Critical Care in

Obstetrics:

An Innovative and Integrated Model for

Learning the Essentials

Peripartum Cardiomyopathy

Leo R. Brancazio, M.D.

Division of Maternal-Fetal Medicine

Department of Obstetrics & Gynecology

Duke University Medical Center

I have no conflicts of interest to disclose

I will be discussing one off-label or

investigational drug: bromocriptine in the

management of peripartum cardiomyopathy

Disclosure

Learning Objectives

Background

Etiologies/ Pathophysiology

Diagnosis

Treatment/ Management

Prognosis/ Future Pregnancies

Summary

Evidence

Outline

Review current epidemiology of

peripartum cardiomyopathy (PPCM)

Understand pathophysiology of PPCM

Discuss signs, symptoms, and diagnosis of

PPCM

Discuss management and prognosis of

PPCM

Learning Objectives

Background

Development of heart failure in last month of

pregnancy or up to 6 months postpartum

Absence of preexisting heart disease

Indeterminate cause

Echocardiographic findings

(a, together with b or c; or all 3)

A. LV end-diastolic dimension >2.7 cm/m2

B. M-mode fractional shortening < 30 %

C. LV ejection fraction < 0.45%

Diagnostic Criteria

Demakis, J. G., & Rahimtoola, S. H. (1971). Peripartum cardiomyopathy. Circulation, 44(5), 964-968.

Manolio, T. A., Baughman, K. L., Rodeheffer, R., et al. (1992). Prevalence and etiology of idiopathic dilated

cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop. Am J Cardiol, 69(17), 1458-1466.

True incidence unknown

Wide variation worldwide

Population differences

Estimates 18-333/100,000 births

In the United states: ~ 1/2066-1/4025 live

births

Clinical presentation highly variable

Incidence

Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy. Heart (British Cardiac Society), 97(23),

1970-1981. doi: 10.1136/heartjnl-2011-300349

Incidence

Harper, Margaret A, Meyer, Robert E, & Berg, Cynthia J. (2012). Peripartum cardiomyopathy: population-based birth prevalence and 7-

year mortality. Obstet Gynecol, 120(5), 1013-1019. doi: 10.1097/AOG.0b013e31826e46a1

Incidence by ICD

both over estimates

and misses cases

Incidence likely

1/2066-1/4025 live

births nationwide

Incidence

Harper, et al

Incidence and case fatality rates are highest in Black, non-

Hispanic women

Age >35 associated with higher prevalence and fatality rates

Distribution by Race

Risk Factors

Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy. Heart (British Cardiac Society), 97(23),

1970-1981. doi: 10.1136/heartjnl-2011-300349

Probable Risk Factors Proposed Risk Factors

Emerging Risk Factors

PPCM

Twin

Pregnancy

High Parity

High Gravidity

Extremes of

Reproductive Age

Prolonged

Tocolysis Preeclampsia

Genetics

Obesity

Smoking

Hypertension

Malnutrition

Cocaine Abuse

African Ancestry

Socioeconomic

Status

Etiologies/

Pathophysiology

Inflammation

Infection

Abnormal immune response to pregnancy

Abnormal response to hemodynamic stress of

pregnancy

Increased myocyte apoptosis

Abnormal hormonal response

Increased adrenergic tone

Excessive prolactin production

Genetics

Proposed Etiologies

Pathophysiology

Blauwet et al

Prolactin

Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin and bromocriptine in postpartum

cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi: 10.1007/s11897-012-0095-7

16-kDA

Prolactin

23-kDA

Prolactin

Cathepsin D

(Vasoinhibin)

Prolactin

Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin and bromocriptine in postpartum

cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi: 10.1007/s11897-012-0095-7

Apoptosis

Migration

Inhibition

Leukocyte

Adhesion

Vaso-

dilatation

Inhibition

16K PRL

Impaired

Vessel

Maturation

Capase

3/8/9

NF-kB

eNOS

Proliferation

Inhibition

MAPKDelta /Notch

Ras-Tiam-Rac1

ICAM

VCAM

SELE

Diagnosis

Signs and Symptoms

Symptoms of PPCM

Dyspnea

Peripheral Edema

Fatigue

Orthopnea

Paroxysmal Nocturnal

dyspnea

Palpitations

Chest pain

Decreased exercise

tolerance

Anorexia

Persistent cough

Abdominal discomfort

Signs of PPCM

Pulmonary Rales

Loud P2

Third Heart Sound (S3) or

Gallop Rhythm

New Mitral Murmur

New Tricuspid Murmur

Lateral / Downward

Displacement of PMI

Jugular Venous Distension

Hepatojugular Reflux

Hepatomegaly

Peripheral Edema

Ascites

Blauwet et al

Blauwet et al

Diagnosis - Adjunct Studies Rule out pneumonia

Rule out pneumothorax

Access for

Cardiac MRI

Useful when echo images are non-diagnostic

May provide prognostic information

Right Ventricular Biopsy

Useful with ventricular tachycardia or high grade failure

Patients who fail to respond to optimal medical therapy

Anemia

Thyroid disease

Liver disease

End stage renal disease

Infection

HIV

Electrolytes

NT-proBNP

hs-CRP

Treatment-

Compensated

Non-pharmaceutical

therapies

Low-sodium diet

≤ 2 liters fluid per day

Decreased activity

Antepartum

management

Beta-blocker

Carvedilol

Metoprolol extended

release

Vasodilator

Digoxin

Diuretic

LMWH for EF < 35%

Treatment (Compensated)

Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.

Postpartum therapy

Angiotensin-converting enzyme (ACE) inhibitor

Angiotensin-receptor blocker (if ACE inhibitor not tolerated)

± Nitrates or hydralazine

Loop Diuretic

Vasodilator

Aldosterone antagonist

Beta-blocker

Warfarin for EF < 35%

Treatment (Compensated)

Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.

ABCs

Loop diuretic

Vasodilator

Positive inotropic agents

Avoid beta-blockers

Heparin

Consider endomyocardial biopsy

Consider cardiac MRI

Assist devices

ECMO

Transplantation

Treatment (Decompensated)

Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.

Possible novel therapy for patients with

PPCM

Still should be considered experimental

May consider use in patients failing

conventional therapy or who are

severely compromised

Bromocriptine

Pilot study – Open-label randomized 10:10

Open-label randomized 10:10

8 weeks of bromocriptine therapy

Improved EF at 6 months vs. standard care

Decreased risk of composite poor outcomes

Bromocriptine

Sliwa et al

Treatment algorithm

Bachelier-Walenta et al.

Treatment algorithm

Bachelier-Walenta et al.

Treatment algorithm

Bachelier-Walenta et al.

Management

– Labor &

Delivery

If possible, delay until heart failure has

resolved (or is resolving)

Route of delivery- ideally vaginal

Decreased hemodynamic burden

Condition may not tolerated prolonged

induction

Supplemental oxygen

Left tilt

Labor & Delivery

Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.

Anesthesia - early epidural

Avoid tachycardia

Avoid hypotension

Careful fluid management

Continuous ECG

± Arterial catheter

± Pulmonary catheter

Intensive care 48 hours postpartum

Labor & Delivery

Heart Failure Society Of America. (2006). Johnson-Coyle et al. Lata, I. et al.

Prognosis

Older studies

50% recovery

25% stable but reduced cardiac function

25% deteriorate

Prognosis

Higher diagnosis and 6 month EF than other causes for

cardiomyopathy

Trend to greater change in EF in 6 months

PPCM vs. other CM

Cooper, L. T. et al

Greater percentage of PPCM patients with EF>50%

Percentage of patients with EF<30% similar between

etiologies

Distribution of EF in PPCM

Cooper, L. T et al

Felker, G M, Thompson, R E, Hare, J M, Hruban, R H, Clemetson, D E, et al. (2000). Underlying causes and long-term survival in patients

with initially unexplained cardiomyopathy. The New England journal of medicine, 342(15), 1077-1084. doi:

10.1056/NEJM200004133421502

Survival PPCM vs. other CM

Future Pregnancy Inadvisable

Elkayam, U et al.

Future Pregnancy Inadvisable

Future Pregnancy Inadvisable

Elkayam, U et al.

Summary

Summary

Widely variable incidence

Rule out other etiologies first

Better long term outcomes that other CM

etiologies

Future pregnancies are not recommended

regardless of recovery

Summary

Initial treatment includes diuretics, beta-

blockers, and inotropes

Consider Bromocriptine for those that do

not respond to maximum therapy

Consider delivery if fetus mature or

cardiac failure decompensated

Evidence

REFERENCES

• Bachelier-Walenta, Katrin, Hilfiker-Kleiner, Denise, & Sliwa, Karen. (2013). Peripartum

cardiomyopathy. Curr Opin Crit Care, 19(5), 397-403. doi: 10.1097/MCC.0b013e328364d7db

(Level III)

• Blauwet, L A, & Cooper, L T. (2011). Diagnosis and management of peripartum cardiomyopathy.

Heart (British Cardiac Society), 97(23), 1970-1981. doi: 10.1136/heartjnl-2011-300349 (Level

III)

• Cooper, L. T., Mather, P. J., Alexis, J. D., Pauly, D. F., et al. (2012). Myocardial recovery in

peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men

and nonperipartum women. J Card Fail, 18(1), 28-33. doi: 10.1016/j.cardfail.2011.09.009

(Level II-2)

• Demakis, J. G., & Rahimtoola, S. H. (1971). Peripartum cardiomyopathy. Circulation, 44(5), 964-

968. Level III)

• Elkayam, U., Tummala, P. P., Rao, K., Akhter, M. W., Karaalp, I. S., Wani, O. R., et al. (2001).

Maternal and Fetal Outcomes of Subsequent Pregnancies in Women with Peripartum

Cardiomyopathy. The New England journal of medicine, 344(21), 1567–1571.

doi:10.1056/NEJM200105243442101(Level II-2)

• Felker, G M, Thompson, R E, Hare, J M, Hruban, R H, Clemetson, D E, et al. (2000). Underlying

causes and long-term survival in patients with initially unexplained cardiomyopathy. The New

England journal of medicine, 342(15), 1077-1084. doi: 10.1056/NEJM200004133421502 (Level

II-3)

Evidence

REFERENCES – continued

• Habli, Mounira, O&apos;Brien, Thomas, Nowack, Elizabeth, Khoury, Saeb, Barton, John R, &

Sibai, Baha. (2008). Peripartum cardiomyopathy: prognostic factors for long-term maternal

outcome. American journal of obstetrics and gynecology, 199(4), 415.e411-415. doi:

10.1016/j.ajog.2008.06.087 (Level II-3)

• Harper, Margaret A, Meyer, Robert E, & Berg, Cynthia J. (2012). Peripartum cardiomyopathy:

population-based birth prevalence and 7-year mortality. Obstet Gynecol, 120(5), 1013-

1019. doi: 10.1097/AOG.0b013e31826e46a1 (Level II-3)

• Heart Failure Society Of, America. (2006). Executive summary: HFSA 2006 Comprehensive

Heart Failure Practice Guideline. J Card Fail, 12(1), 10-38. doi:

10.1016/j.cardfail.2005.12.001(Level III)

• Hilfiker-Kleiner, D., Struman, I., Hoch, M., Podewski, E., & Sliwa, K. (2012). 16-kDa prolactin

and bromocriptine in postpartum cardiomyopathy. Curr Heart Fail Rep, 9(3), 174-182. doi:

10.1007/s11897-012-0095-7 (Level III)

• Johnson-Coyle, L., Jensen, L., Sobey, A., American College of Cardiology, Foundation, &

American Heart, Association. (2012). Peripartum cardiomyopathy: review and practice

guidelines. Am J Crit Care, 21(2), 89-98. doi: 10.4037/ajcc2012163 (Level III)

• Lata, I., Gupta, R., Sahu, S., & Singh, H. (2009). Emergency management of decompensated

peripartum cardiomyopathy. J Emerg Trauma Shock, 2(2), 124-128. doi: 10.4103/0974-

2700.50748 (Level III)

Evidence

REFERENCES – continued

• Manolio, T. A., Baughman, K. L., Rodeheffer, R., Pearson, T. A., Bristow, J. D., et al. (1992).

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart,

Lung, and Blood Institute workshop. Am J Cardiol, 69(17), 1458-1466. (Level II-3)

• Natalie Bello, M. D., Iliana S Hurtado Rendon, M. D., & Zoltan Arany, M. P. (2013). Accepted

Manuscript. Journal of the American College of Cardiology, 1–35.

doi:10.1016/j.jacc.2013.08.717 (Level I)

• Patten, Ian S, Rana, Sarosh, Shahul, Sajid, Rowe, Glenn C, Jang, Cholsoon, et al. (2012).

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature, 485(7398), 333-

338. doi: 10.1038/nature11040 (Level III)

• Sliwa, K, Blauwet, L, Tibazarwa, K, Libhaber, E, Smedema, J P, et al. (2010). Evaluation of

Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy: A Proof-of-

Concept Pilot Study. Circulation, 121(13), 1465-1473. doi:

10.1161/CIRCULATIONAHA.109.901496 (Level I)

Evidence

Thank You for Your Attention!

Planning Committee

Mike Foley, Director Shad Deering, co-Director

Helen Feltovich, co-Director Bill Goodnight, co-Director

Loralei Thornburg, Content co-Chair Deirdre Lyell, Content co-Chair

Suneet Chauhan, Testing Chair Mary d’Alton

Daniel O’Keeffe Andrew Satin

Barbara Shaw