T he NE W ENGL A ND JOUR NA L of MEDICINE

REVIEW ARTICLE

Jane A. Leopold, M.D., Editor

Peripartum Cardiomyopathy

From the Cardiovascular Institute, Perel-

man School of Medicine, University of
P Zoltan Arany, M.D., Ph.D.

ERIPARTUM CARDIOMYOPATHY IS A FORM OF ACUTE AND

Pennsylvania, Philadelphia. Dr. Arany can SOMETIMES SE- vere cardiac degeneration that leads to clinical heart
be contacted at zarany@pennmedicine failure during preg- nancy or in the early postpartum period. The disorder
.upenn.edu or at Perelman School of is generally defined
Medicine, University of Pennsylvania,
TRC11-106, 3400 Civic Ctr. Blvd., Phila- as maternal heart failure with systolic dysfunction (left ventricular ejection frac-
delphia, PA 19104. tion, <45%) that develops in the last month of pregnancy or in the first 5 months
N Engl J Med 2024;390:154-64.
after delivery, in the absence of known preexisting cardiac dysfunction. 1,2 In some
DOI: 10.1056/NEJMra2306667 cases, however, the disease occurs earlier in pregnancy or more than 5 months
Copyright © 2024 Massachusetts Medical Society. after delivery.3-5
CME Peripartum cardiomyopathy complicates approximately 1 in 2000 births
at NEJM.org worldwide, with substantial variation among regions,6 including rates as high as
1 in 300 births in Haiti7 and 1 in 100 in parts of Nigeria.8 In the United States,
the disease is four times as likely to develop in Black women as it is in White
women. One third to one half of cases occur in women with hypertensive dis-
eases of pregnancy, including preeclampsia. 9-11 Other strong risk factors for peri-
partum cardiomyopathy include multiple gestations, advanced maternal age, and
anemia. The mode of delivery, such as cesarean section, is not recognized as a
risk factor.
Peripartum cardiomyopathy is now a leading cause of maternal death in many
parts of the United States and around the world. 12-14 Approximately 60% of cases
of cardiogenic shock during pregnancy or in the early postpartum period are
caused by peripartum cardiomyopathy.15 Although cardiac function typically recov-
ers in more than 50% of affected patients, morbidity and mortality are neverthe-
less high, with some patients requiring a left ventricular assist device (LVAD) or
cardiac transplantation. Black women in the United States are twice as likely as
White women to have persistently impaired heart function, and among Black
women in whom heart function does recover, it takes twice as long to do so. 16
Mortality rates are as high as 20%, and the rates are highest among Black women
in the United States and among women in less developed countries worldwide. 17
Peripartum cardiomyopathy can thus be devastating at a critical time in the lives
of affected persons, their families, and their newborn children.

CLINICAL PRESENTATION AND EVALUATION

Patients with peripartum cardiomyopathy typically present with symptoms and

signs of heart failure, including dyspnea, orthopnea, elevated jugular venous pres-
sure, pulmonary rales, and edema. The diagnosis requires a high index of suspi-
cion and is often delayed because symptoms mirror those of pregnancy itself. The
presentation of peripartum cardiomyopathy can also be accelerated and even cata-
strophic, including cardiogenic shock. Infrequently, affected persons present with
a complication of the disease, such as an arrhythmia or a thromboembolic event.
Sixty to ninety percent of cases of peripartum cardiomyopathy occur after delivery,

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 PERIPARTUM CARDIOMYOPATHY

with the highest incidence in the first postpar-

tum week, although there is substantial geo- Table 1. Differential Diagnosis of Peripartum Cardiomyopathy.*
graphic variation in the timing of Differential Diagnosis Differentiating Markers
presentation.5 In the United States, Black Preexisting cardiomyopathy History, family history, prior
women are more likely than White women to echo- cardiography
present later in the postpartum period, perhaps Preeclampsia-induced pulmonary edema History, preserved ejection
in part accounting for the poorer outcomes in fraction in the absence of systolic dysfunction on echocardiography,
this group.4 sFlt-1
and PLGF levels
Peripartum cardiomyopathy is a diagnosis of
Pulmonary or amniotic embolism History, chest CT
exclusion. The differential diagnosis includes
preexisting structural heart disease, preeclamp- Valvular heart disease, including rheu- History, echocardiography
matic disease
sia-induced pulmonary edema in the absence of
Congenital heart disease that has resulted History, echocardiography
systolic dysfunction, pulmonary embolism, in surgical correction
spontaneous coronary artery dissection, and
Chemotherapy-induced cardiomyopathy History, especially of treatment
exposure to toxins, including alcohol and che- with doxorubicin or other
motherapeutic agents (Table 1). The diagnosis of an- thracyclines,
peripartum cardiomyopathy is generally made by trastuzumab, or sorafenib
means of echocardiography, with documenta- Spontaneous coronary-artery dissection History, echocardiography, ele-
tion of systolic dysfunction in the absence of vated troponin levels
1,18
other structural heart disease. Left ventricular Other causes of myocardial infarction, History, echocardiography, ele-
dilatation is common but not always seen. Find- including MINOCA vated troponin levels
ings such as sinus tachycardia on the electrocar- Myocarditis, including giant-cell myo- History, endomyocardial biopsy
carditis
diogram and pulmonary venous congestion on a
chest radiograph are typically nonspecific. Endo- Takotsubo cardiomyopathy History, apical ballooning on
echo- cardiography
myocardial biopsy is usually not needed to diag-
nose peripartum cardiomyopathy and is rarely Tachycardia-induced cardiomyopathy History, especially atrial fibrillation
performed. Magnetic resonance imaging (MRI) Pulmonary edema resulting from pro- History, preserved ejection
fraction longed tocolysis on echocardiography
can be helpful in evaluating systolic function
and cardiac structure. Although levels of plasma Sepsis, thyrotoxicosis, and other high- History, high output on
echocar- output causes of heart failure diography
brain natriuretic peptide do not change sub-
stantially during a normal pregnancy, they are Aortic dissection History, findings on CT angiogram
usually elevated in patients with peripartum
* CT denotes computed tomography, MINOCA myocardial infarction with no
cardiomyopathy, a finding that can prompt a obstructive coronary artery disease, PLGF placental growth factor, and sFlt-1
1,18
consideration of this diagnosis. Currently, soluble fms-like tyrosine kinase 1.
there is no biomarker that is diagnostic for peri-
partum cardiomyopathy. Genetic testing is in-
creasingly offered to patients with peripartum opathy is thus temporally discordant with the
cardiomyopathy, and it should be considered in hemodynamic changes of pregnancy (Fig. 1).
most cases.19 Myocarditis has also been suggested to cause
peripartum cardiomyopathy, but endomyocardi-
PATHOGENESI al biopsy specimens from patients with peripar-
S tum cardiomyopathy do not appear to contain
The causes of peripartum cardiomyopathy re- any more viral genomes that have been impli-
main poorly understood. Pregnancy increases cated in myocarditis than do control speci-
maternal blood volume, cardiac output, and mens,22 and cardiovascular MRI studies with late
cardiac mass beginning in the second trimester gadolinium enhancement in women with peri-
of gestation.20 Peripartum cardiomyopathy has partum cardiomyopathy of recent onset rarely
thus often been proposed to represent a failed reveal evidence of myocarditis.23
hemodynamic stress test. However, the disorder Over the past few years, an alternative model
typically develops after delivery, and systolic of the pathogenesis of peripartum cardiomyopa-
function appears to be preserved earlier during thy has emerged. Studies have suggested that
gestation.21 The onset of peripartum cardiomy- the disorder is triggered by hormones that ema-

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 T he NEW ENGL A ND JOUR NA L of MEDICINE

tocin, which is secreted by the pituitary to pro-

Incidence PPCM mote lactation, can also have vasculotoxic ef-
Plasma volume, fects, promoting postpartum aortic dissection in
cardiac stroke volume,
cardiac output, sFlt-1, Activin A, models of Marfan’s syndrome,26 but a definitive
cardiac mass with role in peripartum cardiomyopathy has not been
preeclampsia
directly established.
Relative Increase

The human placenta is also intensely secre-

Prolactin,
oxytocin, with tory in late gestation. Syncytiotrophoblasts pro-
lactation duce glycoprotein hormones, growth hormones,
Estrogen, metallopeptidases, steroids, neuropeptides (de-
progesterone spite the absence of neurons), and senescence-
sFlt-1, associated secretory proteins.27 Soluble fms-like
Activin A
tyrosine kinase 1 (sFlt-1), a soluble decoy recep-
Gestation Postpartum Period
Delivery
tor for vascular endothelial growth factor that is
abundantly secreted by the placenta in late ges-
Figure 1. Temporal Hormonal and Hemodynamic Changes during Pregnancy tation, has been shown to trigger cardiovascular
in Relation to the Incidence of Peripartum Cardiomyopathy (PPCM). rarefaction, leading to peripartum cardiomyopa-
Hemodynamic changes of pregnancy, including increases in plasma volume thy in mice.28 The latter observation may explain
and cardiac stroke volume, cardiac output, and cardiac mass, occur during the strong epidemiologic associations of pre-
early gestation; these changes are temporally discordant with the typical eclampsia and multiple gestations with peripar-
postpartum presentation of PPCM. Late gestation and the postpartum
period are also characterized by profound changes in hormones. The ab-
tum cardiomyopathy, because large increases in
breviation sFlt-1 denotes soluble fms-like tyrosine kinase 1. placental secretion of sFlt-1 are seen in both
contexts.29 In fact, subclinical cardiac dysfunc-
tion can be detected in patients with preeclamp-
sia even in the absence of peripartum cardiomy-
nate from the pituitary and placenta during the opathy, and the extent of dysfunction correlates
peripartum period, synergizing, in ways still with levels of circulating sFlt-1.30
poorly understood, with intrinsic cardiac factors Numerous other peptide hormones secreted
that render some women susceptible to these by the late-gestation, senescing placenta, includ-
hormonal imbalances. Hormones produced by ing activin A, are likely to contribute directly to
the pituitary and the placenta normally modu- cardiomyocyte dysfunction.31 Peripartum levels
late maternal physiology to support fetal and of activin A in women with preeclampsia, like
newborn growth and development (Fig. 1). Un- sFlt-1 levels, correlate with subclinical cardiac
der certain circumstances, however, some of dysfunction, including 1 year after delivery.32
these processes can lead to cardiac dysfunction The late-gestation placenta is also abundantly
(Fig. 2). For example, prolactin, secreted from ste- roidogenic. Progesterone, highly secreted by
the pituitary in late gestation and after delivery the placenta, suppresses the burning of carbohy-
in lactating persons, was shown in mouse models drates by the heart, promotes cardiac hypertro-
of peripartum cardiomyopathy to be cleaved to a phy, and may have direct negative-inotropic ef-
breakdown product that damages the cardiac fects, all of which probably sensitize the heart to
vasculature. The damaged vessels, in turn, further insults.33-35 Conversely, secretion of some
trigger ventricular systolic dysfunction through a pregnancy-associated vasculoprotective hormones,
com- bination of cardiac ischemia and paracrine such as relaxin-2, are suppressed in patients
signal- ing, including the secretion by endothelial with peripartum cardiomyopathy.36,37 Together,
cells of exosomes containing microRNAs these studies of pregnancy hormones have sug-
(miRNAs) that, when taken up by gested a vasculohormonal model of the patho-
cardiomyocytes, promote cardiomyocyte genesis of peripartum cardiomyopathy, whereby
apoptosis.24,25 These observations have suggested imbalances in peripartum hormones cause car-
that suppression of prolactin secretion, either by diovascular dysfunction and consequent heart
pharmacologic means or by cessation of breast- failure in susceptible women.38
feeding, may be beneficial in patients with What intrinsic cardiac factors render some
peripartum cardiomyopathy. Oxy-

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 PERIPARTUM CARDIOMYOPATHY

↑Vasoinhibin → vascular toxicity

23kD ↑sFlt-1 → vascular dropout
PRL ↓Relaxin → vasoconstriction
↑Activin A → cardiotoxicity
Pituitary
CathD

Cardiac
vasculature

16kD PRL
vasoinhibin

TTNtv
FLNCtv
BAG3tv uPAR
DSPtv etc.

Heart miRNA
ERB B4
ERBB4 146a
Cardiomyocyte
Carbohydrate KDR
burning (VEGFR2)

PDK4
VEGFA
Placenta ACVR2A VEGFB
Progesterone
ACVR2B

Activin A sFlt-1

RXFP1

Relaxin

Figure 2. Hormonal Model of PPCM.

Hormones secreted from the pituitary and the placenta affect cardiac vasculature and function. Prolactin (PRL), secreted by the
pituitary during lactation, can be converted by cathepsin D (CathD), secreted by cardiomyocytes, to a vasoinhibin, which acts on the
urokinase- type plasminogen activator receptor (uPAR) to inhibit vascular function and promote vascular secretion of vesicles
containing microRNA (miRNA) 146a. These vesicles transduce cardiomyocytes to suppress prosurvival signaling by Erb-B2 receptor
tyrosine kinase 4 (ERBB4). As a decoy receptor for vascular endothelial growth factor (VEGF), sFlt-1 is secreted by the placenta and
potently suppresses provascular signaling by VEGF. Activin A, also secreted by the placenta, directly affects cardiomyocyte function through
activin receptor type 2 (ACVR2). Progesterone, largely secreted by the placenta in late gestation, induces pyruvate dehydrogenase kinase 4
(PDK4) in cardiomyocytes, suppressing carbohydrate oxidation by the heart and sparing glucose for fetal use but also resulting in a
cardiac vulnerability. Placental secretion of both sFlt-1 and activin A is accentuated in patients with preeclampsia. Relaxin, secreted by
the corpus luteum early in preg- nancy and by the placenta late in pregnancy, promotes vascular health through multiple mechanisms.
Relaxin levels are reduced in pa- tients with PPCM.

women but not others susceptible to these hor- known to be associated with nonischemic di-
monal imbalances? This question remains large- lated cardiomyopathy, a disease that in part
ly unanswered, but recent studies have revealed resembles peripartum cardiomyopathy.39,40 The
a strong genetic predisposition to peripartum frequencies of identified variants in dilated car-
cardiomyopathy in some cases (Table 2). Ap- diomyopathy and in peripartum cardiomyopathy
proximately 15% of women with peripartum are nearly identical, suggesting that these two
cardiomyopathy have heterozygous loss-of-func- diseases may lie on a spectrum, reflecting dif-
tion genetic variants in one of several genes ferent environmental insults superimposed on

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 T he NEW ENGL A ND JOUR NA L of MEDICINE

Table 2. Prevalence of Rare Loss-of-Function Genetic Variants in Patients with Peripartum Cardiomyopathy (PPCM)
or Dilated Cardiomyopathy (DCM).*

Prevalence Prevalence
Gene Protein in PPCM in DCM

percent
TTN Titin: large protein that spans the sarcomere 10.5 11.3
DSP Desmoplakin: desmosomal protein critical for cell junctions 1.3 1.4
FLNC Filamin C: actin-binding protein at the Z disk 0.8 3.0
MYH7 Myosin heavy chain 7: contractile component of sarcomere 0.4 0.2
MYH6 Myosin heavy chain 6: cardiac-specific sarcomeric protein 0.4 0.3
BAG3 Regulator of chaperone-assisted selective autophagy 0.2 0.3
FKTN Fukutin: regulates α-dystroglycan glycosylation 0.2 0.2
VCL Vinculin: transmits force from cytoplasmic actin to membrane 0.2 0.1
integrins

* The information presented in the table is from Goli et al.39

the background of a similar genetic predisposi- autoimmunity48 and microchimerism,49 although

tion to disease. But how the genetic predisposi- the supportive data for these mechanisms are
tion synergizes with the hormonal changes dis- limited. Biomarker studies,50 including recent
cussed above remains unclear. Cardiomyopathy proteomic analysis in human cohorts,51 have
caused by chemotherapeutic agents41 or by alco- suggested a role of inflammation in peripartum
hol consumption42 is also more frequent among cardiomyopathy, but whether these inflamma-
persons with some of these variants, which tory signatures reflect the course of disease or
suggests a common yet unidentified pathophysi- contribute to its progression is not clear, and the
ology. answer will require further research. Selenium
Two thirds of the identified genetic variants deficiency appears to contribute to peripartum
in both women with peripartum cardiomyopathy cardiomyopathy in some parts of Nigeria,
and patients with dilated cardiomyopathy lie in through unknown mechanisms,52,53 but selenium
TTN, the gene encoding the large sarcomeric deficiency is rare in most other areas of the
protein, titin.39 How variants in TTN cause dis- world and thus is not likely to contribute to peri-
ease also remains uncertain, although recent partum cardiomyopathy generally.
work has shown that the encoded truncated titin
proteins are expressed and detectable in failing
hearts.43,44 The penetrance of TTN loss-of-func- M A N A G E M E N T AND
tion variants that cause disease is less than 5%, 45 OUTCOMES
Few randomized trials have evaluated therapies
a finding that is consistent with the notion that
for peripartum cardiomyopathy, and none of
other, unknown factors, genetic and environ-
these studies have had conclusive results. Cur-
mental, contribute to the pathogenesis of car-
rent management is thus largely extrapolated
diomyopathy. Only about 100 genes have thus
from guideline-directed medical treatment for
far undergone targeted sequencing in cohorts of
nonischemic dilated cardiomyopathy and other
women with peripartum cardiomyopathy, and
forms of heart failure with a reduced ejection
data on the landscape of common variants in
fraction.1,54 Diuretics and nitrates are used to
peripartum cardiomyopathy are limited.46,47 Poten-
control volume, but caution is required to avoid
tially causal variants in other genes thus await
hypotension if they are used before delivery.
discovery.
Neurohormonal blockade with angiotensin-con-
Other pathogenic contributors to peripartum verting–enzyme inhibitors, angiotensin II recep-
cardiomyopathy have been proposed, including tor blockers, and aldosterone receptor antago-

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 PERIPARTUM CARDIOMYOPATHY

nists can be administered after delivery but are with peripartum cardiomyopathy during gesta-
contraindicated before delivery. Hydralazine plus tion can be complex and should be carried out
isosorbide dinitrate is an alternative regimen by a multidisciplinary team that includes an
for afterload reduction during pregnancy. Beta- obstetrician with expertise in maternal–fetal
blockers are routinely indicated and are safe medicine, an anesthesiologist, a cardiologist,
during pregnancy. There are no data on the and a specialist in advanced heart failure, espe-
safety and use, either during or after pregnancy, cially when the patient is hemodynamically un-
of more recently developed pharmaceutical stable. Patients who are hemodynamically stable
agents for heart failure with a reduced ejection can deliver vaginally. Lactation is generally not
fraction, including sacubitril–valsartan and contraindicated. There are no proven disease-
sodium–glucose cotransporter 2 inhibitors, but specific therapies for peripartum cardiomyopa-
these agents are increasingly used after delivery thy, but the use of bromocriptine to suppress the
in patients with peripartum cardiomyopathy, on release of prolactin from the pituitary is cur-
the basis of extrapolation from guideline-directed rently under investigation and may be consid-
medical treatment for dilated cardiomyopathy ered in patients with a left ventricular ejection
and other forms of heart failure with a reduced fraction of less than 35%.
ejection fraction. Most standard heart failure A referral for genetic counseling and testing
medications are compatible with breast-feeding, should be considered, even in the absence of a
but no safety information is available for the family history of peripartum cardiomyopathy
newer agents. or dilated cardiomyopathy.19,60 The presence of
Advanced therapies are used as needed, in- pathogenic variants in TTN does not presage a
cluding mechanical circulatory support with an different prognosis, but variants in filamin C
intra-aortic balloon pump, percutaneous ven- (FLNC) and desmoplakin (DSP) are associated
tricular assist devices, extracorporeal membrane with ventricular arrhythmias in patients with
oxygenation, and LVADs. There is some evi- dilated cardiomyopathy, and the same may be
dence, however, that adrenergic support may be true in patients with peripartum cardiomyopa-
deleterious.55 In general, aggressive treatment is thy.39 Peripartum cardiomyopathy can also be
often appropriate, given the young age of the the first presentation of rare diseases such as
patients and the frequent recovery of cardiac Danon’s disease (LAMP2 variants) or
function. Duchenne’s muscular dystrophy (DMD
Several aspects of the management of peri- variants).40 When a pathogenic variant is
partum cardiomyopathy, as compared with the identified, cascade testing of family members
management of other forms of heart failure with may be beneficial in order to provide reassurance
a reduced ejection fraction, warrant special con- and obviate the need for close monitoring during
sideration. The hypercoagulable state of preg- pregnancy in relatives who do not carry the
nancy, especially the peripartum period, in- variant identified in the proband.
creases the risk of thrombotic complications, Clinical outcomes for patients with peripar-
including left ventricular thrombus and throm- tum cardiomyopathy vary widely and are gener-
boembolic events, which occur in 5 to 20% of ally better in developed countries.5 In most
cases.56,57 The threshold for initiating anticoagu- women, the left ventricular ejection fraction in-
lant therapy should therefore be low — for ex- creases to more than 50% within 6 months after
ample, an ejection fraction of less than 30 to diagnosis, but in many women, a return to nor-
35% or the presence of atrial fibrillation. Ven- mal cardiac function takes longer, and in some
tricular arrhythmias are common in patients women, cardiac function never fully recovers.61,62
with peripartum cardiomyopathy, and when a Implantation of an LVAD or heart transplanta-
defibrillator is indicated, use of a temporary, tion is required in up to 10% of cases, and sur-
wearable defibrillator should be considered vival among transplant recipients is inferior to
instead of an implantable cardioverter–defi- survival among age-adjusted patients who re-
brillator because cardiac contractility often re- ceived heart transplants for other reasons.63,64
covers.58,59 Overall, mortality among patients with peripar-
Management of labor and delivery in patients tum cardiomyopathy can be as high as 20%, and

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 T he NEW ENGL A ND JOUR NA L of MEDICINE

it is higher in low-income countries than in

high-income countries, despite a generally lower
incidence of known risk factors in low-income cebo (ClinicalTrials.gov number,
countries.11,17,65 A lower left ventricular ejection NCT05180773) is expected to be completed in
fraction at presentation most strongly correlates 2026, and the results may resolve the question of
with persistent systolic dysfunction but does whether bro- mocriptine provides a benefit.
not have a high predictive value. Other indica- The limited data available to date suggest that
tors of adverse outcomes include a late presen- breast-feeding is safe in women with peripartum
tation (more than 1 week after delivery),4,61 late cardiomyopathy.76,77 Currently, the theoretical
gadolinium enhancement on MRI, left ven- benefits of suppressing prolactin, whether with
tricular dilatation,61 and right ventricular dys- bromocriptine or by cessation of breast-feeding,
function.66-69 The occurrence of preeclampsia must therefore be weighed against the benefits
with peripartum cardiomyopathy has been of breast-feeding to mother and child. Withhold-
associated with better left ventricular recovery 70 ing breast-feeding increases infant mortality by
and with a higher incidence of adverse cardio- a factor of more than 10 in many parts of the
vascular outcomes.71 world. The World Health Organization and the
American Academy of Pediatrics recommend
exclusive breast-feeding for the first 6 months,
with continued breast-feeding for up to 2 years.78
Counseling patients who are considering a
A R E A S OF UNCERTAINT Y
The dearthANDof data subsequent pregnancy is difficult. The disease
F U Tfrom
U R Erandomized trials of
therapies or treatment strategies in patients with
DIRECTIONS recurs in 10 to 50% of cases, and recurrent
peripartum cardiomyopathy and the lack of data disease can have worse outcomes, including
from long-term longitudinal studies in this death.79-82 Lack of recovery of systolic function
population leave much uncertainty about the before a subsequent pregnancy is associated
management of peripartum cardiomyopathy and with worse outcomes but is not a strong predic-
the long-term prognosis. Preclinical studies sug- tor. Counseling must therefore weigh uncertain
gest that suppression of prolactin secretion, with risks with an often strong desire on the part of
the use of the dopamine agonist bromocriptine the patient to expand the family. Careful moni-
or by cessation of breast-feeding, may be bene- toring by a multidisciplinary team during and
ficial. However, clinical data are less clear. A after a subsequent pregnancy is likely to improve
small, open-label trial involving 20 women ran- outcomes.81,83
domly assigned to receive bromocriptine or pla- Long-term outcomes (i.e., at >5 years) have
cebo suggested a benefit of bromocriptine treat- not been studied extensively, despite the young
ment, but mortality in the control group was age of patients at presentation. The impact of
high.72 A larger trial, with 60 women randomly peripartum cardiomyopathy on lifelong mental
assigned to one of two bromocriptine dosing well-being, including that of family members,
regimens, revealed no significant differences in appears to be substantial but is understudied. As
the recovery of left ventricular ejection fraction many as half of women with peripartum cardio-
between the regimens, but the trial did not have myopathy may meet criteria for mental disorders
a placebo control group.73 A meta-analysis of such as depression or post-traumatic stress dis-
these two trials and nonrandomized studies order.84,85
pointed to a benefit with bromocriptine treat- When and how to withdraw medications once
ment.74 The European Society of Cardiology systolic function has recovered is also uncertain.
guidelines suggest that the use of bromocriptine Cellular and molecular recovery are likely to lag
be considered,75 but there is less consensus behind echocardiographic evidence of recovery,
among U.S. experts. The ongoing Randomized and persistent cardiac dysfunction can often
Evaluation of Bromocriptine in Myocardial Re- be evoked by exercise or dobutamine testing,
covery Therapy for Peripartum Cardiomyopathy despite a return to a normal ejection fraction,
(REBIRTH), a trial involving 200 women ran- indicating incomplete recovery.86,87 Premature
domly assigned to receive bromocriptine or pla- withdrawal of medications can precipitate a re-
currence in patients with dilated cardiomyopa-
thy, but similar studies in patients with peripar-

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 PERIPARTUM CARDIOMYOPATHY

tum cardiomyopathy have not been reported. 88 A limits how much can be studied in a murine
reasonable approach to withdrawing medica- model.
tions may be to wait for 1 year after echocardio-
graphic studies suggested recovery and to with-
draw one medication at a time, with close and SUMMARY
long-term clinical and echocardiographic moni-
Peripartum cardiomyopathy has become an im-
toring.1,18
portant cause of maternal morbidity and mortal-
Racial disparities in peripartum cardiomy- ity. The pathogenesis of the disorder remains
opathy are substantial but poorly understood. incompletely understood. Genetic studies sug-
In the United States, peripartum cardiomyopa- gest that peripartum cardiomyopathy may lie
thy is more frequent in Black women than in on a spectrum with dilated cardiomyopathy,
White women, and the outcomes are worse. and genetic testing should be offered to pa-
Studies suggest that socioeconomic factors tients and families. The neurohormonal chang-
such as neighborhood deprivation and pro- es of late gestation and parturition probably
vider bias, rather than genetic factors, may be trigger peripartum cardiomyopathy in geneti-
driving this inequity,11,89 but more work is cally or otherwise susceptible women. Manage-
needed in this area. Wider use of diagnostic ment of peripartum cardiomyopathy largely mir-
biomarkers such as brain natriuretic peptide rors guideline-directed medical treatment for
may reduce disparities by preventing delayed heart failure with a reduced ejection fraction. No
diagnoses. Various other potential biomark- disease-specific therapy has proven efficacy to
ers, such as high-sensitivity troponin and date, but an ongoing randomized trial is evaluat-
miRNAs, as well as evaluation of electrocar- ing suppression of prolactin as a therapeutic
diograms with the use of artificial intelli- approach. The short-term prognosis for patients
gence, are being investigated, but none of with peripartum cardiomyopathy is usually fa-
these diagnostic approaches are yet sufficient- vorable, but a subset of patients fare poorly and
ly reliable for clinical use.25,90-93 face chronic heart failure, a need for heart trans-
Research into the mechanisms underlying plantation, or death. Racial inequities in peri-
peripartum cardiomyopathy remains challeng- partum cardiomyopathy are profound and poorly
ing. Much research has been done with mice, understood. Little is known about the long-term
but the human placenta differs substantially outcomes of this disorder.
from the murine placenta, which is less inva-
Disclosure forms provided by the author are available with the
sive and less endocrinologically active94; this full text of this article at NEJM.org.

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