Key result
Peripartum cardiomyopathy is a life-threatening condition driven by multiple mechanisms that may merge into a common pathway involving oxidative stress and prolactin cleavage.
Why the study?
Variation in the etiology and mechanisms of peripartum cardiomyopathy poses ongoing challenges for diagnosis, treatment, and clinical management.
This review highlights the complex pathophysiology of peripartum cardiomyopathy, emphasizing the role of the 16 kDa-prolactin fragment and oxidative stress as targets for emerging therapies.
May inform targeted therapy development for peripartum cardiomyopathy; leaves open prospective trials before any practice change.
Peripartum cardiomyopathy (PPCM) is a life-threatening cardiomyopathy characterized by acute or slow progression of left ventricular (LV) systolic dysfunction (LV ejection fraction of <45%) late in pregnancy, during delivery, or in the first postpartum months, in women with no other identifiable causes of heart failure. PPCM patients display variable phenotypes and risk factor profiles, pointing to involvement of multiple mechanisms in the pathogenesis of the disease. The higher risk for PPCM in women with African ancestry, the prevalence of gene variants associated with cardiomyopathies, and the high variability in onset and disease progression in PPCM patients also indicate multiple mechanisms at work. Experimental data have shown that different factors can induce and drive PPCM, including inflammation and immunity, pregnancy hormone impairment, catecholamine stress, defective cAMP-PKA, and G-protein-coupled-receptor signalling, and genetic variants. However, several of these mechanisms may merge into a common major pathway, which includes unbalanced oxidative stress and the cleavage of the nursing hormone prolactin (PRL) into an angiostatic, pro-apoptotic, and pro-inflammatory 16 kDa-PRL fragment, resulting in subsequent vascular damage and heart failure. Based on this common pathway, potential disease-specific biomarkers and therapies have emerged. Despite commonalities, the variation in aetiology and mechanisms poses challenges for the diagnosis, treatment, and management of the disease. This review summarizes current knowledge on the clinical presentation of PPCM in the context of recent experimental research. It discusses the challenge to develop disease-specific biomarkers in the context of rapid changing physiology in the peripartum phase, and outlines possible future treatment and management strategies for PPCM patients.
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Ricke‐Hoch et al. (2019) conducted a review in Peripartum cardiomyopathy. Peripartum cardiomyopathy is a life-threatening condition driven by multiple mechanisms that may merge into a common pathway involving oxidative stress and prolactin cleavage.
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