Metabolic Dysfunction-Associated Steatotic Liver Disease and Sudden Cardiac Death: Epidemiology, Mechanisms, Risk Stratification, and Prevention

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic metabolic liver disease worldwide. Cardiovascular adverse events have long been the leading cause of death in the MASLD population, far exceeding liver-related mortality. Sudden cardiac death (SCD) represents the most insidious and rapidly progressing extreme clinical phenotype among these cardiovascular complications. However, the relationship between MASLD and SCD has long received insufficient attention. Accumulating evidence from clinical studies indicates that MASLD is associated with elevated sudden cardiac arrest (SCA) risk independent of conventional cardiometabolic risk factors. Notably, while non-invasive clinical proxies of hepatic steatosis (such as the fatty liver index) identify individuals with heightened susceptibility to SCA, advancing liver fibrosis shows the strongest, gradient-dependent association with adverse cardiovascular outcomes, although its relation to SCA or SCD specifically requires confirmation. Sudden death in MASLD may result from primary ventricular arrhythmias or, in advanced cirrhosis, from non-shockable arrest due to hemodynamic, infectious, or metabolic decompensation. Although shared cardiometabolic risk factors account for a substantial portion of this association, proposed mechanisms include insulin resistance-related myocardial energy disturbances, inflammation-associated myocardial and electrophysiological remodeling, cirrhosis-associated circulatory dysfunction, and gut-derived endotoxemia. In clinical practice, non-invasive fibrosis scores, circulating biomarkers, and imaging parameters represent promising candidate risk markers for evaluating electrophysiological vulnerability, though a validated, MASLD-specific SCD risk prediction model remains to be established. Strategies such as lifestyle intervention, metabolic-targeted pharmacotherapy, and intensive management of cardiovascular risk factors may interrupt the progression from MASLD to SCD. This review summarizes the current evidence to inform cardiovascular risk management across the course of MASLD.