ECG-based estimation of dispersion of APD restitution as a tool to stratify sotalol-induced arrhythmic risk

•Several rate-dependent ECG-based biomarkers were evaluated in three patients who develop Torsades des Pointes after sotalol intake and in twenty five healthy volunteers who do not.•Dispersion of restitution quantified from the ECG, DRest, identified better drug-induced cardiotoxicity than the conventionally used QTc.•Neither DRest nor QTc shows sotalol-induced changes in subjects who do not develop TdP.•Computer simulations corroborate the results of the ECG analysis and suggest that DRest is able to quantify the arrhythmogenic substrate in patients at risk of developing drug-induced arrhythmias.

BackgroundIncreased spatial dispersion of restitution properties has been associated to arrhythmic risk. An ECG-based index quantifying restitution dispersion, DRest, is evaluated in patients who experienced Torsades de Pointes (TdP) under sotalol challenge and compared with the response in healthy subjects.Methods and ResultsECG recordings were analyzed for quantification of DRest and QTc, among others biomarkers. DRest provides improved discrimination following sotalol administration between TdP and healthy subjects ([min-max]: [0.18-0.22] vs [0.02-0.12]), compared to other biomarkers including QTc ([436-548 ms] vs [376-467 ms]). Results in healthy subjects are in agreement with simulations of sotalol effects on a human tissue electrophysiological model.ConclusionsThis case study supports the potential of DRest for improved arrhythmia risk stratification even with QTc values below 450 ms.