t In this issue of Heart Rhythm, Antzelevitch et al present succinct review of the antiarrhythmic actions of ranolaine. This drug originally was developed with the aim of roducing a novel antianginal medication working via a echanism other than negative inotropy or chronotropy. As it happened, randomized trials showed that ranolazine, either as monotherapy or on top of beta-blockers or calcium channel blockers, decreased the frequency of angina and increased exercise tolerance in comparison to placebo. This ed the U.S. Food and Drug Administration to approve the linical use of ranolazine “for the treatment of chronic ngina by patients who have not responded to standard ntianginal medications.” At first, the presumed antiangial mechanism was thought to be partial inhibition of free atty acid oxidation by the stressed myocyte, but these ffects were observed only at supratherapeutic levels. More ecent evidence suggests that ranolazine prevents ischemiaelated calcium and sodium overload by blocking the late odium current. It is this fairly selective blocking effect of he late (rather than the peak) sodium current that led to the nvestigation of ranolazine as a novel antiarrhythmic agent. Based on the impressive data reviewed by Antzelevitch et al, it seems that the antiarrhythmic actions of ranolazine ay soon dominate its clinical use. In this regard, the istory of ranolazine is reminiscent of the amiodarone tory. Amiodarone, too, was synthesized as an antianginal agent during a systemic search for potent coronary vasodilators. Here, too, the clinical benefits of amiodarone iniially were attributed to its antianginal properties, and the appreciation of its unique antiarrhythmic properties came later. Clinical reports from Argentina and France soon followed, and eventually amiodarone was recognized as the most effective antiarrhythmic drug. It is too early to tell if ranolazine will replace amiodarone on the “best seller” list of antiarrhythmic drugs, but the unique antiarrhythmic properties of the former, emphasized in this issue of Heart Rhythm, suggest it might just do that. ecause sodium overload is instrumental in the pathogeneis of arrhythmias related to myocardial ischemia or heart ailure, ranolazine may prove particularly effective for pre-