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ABSTRACT
Peripartum cardiomyopathy (PPCM) is a rare and
potentially fatal disease which presents with symptoms
of heart failure primarily due to left ventricular (LV)
systolic dysfunction in the last month of pregnancy and
up to 5e6 months after delivery. PPCM is still regarded
as a disease of unknown aetiology, although recent
evidence suggests a role for a 16 kDa prolactin derivative
produced by proteolytic cleavage of prolactin secondary
to unbalanced oxidative stress present during late
pregnancy and early puerperium. The medical
management of PPCM is similar to other forms of nonischaemic dilated cardiomyopathy, but with the
management tailored to choose safe drugs in pregnancy
and lactation to minimise maternal and fetal morbidity.
There is an increased risk of venous thromboembolism,
and anticoagulation is recommended. About 30e50% of
the patients recover without complications, with their
baseline LV systolic function at rest returning to normal.
The risk of recurrence of PPCM is high, especially if the
LV systolic function has not fully recovered. However, for
those women who have normal LV systolic function as
demonstrated on echocardiography and dobutamine
stress test, the risk of severe cardiomyopathy including
death is relatively low in a subsequent pregnancy.
INTRODUCTION
Peripartum cardiomyopathy (PPCM) is a rare and
potentially fatal disease which presents with
symptoms of heart failure primarily due to left
ventricular (LV) systolic dysfunction presenting in
the last part (mean 32e38 weeks) of pregnancy and
up to 5e6 months after delivery.1e5 Usually, it
occurs early in the postpartum period, with about
45% in the rst week and 75% within the rst
month.3 Clinically, it is very similar to other forms
of non-ischaemic dilated cardiomyopathy except for
its unique relationship with pregnancy3 4 and the
higher likelihood for full recoverydthat is, normalisation of ejection fraction (EF) in almost half of the
cases.5 However, it can still result in chronic
disability and ultimately death in relatively young
women in their reproductive years. This emphasises
the need for a thorough understanding of PPCM, as
its care will transcend many different specialities
and mandates a multidisciplinary approach to its
management. The following review will provide
a comprehensive overview of the condition, especially focusing on its clinical features and management during pregnancy, treatment after pregnancy,
and implications for future conception, as well as
highlighting exciting recent new developments.
34
AETIOLOGY
Despite extensive research into its underlying aetiology, it is still not clear exactly how it occurs, so
PPCM is still regarded as a disease of unknown
aetiology.1e3 5 However, many studies lend support
to the idea of an inammatory pathology leading to
myocarditis,6 due to either a viral infection2 4 7e10
or an autoimmune response in pregnancy against
maternal myocardium provoked by the release of
fetal antigen into maternal blood or by some, as
yet, unknown agents.11e14 None of these proposed
mechanisms are strongly supported by clinical
evidence, as there has been great variability in the
results of endomyocardial biopsies and in the
nding of autoantibodies against myocardium.
Endomyocardial biopsies of the reported cases have
shown features of myocarditis ranging between 9%
and 78%.12 15e17 However, there may be a role for
proinammatory cytokines such as tumour
necrosis factor10 and interleukins (IL-1, IL-6) in the
aetiology as well.18e20
Recent evidence in an animal (mice) model
suggests a role for a 16 kDa prolactin derivative
produced by proteolytic cleavage of prolactin
secondary to unbalanced oxidative stress present
during late pregnancy and early puerperium.21 This
derivative has been found to be cardiotoxic, antiangiogenic, proapoptotic and proinammatory,
which can potentially damage or impair metabolism and contractility of cardiomyocytes.22e24 This
theory is further supported by small clinical reports
of postpartum women with PPCM responding
(recovery from PPCM) when treated with medicines causing reduced secretion of prolactin from
posterior pituitary gland or working as a D2
receptor antagonist such as bromocriptine and
carbergoline.25e27
Other theories include impaired cardiac microcirculation, programmed cell death (apoptosis),2 5
deciency of micronutrients such as selenium,
possible genetic links, and other environmental
factors.28e30 Indeed, in certain cultures where the
incidence of PPCM is high, certain cultural practices
performed during the puerperium such as
consuming lake salt or rock salt (known as kanwa
which has a particularly high sodium content) to
promote the ow of breast milk and the heating of
the body by sitting on a clay bed with a re beneath
to keep warm (a belief felt to ward off infection)
have both been suggested as contributory factors in
its development as well.31 32
Overall it appears that there is a multifactorial
aetiology albeit currently unknown. However,
whatever the initial trigger or combination of
Postgrad Med J 2011;87:34e39. doi:10.1136/pgmj.2009.096594
Review
initiating processes, myocardial biopsy in PPCM shows damage
to myocardium with progressive death of cardiomyocytes and
destruction of the cytoskeleton of the heart, resulting in
progressive loss of heart muscle, ultimately leading to clinical
heart failure.33
EPIDEMIOLOGY
PPCM is not restricted to any particular childbearing age, but in
58% of cases the age at presentation was older than 30 years,
with primigravida occurring in approximately a third of women
(27e33%).3 Its highest incidence occurs in African women or
African American women from southern USA, with the lowest
incidence in Hispanic women in the USA. It has also been
reported in Caucasians, Japanese, Chinese, Indians and Korean
women. Recent reports suggest an estimated incidence of one
case per 299 live births in Haiti,34 35 one case per 1000 live births
in South Africa, and one case per 2289e4000 live births in the
USA.36 These more recent data from the USA suggest a higher
incidence than reported in earlier studies, especially in certain
ethnic groups.4 36 37 Its true incidence in the UK has not been
estimated.
On the basis of several large reported series of PPCM, the
following have been recognised as risk factors favouring development and recurrence of PPCM: advanced maternal age, multiparity, Afro-American race, twin pregnancy, pre-eclampsia,
gestational hypertension1 2 4 5 and use of tocolysis (b2 stimulants).38 PPCM appears not to have a hereditary association.12 18 39
DIAGNOSIS OF PPCM
It is largely a diagnosis of exclusion. Other causes of heart
disease such as congenital heart disease or acquired conditionsdthat is, myocardial infarction causing LV dysfunction,
pulmonary hypertension or valvular heart diseasedmust be
ruled out rst before making a diagnosis of PPCM.12 37 40 It is
then diagnosed in previously healthy women presenting with
symptoms of heart failure and evidence of decreased LV systolic
function from late pregnancy to early puerperium.
However, the diagnosis of PPCM poses many challenges,
as many women in the last month of normal pregnancy experience similar symptoms to that of early heart failure, such as
shortness of breath on exertion, nocturnal dyspnoea and cough,
fatigue, palpitations and pedal oedema, making differentiation
difcult.5 16 17 37 38 Clinical examination remains important for
making the diagnosis, and ndings of a pulse rate >100 beats/min,
elevated jugular venous pressure, third heart sound and basal
crepitations on lung auscultation are abnormal in pregnancy and
suggest heart failure.
Although, PPCM presents in late pregnancy and early puerperium, early onset of pregnancy-associated cardiomyopathy has
been reported, albeit in relatively few women from one series.3
Also, recent observations from Haiti suggest that a subclinical
form of PPCM without overt clinical symptoms may exist. The
investigators identied four clinically normal postpartum
women with asymptomatic systolic dysfunction on echocardiography, who subsequently either developed clinically detectable
dilated cardiomyopathy or improved their LV function and
Postgrad Med J 2011;87:34e39. doi:10.1136/pgmj.2009.096594
35
Review
pregnancy in patients with dilated cardiomyopathy, especially
PPCM, is associated with high maternal and fetal morbidity.
Early diagnosis and prompt initiation of treatment are essential
to optimise pregnancy outcome.
Review
Implanon are the most efcacious and safe methods of contraception for women who have had PPCM. They also have the
added advantage of reducing menstrual loss, which is often
increased in patients receiving warfarin. The combined oral
contraceptive pill is contraindicated because of its thrombogenic
potential. Barrier methods have a high failure rate.
pregnancy is lower than previously believed.75 In this retrospective study, subsequent pregnancy was strongly associated
with further decline in LV function which could induce clinical
heart failure and, in some cases, prove fatal. Heart failure
occurred in 21% of subjects who had normal LV function before
their further pregnancy compared with 44% of those who had
decreased function, and all the deaths occurred in the group with
abnormal LV function before subsequent pregnancy. Furthermore, recovery of LV function was more likely in those women
with EF >30% at their rst diagnosis of PPCM. Therefore LV
systolic function seems to be a major prognostic factor and forms
the basis of decision-making when counselling patients with
peripartum cardiomyopathy about the risks during a future
pregnancy.
Ideally, every woman planning a future pregnancy should
have echocardiography performed, and, even if it is normal, they
ought to have dobutamine stress echocardiography as well.
Women with a full recovery of LV function on both echocardiography and dobutamine stress test can be advised that the risks
of major complications are relatively low (w35% risk of recurrence but with low mortality and the majority of women
experiencing a successful pregnancy).
NEW DEVELOPMENTS
In two cases reported from Germany, the patients showed very
good improvement in cardiac function when treated with
bromocriptine.27 As yet, bromocriptine has not been established
as a treatment option because of lack of evidence from clinical
trials and the potential for serious complications such as
myocardial infarction.76e79 A randomised control trial on the use
of bromocriptine in PPCM is on-going in Haiti and South Africa.
However, at present, bromocriptine is not recommended until
the results of these clinical trials are known.
Pentoxifylline, a vasodilator drug that also inhibits tumour
necrosis factor a, has been shown to improve outcome in a small
study when added to conventional treatment.80 In addition,
intravenous immunoglobulin therapy has been found to be
benecial in a selected group of patients (those with proven
myocarditis of autoimmune origin) in improving symptoms and
LV function.61 80
AREAS OF UNCERTAINTY
Collaborative and multicentre prospective, randomised and
double-blind international studies would be of great help
in nding the correct aetiology, diagnostic methods, best
management options and outcomes (mortality and morbidity).
Main messages
< Peripartum cardiomyopathy is a rare and potentially fatal
37
Review
aetiology
< Identification and treatment of the disease in the very early
Key references
< Demakis JG, Rahimtoola SH. Peripartum cardiomyopathy.
Circulation 1971;44:964e8.
< Fett JD. Understanding peripartum cardiomyopathy, 2008.
Int J Cardiol 2008;130:1e2.
< Hilfiker-Kleiner D, Silva K, Drexeler H. Peripartum
cardiomyopathy: Recent insight into its pathophysiology.
Trends Cardiovasc Med 2008;18:173e9.
< Elkayam U, Akhter MW, Singh H, Khan S, Bitar F, Hameed A,
et al. Pregnancy-associated cardiomyopathy: clinical
characteristics and a comparison between early and late
presentation. Circulation 2005;111:2050e5.
< Sliva K, Tibazarwa K, Hilfiker-Kleiner D. Management of
peripartum cardiomyopathy. Curr Heart Fail Rep
2008;5:238e44.
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2.
3.
4.
5.
A. Is a rare disease.
B. Is a disease of only middle-aged women.
C. Commonly presents in late pregnancy only.
D. Commonly presents up to 12 month post partum.
E. Always leads to full recovery of cardiac function.
7.
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ANSWERS
1.
2.
3.
4.
5.
6.
A
A
A
A
A
A
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(F);
(F);
(F);
(F);
(F);
B
B
B
B
B
B
(F);
(T);
(F);
(F);
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(F);
C
C
C
C
C
C
(F); D
(F); D
(T); D
(F); D
(T); D
(T); D
(F); E (F)
(T); E (T)
(F); E (T)
(F); E (F)
(F); E (T)
(T); E (F)
39
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