BROMOCRIPTINE NOT YET A THERAPEUTIC OPTION IN PERIPARTUM CARDIOMYOPATHY

Abstract

The idea of late pregnancy hormones causing peripartum Cardiomyopathy1 (PPCM) was put forward in 1985. Reduced expression of STAT 3 (signal transduction and activation of transcription) was found in the left ventricles frompatients with end-stage heart failure due to PPCM compared with non-failing2 control subjects. This triggered research on STAT 3 knockout murine hearts. Alandmark article in 2007 substantiated this idea. Loss of STAT3 in murine heartsled to reduced expression of manganese superoxide dismutase (MnSOD), which neutralizes superoxides generated by highly active cardiomyocytes. Superoxides accumulation stimulate cathepsin D secretion which cleaves prolactin into a 16-kDa fragment that promotes apoptosis in endothelial cells causing PPCM. Blocking prolactin secretion from pituitary with bromocriptine in STAT3 knockout mice completely reversed the PPCM.3

After an exhaustive and convincing research on the causative role of prolactin in amurine model of PPCM in 2007 by Hilfiker et al, their clinical research in Germany6 in July 2017 was not very convincing. The term multicentre randomized in its titleis misleading. There was no placebo group in the study for comparison with bromocriptine group. Both the groups received bromociptine rather. The comparison with IPAC study is having a profound racial bias. Black women were 30% in the IPAC US study versus 1.6% in the recent German study. Moreover selecting those with LVEF less than 30% from the IPAC subjects further biased the study to represent blacks than whites because the mean LVEF in blacks was 31% compared to 36% in whites. The black race significantly predicted the poor recovery in LV7 function in both univariate and multivariate analyses. Fourfold higher incidence of and fatality from PPCM in black8 versus white women was observed by Harper et al. Till theavailability of convincing data from ethnically matched population, bromociptine cannot be considered as atherapeutic option in peripartum cardiomyopathy.