Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs.

The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved antiarrhythmic drug therapy to be developed, it is essential to understand the fundamental mechanisms that cause proarrhythmic reactions to antiarrhythmic drugs. The present article reviews the experimental evidence that has been obtained regarding the mechanisms of proarrhythmia. The evidence available provides important insights, and points to potential strategies for developing newer and safer antiarrhythmic compounds.