Mechanisms and risk factors for proarrhythmia with type Ia compared with Ic antiarrhythmic drug therapy.

Proarrhythmia defined as the exacerbation of existing arrhythmias or the genesis of new arrhythmias de novo may result from any antiarrhythmic agent. The two general clinical syndromes of sustained arrhythmias that result appear to have distinct clinical properties that are consistent with the proposed basic mechanisms of arrhythmogenesis. Torsades de points occurs most commonly in association with administration of type Ia antiarrhythmic agents and has characteristics most consistent with triggered activity mediated by early after depolarization. Conversely, incessant, sustained, monomorphic, wide complex ventricular tachycardia occurs most commonly in association with type Ic antiarrhythmic agents and has characteristics most consistent with incessant reentry. These general subdivisions are probably oversimplified, and in fact, much overlap likely exists. In addition, these proposed mechanisms may not apply to other forms of proarrhythmia such as an increased frequency of isolated ventricular premature couplets or repetitive forms. Furthermore, proarrhythmia may also occur during treatment of supraventricular arrhythmias; although some of these described syndromes are consistent with incessant reentry, the clinical syndromes are not sufficiently defined to better characterize potential mechanisms. Further investigation, therefore, is needed to better define the mechanisms in question, but the mechanisms proposed in this article help to provide a rational approach toward understanding and dealing with clinical proarrhythmia.