Analyses of dynamic Beat-to-Beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of Torsades de Pointes during QT prolongation caused by Sotalol

Background: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantity ECG restitution changes under normal sinus rhythm. Methods: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. Results: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio > 1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the heats prior to torsades de pointes had a QT/TQ ratio > 1 and the median TQ interval was below the lower 981% confidence bounds of normals before and after sotalol. Conclusions: ECG restitution changes are quantifiable under varying states (nocturnally, beta-acrenergic blockade, QT prolongation) in healthy subjects.