The Future of Antiarrhythmic Drug Therapy: Will Drugs Be Entirely Replaced by Procedures?

Antiarrhythmic drug therapy has traditionally been centered in modulating the generation or propagation of the cardiac action potential by drugs acting on membrane ion channels. The history of this approach has been disappointing, marked by catastrophic failures such as those of sodium channel blockers or sotalol to treat ventricular arrhythmias in the setting of structural cardiomyopathies, which led to increased mortality, and by modest clinical efficacy in paroxysmal atrial fibrillation. As catheter ablation has become an established effective therapy for most tachyarrhythmias, membrane-acting drugs have been relegated to symptomatic control of benign arrhythmias in normal hearts or to adjunctive treatments of ventricular tachycardia (combined with catheter ablation and cardiac defibrillators) in the setting of cardiomyopathies. Novel targets of biological modulation of arrhythmia substrates beyond the membrane potential appear promising and could represent future opportunities for arrhythmia pharmacotherapy.