Advances in basic research on sepsis-associated myocardial injury: a narrative review

In this review, sepsis-associated myocardial injury (SAMI) is used as an operational umbrella term, rather than a universally accepted diagnostic category, for a heterogeneous spectrum of myocardial stress, injury, and functional impairment that extends beyond the acute dysfunction characteristic of sepsis-induced cardiomyopathy. This narrative review critically synthesizes literature identified through PubMed, Embase, and Web of Science searches for publications from 3 August 2016 to 3 August 2026, supplemented by selected foundational and contextual sources. Evidence is organized by cardiac phenotype, disease phase, biological compartment, and cell type, distinguishing human observations, preclinical support, and exploratory interpretations. The review examines inflammatory and microvascular dysfunction, calcium dysregulation, mitochondrial quality control, metabolic reprogramming, and regulated cell death, alongside immune and stromal cell responses, lymphatic function, interorgan interactions, and epigenetic and RNA regulation. Pyroptosis, necroptosis, and ferroptosis have experimental support in selected models, whereas PANoptosis and cuproptosis remain emerging mechanistic hypotheses requiring validation. We also compare major experimental models and discuss how single-cell, spatial, and multi-omics approaches can connect cellular states with cardiac phenotypes. The synthesis conceptualizes SAMI as a dynamic disturbance of cardiac–systemic adaptation, emphasizing that molecular changes should be interpreted in relation to their cellular source, disease phase, and physiological context. The proposed framework links mechanistic research to serial assessment of biventricular function, myocardial injury biomarkers, strain, and recovery trajectories, informing questions about patient phenotyping, assessment timing, and endpoint selection. Translational priorities include clinically relevant models, interventions initiated after disease recognition, and trials combining cardiac function, organ support requirements, and safety endpoints to strengthen the connection between mechanistic discoveries and patient phenotypes.