Mechanisms of disease: new mechanisms of antiarrhythmic actions

Cardiac arrhythmias are a leading cause of morbidity and mortality in many developed countries. Despite intensive investigation, the cellular mechanisms for most cardiac arrhythmias have not been clearly established. As a consequence, drug therapy for most forms of atrial and ventricular arrhythmias remains largely empirical and ineffective, leading to the increased use of nonpharmacologic treatments. Clearly, new approaches to the prevention of cardiac arrhythmias are needed. Here we review the current experimental basis for several promising antiarrhythmic strategies, with a focus on those targeted against atrial and ventricular fibrillation. Although none of these strategies is yet ready for clinical application, they provide a basis for cautious optimism that effective pharmacologic therapy for fatal cardiac rhythm disturbances could be forthcoming.