Cardiac Diseases in Pregnancy

1. February 18, 2005 Cardiac Diseases in Pregnancy Ibrahim Elias Fahdi, MD University of Arkansas for Medical Sciences & Central Arkansas Veterans Healthcare System Division of Cardiovascular Medicine

2. Objectives • Normal Physiology during pregnancy • Cardiac Testing • Common cardiac problems

3. Cardio-circulatory changes during normal pregnancy

4. “Our only hope is if we all write a letter to Santa…” The Wall Street Journal

5. Changes in plasma volume, erythrocyte volume, and hematocrit during pregnancy • Plasma volume ↑ 50% (20-100%). • “Physiologic anemia of pregnancy”. • Estrogen-mediated stimulation of the RAS. • Role of other hormones • deoxycorticosterone, prostaglandins, estrogen, prolactin, placental lactogen, GH, ACTH, ANP From Pitkin RM, Nutritional support in obstetrics and gynecology. Clin Obstet Gynecol 1976;19:489.

6. Percent change in heart rate, stroke volume, and cardiac output measured in the lateral position throughout pregnancy compared with pregnancy values Modified from Robson SC, Hunter S, Boys RJ, Dunlop W. Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol 1989;256:H1060-H1065

7. Cardio-circulatory changes during normal pregnancy

8. Hemodynamic changes during labor and delivery • Anxiety, pain, uterine contraction. • Oxygen consumption ↑ threefold. • ↑ CO during labor (↑ SV and ↑ HR). • ↑ SBP & DBP (especially 2nd stage) • Those changes are influenced by the form of anesthesia and analgesia.

9. Hemodynamic changes post partum Blood shifting “auto-transfusion” (from the contracting uterus to the systemic circulation) Increase in venous return (relief of caval compression) - Blood loss during delivery Increase in effective blood volume Substantial increase in LV filling pressure, SV and CO Clinical deterioration • HR and CO return to pre-labor values within 1 hour. MAP and SV within 24 hours. • Hemodynamic adaptation persists post partum and return to pre-pregnancy values within 12-24 weeks after delivery.

10. History Exercise capacity Current or past evidence of HF Associated arrhythmias Before conception Physical exam Cardiac Hemodynamics Severity of heart disease, PA pressures Echo, MRI. Exercise testing Useful if the history is inadequate to allow assessment of functional capacity During pregnancy Evaluate once each trimester and whenever there is change in symptoms Multidisciplinary approach, Fetal Echo During Labor & Delivery Multidisciplinary approach (Obstetrician, Cardiologist, Anesthesiologist) Tailor management to specific needs Reimold, S. C. et al. N Engl J Med 2003;349:52-59

11. High-risk pregnancy • Pulmonary HTN and Eisenmenger’s syndrome. • Symptomatic obstructive cardiac lesions: • AS, PS, uncorrected coarctation of the aorta. • Marfan’s Syndrome with dilated aortic root. • Systemic ventricular dysfunction (LVEF < 40%). • Severe cyanotic heart disease. • Patients with prosthetic valves. • Significant uncorrected CHD.

12. Contraindications to Pregnancy

13. Pregnancy Outcomes • The prevalence of clinically significant maternal heart disease is low (<1%)1. • Its presence increases the risk of adverse maternal, fetal, and neonatal outcomes2. • Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521. • Siu SC, Colman JM, Sorensen S, et al. Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 2002;105:2179-2184.

14. CARPREG • Cardiac disease in pregnancy; prospectively enrolled 563 consecutive pregnant women with heart disease • Outcomes were determined in 599 pregnancies not ending with miscarriage Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.

15. Adverse maternal cardiac events • Primary cardiac events: • Pulmonary edema. • Sustained brady- or tachy- arhythmias requiring therapy. • Stroke. • Cardiac arrest. • Death • Secondary adverse cardiac events: • Worsening of NYHA class by > 2 classes. • Need for urgent invasive cardiac procedure (percutaneous cardiac valvuloplasty, permanent pacing). 62% 27% 4% N.B.: There was no association between the type of delivery and peripartum cardiac event rate (3% vs. 4%, P=0.46). Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.

16. Adverse neonatal events • Neonatal events: • Premature birth • Small-for-gestational-age birth weight. • Respiratory distress. • Inter-ventricular hemorrhage. • And death. N.B.:in the 6 pregnancies in which the mother received warfarin during all (n=2) or part of pregnancy (n=4), embryopathy was not observed in this small series. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.

17. Cardiac Tests Performed 1 • Doppler echocardiography • Stress testing • Radiation of the embryo • Age o to 10 days: no effect or resorption • Age 10 to 50 days: teratogenic effects • Age 50 to delivery • Intrauterine growth retardation • Central nervous system abnormalities • Increased incidence of childhood cancer or leukemia

18. Cardiac Tests Performed 2 • Routine chest radiography delivers 20 m.rads • Standard fluoroscopy delivers 1-2 rads/min • Current recommendation • >5 rads: very low risk • 5-10 rads: counseling for low risk • 10-15 rads during 1st 6 weeks: individual • >15 rads: termination pf pregnancy Colletti PM, Lee K: Cardiac Problem in Pregnancy.3rd ed. New York, Wiley Liss, 1998, pp 33-36

19. Cardiac Tests Performed 3 • Magnetic Resonance Imaging • Pulmonary Artery Catheterization: Great help in managing high risk patient during pregnancy, labor and delivery • Cardiac Catheterization • Can be done

20. Pulmonary hypertension as a risk of adverse outcome Pulmonary hypertension (Eisenmenger Syndrome) Increased rate of adverse maternal events Up to 30-40% (↑ PVR) When systolic PAP > 75% systemic pressure ↑ intravascular volume HF (CO limited by Pulmonary vascular disease and Ventricular dysfunction) ↓ SVR (after 1st trimester) ↑R-L Shunt Cyanosis Exacerbated during labor and delivery Bed rest (2nd trimester), O2 (if helpful), ? Anticoagulation, Cesarian section, invasive monitoring, early ambulation

21. Aortic stenosis • Severe AS is poorly tolerated. • AVA < 0.7 cm2, Mean PG > 50 mmHg. • Mortality up to 17%. • Symptomatic patients or Mean gradient > 50 mmHg • → Delay conception until after surgical or interventional correction. • Consider balloon valvuloplasty, Ross procedure, tissue valve (no need for anticoagulation). • Symptomatic patients before end of 1st trimester • Terminate pregnancy. • Β-Blockade, Bed rest. • Palliative aortic balloon valvuloplasty or AVR. • Early Delivery. Hameed A, et al. The effects of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 2001;37:893-9. Reimold, S. C. et al. N Engl J Med 2003;349:52-59

22. Prosthetic valves and pregnancy Anticoagulation

23. Warfarin Crosses the placenta. ↑early abortion, prematurity, and embryopathy when used in 1st trimester (6th–12th weeks). CNS & Eye abnormalities (2nd & 3rd trimester). Bleeding in the fetus (especially at delivery) Should be stopped before delivery. Heparin Does not cross the placenta No teratogenicity No fetal bleeding Twice daily SC injection Risk of osteoporosis <2% symptomatic fractures. but 30% decrease in bone density. Risk for thrombocytopenia ↑↑ Risk of thrombosis Warfarin vs. Heparin “warfarin embryopathy”: Nasal hypoplasia, Bone epiphysis, optic atrophy, blindness, seizures. Overall risk around 5%. Decreases with the use of UFH in the first 3 months

24. Dose-dependent Fetal Complications of warfarin in pregnant women with Mechanical Heart ValvesOutcome of pregnancies Vitale N, et al. J Am Coll Cardiol 1999;33:1637-41.

25. Unfractionated Heparin • 4X higher incidence of Thrombo-embolism during pregnancy than oral anticoagulants1. • Hanania G, et al. pregnancy in patients with valvular prosthesis-retrospective cooperative study in France (155 Cases). J Arch Mal Coeur Vaiss 1994;87:429-437. • Failure of adjusted dose SC heparin to prevent thrombo-embolic phenomena in pregnant women (n= 40) with mechanical valve prosthesis. • Adjusted doses of SC heparin does not improve fetal outcome and increases maternal mortality2. • Salazare E, et al. Filure of adjusted dose heparin to prevent thromboembolisc phenomena in pregnant patients with mechanical cardiac valve prosthesis. J Am Coll Cardiol 1996;1698-1703.

26. Frequency of fetal and maternal complications according to the anticoagulation regimen used during pregnancy in women with mechanical heart valve prosthesis. Adapted from Chen et al. (976 women, 1234 pregnancies) Chan WS. What is the optimal management of pregnant women with valvular heart disease in pregnancy? Haemostasis 1999,29 suppl S1:105-6

27. Low-dose ASA • The additional use of low-dose aspirin should be considered, particularly in • Women with high-risk valves. • Patients with cyanosis. • Patients with intra-cardiac shunts. • Women with previous TIAs and/or strokes. • And women with atrial fibrillation. Chan WS. What is the optimal management of pregnant women with valvular heart disease in pregnancy? Haemostasis 1999,29 suppl S1:105-6

28. LMWH • Do not cross the placenta. • Do not require frequent PTT monitoring • and have a longer half-life than UFH. • The data to support the use of LMWH, however, is not yet available. • A successful use of LMWH was reported in small number of patients and more information is required before LMWH can be recommended for anticoagulation in a patient with a prosthetic valve during pregnancy1. • Recently, two cases of LMWH treatment failure resulting in thrombosed prosthetic heart valves were reported in 20002. • LMWH should not be recommended at the present time in patients with heart valve prostheses during pregnancy. • Elkayam U. Pregnancy through a prosthetic heart valve. J Am Coll Cardiol 1999;33:1642-5. • Lev Rano, Kamer A, Gurevitch J, Shapira, Mohr R. Low-molecular weight heparin for prosthetic heart valves: treatment failure. Ann Thoracic Surg 2000; 69: 264-5.

29. Mechanical Valves and Anticoagulation during Pregnancy • Heparin may not prevent valve thrombosis: ?how much ?route. • Adequate anticoagulation difficult. • Heparin can produce osteoporosis. • Little data regarding LMWH. • Warfarin can cause embryopathy. • Baby ASA safe + probably beneficial. 1-4% mortality in pregnant women with mechanical valve prosthesis, Whatever the anticoagulation regimen. No Ideal Solution

30. Suggested algorithm for the management of anticoagulation in patients with mechanical prosthetic heart valves during pregnancy Pregnancy in patients with prosthetic heart valves Lower risk Second-generation prosthesis (e.g., St Jude Medical, Medtronic Hall) And any mechanical prosthesis in the aortic position Higher risk First-generation prosthesis (e.g Starr-Edwards, Bjork- Shiley) In the mitral position Coumadin to INR 3.0-4.5 for 36 weeks followed by IV heparin to aPTT of > 2.5-3.5 SC or IV (better) heparin-(aPTT 2.5-3.5) for 12 weeks Coumadin (INR 3.0-4.5) to 36th week IV heparin (aPTT > 2.5) SC Heparin (aPTT 2.0-3.0) for 12 weeks Coumadin (INR 2.5-3.0) to 36th week SC Heparin (aPTT 2.0-3.0) SC heparin (aPTT 2.0-3.0) Throughout pregnancy 1-4% mortality in pregnant women with mechanical valve prosthesis, Whatever the anticoagulation regimen. Braunwald textbook of cardiovascular medicine, 6th edition

31. Vaginal delivery With facilitated second stage is preferred & safe Invasive hemodynamic monitoring only in: Severe valve stenosis Recent heart failure. Severe cyanotic heart disease Pulmonary HTN. Cesarean section Avoids physical stress of labor but not free from hemodynamic consequences. Indications in CHD only for: Obstetric reasons. Therapeutic anticoagulation with coumadin at onset pf labor. Pulmonary hypertension. Unstable aortic lesion with risk of dissection. Severe obstructive lesions Mode of delivery Breast-feeding • Can be encouraged in women taking anticoagulants. • Heparin is not secreted in breast milk • and the amount of warfarin is low. • Hameed A et al. J Am Coll Cardiol 2001;37:893–9. • Elkayam U, et al. New Engl J Med 2001;344:1567–71. • Bozkurt B, et al. J Am Coll Cardiol 1999;34:177–80.

32. Endocarditis prophylaxis • Antibiotic prophylaxis at the time of delivery is not recommended for patients expected to have uncomplicated vaginal delivery or cesarian section, unless clinically overt infection is present 1,2 • Patients at high risk for endocarditis may receive antibiotics at the discretion of their physician2: • Those with prosthetic heart valves. • Previous IE. 1 Sugrue D, Troy P, McDonald D. Antibiotic prophylaxis against infective endocarditis after normal delivery -- is it necessary? Br Heart J 1980;44:499-502. 2 Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA 1997;277:1794-1801.

33. Pregnancy and CHDConclusions • Most women with heart disease can have a pregnancy proper care. • Pre-pregnancy evaluation mandatory. • High-risk cases benefit from combined high-risk OB and cardiac care in the same center.

34. Questions