Suppressing and Aggravating Cardiac Arrhythmias

T he increased mortality associated with the use of the class Ic agents encainide and flecainide in the Cardiac Arrhythmia Suppression Trial (CAST)' has led to a critical reexamination of the adequacy of existing therapies for the control of cardiac arrhythmias. Although the reasons for the findings in CAST remain unclear, proarrhythmia due to excessive slowing of conduction has been suggested as a possible contributing cause.2 Consequently, drugs that act by mechanisms other than sodium channel block, for example, /8-blockers and the class III antifibrillatory agents, are currently receiving renewed interest as possible alternative therapies. Although the beneficial effect of ,8-blockade in postinfarction patients has been clearly established in several randomized trials,3 much less is known about the efficacy and overall safety of the class III antiarrhythmic agents. Preliminary results, however, suggest that the class III agents generally demonstrate greater efficacy than conventional class I agents in preventing ventricular arrhythmias occurring during acute ischemia or evoked by programmed electrical stimulation, while producing less cardiac depression than other antiarrhythmic drug classes.4-6 Available data suggest that most class III agents exert their effects on repolarization by blocking one or more potassium channels.7 In a recent "Point of View," Hondeghem and Snyders8 suggest that the therapeutic potential of currently available class III antiarrhythmics is limited by 1) a diminished ability to prolong repolarization at fast heart rates, which would reduce their effectiveness in terminating tachycardias, and 2) a tendency to produce excessive