Post on 15-Mar-2018
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
§ 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
Background
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
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 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%
§ History, exam, ECG, CXR, med review
§ Exercise testing, Echo and additional imaging
§ Cardiac catheterization to evaluate possible pulmonary hypertension
§ Genetic considerations
Pre-pregnancy Evaluation
§ 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%
Pregnancy Outcome
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
2.9 7.5
17.5
43.1
70.0
0
20
40
60
80
0-0.50 0.51-1.50 1.51-2.50 2.51-3.50 >3.51
Ca
rdia
c c
om
plic
atio
ns
in
% o
f to
tal n
um
be
r p
reg
na
nc
ies
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
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 cm2) 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
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%
26-Year-Old Female, G2, P1
§ 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)
Pregnancy Case Management (3)
Management during pregnancy?
1. Surgical intervention
2. Device intervention
3. Observation
4. Warfarin anticoagulation
§ 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
ASD and Pregnancy
Warnes et al: JACC 2008
§ History, exam, ECG, med review
§ Echo and additional imaging
§ +/- Cardiac catheterization
§ Genetics referral/testing
§ Frequency of cardiac follow-up depends
on type of CHD
Evaluation during pregnancy
Pregnancy Case Management (3)
Management during pregnancy?
1. Surgical intervention
2. Device intervention
3. Observation
4. Warfarin anticoagulation
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
Pregnancy Case Management (4)
§ Pregnancy usually well tolerated unless very severe
§ Percutaneous valvotomy can be performed during pregnancy
Pulmonic Stenosis
§ 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
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
Pregnancy Case Management (4)
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
§ Unpredictable maternal risk
§ Dissection, rupture, IE, CHF
§ Risk based on
§ Preexisting medial changes
§ Changes with pregnancy- Physiologic, hormonal
§ Fetal risks- 50% inheritance
§ Autosomal dominant
Marfan Syndrome
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
§ Management in Marfan and other aortic disorders similar
§ During pregnancy
§ Beta-blocker
§ Regular aortic imaging (individualize), Fetal echo
§ Peripartum
§ Assisted vaginal delivery
§ Consider C-section for aorta >40 mm or increasing in size
§ Endocarditis prophylaxis
§ Postpartum
§ FU - dissection risk persists § Future evaluation of lactation risk
Pregnancy Management
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
31-Year-Old Female (5b)
§ Turner syndrome diagnosed at birth
§ Webbed neck, puffy feet
§ Genetic consult and testing, age 5
§ BAV identified around that time
§ Regular CV follow-up
§ Consultation for possible IVF
§ Asymptomatic
§ Metoprolol 25 BID, Synthroid 150 QD
Echocardiogram
§ Bicuspid AV, no stenosis, trivial regurg
§ Asc aorta 40 mm
§ Normal LV size and function, EF 60%
What would you recommend?
1. OK to proceed with IVF
2. No IVF but no aortic intervention
3. Proceed with aortic intervention
4. Not sure
Turner Syndrome 45, X karyotype
§ Common chromosomal disorder § Partial or complete loss of
chromosome X § 1:2500 female live births
§ CV abnormalities – 45%
§ BAV – 30%
§ Aortic – 20%
§ Anomalous veins – 8%
§ VSD – 5%
§ 166 volunteers with TS; 26 controls
§ Aortic dimension normalized to BSA
Aortic size index (ASI cm/m2)
§ 24% of TS pts >95th percentile (3.4 cm; ASI >2.0)
§ 3 year follow-up – 3 dissections
All with ASI >2.5 cm/m2
Prophylactic surgery if ASI >2.5 cm/m2
Circulation, 2007; 116: 1663-70
Our patient Aorta 4.0 cm
ASI 4.0/1.8 = 2.2
Aortic Dissection in Turner Syndrome
§ 85 dissections 1961 - 2006
§ Mean age 31 yr (4-64)
§ Associated with assisted reproduction: high mortality (6 of 7)
Carlson and Silverbach. J Med Genet 2007
11%
14%
40%
35%
Dissection TS only HTN only
CHD + HTN CHD only
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
§ 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
Warfarin in Pregnancy
Oakley: Br Heart J, 1995 Vitale: J Am Coll Cardiol, 1999
Prosthetic Valves And Pregnancy
Vitale N et al. JACC, 1999
Fetal complications
Warfarin ≤5 mg 5/33 (15%)
No embryopathy
Warfarin >5 mg 22/25 (88%)
9% embryopathy
UF Heparin in Pregnancy
§ High molecular weight – doesn’t 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
§ Weight based LMWH inadequate during 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
LMWH in Pregnancy
Barbour L: Am J Obstet Gynecol 2004 McLintock et al: BJOG 2009
Therapeutic anticoagulation with
frequent monitoring (I)
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)
Dose-adjusted continuous infusion of UFH (with an aPTT at
least 2× control) (IIa)
Class IIb
Class IIa
Class I
OR
Baseline warfarin dose ≤5 mg/d
Baseline warfarin dose >5 mg/d
First trimester Continue warfarin with
close INR monitoring (IIa)
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)
Dose-adjusted continuous infusion of UFH (with an aPTT at
least 2× control) (IIb)
OR
OR
Baseline warfarin dose ≤5 mg/d
First trimester
ACC/AHA VHD Guidelines 2014
Pregnant Patient with Mechanical Prosthesis
Warfarin to goal INR plus ASA 75 mg to 100 mg QD (I)
Discontinue warfarin and dose-adjusted continuous infusion of
UFH (with an aPTT at least 2× control) (I)
Class I Second and third trimesters
Before planned vaginal delivery
ACC/AHA VHD Guidelines 2014
Pregnant Patient with Mechanical Prosthesis
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 1st 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.
§ 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
Summary