Novel therapeutics for treatment of long-QT syndrome and torsade de pointes

Long-QT syndrome is a clinically and genetically heterogeneous syndrome characterized by lengthening of the QT interval and increased dispersion of the ventricular repolarization on surface electrocardiogram and a propensity to malignant ventricular arrhythmias, torsade de pointes and ventricular fibrillation, which may lead to sudden cardiac death. Long-QT syndrome mostly affects adolescents and young adults with structurally and functionally normal hearts and is caused by aberrations in potassium and sodium ion channels. Standard therapies for long-QT syndrome include correction of the underlying cause, alleviation of the precipitating factors, magnesium sulfate, isoproterenol, antiadrenergic therapy (beta-adrenergic receptor blockers, left cervicothoracic sympathectomy), cardiac pacing, and implantable cardioverter defibrillator. The potential therapies include sodium channel blockers (mexiletine, flecainide, lidocaine, pentisomide, phenytoin), potassium, potassium channel activators (nicorandil, pinacidil, cromakalim), alpha-adrenergic receptor blockers, calcium channel blockers, atropine, and protein kinase inhibitors. The purpose of this review is to outline the established therapies and update the recent advances and potential future strategies in the treatment of long-QT syndrome and torsade de pointes.