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

I have no conflicts of interest to disclose

Disclosure

§  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

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

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

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%

§ History, exam, ECG, CXR, med review

§  Exercise testing, Echo and additional imaging

§ Cardiac catheterization to evaluate possible pulmonary hypertension

§ Genetic considerations

Pre-pregnancy Evaluation

CARPREG

WHO Classification

Prepregnancy Risk Assessment

ZAHARA

§  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%

Case 3

Pregnancy management

Management of shunt lesions in

pregnancy

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

Case 4

Congenital Valve and Stenotic Lesions

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)

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

§  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

Max aortic diameter 41 mm (mid ascending)

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

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

§  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

Questions? connolly.heidi@mayo.edu