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Received: 22 December 2017 Revised: 28 December 2017 Accepted: 3 January 2018

DOI: 10.1002/clc.22888

REVIEW

Peripartum cardiomyopathy: Status 2018


Divya Gupta1 | Nanette K. Wenger2

1
Division of Cardiology, Emory University
Hospital, Atlanta, Georgia Peripartum cardiomyopathy is a rare cardiac condition, overall. However, in certain populations
2
Division of Cardiology, Emory University can be found frequently enough and the signs, symptoms, and management should be readily
School of Medicine, Grady Memorial Hospital, understood. Here we provide an updated overview of this topic.
Atlanta, Georgia
Correspondence KEYWORDS
Nanette Wenger, MD, 49 Jesse Hill Jr. Drive,
Atlanta, GA 30303 Peripartum Cardiomyopathy, outcomes
Email: nwenger@emory.edu

1 | I N T RO D UC T I O N Although there was significant variance with regard to socioeco-


nomic profiles in the occurrence of PPCM worldwide, the clinical var-
Peripartum cardiomyopathy (PPCM) is a rare, idiopathic dilated cardio- iables considered risk factors were consistent among all populations.
myopathy defined by the clinical manifestation of signs and symptoms Multiparity (mean = 3.1), twin pregnancies, as well as preeclampsia
of heart failure in the last month of pregnancy through the fifth month and other hypertensive disorders were commonly found among
postpartum. There must be no other identifiable cause for cardiac fail- women with PPCM.10,11 Within the United States, 43% of women
ure and no identified heart disease before the last month of pregnancy. with PPCM had a hypertensive disorder associated with their preg-
Echocardiographic parameters require 1 of the following to be present: nancy.11 Advanced maternal age (≥30 years of age) is a significant
ejection fraction <45%, fractional shortening <30%, or both, with a pos- risk factor, with increasing risk of PPCM with increasing maternal
sible additive left ventricular end diastolic dimension >2.7 cm/m2 body age.12
surface area.1–3 The incidence varies by region and affects less than Human immunodeficiency virus (HIV) has also emerged as a
0.1% of all pregnancies globally but carries devastating effects, with potential risk factor for peripartum cardiomyopathy and was seen most
morbidity and mortality rates as high as 5% to 32%.4–6 often in patients diagnosed with PPCM outside of Europe.10 This cor-
relation may be related to the higher incidence of HIV in populations
living outside of Europe, but further investigation is warranted.

2 | EPIDEMIOLOGY
3 | ET IOL OG Y
Significant regional variability in the populations that present with
PPCM has been found with very low rates among the Japanese (1:20 Multiple etiologies have been identified as potentially leading to
000 births) and higher rates in black populations reaching upward of PPCM, making this diagnosis a broader umbrella term that includes
1:100 births as seen in Nigeria.7–9 A more recent assessment of heart failure caused by various pathologies that occur in the specified
global PPCM burden by Sliwa et al. indicated that the disease mani- time period. However, the overarching concept of unbalanced oxida-
fested more equally among black and Caucasian populations.10 tive stress and decreased angiogenesis appears to be an overlying
Within countries associated with the European Society of Cardiology, theme with most identified etiologies. Hypertension, abnormal hemo-
the disease was prevalent among Caucasians and more commonly dynamic stress response, viral etiology, and nutritional deficiencies
presented among blacks outside of Europe. Women with lower socio- have all been identified as potential causes of oxidative stress leading
economic profiles were more likely to be afflicted by this disease out- to PPCM.4,13
side of Europe. The human development index (HDI) evaluates Several dysregulated immune responses have been associated
longevity, education, and income to determine a nation's social and with the development of PPCM. Fetal cells often gain access to the
economic ranking. HDI was significantly higher in women with PPCM maternal circulation but maternal immunity destroys them. These
within Europe compared to other nations. fetal chimerisms may escape weakened maternal immunity and nestle

Clinical Cardiology. 2018;1–3. wileyonlinelibrary.com/journal/clc © 2018 Wiley Periodicals, Inc. 1


2 GUPTA AND WENGER

in maternal myocardium. After delivery, maternal immunity returns to fetal complications.4 In the postpartum phase, drug choice will need
normal, attacking the foreign pathogens. Antibodies to cardiac myosin to be made based on the women's desire to breastfeed. Profound
heavy chains have been found in women with PPCM, but not in the hypotension in the infant may result with the use of angiotensin
14,15 receptor blockers (ARBs) or angiotensin converting enzyme inhibitors
serum of those with idiopathic dilated cardiomyopathy.
Abnormal prolactin metabolism caused by oxidative stress–related (ACEIs), especially in the first few weeks of neonatal life. ARBs are
improper cleaving of the hormone into an active, antiangiogenic form not recommended in nursing women at any time for the same reason.
disturbs cardiomyocyte angiogenesis leading to heart failure.13,16 Enalapril, captopril, and quinapril are acceptable ACEIs and are pre-
ferred for use after the infant is a few months old. All other heart fail-
ure medications are appropriate for use by new mothers (ie, loop
4 | MANAGEMENT diuretics, hydralazine, isosorbide dinitrate, and aldosterone antago-
nists).17,22 β-blockers are extremely important for left ventricular
There are no clinical trials to date assessing the appropriate manage- recovery in this cohort of heart failure patients as well. Unfortunately,
ment of acute heart failure due to PPCM. Therefore, standard man- they are terribly underutilized in non-European countries with
agement for acute systolic heart failure is employed in these cases. In significantly higher rates of symptomatic heart failure 1 month after
women presenting with severe acute decompensated heart failure, it delivery 10
is important to protect the airway, manage breathing, and maintain Use of an implantable cardioverter-defibrillator (ICD) should be
circulation.4 Intubation or bilevel positive airway pressure may be deferred until the patient has been given a chance at recovery. A sig-
required to provide appropriate oxygenation, especially in the setting nificant proportion of women with PPCM have normalization of ejec-
of acute pulmonary edema. Loop diuretics are safe antepartum and tion fraction within 6 months of diagnosis, with only 3% having
postpartum, and provide the required diuresis. Continuous infusions residual deficit that warrants use of an ICD.11 While awaiting recov-
of vasodilators, such as nitroglycerin and nitroprusside, can provide ery of left ventricular function, an external wearable defibrillator can
the needed reductions in afterload and preload. If there is significant be utilized to protect against ventricular arrhythmias in the interim.
cardiac dysfunction, an inotrope such as milrinone or dobutamine
may be initiated to provide support; other mechanical support (ie,
intra-aortic balloon pump, left ventricular assist device, or extracorpo- 5 | OUTCOMES
real membrane oxygenation) may be needed for more severe cardio-
genic shock.17 If the woman presents antepartum, fetal monitoring is With current improved understanding of heart failure management,
crucial during the decompensation period.4 If the ejection fraction is PPCM mortality rates have decreased to as low as approximately 3%
<35%, low-molecular-weight heparin may be used to prevent left within 6 months postpartum.6,23 Fortunately, recovery of left ventric-
ventricular thrombi in this population of patients already at high risk ular function is markedly higher in PPCM than in other dilated cardio-
for clotting if antepartum and Coumadin can be used in the postpar- myopathies. Approximately 50% of patients will recover to normal
tum period.18 Treatment would continue for 3 to 6 months after ejection fraction within 6 months to 5 years.24,25
delivery or until left ventricular recovery takes place.18,19 Despite appropriate heart failure management, transplant may be
By definition, these patients present in the last month of preg- needed in up to 4% of PPCM patients.11 At times, mechanical circula-
nancy at the earliest, if the patient is antepartum, delivery of the tory support may be needed as well. However, given the high likeli-
fetus may reduce hemodynamic stress on the heart with the method hood of recovery to normal ejection fraction within a relatively short
of delivery based on obstetric indications.18 period of time, such permanent mechanical strategies should be
It has been suggested that if the heart failure remains refractory avoided, if possible.
despite these extensive efforts, it may be beneficial to refrain from
breastfeeding and initiate bromocriptine therapy to suppress prolac-
tin production.4,20 A recent study by Hilfiker-Kleiner et al. revealed 6 | S U B S E Q U E N T P R E G NA NC I E S
that patients who received bromocriptine treatment, even if only for
1 week, had higher rates of left ventricular recovery with lower mor- Approximately 50% of patients will recover to a normal or near-
bidity and mortality compared to women with PPCM from a different normal ejection fraction after developing PPCM. These women had
study who were not treated with this drug. Unfortunately, this study significantly lower mortality rates and better chances of improved
did not have a placebo arm to allow for a control group within the cardiac function.26 Of the women who continue to have diminished
study. However, patients who received the drug for as little as a cardiac function, subsequent pregnancies are associated with a 25%
week had improvements in ejection fraction of approximately 20%.20 mortality rate and further decline in cardiac function.26 When com-
To the contrary, a survey of women with a history of PPCM revealed pared to standard heart failure management strategies, initiation of
that breastfeeding was associated with a higher rate of left ventricu- bromocriptine therapy immediately after delivery was associated with
lar function recovery.21 significant improvement in left ventricular function and 0% mortal-
Once stabilized, management of heart failure involves medica- ity.26 If a woman with a history of PPCM is considering a subsequent
tions that are least teratogenic in the antepartum period. β-blockers, pregnancy, a care team involving cardiology, high-risk obstetrics, and
specifically carvedilol and metoprolol succinate, hydralazine for vaso- perinatology will be needed to provide the best management strat-
dilation, digoxin, and loop diuretics all carry acceptably low risks of egy for mother and baby. There may be benefit from performing
GUPTA AND WENGER 3

routine assessment with brain natriuretic peptide levels and tropo- conjunction with the Heart Failure Association of the European
nins to determine if the etiology of shared symptoms are due to Society of Cardiology Study Group on PPCM. Eur J Heart Fail.
2017;19:1131–1141.
heart failure or pregnancy. MiR-146a is a microRNA found in 11. Elkayam U, Akhter MW, Singh H, et al. Pregnancy-associated cardio-
women with PPCM, not in unaffected women, and could be consid- myopathy: clinical characteristics and a comparison between early
ered a novel method of identifying postpartum women with this dis- and late presentation. Circulation. 2005;111:2050–2055.
12. Gunderson EP, Croen LA, Chiang V, Yoshida CK, Walton D, Go AS.
ease.27 Dobutamine stress echo may provide a greater assessment
Epidemiology of peripartum cardiomyopathy: incidence, predictors,
of a woman's ability to endure a subsequent pregnancy without and outcomes. Obstet Gynecol. 2011;118:583–591.
recurrence after PPCM.28 13. Hilfiker-Kleiner D, Haghikia A, Nonhoff J, Bauersachs J. Peripartum
cardiomyopathy: current management and future perspectives. Eur
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14. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N,
7 | PREVENTION Sundstrom JB. Autoimmune mechanisms as the basis for human peri-
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Currently, no risk calculator exists to help determine the probability a 15. Lapaire O, Hosli I, Zanetti-Daellenbach R, et al. Impact of
fetal-maternal microchimerism on women's health—a review.
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J Matern Fetal Neonatal Med. 2007;20:1–5.
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exercise, refraining from alcohol consumption and smoking, as well as to peripartum cardiomyopathy. Nature. 2012;485:333–338.
17. Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incor-
a balanced diet all help the heart. Bromocriptine may be beneficial in
porated into the ACC/AHA 2005 Guidelines for the Diagnosis and
reducing mortality and preventing further reduction in ejection frac- Management of Heart Failure in Adults A Report of the American
tion in women with a history of PPCM when presenting for a subse- College of Cardiology Foundation/American Heart Association Task
quent pregnancy.26 Force on Practice Guidelines Developed in Collaboration With the
International Society for Heart and Lung Transplantation. J Am Coll
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Conflicts of interest 18. Lata I, Gupta R, Sahu S, Singh H. Emergency management of decom-
pensated peripartum cardiomyopathy. J Emerg Trauma Shock. 2009;2:
The authors declare no potential conflicts of interest. 124–128.
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ORCID 20. Hilfiker-Kleiner D, Haghikia A, Berliner D, et al. Bromocriptine for the
Nanette K. Wenger http://orcid.org/0000-0002-6503-9139 treatment of peripartum cardiomyopathy: a multicentre randomized
study. Eur Heart J. 2017;38:2671–2679.
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How to cite this article: Gupta D, Wenger NK. Peripartum
cardiomyopathy in a tertiary care hospital. Ethn Dis. 2007;17:
228–233. cardiomyopathy: Status 2018. Clin Cardiol. 2018;1–3. https://
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of patients from the worldwide registry on peripartum cardiomyop-
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