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

Figures

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  FIGURE 1. The Pregnant Heart: Progression from physiological to pathological cardiac hypertrophy. (Top panel) During pregnancy, increased blood volume induces excessive hemodynamic load on the healthy maternal heart, leading to myocardial stretch (blue double-sided arrow) and initiating physiological cardiac hypertrophy. Under healthy conditions, this adaptive hypertrophy is tightly regulated and preserves cardiomyocytes survival and cardiac function (Bottom panel) Dysfunction or loss of regulatory signals, such as genetic mutations, impaired integrin-mediated mechanotransduction or oxidative stress induces sustained, unchecked myocardial stretch (red double-sided arrow) promoting pathological hypertrophy. This maladaptive remodeling impairs cardiac function causing PPCM and subsequent HF. Created in BioRender. Matter, M (2026) https://BioRender.com/14d21ea.

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  FIGURE 2. Maternal cardiovascular adaptations during pregnancy. Pregnancy is associated with an increased hemodynamic load characterized by a progressive rise in cardiac output and blood volume, alongside a decrease in systemic vascular resistance. These physiological changes evolve across the three trimesters, supporting the growing metabolic demands of developing fetus. Created in BioRender. Matter, M (2026) https://BioRender.com/orv27kl.

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  FIGURE 3. Dysregulation of key signals in the pregnant heart leads to PPCM and HF. Pregnancy increases the hemodynamic load on the maternal heart, typically resulting in adaptive hypertrophy characterized by preserved cardiac function and activation of protective signaling pathways, including increased PI3K-AKT, MAPK, PTRH2. Angiogenesis and anti-oxidant defenses are also upregulated. PPCM shifts responses towards maladaptive hypertrophy, marked by pathological remodeling and impaired cardiac function. This maladaptive state increases oxidative stress and downregulates PTRH2 and PI3K-AKT signaling promoting cardiomyocyte apoptosis, endothelial cell dysregulation, and increased fibrosis inducing PPCM and HF. Created in BioRender. Matter, M (2026) https://BioRender.com/4h4s1yx.

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  FIGURE 4. PPCM Progression from Adaptive Remodeling to Heart Failure, Highlighting Therapeutic Interventions. Pregnancy-induced hemodynamic stress normally promotes a reversible state of adaptive hypertrophy (Stage 1), allowing the maternal heart to accommodate increased circulatory demand and return to baseline in the postpartum period. In PPCM, this adaptive response is destabilized, leading to DCM (Stage 2) and HF (Stage 3). This transition is driven by impaired mechanotransduction and pro-survival signaling, resulting in increased cardiomyocyte apoptosis. A current clinical trial targets prolactin signaling with Bromocriptine. Pre-clinical mouse models of PPCM were rescued by caspase three inhibition. Created in BioRender. Matter, M (2026) https://BioRender.com/i424prf.