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Abstract
The nature of the proarrhythmic reactions induced by antiarrhythmic drugs is linked
to the electrophysiologic effects of these agents. Torsades de pointes is the classic
form of proarrhythmia observed during therapy with any drug that prolongs repolarization,
for example, the class III agents. Its precise electrophysiologic mechanism is not
fully elucidated, although the arrhythmia is generally considered to be due either
to early afterdepolarization in the context of prolonged cardiac repolarization or
to an increase in spatial or temporal dispersion of repolarization. Among the class
III drugs the proarrhythmic risk appears to be lowest for amiodarone, probably due
to its complex electrophysiologic profile that may create significant myocardial electrical
homogeneity. In the case of d,l-sotalol, the incidence of torsades de pointes increases
with dose and the baseline values of the QT interval. Where d-sotalol and other pure
class III agents might fall into the varying spectrum of proarrhythmic potential remains
unclear. That d-sotalol has been found to increase mortality in postinfarction patients
with ventricular dysfunction (the Survival With Oral d-Sotalol [SWORD] trial) is a
matter of considerable concern. It raises the possibility that such a phenomenon may
be a common property of most, if not all, pure class III compounds. Accordingly, care
must be taken to minimize the likelihood of proarrhythmia; in particular, therapy
with a class III agent should only be initiated in the presence of a defined indication
established on the basis of clinical trials. When class III antiarrhythmic drug-induced
proarrhythmia occurs, immediate cessation of therapy with the responsible agent and
correction of predisposing factors, such as electrolyte disorders or bradycardia,
is mandatory. Intravenous administration of high-dose magnesium sulfate has been demonstrated
to be effective in terminating and preventing new episodes of torsades de pointes.
Temporary pacing may be necessary.