Beyond the Pump: Unravelling Immunometabolic Crosstalk and Organelle Dynamics in Sepsis-Induced Cardiomyopathy

Sepsis-induced cardiomyopathy (SICM) has traditionally been viewed as pump-centered contractile failure, but this paradigm fails to explain the clinical spectrum and recovery patterns. This review presents an integrative framework where immunometabolic crosstalk and organelle dysfunction drive disease, including metabolic routing defects, mitochondrial fission, ER stress, and epigenetic regulation via m6A modification and lactylation. Clinically, it proposes a four-phenotype taxonomy (hyperdynamic, hypodynamic, right ventricular-predominant, Takotsubo-like) and advocates for strain imaging and MRI over ejection fraction. Diagnostic innovation includes liquid biopsy for mitochondrial DNA, extracellular vesicles, and metabolomics. Therapeutically, metabolic resuscitation and phenotype-guided vasopressors offer disease modification. The authors call for adaptive trials, biobanking, and organelle-targeted interventions, positioning SICM as a model for precision immunometabolic medicine.