Electrocardiographic indices associated with disability in relapsing-remitting multiple sclerosis: a retrospective cross-sectional study

Autonomic dysfunction and increased cardiovascular risk are increasingly recognized in people with multiple sclerosis (MS). Although several electrocardiographic (ECG) abnormalities have been described in MS, the relationship between ventricular repolarization markers and disability burden remains poorly understood. We investigated the association of selected ECG repolarization indices with disability severity in patients with relapsing-remitting multiple sclerosis (RRMS). In this retrospective cross-sectional study, 101 clinically stable patients with RRMS and 101 age- and sex-matched healthy controls underwent standard 12-lead ECG evaluation. Disability severity was assessed using the Expanded Disability Status Scale (EDSS) and categorized into four ordinal disability groups. Frontal QRS-T angle, Tpeak–Tend (Tp-e) interval, and index of cardiac electrophysiological balance (iCEB) were analyzed. Associations with disability burden were evaluated using Spearman correlation and multivariable proportional-odds ordinal logistic regression analyses adjusted for age, sex, heart rate, serum potassium level, and fingolimod exposure. Compared with controls, patients with RRMS exhibited significantly wider frontal QRS-T angles, longer Tp-e intervals, and higher iCEB values (all p < 0.05). Across EDSS quartiles, QT interval, QTc, Tp-e interval, frontal QRS-T angle, iCEB, and iCEBc increased progressively with greater disability burden. Higher EDSS scores correlated with frontal QRS-T angle (ρ = 0.24, p = 0.012), iCEB (ρ = 0.30, p = 0.020), and Tp-e interval (ρ = 0.26, p = 0.018). In adjusted ordinal logistic regression analyses, frontal QRS-T angle (OR 1.023, 95% CI 1.005–1.042; p = 0.014), iCEB (OR 2.264, 95% CI 1.188–4.311; p = 0.013), and Tp-e interval (OR 1.033, 95% CI 1.011–1.056; p=0.003) were independently associated with higher disability categories. ECG markers of ventricular repolarization are altered in RRMS and independently associated with disability burden. Frontal QRS-T angle, Tp-e interval, and iCEB may represent readily available electrophysiological indicators of disability-related autonomic and cardiovascular involvement in RRMS. Prospective longitudinal studies are required to determine their prognostic significance.