Sudden Unexpected Death in Epilepsy (SUDEP) and Cardiovascular Dysfunction - Unraveling the Link: A Narrative Review

Sudden unexpected death in epilepsy (SUDEP) represents a major cause of mortality in individuals with epilepsy, accounting for 8-17% of epilepsy-related deaths. Its multifactorial pathogenesis implicates autonomic dysfunction, impaired heart rate variability, seizure-related arrhythmias, genetic channelopathies, and the potential influence of antiepileptic drugs. Epidemiological studies demonstrate increased SUDEP risk in patients with refractory epilepsy, poor seizure control, and polytherapy, with additional contributions from genetic predisposition and sleep-related seizures. Cardiac abnormalities, including ictal tachyarrhythmias, bradyarrhythmias, and altered QT dynamics, may provide the electrophysiological substrate for lethal events. This review synthesizes current understanding of epidemiology, neuro-cardio-respiratory mechanisms, and cardiovascular contributions to SUDEP, highlighting the role of autonomic and genetic factors, as well as peri-ictal cardiac disturbances. The Mortality in Epilepsy Monitoring Unit Study has provided central insights into the cardiorespiratory cascade leading to SUDEP, while emerging risk-stratification tools such as the SUDEP-7 and SUDEP-3 inventories offer promise for clinical risk assessment. Molecular autopsy approaches identifying channelopathies in DEPDC5 , SCN1A , and cardiac ion channel genes may inform family screening and personalized prevention strategies. Preventive strategies remain limited, although closer collaboration between neurology and cardiology, improved seizure control, adherence to antiepileptic regimens, and consideration of cardiac monitoring or device therapy may help reduce risk. Future research should focus on large-scale prospective studies incorporating implantable monitoring and systematic molecular autopsies to clarify mechanisms and guide individualized preventive strategies tailored to resource settings.