Peripartum cardiomyopathy—a new treatment option by inhibition of prolactin secretion

doi:10.1016/j.ajog.2008.06.051

American Journal of Obstetrics and Gynecology

Volume 199, Issue 4, October 2008, Pages e5-e6

https://doi.org/10.1016/j.ajog.2008.06.051 Get rights and content

Peripartum cardiomyopathy (PPCM) is a rare disease of unclear etiology with a frequent poor outcome, despite optimal medical therapy. Recent experimental data implicate a causal role of prolactin. We report a patient with PPCM who responded well to treatment with Bromocriptine in addition to standard therapy of heart failure.

Section snippets

Case Report

A 43-year-old primigravida with uneventful history and family history was transferred at 34 +2 weeks of gestation due to preeclampsia and suspected hemolysis, elevated liver enzyme levels, low platelet count (HELLP) syndrome. The patient showed slightly elevated blood pressure (145/95 mmHg) and proteinuria (protein 100 mg/dL). Ultrasonography showed apart from oligohydramnion (amnion fluid index 4) a fetal weight estimation and Doppler measuments of fetal and maternal vessels within normal

Comment

A 16 kDa prolactin derivate promotes endothelial cell apoptosis, disrupts capillary structures, and impairs cardiomyocyte metabolism and contractility.7, 8, 9 Recent experimental data implicate a causal role of the cleaved 16 kDa prolactin for the development of PPCM in mice with a cardiac restricted deletion of the signal transducer and activator of transcription-3 (STAT-3).⁷

Suppression of prolactin secretion with Bromocriptine averts PPCM in these mice. Most importantly, Bromocriptine

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Cardiovascular diseases are major complications in pregnancy worldwide and the number of patients who develop cardiac problems during pregnancy is increasing. Pregnancy-associated hypertensive complications such as pre-eclampsia (PE) or peripartum cardiomyopathy (PPCM) are potentially life-threatening heart diseases emerging during pregnancy, under delivery or in the first postpartal months in previously healthy women. Both disease entities display substantial morbidity and mortality in the acute phase. Long-term effects are just beginning to be evaluated. Pathophysiologies are not clear but may to some degree overlap with regard to angiogenic imbalance and endothelial damage. Genetics, lifestyle, and comorbidities are important modulators of PE and PPCM. The present review summarizes the current knowledge on epidemiology and pathophysiology, provides information on diagnostic and prognostic biomarkers and highlights promising novel therapeutic approaches for PE and PPCM.
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Citation Excerpt :
In addition, cardiac valve fibrosis and regurgitation have been reported with the long-term use of dopamine agonists for Parkinson disease.34,35 The promise of bromocriptine as a therapeutic option in adults with acute PPCM was first reported in a case report of 2 patients in 2007.36,37 After these results, an open-label randomized trial published in 2010 was conducted to investigate bromocriptine (2.5 mg orally twice daily for 2 weeks, followed by bromocriptine 2.5 mg orally once daily for 6 weeks) added to usual medical care compared with usual medical care alone in 20 South African patients with PPCM.18
Peripartum cardiomyopathy (PPCM) is a rare disorder with potentially fatal consequences, which occurs mainly in previously healthy women. The aetiology of PPCM remains unknown and various pathologic mechanisms have been proposed, including immune-mediated injuries and impaired response to oxidative stress and inflammatory cytokines. Several therapies have been studied, but few have been validated in a well-designed randomized controlled trial.
In the present study we sought to review the medical treatment intended for acute PPCM. To this end, we performed a systematic review of the literature of randomized and nonrandomized prospective clinical studies.
We identified 2 randomized controlled trials that evaluated the dopamine agonist bromocriptine and the inotrope levosimendan, respectively, and 1 nonrandomized study that evaluated the nonselective phosphodiesterase inhibitor pentoxifylline. We reviewed the pathophysiological, pharmacological, and clinical properties for each treatment option identified. Bromocriptine and pentoxifylline both improved left ventricular systolic function and patient-oriented clinical end points and levosimendan did not improve mortality or echocardiographic findings of PPCM.
In this review we identified bromocriptine and pentoxifylline, but not levosimendan, as potentially useful agents to improve left ventricle function and outcomes in PPCM.
La cardiomyopathie du péripartum (CMPP) qui est un trouble rare dont les conséquences sont potentiellement fatales apparaît principalement chez des femmes auparavant en bonne santé. On ignore l’étiologie de la CMPP, mais de nombreux mécanismes pathologiques ont été proposés, dont les lésions à médiation immunitaire et la détérioration de la réponse au stress oxydatif, ainsi que les cytokines inflammatoires. Plusieurs traitements ont été étudiés, mais peu ont été validés au cours d’un essai clinique à répartition aléatoire bien conçu.
Dans la présente étude, nous avons cherché à passer en revue le traitement médical prévu contre la CMPP aiguë. À cette fin, nous avons réalisé une revue systématique des études cliniques prospectives à répartition aléatoire et non aléatoire.
Nous avons trouvé 2 études cliniques à répartition aléatoire qui évaluaient respectivement l’agoniste dopaminergique, la bromocriptine, et l’agent inotrope, le lévosimendan, et 1 étude à répartition non aléatoire qui évaluait l’inhibiteur non sélectif des phosphodiestérases, la pentoxifylline. Nous avons passé en revue les propriétés physiopathologiques, pharmacologiques et cliniques de chacune des options de traitement établies. La bromocriptine et la pentoxifylline ont amélioré la fonction systolique du ventricule gauche et les critères cliniques axés sur le patient, et le lévosimendan n’a pas amélioré la mortalité ou les résultats échocardiographiques de la CMPP.
Dans cette revue, nous avons établi que la bromocriptine et la pentoxifylline, mais non le lévosimendan, sont des agents potentiellement utiles à l’amélioration de la fonction du ventricule gauche et des résultats de la CMPP.
Sex differences in cardivascular diseases
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Case reportPeripartum cardiomyopathy—a new treatment option by inhibition of prolactin secretion

Section snippets

Case Report

Comment

Lancet

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Cell

Case report
Peripartum cardiomyopathy—a new treatment option by inhibition of prolactin secretion