Cardiac repolarization abnormalities and SUDEP risk in epilepsy

Abstract Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy‐related mortality, yet its mechanisms remain complex and multifactorial. Cardiac repolarization abnormalities are proposed biomarkers, but evidence is scarce, especially in low‐ and middle‐income countries where epilepsy is highly prevalent. Methods We conducted a cross‐sectional case‐control study including 73 adults with epilepsy and 73 age‐ and sex‐matched controls. Participants with cardiovascular risk factors or medications affecting QTc were excluded. All subjects underwent 24 h Holter ECG, and QTc values were categorized using standard cutoffs. Clinical, electroencephalographic, radiological, and therapeutic data were collected. SUDEP risk was evaluated using the SUDEP‐7 inventory. Results Patients with epilepsy had significantly longer QTc intervals than controls (mean QTc 474.1 vs. 432.9 ms, p = 0.001 ) . QTc prolongation was more frequent in patients (47.9% vs. 15.1%, p = 0.02), and highly abnormal QTc values (>500 ms) occurred only in the epilepsy group (6.8%). The SUDEP‐7 score correlated positively with QTc duration ( r = 0.462, p = 0.04). Several factors were significantly associated with QTc prolongation: longer disease duration (OR = 1.10; 95% CI: 1.02–1.18; p = 0.002), carbamazepine use (OR = 2.08; 95% CI: 1.20–3.61; p = 0.009), and polytherapy (OR = 1.81; 95% CI: 1.10–2.95; p = 0.019). Higher seizure burden (≥3 GTCS/year) was strongly associated with longer QTc ( p = 0.001). No significant association was found between sex, seizure type, and QTc prolongation. Significance QTc prolongation is frequent in people with epilepsy and correlates with SUDEP‐7 scores, supporting its potential value as a simple, noninvasive marker of SUDEP risk. Routine ECG monitoring, particularly in patients with established risk factors, may help identify individuals at higher risk of SUDEP and guide preventive strategies.