From Idiopathic to Immune–Angiogenic: A Systematic Review of Actionable Biomarkers and Targeted Therapy Pathways in Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) has traditionally been framed as an idiopathic form of pregnancy-associated heart failure, a designation that has persisted largely because its biological underpinnings were poorly integrated into clinical thinking. Over the past decade, this view has become increasingly untenable. Experimental models, translational studies, and human cohorts now converge on a more complex picture in which immune activation, angiogenic imbalance, and maladaptive hormonal signaling interact to produce myocardial injury in a susceptible postpartum milieu. Against this background, we conducted a systematic review, in accordance with PRISMA 2020 guidance, to synthesize evidence on immune–angiogenic mechanisms, circulating biomarkers, and targeted therapeutic strategies in PPCM, with a focus on clinical actionability. Comprehensive searches of major databases and trial registers identified 32 studies meeting predefined inclusion criteria, encompassing mechanistic investigations, randomized and observational clinical studies, and systematic reviews. Across these data, several reproducible biological signals emerged. Oxidative stress–dependent prolactin cleavage, excess soluble fms-like tyrosine kinase-1, inflammatory cytokine activation, and microRNA-mediated endothelial–cardiomyocyte crosstalk appear central to disease expression. Established biomarkers such as BNP and troponin, together with emerging markers including sFlt-1, cathepsin-D, and microRNA-146a, provide complementary information on hemodynamic stress, myocardial injury, and underlying mechanisms, rather than redundant prognostication alone. Evidence supporting prolactin blockade with bromocriptine, anticoagulation in high-risk phenotypes, and structured postpartum surveillance is critically appraised within this framework. Taken together, the literature supports reframing PPCM as a mechanistically heterogeneous immune–angiogenic syndrome rather than a single idiopathic entity. This perspective enables biomarker-informed risk stratification and more rational therapeutic decisions. Future progress will depend on validating integrated biomarker panels, refining treatment timing, and embedding PPCM-specific pathways into postpartum and maternal mortality prevention care.