European Journal of Heart Failure 2008 10(11):1149-1151; doi:10.1016/j.ejheart.2008.09.001
© 2008 European Society of Cardiology
Recovery from peripartum cardiomyopathy after treatment with bromocriptine
Dirk Habedanka,*,
York Kühnlea,
Thomas Elgetib,
Joachim W. Dudenhausenc,
Wilhelm Haverkampa and
Rainer Dietza
a Department of Cardiology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum Berlin, Germany
b Department of Radiology, Charité – Universitätsmedizin Berlin, Campus Charité-Mitte Berlin, Germany
c Department of Obstetrics, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum Berlin, Germany
* Corresponding author. Universitätsmedizin Berlin, Campus Virchow-Klinikum Department of Cardiology Subdepartment Intensive Care Unit Augustenburger Platz 1 D 13353 Berlin, Germany. Tel.: +49 30 450653625; fax: +49 30 450553915. E-mail address: dirk.habedank{at}charite.de (D. Habedank).
 |
Abstract
|
|---|
Peripartum cardiomyopathy (PPCM) is a potentially devastating
cause of heart failure that affects women late in pregnancy
or in early puerperium. Recent findings showed that a 16 kDa
fragment of prolactin may induce myocardial damage, and this
offered a new option of treating PPCM by blocking prolactin
with bromocriptine. We report on a 35-year-old woman with a
twin gravidity who gave birth to two healthy boys at day 36/6
and developed a potentially fatal PPCM. Within 3 days since
delivery she suffered from severe symptoms of heart failure
(orthopnoea, pleural and pericardial effusion, reduced systolic
function LVEF 15%). Bromocriptine 2.5 mg bid was added to standard
heart failure therapy at day 6 after delivery, and within a
week the patient recovered to NYHA functional class II. 2 months
later she presented in a good state, NYHA class I, and MRI confirmed
an LVEF of 60%. Balancing the potential side effects of bromocriptine
against the very poor prognosis in severe PPCM our case supports
the use of bromocriptine as a specific novel therapy.
Key Words: Peripartum • Cardiomyopathy • Bromocriptine
Received March 22, 2008; Revised June 18, 2008; Accepted September 8, 2008
|
1. Introduction
|
|---|
Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating
cause of heart failure that affects women late in pregnancy
or in early puerperium. It has an incidence of approximately
1 in 4000 deliveries
[1] and occurs more often in twin births
[2]. The origins of this disease were unknown until recently,
and thus treatment was empirical and restricted to standard
heart failure therapy with ACE-inhibitors, beta-blockers, diuretics,
aldosterone antagonists and, in most severe cases, biventricular
assist systems or heart transplantation. The prognosis of PPCM
is controversial, but a left ventricular ejection fraction (LVEF)
below 27% is associated with a mortality of between 9 and 30%
[2,
3]. According to a new pathophysiological explanation reported
recently by Hilfiker-Kleiner et al., a 16 kDa form of the post-partally
upregulated hormone prolactin initiates cell apoptosis and disrupts
capillaries, thus inducing myocardial damage and heart failure
[4]. This concept offers a new and causal option of treating
PPCM by blocking prolactin with bromocriptine
[5]. In this letter
we report on a patient with potentially fatal PPCM after a twin
birth and her recovery after treatment with bromocriptine.
|
2. Case report
|
|---|
A 35-year-old woman (first and twin gravidity, BMI 21.8 kg/m
2)
was admitted to our department of obstetrics at the 35th week
of gestation (35 weeks+1 day) due to imminent premature birth.
She was free of cardiac symptoms before and had no family history
of cardiomyopathy. On admission, she had proteinuria (3583 mg/d),
slightly elevated blood pressure (138/90 mmHg) and leg oedema,
which led to the diagnosis of preeclampsia. No cerebral symptoms
were present. Liver enzymes, serum creatinine and platelets
were within reference values. Bed rest was recommended and at
day 36/6 she gave birth spontaneously to two healthy boys with
birth weights of 2380 g and 2000 g. Over the following 3 days
she developed severe symptoms of heart failure with dyspnoea
and tachypnoea at rest (30/min), tachycardia (111/min), leg
oedema and weight gain of 5 kg since delivery, and was transferred
to our ICU. ECG showed sinus tachycardia but was otherwise normal.
Blood pressure had normalized and proteinuria was less severe
(2471 mg/d), hence a diagnosis of PPCM was probable and was
confirmed by echocardiography. It showed left ventricular dilatation
(LVEDd 60 mm), severe reduced systolic function (LVEF 25%),
moderate mitral regurgitation 1-2° (out of a scale of 4°)
and moderate to severe pulmonary hypertension (right ventricular
pressure calculated via tricuspidal regurgitation 2° of
52 mmHg, not including right atrial pressure). Laboratory findings
at ICU admission were (normal range in brackets): NT-proBNP
2661 pg/mL (<125 pg/mL), Troponin T 0.33 µg/L (<0.03
µg/L), creatine kinase 161 U/L (<145 U/L), ALAT 72
U/L (<34 U/L), ASAT 78 U/L (<35 U/L), Leukocytes 13.7/nL
(4.5-11.0/nL), C-reactive protein 1.0 mg/dL (<0.5 mg/dL),
S-creatinine 0.72 mg/dL (<1.0 mg/dL). Heart failure therapy
was initiated with torasemide 5 mg, ramipril 2.5 mg, spironolactone
25 mg, bisoprolol 2.5 mg and stepwise increased. The patient
was still nursing, but after the first dose of these medications
the mother's milk was discarded due to the risk of potential
drug transmission. Over the next 3 days, the patient had a slight
weight loss (–2 kg) and a decrease in pulmonary hypertension,
but her clinical status worsened with dyspnoea in upright position,
bilateral pleural effusions and a circular pericardial effusion.
MR-imaging showed an LVEF of 15%. Remarkably, there was no delayed
enhancement in T1-weighted images after injection of Gd-DTPA,
which made myocardial necrosis or fibrosis unlikely (
Fig. 1,
left side). This continuous deterioration stimulated a change
in treatment and according to the theory of the damaging prolactin
derivative mentioned previously we started treatment with bromocriptine
2.5 mg bid. Dyspnoea and tachycardia eased rapidly, by the 5th
day of bromocriptine use the patient was able to stand upright
and was transferred to a normal ward, and on day 12 she was
discharged home in a stable condition and in NYHA class II-III.
Bromocriptine was continued for a total of 6 weeks. At an outpatient
visit 2 months later she presented in a good state, NYHA class
I, with normalized laboratory parameters and without oedema.
Echocardiography showed a still dilated (LVEDd 56 mm) but near
normally contracting LV, mild residual regurgitation of aortic,
mitral and tricuspid valves (1°), absence of pleural or
pericardial effusion and normalized right ventricular pressure.
MRI confirmed these findings with an LVEF of 60%, and additionally,
myocardial oedema was excluded by T2 weighted image and fibrosis
by T1 weighted image after contrast media (
Fig. 1, right side).
View larger version (102K):
[in this window]
[in a new window]
[Download PowerPoint slide]
|
Fig. 1 Left side. Cardiac MRI at 3rd ICU day. Cine SSFP-sequence, four chamber view, end-diastole. Significant cardiac effusion with notching of the right atrium (arrow). Pleural effusion right and left sided (arrowheads). Right side. MRI 2 months later. Corresponding four chamber view. Only minimal pericardial effusion. Completely recovered left ventricular systolic function.
|
|
|
3. Discussion
|
|---|
The rapid recovery of our patient after bromocriptine treatment
was all the more impressive because her condition deteriorated
despite adequate heart failure medication and a poor prognosis
was expected. Duran et al.
[3] very recently published a report
suggesting that persistent left ventricular dysfunction is probable
in PPCM patients with LVEDd>55 mm and LVEF
27%. Both of these
criteria were applicable to our patient. Due to the novelty
of the 16 kDa prolactin derivative theory
[4], systematic clinical
studies on bromocriptine are still lacking. Nevertheless, the
MRI data presented here support the assumption of a PPCM aetiology
beyond myocardial inflammation because no late enhancing structures
were detected. Despite this, myocardial damage was obvious with
increased troponin and creatine kinase levels and could be explained
better by toxicity rather than by immune response. Balancing
the potential side effects of bromocriptine against the very
poor prognosis in severe PPCM our case supports the use of bromocriptine
as a specific novel therapy
[5]. In patients with mild to moderate
PPCM the immediate termination of nursing/breast feeding may
be sufficient.
|
References
|
|---|
- Brar S.S., Khan S.S., Sandhu G.K., et al. Incidence, mortality, and racial differences in peripartum cardiomyopathy. Am J Cardiol (2007) 100(2):302–304.[CrossRef][Web of Science][Medline]
- Elkayam U., Akhter M.W., Singh H., et al. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation (2005) 111(16):2050–2055.[Abstract/Free Full Text]
- Duran N., Günes H., Duran I., Biteker M., Ozkan M. Predictors of prognosis in patients with peripartum cardiomyopathy. Int J Gynaecol Obstet (2008) 101(2):137–140.[CrossRef][Medline]
- Hilfiker-Kleiner D., Kaminski K., Podewski E., et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell (2007) 128(3):589–600.[CrossRef][Web of Science][Medline]
- Hilfiker-Kleiner D., Meyer G.P., Schieffer E., et al. Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine. J Am Coll Cardiol (2007) 50(24):2354–2355.[Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
Top
Abstract
1. Introduction