Peripartum cardiomyopathy: a comprehensive and contemporary review

Abstract

Cardiovascular disease is a major non-communicable disease globally, with increasing prevalence, posing a significant public health challenge. It is the leading non-obstetric cause of perinatal morbidity and mortality, with a substantial number of cardiac fatalities occurring in individuals without any known pre-existing cardiovascular disease. Peripartum cardiomyopathy is a type of de novo heart failure that occurs in pregnant women in the late stages of pregnancy or following delivery. Despite extensive research, diagnosing and managing peripartum cardiomyopathy remains challenging, resulting in significant morbidity and mortality. Recent advancements and novel approaches have been made to better understand and manage peripartum cardiomyopathy, including molecular and non-molecular biomarkers, genetic predisposition and risk prediction, targeted therapies, multidisciplinary care, and improved patient education. This narrative review provides a comprehensive overview and new perspectives on peripartum cardiomyopathy, covering its epidemiology, updated pathophysiological mechanisms, diagnosis, management, and future research directions for healthcare professionals, researchers, and clinicians.

Keywords: Biomarkers; Management; Novel approaches; Pathophysiology; Peripartum cardiomyopathy.

Fig. 1

Novel pathophysiological mechanisms of peripartum cardiomyopathy. Oxidative stress triggered by pregnancy, genetic susceptibility, infections, and autoimmune factors promotes the release of cathepsin-D from the cardiomyocyte, which promotes the proteolytic cleavage of 23 kDa prolactin to an anti-angiogenic form known as 16 kDa prolactin (also known as vasoinhibin) leading to angiogenic imbalance and, subsequently, endothelial dysfunction and cardiomyocyte apoptosis. kDa, kilodalton; miRNA-146a, micro-ribonucleic acid 146a; MnSOD, manganese superoxide dismutase; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ROS, reactive oxygen species; sFLt-1, soluble Fms-like tyrosine kinase 1; STAT3, signal transducer and activator of transcription 3; VEGF, vascular endothelial growth factor. Created with BioRender.com

Fig. 2

Summary of the clinical utility of biomarkers in peripartum cardiomyopathy. Several established and novel biomarkers involved in the pathophysiology of peripartum cardiomyopathy are used in diagnosing, prognosis, and monitoring treatment response. The green tick indicates the purpose for which a biomarker is used in clinical practice. Fas/Apo1, Fas cell surface death receptor/ apoptosis antigen 1; IL-4/6, interleukin 4 and 6; INF-y, interferon-gamma; microRNA-146a, microribonucleic acid-146a; NT-proBNP, N-terminal Pro B-type natriuretic peptide; Ox-LDL, oxidized low-density lipoproteins; sFlt-1, soluble Fms-like tyrosine kinase 1; sST2 soluble suppression of tumourigenicity-2; TGF- β, transforming growth factor- beta; TNF-α, tumor necrosis factor-alpha. Created with BioRender.com

Fig. 3

Pharmacological therapy in peripartum cardiomyopathy. Drug therapy of PPCM during pregnancy includes the following: beta-1 receptor selective blockers (metoprolol is preferred while atenolol should be avoided); diuretics such as furosemide and hydrochlorothiazides should be used only in the presence of pulmonary congestion as they may decrease blood flow to the placenta; and anticoagulation therapy such as LMWH or vitamin k antagonists can be used at prophylactic dose or at therapeutic dose in the presence of intracardiac or systemic thrombo-embolism according to the stage of pregnancy. ACE-I, ARNI, and MRA are contraindicated during pregnancy. Drug therapy post-partum includes the aforementioned therapies in addition to ACE-I/ARNI, MRA, vasodilators, SGLT2-I, and bromocriptine. ACE-I, angiotensin-converting enzyme inhibitor; ARNI, angiotensin receptor/ neprilysin inhibitor; HCTZ, hydrochlorothiazide; LMWH, low-molecular-weight heparin; MRA, mineralocorticoid receptor antagonist; SGLT2-I, sodium-glucose cotransporter-2 inhibitors. Created with BioRender.com

Fig. 4

The integrated care of peripartum cardiomyopathy. The integration of biomarkers, genetic profiling, conventional and disease-specific guideline-directed therapy, patient education, and a multi-disciplinary team contributes to early diagnosis and individualized care of peripartum cardiomyopathy, which leads to improved fetomaternal and safety outcomes. NT-proBNP, N-terminal pro b-type natriuretic peptide; sFLt-1, soluble Fms-like tyrosine kinase 1; PPCM, peripartum cardiomyopathy; TTN, titin protein. Created with BioRender.com