Effects of Sotalol on the Circadian Rhythmicity of Heart Rate and QT Intervals With a Noninvasive Index of Reverse-Use Dependency

Background: The effects of sotalol on the 24-hour profile of the QT interval relative to that of the heart rate (HR) may be helpful in determining the time course of the drug's action in controlling cardiac arrhythmias. This has not been previously determined. Thus, the objec tive of the current study was to evaluate the influence of the drug on the circadian rhyth micity of HR and QT intervals from Holter recordings in ambulatory patients. Reverse-use dependency (RUD) of sotalol was also studied noninvasively from Holter recordings.

Methods and Results: Holter recordings of 18 patients with ventricular arrhythmias were analyzed before and after 3-7 days of treatment with sotalol. We developed and used a sig nal processing system. A new noninvasive index to evaluate RUD was defined and applied to sotalol as a test agent. Sotalol significantly reduced HR from 76.9 ± 3.2 to 60.0 ± 1.1 (P < .001). The mean QT interval increased from 393 ± 11 ms to 489 ± 9 ms, whereas the mean normalized QT (QTc) interval increased from 415 ± 5 ms to 487 ± 5 ms (P < .001) during the drug treatment. Circadian rhythmicity of RR interval was abolished, but the circadian rhythms of the QT and QTc intervals were maintained during continuous treatment with sotalol. This finding is in contrast to amiodarone, which abolished the circadian rhythmicity of QTc interval while maintaining that of RR interval. RUD index was increased from 0.13 ± 0.08 to 0.24 ± 0.10 (P < .001) after sotalol, consistent with increased RUD with sotalol.

Conclusions: The effects of sotalol on the circadian rhythmicity of HR and QTc interval are dissociated. They are in direct contrast to those reported for amiodarone, a difference that may be of clinical significance. The RUD index introduced here provides a noninvasive parameter for comparing short-term as well as long-term effects of class III antiarrhythmic drugs on RUD.