Different effects of antiarrhythmic drugs on the rate-dependency of QT interval: a study with amiodarone and...

To describe the QT/RR relationship in normal subjects, a previous study validated experimentally and used in healthy subjects a function that separately considered rate-dependent and rate-independent components of ventricular repolarization. The analysis is now extended to the effects on the QT/RR relationship of amiodarone and flecainide, 2 widely used antiarrhythmic drugs affecting repolarization.

The QT/RR relationship was obtained in 45 subjects without heart disease (20 men, 25 women); 20 were taken as controls, and 30 were under antiarrhythmic prophylaxis for lone atrial fibrillation (15 with amiodarone, 15 with flecainide). All subjects underwent a bicycle stress test; RR and QT (V5) were measured at the end of each load step; QTc (Bazett's formula, lead II) was obtained at rest. The QT/RR relation was fitted (R > or = 0.90) by the function QT = QTmax*R/(RR50 + RR). Here, QTmax (QT extrapolated at infinite RR) is a rate-independent measure of repolarization, RR50 (RR at which 50% of QTmax is reached) and S evaluate the rate-dependency of QT.

In controls, QTmax was 436 +/- 67 ms, RR50 was 355 +/- 55 ms, and S was 2.9 +/- 0.2. Amiodarone increased QTc, QTmax, and RR50 and decreased S significantly. Flecainide slightly prolonged QTc, increased QTmax but did not modify RR50 or S.

The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide. These differences might reflect the specific effects of each drug on ionic currents and their properties.