From Ischemic Injury to Arrhythmogenic Substrate: Molecular and Histopathological Insights into Post-Infarction Sudden Cardiac Death

Myocardial infarction is a major cause of cardiovascular death and a key substrate for sudden cardiac death. Traditionally, histopathological analysis of infarction has focused on the temporal sequence of morphological changes, from coagulative necrosis to inflammatory infiltrate and cicatricial fibrosis. However, recent molecular studies have highlighted how these processes are tightly regulated by cell death pathways, including apoptosis, autophagy, and ferroptosis, and by electrical and microvascular remodeling mechanisms that contribute to cardiac instability. This review integrates histopathological and molecular evidence relating to post-infarction evolution, with particular attention to the infarct border zone, the privileged substrate for arrhythmogenesis. Key molecular markers and cells involved in the inflammatory response and wound healing are discussed, as well as implications for ventricular reentry circuit formation and sudden cardiac death risk. An integrated understanding of these mechanisms offers innovative perspectives for the identification of predictive biomarkers and the development of therapeutic strategies aimed at reducing post-infarction arrhythmic outcomes.