Current and Emerging Antiarrhythmic Drug Therapy for Ventricular Tachycardia

摘要

Ventricular arrhythmias, including ventricular fibrillation (VF) and sustained ventricular tachycardia (VT), are the principal causes of sudden cardiac death in patients with structural heart disease. While coronary artery disease is the predominant substrate associated with the development of VT, these arrhythmias are known to occur in a variety of disorders, including dilated cardiomyopathy, valvular and congenital heart disease, and cardiac ion channelopathies such as the long QT syndrome. In a minority of patients, VT occurs in the absence of structural heart disease. Despite the established mortality benefit of the implantable cardioverter defibrillator (ICD) in patients at risk of lethal arrhythmias, recurrent VT/VF events continue to be a source of morbidity and impaired quality of life in such patients. Antiarrhythmic therapy is indicated in select patients to treat symptomatic VT episodes, to reduce the incidence of ICD shocks, and potentially to improve quality of life and reduce hospitalizations related to cardiac arrhythmia. The primary adverse effects of antiarrhythmic medications are related to both cardiac and extracardiac toxicity, including the risk of proarrhythmia. Current drug therapy for ventricular arrhythmia has been limited by suboptimal efficacy in many patients, resulting in recurrent VT/VF events, and by drug toxicity or intolerance leading to discontinuation in a large percentage of patients. Amiodarone and sotalol are the principal agents used in the chronic treatment of VT. In addition, dronedarone and dofetilide, agents approved for the treatment of atrial fibrillation, and ranolazine, an antianginal agent, have been demonstrated to be protective against ventricular arrhythmia in small clinical studies. Finally, advances in basic electrophysiology have uncovered new molecular targets for the treatment of ventricular arrhythmia, and pharmacologic agents directed at these targets may emerge as promising VT treatments in the future. The roles of these current and emerging therapies for the treatment of VT in humans will be summarized in this review.