Peripartum cardiomyopathy in the twenty-first century: a review of the pathophysiology and clinical trials for novel disease-specific therapeutics.

Peripartum cardiomyopathy is an idiopathic and nonischemic systolic dysfunction with onset toward the end of pregnancy and up to 5 months postpartum. Its clinical phenotype overlaps with pregnancy-associated cardiomyopathy rendering both a continuum of the same disease. Incidence varies geographically and is highest in areas where risk factors are prevalent. The understanding of its pathophysiology is constantly evolving, but a proposed two-hit model of dysfunctional vasculogenesis and genetic predisposition exacerbated by the hemodynamic stressors of pregnancy is widely accepted. The catalysis of the cleavage of prolactin into an anti-angiogenic fragment provoked by unbalanced oxidative stress forms the bedrock of its pathogenesis. Furthermore, miRNA signaling, placenta-produced factors, and a potential underlying genetic susceptibility convene to disrupt cardiac and endothelial metabolic homeostasis. The role of anti-adrenergic and anti-sarcomeric antibodies, nutritional deficiency, and mutated viral cardiotropes are understudied. There are limited randomized controlled trials for disease-specific drugs; however, most trials are targeted at the D2 receptor agonist bromocriptine. Positive primary endpoints in a large German clinical trial led to its approved use in Europe, but the U.S.A. still renders it experimental with ongoing trials evaluating its long-term efficacy and safety. Despite its popularity since the 1900s, multiple gaps in evidence regarding long-term management after myocardial recovery, management of subsequent pregnancies, optimal anticoagulation strategy, and alternative pathophysiological pathways remain unknown.