Critical Care in Obstetrics: An Innovative and Integrated Model for Learning the Essentials

Pregnancy and Congenital Heart Disease Case Review Heidi M. Connolly, M.D. Professor of Medicine Chair for Education Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN

Disclosure I have no conflicts of interest to disclose

Background 2% of pregnancies involve maternal CV disease Congenital heart disease (CHD) is the most common form of HD to affect women of childbearing age in North America CV disease does not preclude pregnancy but poses risk to mother and fetus Informed CV evaluation ideal pre-pregnancy

Question 1

Pregnancy Not Advised (1) Which of the following patients would you advise avoid pregnancy? 1. Bicuspid aortic valve with moderate AS 2. Asymptomatic pt with LVEF 45% 3. Marfan syndrome pt with aorta 46 mm 4. Repaired cyanotic CHD

Pregnancy Not Advised Severe pulmonary arterial hypertension Severe obstructive lesions AS, MS, PS, HCM, Coarctation Ventricular dysfunction CHF - NYHA Class III or IV, EF <40% Prior peripartum cardiomyopathy Dilated or unstable aorta Marfan with aorta 40-45 mm Severe cyanosis

Pregnancy Risk Regurgitant valve lesions generally well tolerated Complex lesions assess on case by case basis Risk of inheritance 3-5% with most CHD Genetic disorders

Case 2

Risk Assessment

Pregnancy Risk Assessment (2) 32-Year-Old seeks pre-pregnancy counseling Remote history ASD closure and mitral valve repair Paroxysmal atrial fibrillation Warfarin and beta-blocker What is the risk of maternal pregnancy related complication 1. <10% 2. 10 20% 3. >20%

Pre-pregnancy Evaluation History, exam, ECG, CXR, med review Exercise testing, Echo and additional imaging Cardiac catheterization to evaluate possible pulmonary hypertension Genetic considerations

Prepregnancy Risk Assessment CARPREG WHO Classification ZAHARA

Pregnancy Outcome ZAHARA study Observational data on CHD in pregnancy 1802 women, 1302 completed pregnancies Cardiac complications in 7.6% Most common CV complications Arrhythmias 4.7% Heart failure 1.6% Drenthen et al: Eur Heart J 2010

Predictors of Maternal CV Complications Cyanotic heart disease (p < 0.0001) Cardiac meds pre-pregnancy (p < 0.0001) Left heart obstruction (p < 0.0001) Mechanical valve prosthesis (p = 0.0014) Systemic or pulmonary AV valve regurgitation related to complex CHD (p = 0.03) Drenthen et al: Eur Heart J 2010

Modified Risk Score of CV Complications During Pregnancy Cardiac complications in % of total number pregnancies 80 60 40 20 0 1. History of arrhythmias 1.50 points 2. Cardiac medication before pregnancy 1.50 points 3. NYHA class prior to pregnancy 1 0.75 points 4. LHD (PG >50 mm Hg or AVA <1.0 cm 2 ) 2.50 points 5. Syst AV valve regurgitation (moderate/severe) 0.75 points 6. Pulm AV valve regurgitation (moderate/severe 0.75 points 7. Mechanical valve prosthesis 4.25 points 8. Cyanotic heart disease (corrected/uncorrected) 1.00 points Total number of points 0-13 points 2.9 7.5 17.5 43.1 70.0 0-0.50 0.51-1.50 1.51-2.50 2.51-3.50 >3.51 Risk score Pregnancies at risk (no.) 828 280 126 58 10 Percentage of total population 63.6 28.1 6.1 1.4 0.8 * Drenthen et al: Eur Heart J 2010

Pregnancy Risk Assessment (2) 32-Year-Old seeks pre-pregnancy counseling Remote ASD closure and mitral valve repair Paroxysmal AF, warfarin and B-blocker What is the risk of maternal pregnancy related complication 1. <10% 2. 10 20% 3. >20%

Case 3

Pregnancy management

Management of shunt lesions in pregnancy

Pregnancy Case Management (3) 26-Year-Old Female One prior uncomplicated pregnancy Currently 19 weeks pregnant Occasional palpitations Low dose aspirin Murmur on physical exam Echo Secundum ASD, Right heart enlarged No pulmonary hypertension

Pregnancy Case Management (3) Management during pregnancy? 1. Surgical intervention 2. Device intervention 3. Observation 4. Warfarin anticoagulation

ASD and Pregnancy Unrepaired ASD neonatal risk vs repaired pre-eclampsia risk, SGA births fetal mortality L to R shunt may with CO change during pregnancy, balanced by PVR Paradoxical embolism risk Familial types- consider screening Warnes et al: JACC 2008

Evaluation during pregnancy History, exam, ECG, med review Echo and additional imaging +/- Cardiac catheterization Genetics referral/testing Frequency of cardiac follow-up depends on type of CHD

Pregnancy Case Management (3) Management during pregnancy? 1. Surgical intervention 2. Device intervention 3. Observation 4. Warfarin anticoagulation

Case 4

Congenital Valve and Stenotic Lesions

Pregnancy Case Management (4) 30-Year-Old Female Murmur since childhood, no symptoms Presents for pre-pregnancy evaluation Systolic murmur along left sternal border Echo Pulmonic valve stenosis Moderate PS mean gradient 15 mmhg Mild PR Normal right heart size and function

Pregnancy Case Management (4) What do you suggest? 1. OK to proceed with pregnancy 2. Balloon pulmonary valve intervention prior to pregnancy 3. Surgical intervention prior to pregnancy 4. Consultation with congenital heart specialist prior to pregnancy

Pulmonic Stenosis Pregnancy usually well tolerated unless very severe Percutaneous valvotomy can be performed during pregnancy No maternal CV events >100 preg Outcome Preterm delivery in 14.5% Fetal mortality 0.8% Perinatal mortality 4% Recurrent CHD 3% Noonan s syndrome Drenthen et al: JACC 2007

Case 5

Genetic/Aortic Disorders

Genetic/Aortic Disorders (5) 20-Year-Old Female Pre-pregnancy counseling FH of Marfan, dissection, ectopia lentis Asymptomatic Ao root 41 mm

Genetic/Aortic Disorders (5) What would you recommend? 1. OK to proceed with pregnancy 2. Avoid pregnancy 3. Start beta-blocker before pregnancy 4. Start angiotensin receptor blocker before pregnancy

Marfan Syndrome Unpredictable maternal risk Dissection, rupture, IE, CHF Risk based on Preexisting medial changes Changes with pregnancy- Physiologic, hormonal Fetal risks- 50% inheritance Autosomal dominant

Preconceptual Counseling In addition to routine obstetric screening Detailed CV history, FH, medications and exam Echo aorta and valves Aortic imaging Aorta >45 mm no pregnancy Aorta 40 mm reasonable if low risk Aorta 40-45 mm individualize Genetics, prenatal diagnosis

Pregnancy Management Management in Marfan and other aortic disorders similar During pregnancy Beta-blocker Regular aortic imaging (individualize), Fetal echo Peripartum Facilitated vaginal delivery C-section for aorta > 40 mm or increasing in size Endocarditis prophylaxis Postpartum FU - dissection risk persists Future evaluation of lactation risk

Genetic/Aortic Disorders (5) 20-yo Pre-pregnancy counseling FH of Marfan, dissection, ectopia lentis Ao root 41 mm What would you recommend? 1. OK to proceed with pregnancy 2. Avoid pregnancy 3. Start beta-blocker before pregnancy 4. Start angiotensin receptor blocker before pregnancy

Anticoagulation for Mechanical Prosthetic Valve Valve in Pregnancy

25-Year-Old Female (6) Mechanical St. Jude MVR Seeks prepregnancy counseling Asymptomatic Warfarin 4 mg per day, aspirin 81 mg daily Exam BP 110/60 Normal mechanical S1, no murmur Otherwise normal examination

Question (6) Which of following is most appropriate AC regimen for this patient when pregnant? 1. Stop warfarin; start aspirin and clopidogrel 2. Stop warfarin; start weight-based LMWH 3. Stop warfarin; start unfractionated heparin 5000 units subcutaneously twice daily 4. Continue INR adjusted warfarin

Anticoagulation in Pregnancy Hematologic changes clotting factor concentration platelet adhesiveness fibrinolysis and protein S activity risk thrombosis and embolism

Anticoagulation During Pregnancy Maternal Risks Fetal Risks

Warfarin in Pregnancy Low molecular weight crosses placenta Fetal AC effect and duration vs maternal Vit K dependent factors in fetal liver risk of fetal loss, prematurity, stillbirth, fetal IC hemorrhage, retroplacental hemorrhage Embryopathy risk exposure 6-12 weeks Incidence 4-10% Dose related Oakley: Br Heart J, 1995 Vitale: J Am Coll Cardiol, 1999

Prosthetic Valves And Pregnancy Fetal complications Warfarin 5 mg 5/33 (15%) No embryopathy Warfarin >5 mg 22/25 (88%) 9% embryopathy Vitale N et al. JACC, 1999

UF Heparin in Pregnancy molecular weight does not cross placenta Short half-life variable response risk pt PTT 2.5-3.5 x control, 6 hr Treatment of choice late pregnancy, delivery risk of prosthetic valve thrombosis TE events, maternal and fetal mortality Long-term use osteoporosis ~30%, sterile abscesses, platelets, alopecia

LMWH in Pregnancy Does not cross the placenta No teratogenic effects Antithrombotic protection Potential advantages Bioavailability, administration ease osteoporosis and thrombocytopenia Melissari: Thromb & Hemost, 1992

LMWH in Pregnancy Weight based LMWH inadequate in pregnancy Measure anti-xa activity Peak (4 hr post) anti-xa level ~1.0 U/mL Anti-Xa adjusted LMWH with ASA vs warfarin PV thrombosis Improved fetal outcomes Barbour L: Am J Obstet Gynecol 2004 McLintock et al: BJOG 2009

Pregnant Patient with Mechanical Prosthesis Therapeutic anticoagulation with frequent monitoring (I) Class I Class IIa First trimester Baseline warfarin dose 5 mg/d Continue warfarin with close INR monitoring (IIa) OR Dose-adjusted LMWH 2 /d (target anti-xa level 0.8 U/mL to 1.2 U/mL 4 to 6 h post dose) (IIb) OR Dose-adjusted continuous infusion of UFH (with an aptt at least 2 control) (IIb) Baseline warfarin dose >5 mg/d Dose-adjusted LMWH 2 /d (target anti-xa level 0.8 U/mL to 1.2 U/mL 4 to 6 h post dose (IIa) OR Dose-adjusted continuous infusion of UFH (with an aptt at least 2 control) (IIa) Class IIb First trimester ACC/AHA VHD Guidelines 2014

Pregnant Patient with Mechanical Prosthesis Second and third trimesters Class I Warfarin to goal INR plus ASA 75 mg to 100 mg QD (I) Before planned vaginal delivery Discontinue warfarin and doseadjusted continuous infusion of UFH (with an aptt at least 2 control) (I) ACC/AHA VHD Guidelines 2014

25-Year-Old with Mechanical MVR Warfarin 4 mg with Therapeutic INR Which of following is most appropriate AC regimen for this patient when pregnant? 1. Stop warfarin; start aspirin and clopidogrel 2. Stop warfarin; start weight-based LMWH 3. Stop warfarin; start unfractionated heparin 5000 units subcutaneously twice daily 4. Continue INR adjusted warfarin

AC in Pregnancy for Mechanical Valve AC must be therapeutic Warfarin preferred in 1 st trimester if therapeutic dose is 5 mg UFH is treatment of choice near delivery LMWH can be used but for mechanical valves must be adjusted to anti-xa level

Conclusions Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.

Summary 2% of pregnancies involve maternal CV disease CHD is the most common form of HD to affect women of childbearing age in North America CV disease does not preclude pregnancy but poses risk to mother and fetus Informed CV evaluation ideal pre-pregnancy

Questions? connolly.heidi@mayo.edu