Effect of Chronic Amiodarone Therapy on Excitable Gap During Typical Human Atrial Flutter

Abstract

Class I antiarrhythmic drugs increase duration of the excitable gap (EG) during typical atrial flutter whereas intravenous class III drugs decrease the EG. The effect of chronic oral amiodarone therapy on the EG is unknown. EG was prospectively determined by introducing a premature stimulus and analyzing the response pattern during typical atrial flutter in 30 patients without antiarrhythmic drugs and in 20 patients under chronic oral amiodarone therapy. EG was calculated by the difference between the longest coupling interval leading to resetting and the effective atrial refractory period (EARP). A fully EG was defined by the portion of EG where the response curve of the return cycles was flat. A partially EG was defined by the portion of EG where the return cycle increases while coupling interval decreases. A resetting response curve was constructed by plotting the duration of the return cycle against the value of the coupling interval. Cycle length (CL; 222 +/- 17 vs 267 +/- 20 msec, P < 0.0001), EARP (128 +/- 16 vs 152 +/- 18 msec, P < 0.0001), and EG (54 +/- 19 vs 70 +/- 21 msec, P = 0.01) were significantly longer in patients taking amiodarone than in controls. Compared to CL, the relative part of the EARP (57 +/- 7 vs 57 +/- 6%, P = 0.96) and EG (24 +/- 7 vs 26 +/- 8%, P = 0.41) were comparable in both groups. The fully EG was larger in patients under chronic amiodarone therapy than in controls (39 +/- 21 vs 26 +/- 20 msec, P = 0.03). Neither duration of the partially EG (28 +/- 15 vs 31 +/- 15 msec, P = 0.42) nor slope of the ascending portion of the resetting response curve (1.15 +/- 0.5 vs 1.13 +/- 0.4 msec/msec, P = 0.71) differed between the two groups. EG in patients under chronic amiodarone therapy is significantly larger than in controls, mainly because of a longer fully EG. This observation may be explained by opposite effects on conduction velocity and refractoriness.