Heart Disease in Pregnancy November 8, 2008 Henry Green, MD, FACC, FACP Physiology of pregnancy Physiologic changes of pregnancy Pregnancy represents a high output state, with decreased peripheral vascular resistance and increased cardiac output and blood volume. Blood pressure is reduced. These changes peak during the second trimester, and continue through the rest of pregnancy. They may last six months into the postpartum period. Various signs and symptoms may develop during normal pregnancy. Fatigue, lightheadedness, dyspnea and edema are all common. Physical examination may show a displaced apical impulse, prominent splitting of the first and second heart sounds, jugular venous pulsations, and a soft systolic ejection murmur. The ECG may show right or left axis deviation, atrial or ventricular premature complexes, nonspecific ST or T wave changes and sinus tachycardia. The echocardiogram can show increase left ventricular diastolic dimension, functional mitral and tricuspid regurgitation, or a small pericardial effusion. Risk assessment Low risk Small left to right shunt Repaired lesion without residual defect Isolated mitral valve prolapse without significant regurgitation Mild to moderate pulmonary stenosis Valvular regurgitation with normal ventricular function Intermediate risk Unrepaired or palliated cyanotic congenital heart disease Large left to right shunt Uncorrected coarctation of aorta Mitral stenosis Moderate aortic stenosis Prosthetic valve Severe pulmonic stenosis Moderate to severe systemic ventricular dysfunction High-risk features NYHA Class III or IV symptoms Significant pulmonary hypertension Marfan syndrome with aortic root or major valvular involvement Eisenmenger syndrome Severe aortic stenosis

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Drugs used during pregnancy Medications are categorized as to their safe use in the pregnant patient as follows: Category A: Possibility of fetal harm is remote Category B: No studies demonstrate risk to fetus Category C: Only animal studies show fetal risk. Use only if potential risk justified. Category D: Evidence of fetal risk in humans. Use only if the risk is justified. Category X: Risk of drug outweighs benefit because of fetal risk. Valvular heart disease Mitral stenosis Hypervolemia and tachycardia exacerbate mitral stenosis. The occurrence of atrial fibrillation further complicates the problem, and can result in acute pulmonary edema. Anticoagulation is indicated if there is atrial fibrillation. However, thromboembolism can occur even in its absence. Anticoagulation should also be considered if there is severe mitral stenosis, or an enlarged left atrium. Percutaneous mitral valvuloplasty can be performed if necessary. Congenital aortic stenosis In childbearing age group, this is usually the result of a bicuspid aortic valve. Most patients without severe aortic stenosis tolerate pregnancy well. If it is severe, it carries risk to both the mother and fetus. Pregnancy should be delayed until the valve has been corrected surgery. Otherwise, balloon valvuloplasty can get the woman through labor... Aortic dissection has been reported in women with bicuspid aortic valve. Rheumatic aortic stenosis The management is similar to that of congenital aortic stenosis. Aortic and mitral regurgitation These are usually well tolerated during pregnancy Pulmonary valve stenosis Mild or previously valvuloplastied pulmonary stenosis is well tolerated both by the mother and the fetus. Severe stenosis, even if asymptomatic, may result in right heart failure or atrial arrhythmias. It should be corrected before pregnancy, although. valvuloplasty during pregnancy is feasible. Prosthetic valves Tissue valves These carry a relatively low risk of thromboembolism, but have a significant incidence of deterioration. This incidence has been reduced with newer valves. They are reasonable for women who desire pregnancy and wish to avoid the complications of anticoagulation. However, the patient should be aware that there is a strong possibility that she will require reoperation in ten years or so. In excellent hands, this is a low risk procedure...

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Mechanical valves Mechanical valves show excellent durability but are thrombogenic. They require continuous anticoagulation. Pregnancy increases the risk of valve thrombosis and/or peripheral embolism. Because of this, the INR should be kept at 2.5 to 3.5. Older mechanical valves carry a higher risk of thromboembolism. Congenital heart disease Left to right shunts In the absence of pulmonary hypertension, atrial septal defects, ventricular septal defects and patent ductus are well tolerated. However, during labor, there is the risk of paradoxical embolism. Any such defect may eventually lead to Eisenmenger syndrome. Pulmonary artery pressure rises to systemic levels, changing the shunt flow to right-to-left. Maternal and neonatal mortality rates are very high. Patients with Eisenmenger syndrome should be offered sterilization or pregnancy termination.

Coarctation of the aorta Uncorrected coarctation carries a risk during the last trimester and labor of rupture of the aorta. Corrected coarctation can still be associated with hypertension during pregnancy. Cyanotic congenital heart disease Tetralogy of Fallot is the commonest one encountered. Its components include a large ventricular septal defect and pulmonic outflow tract obstruction. If it is uncorrected, pregnancy increased the right to left shunt. Fetal death rate is high and maternal death rate ranges from 4% to 15%. These conditions should be corrected prior to pregnancy. If corrected during pregnancy, there is a 6% maternal risk and a 30% fetal loss. Marfan syndrome Clinical The high-risk features of Marfan syndrome are related to the aortopathy. This can result in aortic root dilatation and dissection and aortic valvular regurgitation. The risk is increased during pregnancy. Management If there is little cardiovascular involvement and the aortic root is less than 40 mm by echocardiogram, pregnancy is well tolerated. However, serial echocardiograms should be done to look for progressive root dilatation, and beta blockers should be given prophylactically. If there is aortic root involvement, pregnancy is best avoided. If seen early in pregnancy, termination should be offered.

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Peripartum cardiomyopathy Clinical features Peripartum cardiomyopathy is diagnosed when heart failure occurs between the last month before or the first five months after delivery, provided there is no other identifiable cause and the patient has not had previous heart disease. Older women, African Americans and multiparous women at greater risk. Multifetal pregnancy, preeclampsia and gestational hypertension also increase the risk. It commonly recurs with subsequent pregnancies. The usual presentation is heart failure. Arrhythmias and embolic episodes may occur. Treatment is similar to that of heart failure due to other causes, using diuretics and sodium restriction. ACE inhibitors are contraindicated during pregnancy, but are a valuable adjunct after delivery. Beta-blocker therapy is advisable during and after pregnancy. Anticoagulation is often advised. The prognosis is variable. Some rapidly improve with normal echocardiographic findings. Others deteriorate rapidly, and may even require cardiac transplantation. Long-term disability is common. The mortality is 18-56%. Monitor these patients by echocardiography even after pregnancy. Persistence of left ventricular dysfunction contraindicates future pregnancies. Coronary artery disease Myocardial infarcion occurs in about 1 in 16,000 deliveries. Etiology Atherosclerosis accounts for about 40% of cases. The usual risk factors are apparently responsible. Spontaneous coronary artery dissection (27% of cases) can occur during pregnancy. Its cause is unknown, but may be related to the hormonal milieu, shear stress or other factors. The hypercoagulable state associated with pregnancy is believed to be another factor. Coronary spasm has been considered as well. Pregnancy and delivery also increase myocardial oxygen demand.. Diagnostic considerations Left axis deviation, non-significant Q waves, and nonspecific ST and T wave changes may all occur during normal pregnancy. These are usually distinguishable from findings of an acute myocardial infarction. On the other hand, pulmonary embolism can cause ST abnormalities that more closely resemble myocardial infarction. Troponin usually does not rise significantly during normal pregnancy, but may do so mildly with preeclampsia and gestational hypertension. Management In general, the medical therapy and indications for revascularization are the same as in other patients. Revascularization Percutanous intervention can be done during pregnancy, but drug-eliuting stents should probably be avoided, so as not to necessitate long-term use of clopidogral. There is limited 4

information about the use of coronary artery bypass surgery. Fibrinolytic therapy is relatively contraindicated, but might be used if there is no other alternative in an ST – elevation myocardial infarction. Drugs Morphine (category C) can be used. It can cause fetal respiratory depression if given close to delivery. It is compatible with breast-feeding. Nitrites (category B) may be used. Care should be taken to avoid hypotension. Beta blockers (metoprolol is category B, atenolol is category C) can be used. Nursing infants should be monitored for adverse effects. Calcium channel blockers (category C) Only nifedipine is known to be safe at this time Caution should be exercised if magnesium sulfate is being administered because of synergy. ACE inhibitors and ARBs (category C) should not be used because of fetal damage. Eplerinone (category B) should be used only with risk/benefit ratio is favorable, as there is little data available. Statins (category X) are not recommended during pregnancy. Heparin (category C) Both unfractionated and low molecular weight heparin can be used during pregnancy. Warfarin (category X) should be avoided during the first trimester because of fetal malformation, and during the last few weeks before delivery because of the risk of fetal intracranial hemorrhage. Aspirin (category C) may not be safe during the first trimester. High-dose aspirin carries the risk of maternal and fetal hemorrhage and other complications. Low-dose aspirin during the second and third trimesters appears to be safe. Clopidogrel (category B) has not been used enough during pregnancy to determine its safety. Glycoprotein IIb/IIIa inhibitors (category C) have not been used extensively. If they are administered, delivery should probably be by caesarean section to avoid fetal intracranial hemorrhage. Principles of management of the pregnant cardiac patient General Higher risk patients should have their activity restricted. It is sometimes advisable to admit patients by the middle of the second trimester. Intercurrent problems, such as hypertension, infection, anemia and hyperthyroidism should be treated early. Positioning the patient on her left side limits hemodynamic fluctuations. Arrhythmias One should try to avoid antiarrhythmic drugs during the first trimester. Those that are teratogenic should be avoided throughout pregnancy. Premature atrial and ventricular beats generally do not need treatment. Sustained tachycardias, such as atrial fibrillation or atrial flutter need prompt treatment.

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If heart rate control is needed in patients with mitral stenosis, beta-blockers are preferred over digoxin. Beta-blockers are often advisable in patients with Marfan syndrome, coarctation or bicuspid aortic valve. Preferred drugs during pregnancy: Digoxin Beta-blockers (possibly not atenolol) Verapamil Less well established: Quinidine Propafenone Contraindicated drugs: Amiodarone

Sotalol

Lidocaine

Adenosine

Flecainide

Diltiazem

Electrical cardioversion is safe during pregnancy. Anticoagulants Warfarin offers the most protection for the mother. Unfortunately, it is teratogenic during the first trimester. At term, it carries the risk of fetal intracranial bleeding, particularly during vaginal delivery. Heparin does not cross the placenta or affect the fetus. It can be given subcutaneously. It is less protective for the mother; maternal mortality is about 3% overall. A common approach is to use heparin during the first trimester, and change to warfarin until the middle of the last trimester. In the final weeks, heparin is restarted. It is discontinued 12 hours before delivery. Some are using low molecular weight heparin as an alternative to unfractionated heparin. Low dose aspirin should be considered in addition in women with prosthetic valves who are considered to be at high risk. A recent statement issued by the American College of Chest Physicians offers the following options: 1. Adjusted dose unfractionated heparin subcutaneously every 12 hours throughout pregnancy. The activated partial thromboplastin time between doses should be at least twice the control level. Alternatively, the anti factor Xa can be maintained at 0.35-0.70 IU/ml. 2. Low molecular weight heparin throughout pregnancy, targeting the dose to maintain the anti-factor Xa at 1.0 IU/ml four hours after a dose. 3. Unfractionated or low molecular weight heparin as above until the 13th week. Then switch to warfarin until the middle of the third trimester. Then resume unfractionated or low molecular weight heparin.

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Recent work seems to indicate that the third recommendation may not be adequate, as the trough levels of anti-factor Xa may be subtherapeutic. These levels should be kept at 0.6-0.7, while avoiding excessive peak levels (>1.5 IU/ml). An 8-hour dosing interval may be preferable to a 12-hour dosing interval. Epidural anesthesia should not be performed within 10-12 hours of the last dose of low molecular weight heparin to avoid the risk of epidural hematoma. Antibiotic prophylaxis Antibiotic prophylaxis has not been recommended for vaginal delivery or Cesarean section. However, recent reports show that bacteremia is not as uncommon as was thought and it seems prudent to offer prophylaxis in these patients. The preferred regimen is ampicillin or vancomycin plus gentamycin. Vaginal delivery is almost always preferred Hemodynamic monitoring is used for high-risk patients during labor and delivery. Cesarean section is only used if there is aortic dissection, Marfan syndrome with a dilated aortic root, or if the patient has been on warfarin within two weeks of delivery. It is sometimes preferred in patients who have had a myocardial infarction to avoid the stress of labor. However it entails use of anesthesia and may cause hemodynamic fluctuations, blood loss, infection, and other complications. The second stage of labor should be shortened, using forceps or vacuum extraction. The patient should be monitored for at least 3 days after delivery, and longer (at least 7 days) if she has Eisenmenger syndrome. ART DISEASE IN PREGNANCY SIU AND COLMAN

References Siu S and Colman JM. Cardiovascular problems and pregnancy: an approach to management. Cleveland Clinic Journal of Medicine 2004;71:977-985 Nallamothu BK et al. Double Jeopardy. New Engl J Med 2005;353:75-80 Elkayam U and Bitar F. Valvular heart disease and pregnancy: Part I: native valves. JACC 2005;46:223-230 Elkayam U and Bitar F. Valvular heart disease and pregnancy: Part II: prosthetic valves. JACC 2005;46:403-410 Pearson GD et al. Peripartum cardiomyopathy. JAMA 2000;283:1183-1188 Reimold SC and Rutherford JD. Peripartum cardiomyopathy. New Engl J Med 2001; 344:1629-30 Roth A and Elkayam U. Acute myocardial infarction associated with pregnancy. JACC 2008; 52:181-180

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