Peripartum cardiomyopathy: challenges and solutions Angela Beatrice Scardovi,1 Renata De Maria2 1Division of Cardiology, S. Spirito Hospital, Rome, 2CNR Clinical Physiology Institute, ASST-Great Metropolitan Hospital Niguarda, Milan, Italy Abstract: Peripartum cardiomyopathy (PPCM) is a rare heart disease which affects previously healthy women toward the end of pregnancy or in the months following delivery. The incidence of the disease shows wide regional variations and has been rising, probably due to greater awareness or socioeconomic changes. The etiology and pathogenesis of PPCM are multifactorial and poorly understood. Several hypotheses have been proposed over the years including myocarditis, oxidized prolactin, autoimmunity, malnutrition, genetic susceptibility, and apoptosis. PPCM is still a diagnosis of exclusion. Biomarkers with a strictly pregnancy-related kinetics are unavailable in clinical practice, and their role has not yet been fully elucidated. Globally, prognosis has slightly improved over the past years. In some patients, the clinical status quickly improves and sometimes returns to normal. In others, clinical conditions rapidly worsen and are unresponsive to medical therapy, and chronic heart failure (HF) from persistent left ventricular dysfunction (LVD) develops. Acute care treatment may involve the use of intravenous vasodilators, inotropes, with a prominent role for levosimendan, intra-aortic balloon pump, ventricular assist devices, and heart transplant. Beta-1-adrenergic agonists may promote myocyte loss and HF in PPCM patients, induce permanent damage, and prevent recovery. Novel disease-specific therapeutic concepts, such as targeting 16 kDa prolactin and its downstream mediator miR-146a and/or the vascular endothelial growth factor (VEGF) system, may promote healing. Bromocriptine, a dopamine 2D agonist which blocks prolactin, may be a disease-specific treatment for PPCM in addition to standard therapy in patients with acute onset of the disease. Survivors of PPCM often recover from LVD; however, they may be at risk for HF recurrence and death in subsequent pregnancies. Women with chronic LVD should be managed according to international guidelines, and subsequent gestations should be avoided. Close follow-up and accurate risk stratification are mandatory for women who have recovered from PPCM and need counseling for future pregnancies. Keywords: peripartum cardiomyopathy, postpartum cardiomyopathy, prolactin, microRNA, biomarker, acute heart failure, subsequent pregnancies