Biomarkers and Their Relation to Cardiac Function Late After Peripartum Cardiomyopathy

Abstract

Background: Angiogenic imbalance involving the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) and cleavage of the nursing-hormone prolactin by the enzyme cathepsin D (CD) both play a role in the pathogenesis of peripartum cardiomyopathy (PPCM). We hypothesized that angiogenic imbalance and increased activity of CD have a long-lasting impact in women with PPCM.

Methods and results: A nationwide Danish cohort of women with PPCM (PPCM group, n = 28), age matched women with previous preeclampsia (n = 28) and uncomplicated pregnancies (n = 28) participated in a follow-up study including biomarker analysis, exercise testing and cardiac magnetic resonance imaging. The median time to follow-up was 91 months (range 27-137 months) for the PPCM group. Levels of sFlt-1, placental growth factor, N-terminal pro-natriuretic brain peptide, and copeptin were all significantly higher in the PPCM group. More women in the PPCM group had detectable CD activity (68%) compared with the preeclampsia group (29%) and uncomplicated pregnancies group (36%) (P = .0002). Levels of angiogenic factors and biomarkers correlated inversely with maximal exercise capacity and cardiac functional parameters assessed with cardiac magnetic resonance imaging.

Conclusions: Women with PPCM had higher biomarker levels and CD activity up to 7 years after diagnosis. Higher biomarker levels correlated inversely with maximal exercise capacity and markers of cardiac dysfunction suggesting that persistent angiogenic imbalance and increased CD activity is associated with residual cardiac dysfunction.

Keywords: Peripartum cardiomyopathy; heart failure; pregnancy.