Cardiac repolarization abnormalities and SUDEP risk in epilepsy

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.

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.

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.

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.