Too long or too short? New insights into abnormal cardiac repolarization in people with chronic epilepsy and its potential role in sudden unexpected death

SUMMARY: Sudden unexpected death in epilepsy (SUDEP) is probably caused by periictal cardiorespiratory alterations such as central apnea, bradyarrhythmia, and neurogenic pulmonary edema. These alterations may occur in people with epilepsy and vary in duration and severity. Seizure-related ventricular tachyarrhythmias have also been hypothesized to be involved in SUDEP, but compelling evidence of these, or of predisposition to these, is lacking. Ventricular tachyarrhythmias are facilitated by pathologic cardiac repolarization. Electrocardiography (ECG) indicators of pathologic cardiac repolarization, such as prolongation or shortening of QT intervals as well as increased QT dispersion, are established risk factors for life-threatening tachyarrhythmia and sudden cardiac death (SDC). Abnormalities in cardiac repolarization have recently been described in people with epilepsy. Importantly, periictal ventricular tachycardia and fibrillation have also been reported in the absence of any underlying cardiac disease. Therefore, pathologic cardiac repolarization could promote SCD in people with epilepsy and could be one plausible cause for SUDEP. Herein, we review abnormal cardiac repolarization in people with epilepsy, describe the putative contribution of antiepileptic drugs, and discuss the potential role of pathologic cardiac repolarization in SUDEP. Based on these, measures to reduce the risk of or prevent SUDEP may include antiarrhythmic medication and implantation of cardiac combined pacemaker-defibrillator devices.