Proarrhythmia.

Proarrhythmia is defined as the provocation of a new arrhythmia or the aggravation of a pre-existing one during therapy with a drug at doses or plasma concentrations below those considered to be toxic. Suggested criteria for proarrhythmia include (1) the new appearance of a sustained ventricular tachyarrhythmia; (2) change from a nonsustained to a sustained tachyarrhythmia; (3) acceleration of tachycardia rate; or (4) the new appearance of a clinically significant bradyarrhythmia or conduction defect. Proarrhythmia can be the direct result of a drug's electrophysiologic effects on conduction velocity, refractoriness, and automaticity. However, it may also be the result of metabolic abnormalities, changes in autonomic state, or drug/drug interactions that amplify or alter the drug's electrophysiologic effects. Some forms of ventricular proarrhythmia, such as torsade de pointes, are difficult to forecast and occur in patients with structurally normal hearts as well as in those with serious heart disease. Other forms of ventricular proarrhythmia, such as monomorphic ventricular tachycardia, occur predominantly in patients with structural heart disease or pre-existing ventricular arrhythmia. Atrial flutter with 1 : 1 conduction and bradyarrhythmias can be manifestations of proarrhythmia, particularly during drug therapy for atrial fibrillation. In patients with pacemakers or implantable cardiac defibrillators, antiarrhythmic drugs can change pacing thresholds and can alter the ability of a device to recognize or terminate a sustained ventricular tachyarrhythmia.