Arrhythmogenesis. The severity and clinical importance of arrhythmogenic effects of antiarrhythmic drugs have been well recognized, but only empirical and naive approaches have been used to define antiarrhythmic and proarrhythmic effects when comparing baseline and on-therapy Bolter recordings. This article suggests a new method for the assessment of these effects, based upon comparisons of statistical distributions of ectopic beats recorded on long-term electrocardiograms. Since these distributions are very individual, the Smirnov test was used for their comparison. This enables the antiarrhythmic and arrhythmogenic effects to be defined on a precise statistical basis. To demonstrate this method, an analysis is reported of Hotter recordings made on six patients suffering from different types of ventricular arrhythmia. In each of these patients, one baseline Hotter recording and one recording on each of three different drugs (flecainide, sotalol, and verapamil) were made. The records were digitized using a commercially available system for the analysis of long-term electrocardiograms and random sampling was used to obtain independent samples of arrhythmic episodes that were subsecjuently statistically analyzed. The results shauy that the problem of the definition of arrhythmogenesis can be partly addressed in a precise mathematical way and that treatment with an antiarrhythmic preparation may not only have general antiarrhythmic or arrhythmogenic effects, but may also cause a significant change in the character of arrhythmia that can neither be classified as antiarrhythmic nor as arrhythmogenic influence. The clinical implications of this approach are discussed. (J Electrophysiol 3:261-277, 1989) antiarrhythmic drugs, statistical definition of proarrhythmia, Smirnov test, evaluation of long-term electrocardiograms For several years, it has been known that drugs used to suppress disorders of cardiac rhythm can actually cause or exacerbate arrhythmias.^ -The potential gravity of this socalled arrhythmogenic effect of antiarrhythmic drugs has also been well recognized.^-^"T heoretical considerations explaining the arProf. Malik of Charles University, Prague, is currently supported by the British Heart Foundation.
