies before the aortic valve is replaced. Labor can be managed in such cases without a high maternal or fetal risk, but assisted shortening of the second stage of labor is recommended.47

Strict limits on physical exertion and prolonged periods of bed rest may be required. Left ventricular failure may appear and may necessi-tate the use of diuretic agents and digitalis. Rarely, even in the presence of severe aortic stenosis, heart failure may be due to another cause (e.g., peripartum cardiomyopathy).48 Prophylaxis against bacterial endocar-ditis at delivery is recommended.

Vasodilators, helpful in patients with heart failure of other etiology, are dangerous in patients with aortic stenosis, because the impeded left ventricle may not be able to fi ll the dilated peripheral vascular bed. It should be remembered that the lowered systemic vascular resistance of pregnancy adversely affects aortic stenosis. The obstructed left ven-tricle is limited in its ability to fi ll the dilated peripheral bed, a situation that can lead to syncope or more serious manifestations of limited, relatively fi xed cardiac output.

Pulmonic StenosisThe murmur of pulmonic stenosis is loud and is often accompanied by a thrill. The lesion is usually detected in early childhood and is likely to have been corrected before the childbearing age. Expectant mothers who have not had adequate health supervision in childhood may have unrecognized pulmonary stenosis.

The diagnosis is suggested by a long, harsh systolic murmur over the upper left sternal border that is usually preceded by an ejection sound. The venous pressure is normal, but there are striking a waves in the jugular venous pulse. The pulmonary valve closure sound is usually too soft to hear when pulmonary stenosis is severe. Severe pulmonary stenosis causes massive concentric right ventricular hypertrophy; this is manifested by a left parasternal heave and by tall R waves and deeply inverted T waves in the right precordial leads of the ECG. Tall, pointed P waves are also present, denoting right atrial enlargement.

Right ventricular enlargement and poststenotic dilatation of the main and left pulmonary arteries are seen on the chest radiograph, which also may show slightly diminished peripheral pulmonary vas-culature. Echocardiography demonstrates limited opening of the pul-monic valve leafl ets (Fig. 39-6), right ventricular hypertrophy, and abnormally high velocity of blood fl ow in the pulmonary artery. Doppler echocardiography also allows calculation of the right ven-tricular pressure and the systolic pressure gradient across the valve. These pressures can also be measured directly in the hemodynamics laboratory (Fig. 39-7).

LA

AV

RVOT

FIGURE 39-5 Transesophageal echocardiographic image of a bicuspid aortic valve. During systole, only two aortic valve (AV) leafl ets are seen. LA, left atrium; RVOT, right ventricular outfl ow tract.

PA

RV

FIGURE 39-6 Transesophageal echocardiographic image of pulmonic stenosis. The pulmonic valve leafl ets exhibit characteristic doming (arrow). PA, pulmonary artery; RV, right ventricle.

Ch039-X4224.indd 806 8/26/2008 4:07:29 PM


Pulmonic stenosis is generally well tolerated so that neither preg-nancy nor labor poses a signifi cant threat.49 Prophylaxis against infec-tive endocarditis is necessary. More severe pulmonary stenosis requires treatment. Unlike aortic stenosis, however, critical pulmonary stenosis does not require valve replacement or open repair. Most cases are treated successfully with transvenous balloon valvuloplasty.50 Ideally, this should be carried out before pregnancy is undertaken; if a woman does become pregnant and develops intractable right-sided heart failure, the procedure can still be safely performed (but at some risk to the fetus). Extreme pulmonary stenosis (right ventricular systolic pressure > systemic systolic pressure) is a contraindication to preg-nancy until the lesion is adequately treated.

Right-to-Left Shunt without Pulmonary Hypertension (Tetralogy of Fallot)The congenital cyanotic heart diseases discussed so far have been asso-ciated with a communication between the pulmonary and systemic circulations and pulmonary vascular resistance suffi ciently high to cause a right-to-left shunt. However, cyanosis occurs in other congeni-tal malformations, in which there is a defect between the right and left sides of the heart but also right ventricular outfl ow obstruction (Figs. 39-8 and 39-9). Examples include the tetralogy of Fallot and tricuspid atresia.

Tetralogy of Fallot is used to illustrate this class of congenital mal-formation of the heart, because it is by far the most common form of cyanotic congenital heart disease encountered in pregnancy. Moreover, the offspring of a mother with tetralogy of Fallot has a 2% to 13% chance of inheriting the condition.51 The syndrome includes (1) a large defect high in the ventricular septum; (2) pulmonary stenosis, which may be at the valve itself but more commonly is in the infundibulum of the right ventricle; (3) dextroposition of the aorta so that the aortic orifi ce sits astride the VSD and overrides, at least in part, the right ventricle; and (4) right ventricular hypertrophy (Fig. 39-10).

A wide spectrum of clinical presentations may be present, depend-ing on the relative size of the VSD and the degree of right ventricular

outfl ow obstruction that diverts blood fl ow through the VSD. In the typical case, right and left ventricular systolic pressures are equal but the pulmonary artery pressure is exceedingly low. A loud, long systolic murmur is audible along the left sternal border. The murmur is caused by an abnormal fl ow pattern through the obstructed right ventricular outfl ow tract. The pulmonary valve closure sound is usually inaudible. Patients are usually cyanotic and often have signifi cant clubbing of the fi ngers and toes. The hematocrit value is greatly elevated because of the severe erythrocytosis. Phlebotomy is not indicated to treat the hematocrit level per se but is indicated if symptoms of hyperviscosity occur. Ignoring this important therapeutic principle leads to a micro-cytic anemia that further complicates pregnancy. The ECG shows severe right ventricular hypertrophy. The chest radiograph is charac-terized by a normal-sized heart and a concavity in the region where the pulmonary artery should be (Fig. 39-11). As in all malformations of this general type, the lung fi elds are oligemic, showing small vessels throughout.

Most adults born with the tetralogy of Fallot and lesions with similar pathophysiology have undergone surgical treatment before reaching young adulthood. Children raised in undeveloped countries are an important exception. Many patients have had surgery to close

FIGURE 39-7 Pressure tracings in severe pulmonary stenosis. Pulmonary pressure is extremely low and appears damped. Right ventricular pressure is suprasystemic. (From Shabetai R, Adolph RJ: Principles of cardiac catheterization. In Fowler NO [ed]: Cardiac Diagnosis and Treatment. Hagerstown, MD: Harper & Row, 1980, p 106.)

Tetralogy of Fallot Normal

LVAorta

Septaldefect

Pulmonaryartery

LV

RVRV

FIGURE 39-8 Tetralogy of Fallot. The anatomic pathology (left) compared with normal (right). Note the ventricular septal defect, the aorta (which overrides the defect), the pulmonary stenosis, and the right ventricular hypertrophy. LV, left ventricle; RV, right ventricle. (Reprinted by permission of the publisher. From Taussig HB: Congenital Malformations of the Heart. Cambridge, Mass, Harvard University Press, 1960. Copyright © 1960 by the Commonwealth Fund of the President and Fellows of Harvard College.)

RV

AOLV

MV

FIGURE 39-9 Transthoracic echocardiographic image of tetralogy of Fallot. A large ventricular septal defect is present, and the aorta (AO) overrides the interventricular septum. LV, left ventricle; MV, mitral valve; RV, right ventricle.

Ch039-X4224.indd 807 8/26/2008 4:07:29 PM


the VSD and relieve the pulmonary stenosis, constituting virtual “total repair” and rendering them potentially safe candidates for pregnancy and delivery. However, the operation is not curative. Signifi cant arrhythmia and conduction defects that may eventually lead to the need for electronic cardiac pacing or an implantable defi brillator may occur years after an apparently successful operation. Other sequelae and residua include only partial relief of the right ventricular outfl ow obstruction and pulmonic regurgitation. This latter problem is usually well tolerated early but may lead to right-sided heart failure, necessitat-ing reoperation. In addition, women with repaired tetralogy of Fallot and signifi cant pulmonic regurgitation have a higher risk of decom-pensation during pregnancy.52

The cyanotic patient with tetralogy of Fallot has special problems during pregnancy. The reduced systemic vascular resistance of preg-nancy causes more blood to shunt from right to left, leaving less to fl ow to the pulmonary circulation. This intensifi es hypoxemia and can lead to syncope or death. Maintenance of venous return is crucial. The most dangerous times for these women are late pregnancy and the early puerperium, because venous return is impeded by the large gravid uterus near term and by peripheral venous pooling after deliv-ery. Pressure-graded elastic support hose are recommended. Blood loss during labor may compromise venous return, and blood volume must be promptly and adequately restored. Anesthetic considerations during delivery are discussed in detail in Chapter 56. Antibiotic prophylaxis should be used in these susceptible patients at delivery.

Because of the combined high maternal risk and high incidence of fetal loss, pregnancy is discouraged in women with uncorrected tetral-ogy of Fallot. The prognosis is particularly bleak in those women with a history of repeated syncopal episodes, a hematocrit level greater than 60%, or a right ventricular systolic pressure greater than 120 mm Hg. If a young woman with untreated tetralogy of Fallot requests prepreg-nancy counseling, she should be advised to undergo surgical correction before pregnancy. Pregnancy does not represent a signifi cantly increased risk for patients in whom the VSD has been patched and the pulmonary stenosis corrected.

Coarctation of the AortaCoarctation of the aorta is a congenital defect in the area of the aorta where the ligamentum arteriosum and the left subclavian artery insert (the distal portion of the aortic arch). The malformation may be simple or complex, and it is either isolated or associated with PDA and other malformations, notably aortic stenosis and aortic regurgitation secondary to a bicuspid aortic valve. It may also occur in women with Turner syndrome. The lesion should be detected and treated surgically or by balloon dilation in infancy or childhood, but it may be present in women who are, or want to become, pregnant.

Typical features include the following:

� Upper extremity hypertension but lower extremity hypotension� Visible and palpable collateral arteries in the scapular area� A late systolic murmur, usually loudest over the interscapular

region� Femoral pulses that lag behind the carotid pulses and are of

diminished amplitude� Notching of the inferior rib borders seen on the chest radiograph

and resulting from erosion by arterial collaterals that bridge the coarctation

Electrocardiographic evidence of severe left ventricular hypertro-phy strongly suggests associated aortic stenosis. Surgical grafting or percutaneous intravascular balloon dilation reduces the upper extrem-ity hypertension, but blood pressure does not always return to normal, and hypertension may recur in later life.

Whenever possible, the operation should be performed before pregnancy; otherwise, the maternal mortality rate is approximately 3%. Coarctation is associated with congenital berry aneurysm of the circle of Willis and hemorrhagic stroke. The risk of stroke may increase during labor because of transient elevations in blood pressure. Patients are at risk for aortic dissection and infective endocarditis involving an abnormal aortic valve; these risks increase during pregnancy.53 Hypertension often worsens as well.54 Coarctation is also associated with an increased frequency of preeclampsia.31 The operation does not

Head andupper extremities

Trunk andlower extremities

Arterial blood(fully saturated)

Small admixture ofvenous bloodNo visible cyanosis

Venous and arterialbloodCyanosis visible

Venous blood

Descendingaorta

LV

LA

RA

RV

IVC

SVC

PV

PV

PA

PA

AortaPA

Rightlung Left

lung

FIGURE 39-10 Tetralogy of Fallot. Blood shunts from left to right through the ventricular septal defect because its fl ow to the lungs is impeded by pulmonary stenosis; this results in cyanosis. IVC, inferior vena cava; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RV, right ventricle; SVC, superior vena cava. (Reprinted by permission of the publisher. From Taussig HB: Congenital Malformations of the Heart. Cambridge, Mass, Harvard University Press, 1960. Copyright © 1960 by the Commonwealth Fund by the President and Fellows of Harvard College.)

Ch039-X4224.indd 808 8/26/2008 4:07:30 PM


require cardiopulmonary bypass and can be carried out with safety for the mother and with less fetal risk than accompanies open heart surgery with cardiopulmonary bypass. Although transvascular balloon dilation of aortic coarctation is a viable option for children and infants with coarctation, its use in adults is controversial.55 The procedure is well accepted for treatment of postsurgical renarrowing of the coarctation, but de novo balloon angioplasty carries a risk of aortic

dissection and rupture. A number of centers are now performing balloon dilation with stent implantation for adults with unoperated aortic coarctation, but large, multicenter studies are currently not available.56

If delivery must be undertaken in cases of unoperated coarctation, blood pressure can be titrated with β-adrenergic–blocking agents delivered by intravenous drip.

A B

C D

FIGURE 39-11 Tetralogy of Fallot. A, Chest radiograph. Note concavity in the area of the pulmonary artery, oligemic lungs, and right aortic arch. B, Right ventriculogram. Note the narrow right ventricular outfl ow tract. C, Further clarifi cation of the pulmonary arteries. The left ventricle is slightly opacifi ed via the ventricular septal defect. D, The associated right-sided aortic arch is now visible. (From Shabetai R, Adolph RJ: Principles of cardiac catheterization. In Fowler NO [ed]: Cardiac Diagnosis and Treatment. Hagerstown, MD: Harper & Row, 1980, p 106.)

Ch039-X4224.indd 809 8/26/2008 4:07:30 PM


Other Congenital Cardiac MalformationsEbstein AnomalyEbstein anomaly is a malformation of the tricuspid valve in which the septal leafl et is displaced apically and the anterior leafl et is abnormally large in size. The deformed tricuspid valve apparatus may be signifi -cantly incompetent or stenotic, depending on the location of the anomalously placed cusps of the valve. In some cases, the malforma-tion causes impediment to right ventricular outfl ow.

The clinical features are easily recognized by a cardiologist, and the echocardiogram is characteristic and reliable (Fig. 39-12). This syn-drome is frequently associated with anomalous atrioventricular con-duction pathways and with the Wolff-Parkinson-White syndrome. Patients may also have an ASD with right-to-left shunting and cyano-sis. Supraventricular arrhythmias are also common.

The most favored treatment is reconstruction of the tricuspid valve, for which satisfactory techniques have now been developed. The opera-tion should be performed before pregnancy is undertaken. Interrup-tion of anomalous conduction pathways also can be performed during surgery.

The Mayo Clinic group57 reported on 111 pregnancies in 44 women with Ebstein anomaly resulting in 95 live births, although most of the infants had low birth weight. Vaginal delivery was performed in 89% and cesarean section in 9%; 23 deliveries were premature. Nineteen pregnancies ended with spontaneous abortion, and seven ended with therapeutic abortion. Congenital heart disease occurred in 6% of the children of mothers with Ebstein anomaly.

Congenital Atrioventricular BlockCongenital atrioventricular block differs somewhat from heart block in adults. The pacemaker is usually junctional, and therefore the QRS complex is normal or only slightly widened and the ventricular rate is

more rapid than in acquired complete atrioventricular block. Although these patients appear to do well during childhood and young adult-hood, the lesion is associated with an unexpectedly high mortality rate. Therefore, treatment with a pacemaker is indicated in many of the cases.58 The pacemaker used should be dual-chamber and rate-responsive, so that normal cardiovascular dynamics at rest and exercise will be preserved. Patients who are untreated or who have received a pacemaker are at slight to no increased risk during pregnancy.

Additional MalformationsA number of other malformations may be present in women of child-bearing age, including

� Other left-to-right or right-to-left shunts� Transposition of the great vessels� Truncus arteriosus� Single-ventricle double-outlet right ventricle� Various obstructive lesions

The malformations may be multiple and complex. Survival to adulthood depends on at least partial correction, which may have been furnished by surgical operation or may be part of the malformation. For example, in D-type transposition of the great vessels, the aorta arises from the right ventricle and the pulmonary artery from the left. Survival requires a shunt at some level (ASD, VSD, or PDA) so that oxygenated blood can enter the systemic circulation.

Some of these women with untreated and delicately balanced lesions bear children, but usually this is not wise to attempt. Transposi-tion of the great vessels is now treated by anastomosis of the aorta to the morphologic left ventricle and of the pulmonary artery to the morphologic right ventricle. Lesions such as single ventricle may be palliated by the Fontan procedure, in which venous return is connected directly to the pulmonary circulation, bypassing the right side of the heart. Neither procedure constitutes a cure, but successful pregnancy can occur.

In summary, patients should be evaluated and tracked by a cardi-ologist who is experienced in congenital heart disease and by a mater-nal-fetal medicine specialist with knowledge and experience in managing pregnancy in women with congenital cardiac lesions.7,31

Rheumatic Heart DiseaseRheumatic FeverRheumatic fever is now distinctly uncommon in the United States, Canada, Western Europe, and Great Britain, but it is still prevalent in less economically developed countries. Young female immigrants to the Western world constitute a large proportion of the patients with a history of rheumatic fever. These women are at risk of developing rheumatic valvular heart disease 10 to 20 years after the initial episode of rheumatic fever.

Chronic Rheumatic Heart DiseaseIn the United States, acute rheumatic fever with carditis has been uncommon for many years, and chronic rheumatic heart disease, which manifests years to decades after the episode of acute rheumatic fever, is becoming uncommon among the native childbearing popula-tion. Control of rheumatic fever has largely shifted the burden of

RV

RA

FIGURE 39-12 Ebstein anomaly. The right atrium (RA) and right ventricle (RV) are markedly dilated, and the tricuspid valve is displaced toward the cardiac apex.

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rheumatic heart disease from teenagers to women in the third and fourth decades of life.

The characteristic lesion of rheumatic heart disease is mitral steno-sis, and the next most common manifestation is the combination of mitral stenosis with aortic regurgitation. The mitral valve may become both stenotic and incompetent, and the valve may calcify. Pure mitral regurgitation is almost always nonrheumatic, except in young people with acute carditis. Similarly, aortic valve disease without mitral involvement is seldom rheumatic. Tricuspid regurgitation is a late secondary manifestation that occurs secondary to pulmonary hyper-tension and right ventricular enlargement.

Mitral StenosisThe principal features are enlargement of the left atrium and right ventricle, a diastolic murmur at the cardiac apex, and pulmonary hypertension. Infl ow to the left ventricle is impeded by the narrowed valve and can be accomplished only by an increased level of pressure in the left atrium (Figs. 39-13 and 39-14). The faster the heart rate, the less time in diastole, and the less time for ventricular fi lling. Left atrial pressure therefore is further elevated by tachycardia. Atrial fi brillation

eventually supervenes, causing a fall in cardiac output and escalation of left atrial hypertension, especially if the ventricular rate is not con-trolled. Atrial fi brillation substantially increases the probability of thrombus in the left atrial appendage and the threat of a subsequent embolic stroke.

Effect of PregnancyPregnancy drastically stresses the circulation in women with severe mitral stenosis. The increased blood volume, heart rate, and cardiac output raise left atrial pressure to a level that causes severe pulmonary congestion, leading to progressive exertional dyspnea, orthopnea, par-oxysmal nocturnal dyspnea, and pulmonary edema. Women who have not been receiving antenatal care often present initially with severe pulmonary edema during pregnancy. In long-standing cases, severe right-sided heart failure develops. Infective endocarditis, pulmonary embolism, and massive hemoptysis may also occur. The maternal risk for death is highest in the third trimester and in the puerperium.10,11

Signifi cant Mitral Stenosis without

Heart FailurePatients who have mitral stenosis without heart failure should be advised to undergo percutaneous balloon mitral valvuloplasty and to postpone pregnancy until after full recovery from the procedure. If they do not follow this advice and do become pregnant, one reasonable course in the fi rst trimester may be pregnancy termination, followed by mitral valve operation and subsequent pregnancy planning. If this is not acceptable, the patient can be advised to remain under frequent close supervision by the cardiologist and obstetrician and to accept long periods of rest, prohibition of strenuous activity, salt restriction, and diuretic treatment. If this type of regimen is followed closely and is expertly supervised, maternal mortality is low.10,11 Atrial fi brillation signals the need for digitalis, a β-adrenergic blocking agent, or a calcium channel blocking agent to maintain a normal heart rate. More than one of these drugs may be needed to achieve the desired result without side effects. For patients with atrial fi brillation and signifi cant mitral stenosis, anticoagulant treatment is recommended.

Depending on her course, the woman may have to spend many weeks in bed and should be admitted to the hospital well in advance

ECG

ECG

mm Hg100

mm Hg40

20

0

75

50

25

0

LA

LV

1 sec.

LV

Wedge

A

B

LA

LV

AO

FIGURE 39-13 Hemodynamics of mitral valve disease. A, Mitral stenosis. The diastolic pressure gradient (shaded area) between the left atrium (LA) and left ventricle (LV) persists to end-diastole. B, Mitral regurgitation. Note the large systolic pressure wave of the pulmonary wedge pressure tracing. The diastolic pressure gradient is limited to early diastole. ECG, electrocardiogram.

FIGURE 39-14 Transesophageal echocardiographic image of mitral stenosis. During diastole, opening of the mitral valve is restricted by scarring and fusion of the leafl et tips. Characteristic doming of the leafl et is also present. AO, aorta; LA, left atrium; LV, left ventricle.

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of labor. The supine posture should be avoided as much as possible, and delivery in the left lateral decubitus position is desirable. The lithotomy position, with the patient on her back and her feet elevated in stirrups, is an invitation to pulmonary edema. The crisis of pulmo-nary edema may appear despite good management. Sedation (to drop the heart rate and promote cardiac fi lling and output) and diuretic treatment must then be followed by prompt delivery if the fetus is viable.

Percutaneous balloon valvuloplasty is a nonsurgical means to dilate mitral stenosis and is the current treatment of choice for most patients with symptomatic mitral stenosis.59,60 The procedure can be done during pregnancy if heart failure is severe, and it appears to be safer for the fetus than open mitral commissurotomy.61 Lead shielding should be used, because fl uoroscopy is required to guide the balloon into the mitral orifi ce. Balloon valvuloplasty should be used with caution during pregnancy, and it should be reserved for women who are unresponsive to aggressive medical therapy.10,11 If possible, the procedure should be put off at least until after the fi rst trimester. Patients with confi rmed mitral stenosis and right-sided heart failure with severe pulmonary congestion should avoid pregnancy until after the valvular disease is corrected, because the risk of maternal mortality is high.

Mitral Valve ProlapseIn the past, a degree of prolapse of the mitral valve was considered so prevalent in the general population,62 particularly among young women, that authorities differed as to whether mitral valve prolapse (MVP) should be considered a normal variant or abnormal. More exacting echocardiographic criteria have yielded more realistic and much lower estimates of the prevalence of MVP (perhaps 1% of the female population).63

True MVP occurs because portions of the mitral valve apparatus are redundant and, therefore, the leafl ets balloon into the left atrium during systole. The leafl ets may remain coapted during systole, or they may separate, causing a variable degree of mitral regurgitation. More severe prolapse may be caused by myxomatous degeneration of the mitral leafl ets. These abnormalities of connective tissue may be isolated to the mitral valve, or they may be a part of Marfan syndrome (see later discussion). MVP (and sometimes tricuspid valve prolapse) may be associated with congenital malformations, notably ASD.

Mitral regurgitation may be absent, intermittent, or permanent and may be of any degree of severity. Severe mitral regurgitation greatly enlarges the left atrium (Fig. 39-15) and ventricle and eventually leads to left ventricular failure and pulmonary hypertension, the latter less severe than with mitral stenosis.

Past reports have associated MVP with a number of disorders, including stroke, dysautonomia, panic attacks, anxiety, and transient ischemic attacks,64,65 but more recent studies66,67 have discounted almost all of these associations. The syndrome of myxomatous mitral valve degeneration with prolapse and mitral regurgitation is quite uncommon, and many women who were diagnosed with MVP more than 10 years ago do not have any actual pathology. For this reason, it may be prudent to order an echocardiogram for any woman who was diagnosed with MVP a number of years ago if she has no symptoms or signs of mitral regurgitation. This may prevent needless and repeated exposure to antibiotics (e.g., before dental procedures).

Some women with MVP complain of chest pain, which can be sug-gestive of angina pectoris. Although the coronary arteriogram is normal, T-wave inversions, especially in leads II, III, and aVF, are found

in a small proportion, and the treadmill exercise test may induce ST-segment depression, indistinguishable from ischemia.68

In most cases, the diagnosis of MVP is made by the physician pro-viding pre-conception counseling and antenatal care. The examination reveals a systolic click occurring between the fi rst and second heart sounds. The click may or may not be followed by a midsystolic or late systolic murmur. The click and murmur vary with the patient’s posture and hydration status. In most patients, no other abnormality is found on clinical examination. Unless signifi cant mitral regurgitation is present, the patient should be told that pregnancy, labor, and delivery will be safe and unaffected by the prolapse.

Patients with MVP and signifi cant mitral regurgitation are far fewer in number than those with simple prolapse. The murmur is louder, longer, and may become pansystolic. Clinical and laboratory evidence of enlargement of the left atrium and ventricle increases with increas-ing severity and duration of regurgitation. Even modest impairment of left ventricular function, especially if it is progressive, indicates that pregnancy may well precipitate heart failure and cannot be lightly undertaken. More obvious left ventricular dysfunction (e.g., EF < 40%) indicates that the woman should be strongly advised to avoid preg-nancy. She should then be referred for complete cardiologic evalua-tion2 and surgery to address the mitral regurgitation. In most cases of MVP, the valve can be repaired rather than replaced. It is important to appreciate that left ventricular function deteriorates after mitral valve replacement but may improve after mitral valve repair.69 Thereafter, if the result is good and ventricular function is signifi cantly improved, pregnancy may be undertaken successfully.

Chest pain and arrhythmias are best managed with β-adrenergic blockers such as atenolol or metoprolol. If symptoms are unusually pronounced, thyroid function tests should be checked as well. Because the gravid uterus and vasodilation may add to postural hypoten-sion, the patient should be informed that she may experience light-headedness, dizziness, or fainting with prolonged standing during pregnancy.

RV LV

RA

LA

FIGURE 39-15 Transthoracic echocardiographic image of severe mitral regurgitation. During systole, the mitral valve does not coapt properly, and an eccentric jet of mitral regurgitation is present (arrows). LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

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Mitral Regurgitation Not Caused by ProlapseIn younger women, mitral regurgitation may be a result of rheumatic or congenital disease. In older women, mitral regurgitation is more often a manifestation of hypertension, ischemia, idiopathic myocardial disease, or infective endocarditis.

Most of the information regarding mitral regurgitation in prolapse also applies here. In older women, the valve is more likely to be calci-fi ed; fewer of the valves are amenable to repair and must be replaced. The problems posed by prosthetic valves in pregnant women are dis-cussed later in this chapter; the hemodynamics are illustrated in Figure 39-13, and echocardiography is illustrated in Figure 39-15.

In patients with far-advanced left ventricular dysfunction or failure who have severe mitral regurgitation, it can be diffi cult to determine which is the cause and which the result. In either case, the patient with a greatly enlarged and hypokinetic ventricle must be advised against becoming pregnant. Most of the pregnancy would be spent in bed, the course would be punctuated by episodes of uncompensated congestive heart failure (any of which could prove fatal or require therapeutic abortion), and the risk to the fetus would exceed 50%.

Pregnancy in patients with mild or moderate mitral regurgitation can be managed safely with a conservative regimen of reduced physical activity, salt restriction, and low doses of a diuretic agent. Low-dose digoxin may be helpful if atrial fi brillation supervenes. As mentioned previously, severe mitral regurgitation indicates a need for repair or replacement of the valve when symptoms and/or early evidence of declining ventricular function appear.2,70 Clearly, surgical treatment is best undertaken before pregnancy. If the woman is already pregnant, the physician should make every effort to help her to carry the preg-nancy to term using strict medical measures. This course is particularly important if clinical, radiologic, and echocardiographic criteria suggest that the valve is irreparable and would require replacement.

Aortic Valve DiseaseAortic Stenosis(see also the earlier section on aortic stenosis under Congenital Obstructive Lesions)

The etiologic mechanism of aortic stenosis commonly is degeneration, often of a congenitally bicuspid valve. The problem may be encoun-tered in women a decade or more older than those with rheumatic or congenital aortic valve disease. The combination of aortic and mitral stenosis is usually caused by rheumatic heart disease. Critical aortic stenosis leads to severe left ventricular hypertrophy and, eventually, to left ventricular failure. Before overt heart failure develops, syncope or even sudden death may occur.

The characteristic fi ndings include an ejection systolic murmur that is harsher and longer and peaks later than the normal ejection murmur of pregnancy. It is usually loudest at the second right intercostal space. If aortic stenosis is severe, the pulse upstroke is slow, and left ventricu-lar hypertrophy is evident on the ECG. The echocardiogram is a more sensitive and more specifi c marker of left ventricular hypertrophy. Doppler echocardiographic measurement of blood fl ow velocity through the aortic valve permits reliable estimation of the systolic pressure drop across the valve, as well as calculation of the valve area. The hemodynamics are illustrated in Figure 39-16. The left ventricle in women remodels differently than in men. The concentric hypertro-

phy is more pronounced, the cavity is smaller, and systolic function is supranormal.

The left ventricle does not dilate until the ventricle fails, and so a dilated ventricle in aortic stenosis is an ominous sign that calls for rapid intervention. In general, aortic valve replacement is preferred to percutaneous balloon aortic valvuloplasty, but open heart surgery presents a high risk to the fetus. For this reason, some have advised balloon aortic valvuloplasty for treatment of aortic stenosis during pregnancy,71 but valve replacement will almost certainly have to be done soon after delivery.

Hemodynamic monitoring is recommended during labor in patients with moderate to severe aortic stenosis. Vaginal delivery is preferred, with assisted second stage of labor. If cesarean section is performed, some have suggested that general anesthesia is preferred.72 See Chapter 56 for more details regarding anesthesia management.

Pregnancy in women with a mechanical aortic valve replacement must be undertaken with great caution and meticulous management, because continuous anticoagulation is necessary (see Pregnancy in Patients with Artifi cial Heart Valves, later).

Aortic RegurgitationThe etiologic mechanism of aortic regurgitation is commonly rheu-matic heart disease, in which case mitral stenosis often coexists. Other diseases, such as Marfan syndrome, bicuspid aortic valve, infective endocarditis, and systemic lupus erythematosus, also may cause severe aortic regurgitation. This valvular lesion imposes a volume rather than a pressure overload on the heart and, as such, is usually well tolerated in pregnancy and labor.15

FIGURE 39-16 Hemodynamic data in aortic stenosis. Left ventricular pressure is 250/40 mm Hg (normal, 120/10 mm Hg). Aortic systolic pressure is 130 mm Hg lower than the left ventricular pressure and shows a slow upstroke and vibrations representing the systolic thrill. The record above the aortic pressure tracing is a phonocardiogram showing the systolic murmur. Also shown is the pulmonary wedge pressure (lowest pressure tracing), which is elevated to equal the left ventricular diastolic pressure. The bottom tracing is the electrocardiogram. (From Shabetai R, Adolph RJ: Principles of cardiac catheterization. In Fowler NO [ed]: Cardiac Diagnosis and Treatment. Hagerstown, MD: Harper & Row, 1980, p 106.)

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The diagnosis is usually based on the fi nding of a typical, high-pitched, blowing diastolic murmur and can be quantifi ed by Doppler echocardiography. Both pregnancy and aortic regurgitation contribute to hypervolemia and peripheral vasodilatation. A prolonged course without decompensation is characteristic of chronic aortic regurgita-tion; once heart failure appears, however, the course may progress rapidly downhill.

Traditionally, aortic valve replacement is not recommended until symptoms of heart failure (most notably exertional dyspnea) occur or left ventricular dysfunction/enlargement is seen on echocardiography. Repair of aortic regurgitation is much less successful than repair of mitral regurgitation. For a woman who is contemplating pregnancy, the need for aortic valve replacement constitutes the grounds on which the medical advisor should caution against pregnancy and make the patient fully understand the consequences of choosing otherwise. If left ventricular dysfunction and heart failure are absent, carefully supervised pregnancy is in order, and the woman should be encour-aged to complete her family before cardiac dysfunction and the need for valve replacement arise.

In many cases, the cause of aortic regurgitation is unclear. Special care must be taken to rule out aortic aneurysm or dissection, especially if aortic regurgitation is associated with Marfan syndrome or coarcta-tion of the aorta, because these conditions can result in aortic rupture and constitute strong reasons to advise against pregnancy.

Drug-Induced Valvular Heart DiseaseA recently recognized cause of deformity and regurgitation of the cardiac valves is ingestion of the drug combination, fenfl uramine-phentermine. The revelation of this side effect led to withdrawal of this drug combination from the market in the late 1990s. The mechanism of the effect of these drugs is unclear, and there is evidence that valvular lesions may sometimes gradually improve after discontinuation of the drugs.73 In some cases, however, valve surgery has been necessary.74

CardiomyopathyCardiomyopathy is a disorder of myocardial structure or function. A number of forms exist, and several types that are seen in pregnant women are discussed here.

Dilated CardiomyopathyIn dilated cardiomyopathy, the cardiac chambers are severely dilated and the left ventricle is diffusely hypokinetic. Left ventricular wall tension is increased, and systolic pump function progressively declines. Consequently, cardiac output falls and fi lling pressures increase; both of these changes cause progressive dyspnea, edema, and fatigue. Serious ventricular arrhythmia develops in most cases.

Despite advances in treatment, the 5-year survival rate in patients with dilated cardiomyopathy and symptomatic heart failure approaches 50%. In some cases, however, improvement or even return to normal has been noted. Both ACE inhibitors and β-adrenergic blocking agents (most notably carvedilol) have been shown to slow the deterioration of left ventricular function in patients with congestive heart failure and occasionally to actually improve the left ventricular EF.75 In addition, some of the patients who recover may have had unrecognized myocar-

ditis that did not progress to cardiomyopathy. Dilated cardiomyopathy may be the outcome of an autoimmune response to a myocardial injury, most commonly viral myocarditis. The exact role of alcohol is unclear, but it is at least a major aggravating factor in some cases.

Patients may have symptoms and signs of heart failure for which no cause can be found on clinical and laboratory examination. Weight is increased, the jugular venous pressure is elevated, and the heart is enlarged. An S3 gallop is often present, frequently accompanied by the murmurs of mitral and tricuspid regurgitation, which develop as a consequence of cardiac dilatation. The ECG is usually abnormal, often showing left ventricular hypertrophy or left bundle branch block. Echocardiography shows enlargement and hypocontractility of the ventricles. The patients are subject to mural thrombus in the cardiac chambers with a consequent risk of stroke or pulmonary embolism. Established dilated cardiomyopathy, even when heart failure is com-pensated, is a contraindication to pregnancy.

It was formerly thought that dilated cardiomyopathy was sporadic and not familial, but inherited cases have now been observed. It is estimated that 20% of cases are genetic in origin.13 Therefore, if an extensive family history of heart failure is present, the prospective mother and father should be informed of the potential risk of genetic transmission.

In a young woman with severe dilated cardiomyopathy, manifested by greatly impaired ventricular function and drastically reduced exer-cise capacity, cardiac transplantation should be considered. Successful pregnancy has been reported in women who have undergone heart or heart-lung tranplantation.76-78

Peripartum CardiomyopathyPeripartum cardiomyopathy is a form of dilated cardiomyopathy that occurs in the last month of pregnancy or during the fi rst 5 months after delivery, in the absence of previous heart disease.79 The incidence in the United States is 1 case per 3000 to 4000 live births. Additional diagnostic criteria include a left ventricular EF of less than 45% and, most importantly, the absence of other identifi able causes of heart failure.80 Whether the peripartum or postpartum state somehow con-stitutes the original myocardial insult or is an aggravating factor in individuals susceptible to cardiomyopathy for other reasons is not known.81 It has been suggested that some cases are caused by active myocarditis,82 but other investigators have reported that the incidence of myocarditis is the same in idiopathic and peripartum cardiomyopa-thy.83 It is also possible that the stress of pregnancy may “unmask” an underlying cardiomyopathic process that might otherwise have mani-fested later in life.84 This devastating disease can affect previously healthy young women and can cause unexpected sudden death.85

The clinical course of peripartum cardiomyopathy is frustratingly variable and diffi cult to predict.86 About 20% of patients have a dra-matic and fulminant downhill course and can be saved only with cardiac transplantation. Others, perhaps 30% to 50%, have partial recovery with persistence of some degree of cardiac dysfunction. The rest show remarkable recovery.81 Apparently, the initial degree of left ventricular dysfunction does not predict the long-term outcome.87 A recent study showed that cardiac function improved gradually over a 5-year period.88

Women who recover from peripartum cardiomyopathy must be informed that cardiomyopathy may recur with a subsequent preg-nancy. For some time, this risk has been believed to be 50%.87 However, one report of four women who had peripartum cardiomyopathy with a previous pregnancy but whose hearts remained normal clinically and by echocardiography in a subsequent pregnancy indicated that the risk

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may be less.89 The largest study to date of patients with a history of peripartum cardiomyopathy who subsequently became pregnant90 showed that heart failure recurred in 20% of those patients whose EF had normalized after the previous pregnancy. None of these patients died during the study period. However, heart failure recurred in 40% of the patients who had persistent left ventricular dysfunction after their previous pregnancy, and the maternal mortality in this group was 19%. A study from Haiti of 15 women with peripartum cardiomyopa-thy showed a recurrence rate of almost 50% during a subsequent pregnancy.91 Therefore, the risk of recurrent heart failure is high in women with peripartum cardiomyopathy, especially in those who do not have complete recovery of left ventricular function.

Treatment is similar to that for other patients with heart failure. Because ACE inhibitors are contraindicated during pregnancy hydrala-zine is the vasodilator of choice. If cardiac dysfunction is severe, anticoagulation is usually recommended, given the prothrombotic tendency of pregnancy. Low-molecular-weight heparin (LMWH) is probably preferred to unfractionated heparin (warfarin is not recommended).86

Idiopathic Hypertrophic CardiomyopathyHypertrophic cardiomyopathy, which is usually inherited as an auto-somal dominant trait with variable penetrance but sometimes is caused by a spontaneous mutation, is being recognized with increasing fre-quency. The phenotypes vary greatly. Left ventricular outfl ow tract obstruction may or may not be present, and the hypertrophy may be either symmetrical or asymmetrical. The chief symptoms are angina, dyspnea, arrhythmia, and syncope. Sudden death is a feature mostly confi ned to patients in whom the diagnosis is established in childhood or youth, patients with a history of syncope or ventricular arrhythmia, and patients with a family history of hypertrophic cardiomyopathy and sudden death. Recent research has shown that certain specifi c genetic defects place patients at great risk for sudden death.

When the disease is fi rst detected in older adults, the course is more benign and sudden death is rare. Left ventricular hypertrophy is often apparent on clinical examination and ECG and is invariably present on the echocardiogram. The echocardiographic fi ndings are often diagnostic and include marked thickening of the ventricular septum, usually with less thickness of the other walls of the left ventricle (asym-metrical hypertrophy), and abnormal systolic anterior movement of the mitral valve (Fig. 39-17). The internal dimensions of the left ventricle are normal to small, and its contractility is increased.

An important feature in many cases is obstruction of the space between the ventricular septum and the anterior leafl et of the mitral valve. This space constitutes the left ventricular outfl ow tract. Outfl ow obstruction by the anterior mitral valve leafl et is worsened by increased inotropy, decreased heart size, and diminished peripheral vascular resistance. The normal fall in peripheral vascular resistance that accompanies pregnancy tends to increase outfl ow tract obstruction, although this effect may be compensated for by the physiologic increase in blood volume. In addition, vena caval obstruction in late pregnancy and blood loss at delivery, both of which may result in hypotension, can have a similar deleterious effect. Outfl ow tract obstruction may also be worsened by the increases in circulating catecholamine levels frequently encountered during labor and delivery. The Valsalva maneu-ver during the second stage of labor may greatly diminish heart size and increase outfl ow tract obstruction. Despite all these problems, however, most pregnant women with hypertrophic cardiomyopathy do tolerate labor and delivery.92

There is a complex interplay between the hemodynamics of the cardiomyopathy and those of pregnancy, neither of which is constant. Exacerbation of symptoms93 and even sudden death94 have been reported during pregnancy in women with obstructive cardiomyopa-thy. Treatment is aimed at avoiding hypovolemia, maintaining venous return, and diminishing the force of myocardial contraction by avoid-ing anxiety, excitement, and strenuous activity.

Because left ventricular diastolic compliance can be greatly reduced in this disease, excessive or too rapid volume repletion can induce pulmonary edema. β-Adrenergic blockade is considered fi rst-line pharmacologic therapy for symptomatic hypertrophic cardiomyopa-thy and can be continued or instituted during pregnancy. The dose

A

B

LA

AO

LV

LA

AO

LV

FIGURE 39-17 Transesophageal echocardiographic images of hypertrophic cardiomyopathy. A, During diastole the anterior leafl et of the mitral valve (arrow) is in a normal position. B, During systole the leafl et (arrow) is pulled by Venturi forces into the left ventricular outfl ow tract, causing obstruction to outfl ow. AO, aorta; LA, left atrium; LV, left ventricle.

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should be the minimal effective dose needed to avoid excessive slowing of the fetal heart.

Esmolol can be given intravenously if the patient fi rst presents with severe symptoms. Volume replacement and vasopressor therapy may be needed, along with β-adrenergic blockers. Calcium channel block-ers, such as verapamil, have been shown to be effective in reducing symptoms, but they must be used cautiously because they can cause pulmonary edema in severe cases. Nifedipine, because of its vasodilator properties, is best avoided.

Vaginal delivery is almost always appropriate in the absence of an obstetric indication for abdominal delivery. Impaired venous return is highly undesirable in hypertrophic cardiomyopathy and can be ame-liorated by managing the second stage of labor with the patient in the left lateral decubitus position.

Acquired Immunodefi ciency SyndromeMyocarditis or cardiomyopathy is frequently discovered on postmor-tem examination of patients with acquired immunodefi ciency syndrome (AIDS).95,96 Symptomatic myocardial disease, although considerably less common, also occurs. If patients with full-blown AIDS are screened for cardiac involvement (e.g., by echocardiography), cardiac or pericardial involvement is found in almost 75% of the cases.97 In some cases, these abnormalities are transient.98 Myocarditis is usually caused by opportunistic infection, but in some cases hybrid-ization studies have proved direct AIDS infection. Clinical fi ndings range from occult ventricular dysfunction to severe uncompensated heart failure. Rarely, even Kaposi sarcoma has been detected in the heart or pericardium. Pericardial effusion, often occult, is one of the more common cardiac manifestations and suggests a worse progno-sis.99 Malignant lymphoma involving the myocardium and endocar-dium has been reported as well. In the current era of highly-active antiretroviral therapy (HAART), myocardial involvement has become considerably less common in patients with human immunodefi ciency virus (HIV) infection. However, some classes of antiretroviral drugs appear to cause dyslipidemia, and this can lead to an increased risk of coronary artery disease (CAD) and subsequent myocardial infarction.100

Cardiac failure ranks low on the list of problems faced by the physi-cian managing pregnancy complicated by AIDS. Nevertheless, physi-cians need to be on guard lest severe dilated cardiomyopathy, myocarditis, or cardiac tamponade develop, and the pregnant woman must be treated appropriately to prevent transmission of HIV to her offspring (see Chapter 38.)

Coronary Artery DiseaseBecause premenopausal women enjoy substantial protection against coronary atherosclerosis,15 ischemic heart disease is rarely relevant to obstetric practice. However, CAD may be found in women of child-bearing age when other risk factors, such as insulin-dependent diabe-tes, smoking, or severe dyslipidemia, overwhelm the natural protection they should normally enjoy. Lupus erythematosus, especially when treated with steroidal agents, may precipitate premature CAD. Coro-nary atherosclerosis appears in a signifi cant proportion of patients who have received a cardiac transplant101 and may be observed in familial lipid disorders. In the latter instance, the exact nature of the lipid disorder must be defi ned by detailed analysis of the patient’s lipid chemistry and lipoproteins to enable the physician to provide an accurate forecast of the risk that the infant would inherit the lipid

disorder and premature CAD. In women with CAD or severe dyslip-idemia, oral contraceptives may be detrimental.102 In addition, spasm of anatomically normal coronary arteries leading to myocardial infarction has been reported.103 Finally, as mentioned earlier, women with HIV infection may develop dyslipidemia on HAART, which can increase the risk of CAD.100

Spontaneous coronary artery dissection is quite rare and occurs chiefl y in young women during or soon after pregnancy.104,105 Treat-ment has included placement of a stent, emergency coronary bypass operation, and thrombolysis.106-109 Although coronary artery dissection is very uncommon, it is extremely important to consider this diagnosis whenever a woman presents with severe chest pain in the peripartum period. If the coronary artery dissection remains undetected, massive myocardial infarction and even death can occur. If the diagnosis is made expediently, however, outcome appears to be quite good, and long-term survival is expected.110

Management of Stable Angina Pectoris

Women with CAD who experience angina pectoris only at high levels of exertion should be treated with β-adrenergic blocking drugs, aspirin, and lipid-lowering agents. In this setting, the likelihood of signifi cant complications during pregnancy, labor, or delivery is low. If there is any question regarding the severity of myocardial ischemia, however, stress testing should be performed before pregnancy is attempted. Similarly, a woman who previously sustained a myocardial infarction but recovered without heart failure, signifi cant left ventricular dysfunc-tion, or unstable angina pectoris can also be advised that her pregnancy and labor should be relatively uncomplicated.

The major indications that pregnancy and labor would pose a sig-nifi cant risk to a woman with ischemic heart disease are the presence of overt heart failure, signifi cant enlargement or dysfunction of the left ventricle, and ischemia at rest or provoked by mild exertion.

Severe Myocardial Ischemic Syndromes: Unstable AnginaThe diagnosis of severe ischemia may be confi rmed if angina occurs at rest or with mild exertion. This unstable angina frequently, but not necessarily, follows a period of classic stable angina pectoris. Unstable angina is a clear warning of the imminence of a major ischemic event, such as acute myocardial infarction or a fatal ventricular arrhythmia. Starting a pregnancy under these circumstances is not advisable, and aggressive treatment (including coronary angiography followed by percutaneous coronary intervention or coronary artery bypass surgery) is recommended. If the outcome is satisfactory, pregnancy can then be considered.

In some women with CAD, the clinical picture is less dramatic but a treadmill exercise test demonstrates that profound and dangerous ischemia can be precipitated by minimal exertion. If the treadmill test provokes an abnormal response at a low level of exercise, and particu-larly if this response is accompanied by either angina pectoris or a fall in blood pressure, the woman is at high risk for a serious and possibly fatal myocardial ischemic event and must not undertake pregnancy unless the myocardium can be revascularized.

Pregnant women who develop unstable ischemia require aggressive treatment in an intensive care unit. If the ischemia proves intractable, percutaneous coronary intervention (e.g., stenting) or bypass graft surgery will be necessary.111 If possible, the coronary bypass operation

Ch039-X4224.indd 816 8/26/2008 4:07:35 PM


should be performed without cardiopulmonary bypass to help decrease the risk to the fetus.112

Myocardial InfarctionAcute myocardial infarction complicates about 1 in 10,000 pregnan-cies.113 The highest incidence appears to occur in the third trimester and in older (>33 years) multigravidas. The maternal mortality rate is high (about 20%), and death usually occurs at the time of infarction or during labor and delivery.114 Coronary angiography in this popula-tion demonstrated atherosclerosis in about 40% of cases, coronary thrombosis without atherosclerosis in 20%, and coronary dissection in 16%, but 30% had normal coronary arteries.114 Treatment of acute myocardial infarction during pregnancy should include use of heparin and β-blockers (unless acute heart failure is present). The use of thrombolytics in pregnancy is controversial, because there is increased risk of maternal hemorrhage. Therefore, percutaneous coronary inter-vention (with stenting) is probably the procedure of choice. Obviously, this exposes the fetus to radiation, and so extensive lead shielding should be used.

A remote myocardial infarction, followed by recovery without angina, major left ventricular dysfunction, or heart failure, should have little infl uence on pregnancy or labor. Patients should wait a year after an infarction before undertaking pregnancy. In many cases, coronary arteriography should be done fi rst so that, if critical coronary stenoses are found, myocardial revascularization can be performed. Severe left ventricular damage and heart failure are contraindications to pregnancy.

For remote myocardial infarction without evidence of ischemia, heart failure, or severe left ventricular dysfunction, simple electrocar-diographic monitoring suffi ces during labor. If a large myocardial infarction has occurred during pregnancy, then arterial blood pressure, central venous pressure, pulmonary arterial and pulmonary wedge pressure, and cardiac output should be monitored invasively. Monitor-ing should be continued until after the completion of labor, because maternal preload abruptly increases with the birth, after which sub-stantial loss of blood can accompany delivery of the placenta.

Heart FailureChronic heart failure is a syndrome that develops when the heart cannot meet the metabolic requirements of the normally active indi-vidual. It may be defi ned as ventricular dysfunction causing dyspnea, fatigue, and sometimes arrhythmia. The lesion may be an intrinsic myocardial abnormality. Examples include myocarditis, the various cardiomyopathies, ischemic heart disease, other specifi c myocardial disorders (e.g., amyloidosis), and metabolic abnormalities (e.g., myx-edema). The myocardial response to chronic pressure overload is con-centric hypertrophy with increased thickness of the ventricular walls; the response to chronic volume overload is dilation (eccentric hyper-trophy). Contractile power is eventually diminished with either type of overload, resulting in decreased pump function of the heart. Causes include valvular disease, systemic and pulmonary hypertension, and congenital malformations. The clinical manifestations result in part from the abnormal loading conditions and in part from the damaged myocardium.

ManifestationsThe principal manifestations of heart failure are caused by increased left and right ventricular diastolic pressure, which engenders pulmo-

nary and systemic congestion, and reduced cardiac output (during exercise or, in severe cases, at rest as well). The combined effects of inadequate cardiac output and congestion are dyspnea, fatigue, and edema. In the later stages of heart failure, these changes lead to progres-sive dysfunction of vital organs, principally the liver and kidneys. The prognosis of severe uncorrectable heart failure is quite poor, and preg-nancy is absolutely contraindicated.

The critical clinical features that enable physicians to diagnose and monitor the course of heart failure are body weight, jugular venous pressure, the S3, cardiac size, radiologic evidence of pulmonary conges-tion, pulmonary rales, and peripheral edema. Echocardiography is an extremely useful tool for evaluating left ventricular function and prog-nosis in heart failure115 and should be performed without delay if heart failure is suspected. Circulating B-type natriuretic peptide (BNP) is increased in congestive heart failure. Serum BNP levels provide an effective, inexpensive, and quickly available test for heart failure. The degree of BNP increase correlates with the severity of heart failure.116

The presence of heart failure greatly limits physical activity and warrants several or all of the following treatments:

� Continuous, usually escalating courses of diuretic drugs� β-Adrenergic receptor blockers� ACE inhibitors (or, if these are not well tolerated, angiotensin

receptor blockers)—note that these agents are contraindicated during pregnancy and should be replaced by hydralazine

� Salt restriction� Digoxin

If heart failure is fi rst discovered during pregnancy, episodes of cardiac decompensation that do not respond to adjustment of orally administered medicine necessitate admission to an intensive care unit. There, the effects of treatment on cardiac output, pulmonary arterial pressure, systemic venous pressure, and pulmonary wedge pressure, along with the maternal and fetal ECGs, can be monitored. If the hemodynamic parameters and clinical condition indicate continuing deterioration despite maximal medical therapy, emergency abdominal delivery may be necessary.

Asymptomatic Left Ventricular DysfunctionThere is a remarkable lack of correlation between symptoms of heart failure and objective evidence of left ventricular dysfunction.117 For example, patients with chronic heart disease after myocardial infarc-tion may have a considerably enlarged and extremely hypokinetic ven-tricle and yet be relatively free from symptoms. For this reason, any woman who has sustained myocardial damage should have left ven-tricular function assessed by echocardiography before deciding on pregnancy.

Cardiac TransplantationSome women with advanced heart failure become successful recipients of a cardiac transplant. Successful pregnancy and delivery in patients with cardiac transplantation have been reported.78 Medical treatment after transplantation is complex because of the immunosuppressive drug regimen, the frequent endomyocardial biopsies, and the uncer-tain long-term prognosis. Women should delay pregnancy for at least 1 year after cardiac transplantation, by which time the risk of acute rejection and the intensity of immunosuppression and biopsy surveys are considerably less.

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Disturbances of Cardiac RhythmIsolated supraventricular and ventricular extrasystoles are very common, and no treatment is necessary. Pre-conception counseling is simplifi ed by a clear appreciation of several general principles.

Arrhythmia that occurs in the absence of organic heart disease is almost always benign and is therefore not an indication for pharma-cologic treatment unless the woman fi nds the symptoms intolerable. Reassuring her of the benign nature of this symptom is often all that is required. Sustained symptomatic arrhythmia, however, requires treatment, which can be pharmacologic or procedural (e.g., transcath-eter ablation of an anomalous conduction pathway, insertion of an implantable cardiac defi brillator).

Pregnancy and labor should be safe except in the group with sustained ventricular arrhythmia, with its attendant risk of cardiac arrest and need for vigorous treatment. Pharmacologic treatment for serious arrhythmia is likely to include newly introduced agents, such as amiodarone or sotalol, for which there is at best limited knowledge of potentially unfavorable effects on the fetus. Ideally, pregnancy should be postponed until the arrhythmia has been eliminated or at least controlled, preferably by nonpharmacologic means. If antiar-rhythmic drugs must be used, whenever possible they should be those that have been used for several decades, allowing prediction of the fetal risk.

High-grade atrioventricular conduction disturbance, especially if it is symptomatic, is treated by artifi cial pacing, which should not infl u-ence pregnancy, labor, or the fetus. Electrical cardioversion or defi bril-lation of the mother’s heart does not disturb or damage the fetal heart.118

It is clearly desirable to evaluate disturbances of cardiac rhythm and conduction before pregnancy, proceeding to full electrophysiologic testing if indicated. This plan avoids exposing a fetus to potentially toxic antiarrhythmic agents and the radiation associated with electro-physiologic investigation.

Marfan SyndromeMarfan syndrome is variably expressed and inherited as an autosomal dominant trait. If it is left untreated, life expectancy is reduced by half in those who exhibit the classic syndrome. The basic defect is one of connective tissue, particularly fi brillin, and connective tissue weakness in the aorta causes the dangerous complications, most notably aortic dissection.119

Symptoms and signs may include dyspnea and chest pain, an aortic diastolic murmur, and a midsystolic click. The best diagnostic test, and apparently the most critical one for determining the outcome of preg-nancy, is the echocardiogram. More than 90% of patients have evi-dence of MVP, and 60% have echocardiographic evidence of aortic root dilatation.120

Pregnancy is particularly dangerous for patients with this syn-drome, because there appears to be a high risk of aortic rupture and dissection, especially if dilatation of the aortic root is present.47 Women with an aortic diameter exceeding 40 mm are at greatest risk of death during pregnancy.121 The physician should also make sure the woman understands the 50% risk of genetic transmission of Marfan syndrome to her children.

Defi ciency of elastic tissue is the cause of myxomatous degenera-tion of the aortic and mitral valves and cystic medial necrosis of the aorta (Figs. 39-18 and 39-19). This abnormality translates to large aneurysms of the aortic root, multiple aneurysms elsewhere along the course of the aorta and great vessels, and severe aortic and mitral regurgitation with resulting heart failure. Surgery is indicated for rapidly expanding aneurysm or if dissection is evident. Pregnancy is poorly tolerated under these conditions, and labor may precipitate rupture of an aneurysm or aortic dissection.

If a woman with Marfan syndrome chooses to become pregnant, therapy is directed at markedly limiting physical activity, preventing hypertensive complications, and decreasing the pulsatile forces on the aortic wall with the use of a β-blocker. Long-acting β-blockers are indicated before, during, and after pregnancy in women with Marfan syndrome.122 Once the aortic root diameter reaches 50 to 55 mm, most authorities recommend prophylactic aortic valve and root replacement because of the high risk of aortic dissection. Abdomi-nal delivery is recommended to avoid the hemodynamic stress of labor.

FIGURE 39-18 Aortic aneurysm. Aortogram showing an aneurysm of the ascending aorta (AO) with regurgitation of contrast through an incompetent aortic valve (arrows) into the left ventricle (LV). (From Shabetai R, Adolph RJ: Principles of cardiac catheterization. In Fowler NO [ed]: Cardiac Diagnosis and Treatment. Hagerstown, MD: Harper & Row, 1980, p 106.)

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Pregnancy in Patients with Artifi cial Heart ValvesPregnancy in women with artifi cial heart valves is one of the most complex and challenging areas where cardiology and obstetrics inter-sect, and it could be the topic of an entire chapter itself. The discussion here covers three basic groups of patients:

1. Women contemplating pregnancy who are likely to need a valve replacement in the medium- to long-term future, such as women with moderate aortic or pulmonic stenosis, severe but asymp-tomatic mitral or aortic regurgitation with normal myocardial function, or mild to moderate mitral stenosis

2. Women who wish to become pregnant but have severe valve disease that must be addressed expediently, including those with severe aortic or mitral stenosis, severe mitral regurgitation with cardiac dysfunction, or severe aortic regurgitation with cardiac dysfunction

3. Women with mechanical valve replacements who become pregnant.

The only group for whom no management controversy exists is the fi rst.123 Without question, women who are likely to need valve surgery in several years should be strongly encouraged to complete their child-bearing as quickly as possible—so that they will not become members of the second or third group.

Women in the second group require valve replacement before preg-nancy. In most adult patients younger than 70 years of age (but not in women who wish to become pregnant), mechanical prosthetic valves would be favored over biologic prostheses, because biologic valves have a shorter life span and deteriorate much more quickly than mechanical valves. This difference appears even more pronounced in younger patients; it was once thought that pregnancy itself hastened biologic valve deterioration, but this does not appear to be true.124 In any case, younger patients with biologic valves will almost certainly require repeat surgery. With mechanical valves, however, the patient faces the

requirement for lifelong anticoagulation and the resultant small increase in risk of bleeding.

It is important to note that the anticoagulant of choice with a mechanical valve is warfarin, not heparin. Although heparin is clearly safer for the fetus,125 it is not equivalent to warfarin in preventing thromboembolic complications (especially during the prothrombotic state of pregnancy). This has been shown in several studies and appears to be most striking in the case of single tilting-disk mechanical pros-theses.8,24 Therefore, many experts agree that women who require valve surgery before pregnancy should receive a bioprosthetic valve—even though repeat surgery will be necessary in the future—because these valves have a much lower thromboembolic risk and do not usually require systemic anticoagulation. Women with normally functioning biologic valve replacements tolerate pregnancy well.

Management of the last group (i.e., women with mechanical cardiac valves who become pregnant) is the most diffi cult. A woman with a mechanical prosthetic heart valve should be counseled strongly that pregnancy is risky, primarily because of the risk of embolic phenom-ena. If the patient decides to proceed with pregnancy, warfarin is supe-rior to heparin for preventing thromboemboli with mechanical valves. However, warfarin is teratogenic and carries a 4% to 10% risk of war-farin embryopathy.126,127 This risk appears to be dose dependent as well.23 For these reasons, the U.S. manufacturer of Coumadin (warfa-rin) states that the drug is absolutely contraindicated during preg-nancy. Although warfarin is used during pregnancy in Europe (after the fi rst 12 weeks) and is recommended until the 35th week of preg-nancy, American physicians face a particularly diffi cult dilemma because of the manufacturer’s contraindication (even though this con-tradicts guidelines from acknowledged expert panels).2,10,11 In addition, many pregnant women would prefer to put themselves rather than the fetus at risk. Therefore, subcutaneous or intravenous heparin is used during pregnancy in many American women with mechanical heart valves, even though thromboembolic risk is higher.127,128 During treat-ment with heparin or LMWH, the activated partial thromboplastin time (or anti-Xa heparin levels) must be monitored frequently. In addition, the dose must be adjusted as the patient gains weight during pregnancy. There is some evidence that LMWH is superior to unfrac-tionated heparin in nonpregnant patients with mechanical prosthe-ses,129 and this approach has been used successfully in a number of pregnant patients.130,131 However, in a recent small study of enoxaparin in pregnant women with prosthetic heart valves, two of eight patients developed prosthetic valve thrombosis leading to maternal and fetal death.132 It is unclear but possible that these women did not receive adequate dosing of enoxaparin. Randomized trials have not been per-formed, and more information is needed before LMWH can be recom-mended over unfractionated heparin in this setting.133

Tables 39-6 and 39-7 show two currently proposed protocols for anticoagulation in the pregnant woman with a mechanical heart valve. Most authorities recommend using heparin through the fi rst trimester, although continuous use of warfarin until week 35 is an option in high-risk patients (those with fi rst-generation tilting-disk prostheses in the mitral position).10,11 The joint American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Man-agement of Patients with Valvular Heart Disease2 stress the impor-tance of discussing the risks and benefi ts of various anticoagulation approaches with the patient, because she must be a full partner in her medical care. She must be informed that if she chooses to change from warfarin to heparin during the fi rst trimester (or for the entire preg-nancy), she has a higher risk of both thrombosis and bleeding, and any risk to her jeopardizes the baby as well. Table 39-6, from Elkayam and

XA

AOLV

LA

FIGURE 39-19 Marfan syndrome. The echocardiogram shows a markedly dilated aortic root, measuring 7.4 cm in diameter (normal, ≤3.5 cm). A, annulus diameter (7.43 cm); AO, aorta; LA, left atrium; LV, left ventricle.

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Bitar,11 stratifi es treatment options by risk of thrombosis and recom-mends consideration of continuing warfarin throughout the preg-nancy (until week 35) for patients with fi rst-generation valves in the mitral position, atrial fi brillation, or a history of previous embolic events. The treatment options in Table 39-7, from the American College of Chest Physicians134 are simpler, but they do not differentiate on the basis of the type of mechanical valve or its position (aortic versus mitral). Consultation and close follow-up during pregnancy with an experienced cardiologist is strongly recommended, as well as meticu-lous attention to blood coagulation testing. Because preterm labor occurs frequently in this group,24 warfarin should be replaced by thera-peutic doses of subcutaneous heparin beginning at the 35th week of

gestation. If labor occurs while a patient is taking warfarin, cesarean section is recommended to avoid fetal cerebral hemorrhage during vaginal delivery.2

All patients with prosthetic heart valves require antibiotic prophy-laxis for dental and surgical procedures and at delivery. Prevention of prosthetic valve endocarditis is essential, because the mortality rate can reach 40%. The patient who experiences endocarditis with a prosthetic valve must receive aggressive antibiotic therapy and often will require valve replacement. Obviously, the risk to the fetus is exorbitant.

Cardiac Surgery during PregnancyWhenever possible, any woman who requires cardiac surgery should undergo the procedure before becoming pregnant. Nevertheless, as explained previously, in rare instances a patient may require surgery during pregnancy. Valvular surgery has been performed successfully during pregnancy for many years, and patients have also undergone coronary artery bypass surgery and emergency aortic dissection repair. Cardiac surgery during pregnancy does not appear to increase the maternal mortality risk.135,136 There is, however, a 10% to 15% risk of fetal mortality because of the nonpulsatile blood fl ow and hypotension associated with conventional cardiopulmonary bypass. Therefore, whenever possible, cardiac surgery should be performed without car-diopulmonary bypass. In addition, hypothermia should be avoided, because this appears to be especially dangerous to the fetus. In one study, fetal mortality was decreased by half when normothermic perfu-sion was used instead of hypothermic perfusion.136 Hypothermia stimulates uterine contractions and impairs oxygen delivery to the fetus, mandating careful monitoring of the uterus and the fetal heart. The deleterious effect of hypothermia on umbilical blood fl ow has been documented by transvaginal ultrasonography.137

Experimental studies suggest that fetal survival can be improved by the use of pulsatile perfusion, but results are not yet clear. If bypass is required for cardiac surgery at an immature gestational age, high-fl ow high-pressure normothermic perfusion should be instituted.138 If pos-

TABLE 39-6 RECOMMENDED APPROACH FOR ANTICOAGULATION PROPHYLAXIS IN WOMEN WITH PROSTHETIC HEART VALVES (PHV) DURING PREGNANCY

Higher Risk* Lower Risk†

Warfarin (INR 2.5-3.5) for 35 wkfollowed byUFH (mid-interval aPTT >2.5) or LMWH (pre-dose anti-Xa ≈ 0.7) +

ASA 80-100 mg qd

SC UFH (mid-interval aPTT, 2.0-3.0) or LMWH (pre-dose anti-Xa ≈ 0.6) for 12 wk

followed byWarfarin (INR 2.5-3.0) for 35 wkthenSC UFH (mid-interval aPTT 2.0-3.0) or LMWH (pre-dose anti-Xa ≈ 0.6)

OR OR

UFH (aPTT 2.5-3.5) or LMWH (pre-dose anti-Xa ≈ 0.7) for 12 wkfollowed byWarfarin (INR 2.5-3.5) to 35th wkthenUFH (mid-interval aPTT >2.5) or LMWH (pre-dose anti-Xa ≈ 0.7) +

ASA 80-100 mg qd

SC UFH (mid-interval aPTT 2.0-3.0) or LMWH (pre-dose anti-Xa ≈ 0.6) throughout pregnancy

aPTT, activated partial thromboplastin time; ASA, acetylsalicylic acid; INR, international normalized ratio; LMWH, low-molecular-weight heparin; SC,

subcutaneous; UFH, unfractionated heparin.

*First-generation PHV (e.g., Starr-Edwards, Bjork-Shiley) in the mitral position, atrial fi brillation, history of thromboembolism on anticoagulation.†Second-generation PHV (e.g., St. Jude Medical, Medtronic-Hall) and any mechanical PHV in the aortic position.

Reproduced with permission from Elkayam U, Bitar F: Valvular heart disease and pregnancy. Part II: Prosthetic valves. J Am Coll Cardiol 46:403, 2005.

TABLE 39-7 RECOMMENDATIONS OF THE SEVENTH ACCP CONSENSUS CONFERENCE ON ANTITHROMBOTIC THERAPY FOR PROPHYLAXIS IN PATIENTS WITH MECHANICAL HEART VALVES

1. Aggressive adjusted-dose UFH, q12h SC throughout pregnancy; mid-interval aPTT time maintained at >2× control levels, or anti-Xa heparin level maintained at 0.35 to 0.70 IU/mL

OR

2. LMWH throughout pregnancy, in doses adjusted according to weight or as necessary to maintain a 4-h postinjection anti-Xa heparin level of about 1.0 IU/mL

OR

3. UFH or LMWH, as above, until the 13th week; then change to warfarin until the middle of the third trimester, then restart UFH or LMWH therapy until delivery

ACCP, American College of Chest Physicians; aPTT, activated partial

thromboplastin time; LMWH, low-molecular-weight heparin; SC,

subcutaneous; UFH, unfractionated heparin.

Data from Bates SM, Greer IA, Hirsh J, Ginsberg JC: Use of

antithrombotic agents during pregnancy: The seventh ACCP

conference on antithrombotic and thrombolytic therapy. Chest

126:627S, 2004.

Ch039-X4224.indd 820 8/26/2008 4:07:36 PM


sible, surgery should be postponed until the third trimester, when the fetal risk is considerably reduced. Fetal bradycardia is often seen during surgery and may require rapid treatment, usually with intravenous nitroprusside. In addition, preterm labor occurs more frequently in women undergoing cardiac surgery.

During surgery and in the immediate postoperative period, these patients should be monitored very closely. In general, use of intra-arterial and Swan-Ganz catheters and electrocardiographic monitoring of the woman and the fetus is recommended. Transesophageal echo-cardiography is also helpful in some cases and provides direct assess-ment of valvular and ventricular function. Maintenance of acceptable arterial oxygen levels and normal blood pressure, plus avoidance of hypothermia, are of utmost importance to the fetus.

The Use of Prophylactic Antibiotics to Prevent Infective Endocarditis in Pregnant Women with Heart DiseaseThe most recent recommendations from the American Heart Associa-tion (AHA) regarding the use of prophylactic antibiotics represent a major departure from previous guidelines and are summarized here because of the importance of this information to those caring for women with heart disease. The most prominent aspect of the new guidelines is that antibiotics to prevent infective endocarditis (IE) are now recommended only for those patients deemed to be at the highest risk. These high risk cardiac conditions include:

1. Prosthetic heart valve or prosthetic material used for cardiac valve repair

2. Previous IE3. Congenital heart disease (CHD)

Unrepaired CHD, including palliative shunts and conduitsCompletely repaired congenital heart defect with prosthetic mate-

rial or device, whether replaced by surgery or by catheter inter-vention, during the fi rst 6 months after the procedure (during the process of endothelialization)

Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)

4. Cardiac transplantation recipients who develop cardiac valvulopathy

The reader is referred to the AHA publication for additional details and the consensus panel’s rationale.139

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