Bromocriptine for peripartum cardiomyopathy

Bromocriptine for peripartum cardiomyopathy

Use of bromocriptine for the treatment of peripartum cardiomyopathy has been there for some time. Prolactin can be cleaved into a toxic 16-kDa prolactin fragment (also called vasoinhibin) mediated by oxidative stress. This prolactin fragment has a role in driving peripartum cardiomyopathy [1]. Hence the role of bromocriptine in the treatment of peripartum cardiomyopathy. Suppression of lactation is a concern while using bromocriptine for peripartum cardiomyopathy.

In a pilot study, 10 patients each with peripartum cardiomyopathy were randomized to open label bromocriptine with standard heart failure care or standard heart failure care alone [2]. One patient died in the bromocriptine group while four died in the control group. Significantly fewer patients in the bromocriptine group experienced the composite end point of poor outcome defined as death, NYHA functional class III/IV or left ventricular ejection fraction <35% at 6 months, compared to controls. Cardiac magnetic resonance imaging did not show any intracardiac thrombi. As the infants of bromocriptine treated mothers could not be breast fed, they were also studied. Infants in both groups showed normal growth and survival.

German peripartum cardiomyopathy registry has demonstrated the beneficial outcome with bromocriptine [3]. The study showed a high recovery rate of 96% in patients on a combination of beta-blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and bromocriptine. Positive family history was present in 16.5% of cases. They suggested the role of several biomarkers in peripartum cardiomyopathy including Cathepsin D, the enzyme that generates 16 kDa prolactin fragment.

A multicentre randomized study from evaluated the role of bromocriptine in 63 peripartum cardiomyopathy patients with left ventricular ejection fraction of 35% or less [4]. They were randomly assigned to either short term treatment for one week or long term treatment for 8 weeks in addition to standard heart failure therapy. Anticoagulant therapy at a prophylactic dose was administered during bromocriptine treatment in both groups to prevent thrombotic side effects of bromocriptine. A placebo group was considered unethical given the previous registry data and pilot studies showing usefulness of bromocriptine. The treatment was well tolerated and left ventricular ejection fraction increased from a mean of 28% to 49% at 6 months as assessed by magnetic resonance imaging in the one week group. It increased from a mean of 27% to 51% in the 8 weeks group. No patient in the study needed heart transplantation, left ventricular assist device or died. They concluded that there is no significant difference between the one week and 8 week treatment group, though there was a trend for better full-recovery in the 8 week group. There were two events of venous embolism and one peripheral artery occlusion. These occurred in the one week group after termination of bromocriptine therapy.

References

1. Koenig T, Bauersachs J, Hilfiker-Kleiner D. Bromocriptine for the Treatment of Peripartum Cardiomyopathy. Card Fail Rev. 2018 May;4(1):46-49.
2. Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema JP, Becker A, McMurray J, Yamac H, Labidi S, Struman I, Hilfiker-Kleiner D. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Circulation. 2010 Apr 6;121(13):1465-73.
3. Haghikia A, Podewski E, Libhaber E, Labidi S, Fischer D, Roentgen P, Tsikas D, Jordan J, Lichtinghagen R, von Kaisenberg CS, Struman I, Bovy N, Sliwa K, Bauersachs J, Hilfiker-Kleiner D. Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy. Basic Res Cardiol. 2013 Jul;108(4):366.
4. Hilfiker-Kleiner D, Haghikia A, Berliner D, Vogel-Claussen J, Schwab J, Franke A, Schwarzkopf M, Ehlermann P, Pfister R, Michels G, Westenfeld R, Stangl V, Kindermann I, Kühl U, Angermann CE, Schlitt A, Fischer D, Podewski E, Böhm M, Sliwa K, Bauersachs J. Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study. Eur Heart J. 2017 Sep 14;38(35):2671-2679. doi: 10.1093/eurheartj/ehx355. PMID: 28934837; PMCID: PMC5837241.