Journal of Cardiology Cases (2010) 2, e28—e31

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Case Report

Effectiveness of bromocriptine treatment in a

patient with peripartum cardiomyopathy
Masaru Ichida (MD, PhD) a,∗, Kenichi Katsurada (MD) a, Takahiro Komori (MD) a,
Jun Matsumoto (MD) a, Akihide Ohkuchi (MD) b, Akio Izumi (MD) b,
Shigeki Matsubara (MD) b, Takeshi Mitsuhashi (MD) a,
Kazuomi Kario (MD, FJCC) a

a
Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
b
Department Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan

Received 31 October 2009; received in revised form 14 January 2010; accepted 19 January 2010

KEYWORDS Summary Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening dis-
order that occurs in late pregnancy or the early puerperium despite optimal medical therapy.
Peripartum
Recently, oxidative stress-mediated generation of antiangiogenic and proapoptotic 16-kDa pro-
cardiomyopathy;
lactin, and subsequent impaired cardiac microvascularization have been related to PPCM. In
Prolactin;
turn, prolactin blockade with bromocriptine has been proven successful in preventing the onset
Bromocriptine;
of PPCM in mice and in patients at high risk for the disease. Here, we report the efficacy of
Heart failure
bromocriptine for treatment of a patient with PPCM.
© 2010 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

Introduction identifiable cause of cardiac failure; (c) absence of recog-

Peripartum cardiomyopathy (PPCM) is a rare but potentially
life-threatening disorder occurring in late pregnancy or the
early puerperium despite optimal medical therapy [1]. Diag-
nosis of PPCM is based on 4 primary diagnostic criteria [2]:
(a) development of cardiac failure in the last month of preg-
nancy or within 5 months of delivery; (b) absence of an
∗ Corresponding author at: Division of Cardiovascular Medicine,
Department of Internal Medicine, Jichi Medical School, 3311-1
Yakushiji Shimotsuke, Tochigi, 329-0498, Japan.
Tel.: +81 285 58 7344; fax: +81 285 44 5317.
E-mail address: bcichida@jichi.ac.jp (M. Ichida).
nizable heart disease before the last month of pregnancy;
(d) left ventricular systolic dysfunction with left ventricular
ejection fraction of <45% by echocardiography. The treat-
ment is empirical and restricted to standard heart failure
therapy, and, in the most severe cases, biventricular assist
systems or heart transplantation.
Little is known about the pathophysiology of PPCM, and
there are few suitable animal models for studying the dis-
ease. There has been speculation about the involvement
of inflammation, myocarditis, autoimmune reactions, and
apoptosis. More recently, oxidative stress-mediated gener-
ation of antiangiogenic and proapoptotic 16-kDa prolactin,
and subsequent impaired cardiac microvascularization have
been related to PPCM [3].

1878-5409/$ — see front matter © 2010 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jccase.2010.01.007
Bromocriptine treatment for peripartum cardiomyopathy
Figure 1 (a) Electrocardiography at admission showed sinus tachycardia, poor R in V2 and V3 leads and flat T waves. (b)
Electrocardiography 6 months after discharge showed sinus rhythm and positive T waves.
We report the efficacy of bromocriptine for treatment of
a patient with PPCM.
Case report
A 21-year-old woman at approximately 38 weeks’ gesta-
tion was admitted to our hospital with acute shortness
of breath and chest tightness [New York Heart Association
(NYHA) functional class IV], which she reported first noticing
1 week before. She had no history of hypertension, diabetes
mellitus, smoking, or dyslipidemia. She had no pre-existing
cardiac disease, pregnancy-induced hypertension, protein-
uria during her pregnancy, exposure to cardiotoxic agents,
or positive family history of pregnancy-related heart dis-
ease. Physical examination revealed a blood pressure of
141/103 mmHg, regular heart rate of 154 beats/min, respi-
ratory rate of 45 breaths/min, and temperature of 37.3 ◦ C.
The oxygen saturation was 94% while the patient was breath-
ing oxygen at 3 l/min by nasal cannula. There was pitting
edema (2+) of the feet and legs. The brain natriuretic pep-
tide (BNP) level was markedly elevated to 2440 pg/ml, and
creatine kinase was up to 487 mU/ml (Table 1). The level
of total prolactin was 51.38 ng/ml (reference: <30.54 ng/ml
Table 1 Plasma levels of biochemical parameters.
At Cesarean section 1 month
Bromocriptine − +
BNP (pg/ml) 2440 44.8
Prolactin (ng/ml) 58.2 <0.5
CRP (mg/l) 1.88 0.08
CK (mU/ml) 487 26
BNP, brain natriuretic peptide; CRP, C-reactive protein; CK, creatine kinase.
e29
in nonpregnant woman). Other laboratory parameters were
normal. Electrocardiography (ECG) showed sinus tachy-
cardia, poor R waves in V2-3, and flat T waves in all
leads (Fig. 1a). Chest radiography disclosed cardiomegaly,
interstitial pulmonary edema, and small bilateral pleural
effusions. Echocardiography revealed that the left ventri-
cle was dilated (left ventricular diastolic dimension: 58 mm)
and diffusely hypokinetic, without segmental wall-motion
abnormalities and an ejection fraction of 21% (Table 2).
The left ventricular wall thickness was 8.7 mm. There was
moderate mitral regurgitation with left atrial enlargement.
Severe tricuspid regurgitation existed and the estimated
right ventricular systolic pressure was 38 mmHg when the
right atrial pressure was assumed to be 10 mmHg. The infe-
rior vena cava was dilated and the collapsibility was poor.
There was no pericardial effusion.
Since termination of pregnancy was considered neces-
sary to prohibit deterioration of PPCM, and since she showed
an immature cervix, we decided to perform an emergent
Cesarean section under general anesthesia. At the 1st hos-
pital day, she abdominally gave birth to a female infant
weighing 2980 g with a 5-min Apgar score of 8. After the
Cesarean section, conventional treatment for heart fail-
ure (diuretics, an angiotensin-converting enzyme inhibitor,
3 months 6 months 12 months
+ − +
78.2 38.3 16.2
<0.5 22.9
0.25
52 52 41
e30 M. Ichida et al.

Table 2 Echocardiographic parameters.

At Cesarean section 1 month 3 months 6 months 12 months

Bromocriptine − + + − −
EF (%) 21 32 45 49 58
LVd (mm) 58 53 48 47 49
LAd (mm) 42 33 27 31 38
IVST (mm) 8.7 10 7.3 7.4 8
PWT (mm) 9.6 11 7.3 7.4 8
MR Moderate Moderate Mild Mild —
TR Severe Mild Mild Mild Mild
PA pressure (mmHg) 38 33 41 30 33
DcT 193 222 157 195
E/A 1.5 1.77 1.31 1.67
LV Tei index 0.89 0.49 0.59 0.50
EF, ejection fraction; LVd, left ventricular diastolic diameter; LAd, left atrial diameter; IVST, intraventricular septum thickness; PWT,
posterior wall thickness; MR, mitral regurgitation; TR, tricuspid regurgitation; PA, pressure, pulmonary artery pressure; DcT, deceleration
time; E/A, peak velocity ratio of the early diastolic to the atrial systolic wave in the transmitral flow; LV, left ventricular.

and a beta-blocker) was started. The patient’s condition
improved, but the ejection fraction of the left ventricle was
lower than 30%. After obtaining informed consent, includ-
ing a full explanation of potential complications, from the
patient on the 7th hospital day, treatment with bromocrip-
tine was started. In parallel with bromocriptine treatment,
the left ventricular function and heart failure symptoms
improved, accompanied by a decrease of BNP (Table 1).
Bromocriptine was continued for 3 months at 5 mg/day.
Thallium myocardial scintigraphy at the 15th hospital day
showed normal uptake in both the early and delayed (4 h
after the early) imaging. At 6 months’ follow-up, the patient
was in NYHA functional class I. An ECG showed that the R
waves in V2 and V3 (Fig. 1b) were recovered. The LV function
and dimensions had further improved (Table 2), and mitral
valve regurgitation was only mild.
Discussion
Although the pathophysiology of PPCM is largely unknown,
Hilfiker-Kleiner et al. recently published an interesting
paper that sheds new light on the pathogenesis of this
disease [3]. In brief, signal transducer and activator of
transcription 3 (STAT3) knock-out mice readily develop
PPCM. STAT3 has several cardioprotective functions in the
heart, including protective effects against oxidative stress.
Oxidative stress and the release of cathepsin D from car-
diomyocytes can result in cleavage of the 23 kDa form of
prolactin into an antiangiogenic and proapoptotic 16 kDa
form. The authors showed that this 16 kDa form induced car-
diomyopathy in these mice. Interestingly, this effect could
be abolished by bromocriptine administration. In a subse-
quent clinical study of 12 women with previous PPCM, 6 were
treated prophylactically with bromocriptine. In the treated
group, all women survived with preserved left ventricular
function, whereas all women in the control group had dete-
riorated left ventricular function and 3 women died.
In the present report, we showed that bromocriptine was
effective for the treatment of a patient with acute PPCM.
Even though there have been three case reports [4—6] show-
ing that bromocriptine improved the clinical symptoms of
PPCM, its indication remains controversial [7,8]. It has also
been reported that patients with an initially low ejection
fraction and ventricular dilatation recovered normal cardiac
function under the combination of a beta-blocker and an
angiotensin-converting enzyme inhibitor.
During pregnancy, maternal serum prolactin levels rise
progressively. After delivery, prolactin levels remain ele-
vated and fall gradually toward the normal range during a
3—4-week interval in non-breast-feeding mothers. For this
reason, the duration of bromociptione treatment is from 6
to 12 weeks [3—6].
Long-term survival of PPCM has been reported to be
between 85% and 94% at 5 years [1]. This is probably due
to the high rate of spontaneous recovery of left ventricular
function in PPCM. However, women with PPCM with a base-
line left ventricular ejection fraction of 25% or less at the
time of diagnosis have been shown to have a poor long-term
outcome, and 57% of these women will subsequently require
cardiac transplant [9].
In light of discoveries regarding the pathology and
secretion pattern of prolactin in this disease, bromocrip-
tine may be a causative therapeutic option in severe
heart failure patients with PPCM. In these patients,
it is too risky to administer conventional heart failure
treatment (angiotensin-converting enzyme inhibitors and
beta-blockers) and wait several months for a possible
improvement. Moreover, adverse effects of bromocriptine
at this dosage and for this treatment duration are rare.
A previous report showed that bromocriptine treatment
had positive effects in heart failure patients without PPCM
[10]. In another study, bromocriptine decreased plasma
norepinephrine levels and improved the hemodynamic pro-
file. It is possible that a multifactorial role of bromocriptine
might ultimately account for its beneficial effects [4].
The present observations were limited for several rea-
sons. We did not evaluate oxidative stress of the heart,
release of cathepsin D, or the levels of 16 kDa prolactin,
mostly due to the difficulties in checking these parameters
during the acute phase of PPCM. In addition, it has been
reported that some PPCM patients recover spontaneously,
Bromocriptine treatment for peripartum cardiomyopathy
so we cannot rule out such an effect in the present case.
Finally, despite our encouraging results, a randomized trial
will be needed to definitively demonstrate the efficacy of
bromocriptine in the treatment of PPCM.
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