Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets

Sepsis-induced cardiomyopathy (SICM) is a frequent and clinically important complication of sepsis, characterized by acute and often reversible myocardial dysfunction and associated with poor outcomes in critically ill patients. Despite growing recognition of its clinical significance, effective mechanism-based therapies remain unavailable, largely because SICM is highly heterogeneous and driven by a complex interplay of inflammatory activation, endothelial and microcirculatory dysfunction, oxidative stress, mitochondrial injury, calcium-handling abnormalities, metabolic reprogramming, and dynamic cardiomyocyte adaptation. In recent years, increasing attention has been directed toward epigenetic regulation, as it provides a mechanistic framework linking septic stress to sustained transcriptional and post-transcriptional remodeling in the myocardium and its immune microenvironment. Numerous studies have therefore investigated epigenetic mechanisms in SICM, including DNA methylation, histone modifications, and non-coding RNA-mediated regulation. This review summarizes recent advances in the understanding of epigenetic mechanisms underlying SICM, with emphasis on their roles in inflammation, mitochondrial dysfunction, immune–cardiac crosstalk, and cardiomyocyte injury. We further discuss the translational relevance of epigenetic remodeling and highlight the emerging therapeutic potential of epigenetically targeted interventions. Collectively, these findings provide important mechanistic insights into SICM and may support the development of biomarker-guided stratification and more precise therapeutic strategies for septic myocardial dysfunction.