The spectrum of pregnancy-induced cardiac remodeling: transitioning from healthy adaptive hypertrophy to peripartum cardiomyopathy.

Pregnancy imposes profound hemodynamic, metabolic, and biomechanical stresses on the heart, requiring coordinated structural and molecular adaptations to preserve cardiac function. To compensate, the cardiovascular system undergoes significant reversible adaptations, such as increased blood volume and elevated cardiac output. Such alterations induce physiological left ventricular hypertrophy that is regulated, in part, by mechanotransduction, a process by which cells convert mechanical stimuli such as stretch and pressure into biochemical pathways. Integrin-mediated complexes link cardiomyocytes with the extracellular matrix (ECM), allowing the myocardium to sense increased wall stress/stretch and activate cardioprotective signaling cascades. Together, these pathways preserve cytoskeletal integrity, sustain cardiomyocyte viability, and promote adaptive hypertrophic growth that regresses post-partum as hemodynamic load returns to pre-pregnancy levels. However, within a subset of pregnant women, this healthy adaptive response becomes dysregulated and adaptive hypertrophy transitions into maladaptive, leading to peripartum cardiomyopathy (PPCM) with heart failure (HF). PPCM has a mortality rate between 7% and 15%, establishing it as a significant cause of maternal death globally. Here, we discuss integration of mechanotransduction and cell survival pathways to support cardiac adaptation during pregnancy. Elucidating the role of gene variants and mechanotransduction in the pregnant heart may lead to improved patient outcomes in PPCM and HF.