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©2011 MFMER | slide-1

Cardiovascular Disease and the Pregnant Patient

June 4, 2012Martha Grogan, MD, FACCACC 2012 Portland, Oregon

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PregnancyHematologic Changes

Am J Physiol, 1983Am J Physiol, 1983

0000

Blood

volumes

(% control)

Blood

volumes

(% control)

1010

2020

3030

4040

5050

1010 2020 3030 4040

Gestational age (weeks)Gestational age (weeks)

PlasmaPlasma

Whole bloodWhole blood

ErythrocytesErythrocytes

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Hemodynamic ChangesHemodynamic Changes

•> 40% ↑ blood volume

• ↓ SVR and PVR

• ↑ HR

•Mild ↓ in BP

•> 40% ↑ blood volume

• ↓ SVR and PVR

• ↑ HR

•Mild ↓ in BP

30-50%

↑ CO

30-50%

↑ CO

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S4occasional

S4occasional

Systolic murmur 96%Systolic murmur 96%

Wide

loud split 1st 88%

Wide

loud split 1st 88%

MCMC TCTC A2A2 P2P2

Diastolic“flow”murmur 18%

Diastolic“flow”murmur 18%

S3loud 84%

S3loud 84%

CV Exam During PregnancyCV Exam During Pregnancy

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CV Exam During PregnancyCV Exam During Pregnancy

• Brisk and full carotid upstroke

• JVP - normal or mildly ↑↑↑↑

• Displaced and enlarged apex

• Varicose veins and edema

• Normal exam can mimic heart disease

• Not normal

S4, loud SM, DM, fixed split S2

• Brisk and full carotid upstroke

• JVP - normal or mildly ↑↑↑↑

• Displaced and enlarged apex

• Varicose veins and edema

• Normal exam can mimic heart disease

• Not normal

S4, loud SM, DM, fixed split S2

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Hemodynamic ChangesLabor and DeliveryHemodynamic ChangesLabor and Delivery

• CO ↑ 60-80%

• Volume changes

↑ Blood volume with uterine contraction

↑ Venous return

Volume loss during delivery

• CO ↑ 60-80%

• Volume changes

↑ Blood volume with uterine contraction

↑ Venous return

Volume loss during delivery

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Heart Disease and Pregnancy: Delivery

• Vaginal Delivery: Preferable in most cases

• Facilitate 2nd stage

• C-Section Indications:

• OB reasons

• Early labor still on warfarin

• Severe PH

• Fixed obstructive lesions

• Unstable aorta

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Pregnancy “Contraindications”

• Severe Pulmonary Hypertension

• Severe obstructive lesions• AS, MS, PS, HCM, Coarct

• Ventricular dysfunction

• Class III or IV HF, EF <40%

• Dilated or unstable aorta

• Marfan with aorta ≥40 – 45 mm

• Severe cyanosis

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CAREPREG Risk Stratification

Predictors

• CHF, arrhythmia, TIA or CVA

• NYHA > II or cyanosis

• Left Heart ObstructionMVA <2 cm2, AVA < 1.5

LVOT > 30 mmHg

• LV EF < 40%

Number of predictors

Siu SC et al. Prospective Multicenter Study of Pregancy Outcomes in Women with Heart Disease. Circ

2001; 104:515-521.

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CARPREG Risk IndexPredictors of Cardiac Events

• Prior CHF, TIA, stroke or arrhythmia

• Baseline NYHA class >II or cyanosis

• Left heart obstruction

• MVA <2 cm2, AVA <1.5 cm2

• LVOT gradient >30 mmHg by Echo

• ↓ systemic vent function (EF <40%)

Risk index predicts CV event rate

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Dilated Cardiomyopathy

What % of Patients will have an Affected Family Member

a. 5%

b. 10%

c. 15%

d. 25%

e. 50%

CP1081586-12

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Familial Dilated Cardiomyopathy

• Mid 1980s - initial reports-

1-2% of pts with IDCM had familial disease

Echo screening changed thatJ

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Dilated Cardiomyopathy A heritable form of heart failureMichels, N Engl J Med 1992

Rationale for clinical screening of families

Impetus for human molecular genetics research

Frequency of familial DCM

• 6-8% by history

• 20-25% by echocardiography

• 35-50% by less stringent criteria

(LV dilation with borderline EF)

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HFSA 2010 Practice GuidelineGenetic Evaluation—Clinical Screening

Clinical screening (includes echo) for cardiomyopathy in asymptomatic first-degree relatives is recommended

• Hypertrophic cardiomyopathy

• Dilated cardiomyopathy

• Arrhythmogenic RV cardiomyopathy

• Left ventricular noncompaction *

• Restrictive cardiomyopathy *

Lindenfeld J., et al, J Card Fail; 16e1-e194

* Level of evidence = B

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27-Year-Old FemaleFamilial DCM

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• Age 15 months

• Pulmonary edema, severely dilated LV, EF 15%

• WPW with SVT

• Index case for family

• Mom and sister: DCM and WPW

• Enrolled in GENES in DCM study (20 yrslater) - actin mutation

27 Year-Old Female – Familial DCM

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• Competitive soccer – high school and college

• Age 22: inderal changed to coreg, continue dig, ACE-I

• MRI EF 47%, MUGA 44%, Echo 30-35 (est), 40% (calc)

27 Year-Old Female – Familial DCM

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• Exercise test

• 10.2 min (87%)

• VO2 (79%) with plateau

• What do you recommend regarding pregnancy ?

• How high would you estimate her risk ?

27 Year-Old Female – Familial DCM

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• At 32 weeks pregnant: exercising 60 min, 4x/ per week

• Asymptomatic

• Echo: EF 35%, increase MR to grade ¾

• Premature Labor – uncomplicated delivery- 35 weeks

• Sister (DCM) uncomplicated preganancy-delivered 4 months later

27 Year-Old Female – Familial DCM

Their Mom J.

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Peripartum Cardiomyopathy

• New diagnosis of HF due to LV dysfunction

• Last trimester → 6 mos postpartum

• Diagnosis of exclusion

• Incidence varies

US 1 in 3200 deliveries (1350/year)

South Africa 1 in 1000

Haiti 1 in 300

Elkayam JACC 2011

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Peripartum Cardiomyopathy

• Standard HF Rx – O2, diuretic, iv NTG, inotrope

• Bromocriptine - blocks prolactin release

↑ EF in PPCM vs standard therapy, with AC - TE risk

• IV immune globulin – immune modulator

↑ EF in PPCM pt vs standard therapy

• Pentoxifylline – inhibits TNF-alpha production

↑ TNF-alpha in PPCM

• Anticoagulation if EF <35%, or with bromocriptine

• VAD or transplantation

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Peripartum Cardiomyopathy

Pathophysiology

• Defective antioxidant defense mechanism

prolactin/bromocriptine

• Viral infection

• Autoimmune response

• Genetic susceptibility

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Peripartum Cardiomyopathy

• Prognosis variable

• Major cause of preg related death in US

• Mortality 6 mos and 2 yr → 10 and 28%

• ↑ mortality with ↓ EF >6 mos postpartum

• ~50% improve in 6 months

• 20 – 40% normalize EF

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ACC Survey: 44 pts with PPCM• Subsequent pregnancy

Gp 1 – 28 pre-preg normal LVEFGp 2 – 16 pre-preg↓ LVEF

• Pregnancies resulted in ↓ in mean LVEF

Gp 1 – 56±7% → 49±10%;Gp 2 – 36±9% → 32±11%

• CHF symptoms Gp 1 = 21%, Gp 2 = 44%

• Mortality rate Gp 1= 0%, Gp 2 = 19% (P=0.06)

• Subsequent preg – ↓ EF, clinical deterioration and death

• Advise against pregnancy – EF <25% at presentationor persistent ↓ EF

Elkayam et al: N Engl J Med, 2001

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FDA Classification of Drugs During Pregnancy

A Controlled studies show no risk

B No evidence of risk in humans, the chance of fetal harm is remote

C Risk not excluded. Adequate studies lacking. Chance of fetal harm but benefits outweigh risks

D Positive evidence of risk. Studies in humans show fetal risk. Potential benefit in pregnant women may outweigh risk

X Contraindicated

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Cardiac Drugs in Pregnancy

• Most CV drugs cross placenta, secretedin breast milk

• Avoid when possible

• Use drugs with long safety record

• Prescribe lowest dose for shortest duration

• Avoid multi-drug regimens

• No drug is completely safe

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Cardiac Drugs in Pregnancy

ACE Inhibitors – contraindicated in pregnancy

• 30% fetal morbidity with administration after week 14

• Fetal renal tubular dysplasia, neonatal renal failure

• Oligohydramnios, ↓ cranial ossification, IUGR

Cooper et al: N Engl J Med 2006

• 1st trimester ACE ↑ risk of congenital malformations

• ↑ CV and CNS malformations

• AT II blocker – contraindicated

• Safe during lactation

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Heart Failure Medications - Pregnancy

• ACE-i/ARBs CONTRAINDICATED

• Metoprolol, Carvedilol– Class C, Atenolol D

• Thiazides – class B

• Loop diuretics – class C

Avoid Hypotension, Placental Hypoperfusion

• Nitrates – class C

• Hydralazine – class C

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Aortic Disease and Pregnancy

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Pregnancy and Marfan Syndrome

• Preexisting medial changes

• Changes with pregnancy

• Physiologic, hormonal

• Unpredictable maternal risk

• Dissection, rupture, IE, CHF

• Fetal risk

• 50% inheritance

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Pregnancy and Marfan Syndrome

ESC GUCH Guidelines 2010

• 50% chance inheritance risk → genetic counseling

• Aorta >45 mm - strongly discourage pregnancy, high

risk of dissection

• Aorta <40 mm rare problem; no safe diameter

• Aorta 40-45 mm, aortic growth and FH important

Even after aortic repair, Marfan patients remain at

risk for dissection of residual aorta

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Valvular Heart Disease and Pregnancy

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Pulmonary Edema

Mitral Stenosis in Pregnancy

↑↑↑↑ HR

↓↓↓↓ diastolic

filling

↓↓↓↓ SV

Reflex ↑↑↑↑ HR

Further ↑ in LA pressure

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Mitral StenosisManagement in Pregnancy

ββββ blockade, maintain NSR

anticoagulation, diuretics

Balloon valvotomy

Surgical valvotomy or MVR

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↓↓↓↓ Placental perfusion

IUGR, preterm labor

Aortic Stenosis in Pregnancy

Unable to

augment CO

Preload and

hypotension

sensitive

CHF and ischemia

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Anticoagulation in Pregnancy

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Complex CHD in Pregnancy

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21-Year-Old FemaleSingle Ventricle, Fontan

• Transfer from pediatric cardiology – due to ?

• Complete AV canal, mitral and pulm.valve atresia, single ventricle-RV

• Atrial septectomy, classic BT(neonate)

• Fontan, age 11, bidirectional Glenn, lateral tunnel baffle IVC-RPA

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21-Year-Old FemaleSingle Ventricle, Fontan

• Pre-pregnancy – asymptomatic

• SVT – digoxin

• EF 45-50% -lisinopril

• Exercise test – 8 min (76%)

• VO2- 21.3 (71%)

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21-Year-Old FemaleFontan, Pregnancy #1

• 28 weeks – palpitations, near syncope

• Rx- heparin

• Fatigue and DOE, 35 wks

• CS – 2485 g

• Post partum – ICU –IV fluids

• Required diuresis

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22-Year-Old FemaleFontan, 10 months post partum

• Presents - 5 months pregnant!

• Uncomplicated

• Planned CS – 37 weeks

• 2855 g

• No ICU – no fluid overload

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25-Year-Old FemalePost Fontan, Pregnancy #3

• No care until 5 months

• More SVT – better with inderal

• IUGR (2nd %tile)

• CS at 36 weeks – 2103 g

• No maternal complications

• Baby – VSD – heart failure - surgery

• Vasectomy planned

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31-Year-Old FemalePost Fontan

•5/2011: Research study

•Guess what?

•“Dr. Grogan will kill me!”

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Echo 2010

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Echo 2010

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Echo 2010

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Pregnancy after Fontan

Contraindications

•EF <40%

•Class III-IV symptoms

•Cyanosis

•PLE

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Pregnancy Post Fontan

• Atrial arrhythmias

• Ventricular Dysfunction

• Edema and Ascites

• Challenges of A/C mgmt.

• Spontaneous Abortion

• IUGR and Premature Birth

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Arrhythmias and Pregnancy

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Arrhythmias and Pregnancy

• Palpitations common – often benign

• SVT most common

• Afib/flutter with CHD

• Hemodynamic instability: DC cardioversion

• Vagal maneuvers, adenosine

• Meds:1st line: Digoxin, metoprolol*

• Antiarrhythmic Rc – reserve for severe symptoms, recurrence

* Avoid atenolol- class D

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Arrhythmias and Pregnancy

• VT – uncommon

• Antiarrhymic Rx: quinidine, procainamide, flecainide, sotolol

• Amiodarone – seldom used

• Ablation has been safely performed in pregnancy (atrial and ventricular arrhythmia)

• PPM and ICD can be performed

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Pregnancy: MI, Radiation, Endocarditis

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Acute MI in Pregnancy

• Exclude coronary anomaly and aortic dissection

• Coronary angio, aortic imaging

• PCI – bare metal stent

• CABG – limited data

• Thrombolysis

• Consider if cath/PCI not available

Roth: JACC 2008

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Cardiovascular Disease and PregnancySummary

• CVD complicates 1-2 % of pregnancies

• CHD most common in US

• Does not preclude successful outcome

• Increased risk: mother and fetus

• Individualized assessment

Preferably Prior to Conception