Expanding clinical role of unique class III antiarrhythmic effects of sotalol

The concept of controlling cardiac arrhythmias by prolonging repolarization was first exemplified in the electrophysiologic properties of sotalol. It has since been shown to be a property shared by an increasing number of compounds. Sotalol has an additional propensity for blocking beta receptors; therefore, its net effects in controlling arrhythmias result from its beta-blocking actions as well as lengthening the refractory period of cardiac muscle. The properties of amiodarone, another class III agent, are even more complex. The potency of these 2 agents must therefore be distinguished from the so-called "pure" class III agents, which may exhibit a more restricted spectrum of action. Available data indicate that prolonged QT interval (the correlate of prolonged cardiac repolarization) merely provides the substrate for antifibrillatory and proarrhythmic actions relative to the absence or presence of associated pharmacologic properties of the compounds or to the clinical setting in which these compounds are used. Thus, class III agents might be expected to exhibit a variable spectrum of efficacy as antifibrillatory drugs with an equally variable incidence of torsades de pointes and so induce a proarrhythmic effect. An understanding of the mechanisms underlying these differences, especially at a cellular level, may provide the basis for the development of newer, clinically relevant antiarrhythmic and antifibrillatory compounds.