Ranolazine Effectively Suppresses Atrial Fibrillation in the Setting of Heart Failure.
Circ Heart Fail. 2014 May 29;
Authors: Burashnikov A, Di Diego JM, Barajas-Martínez H, Hu D, Zygmunt AC, Cordeiro JM, Moise NS, Kornreich BG, Belardinelli L, Antzelevitch C
BACKGROUND: -There is a critical need for safer and more effective pharmacological management of atrial fibrillation (AF) in the setting of heart failure (HF).
METHODS AND RESULTS: -This study investigates the electrophysiological, anti- and pro-arrhythmic effects of a clinically-relevant concentration of ranolazine (5 µM) in coronary-perfused right atrial and left ventricular preparations isolated from the hearts of HF dogs. HF was induced by ventricular tachypacing (2-6 weeks at 200-240 beats/min; n=17). Transmembrane action potentials were recorded using standard microelectrode techniques. In atria, ranolazine slightly prolonged action potential duration but very significantly depressed sodium channel current (INa)-dependent parameters causing a reduction of maximum rate of rise of the action potential upstroke, a prolongation of the effective refractory period secondary to development of post-repolarization refractoriness, an increase in diastolic threshold of excitation and atrial conduction time. Ranolazine did not significantly alter these parameters or promote arrhythmias in the ventricles. Ranolazine produced greater inhibition of peak INa in atrial cells isolated from HF vs. normal dogs. A single premature beat reproducibly induced self-terminating AF in 10/17 atria. Ranolazine (5 μM) suppressed induction of AF in 7/10 (70%) atria. In the remaining 3 atria, ranolazine reduced frequency and duration of AF.
CONCLUSIONS: -Our results demonstrate more potent suppression of AF by ranolazine in the setting of HF than previously demonstrated in non-failing hearts and absence of ventricular proarrhythmia. The data suggest that ranolazine may be of benefit as an alternative to amiodarone and dofetilide in the management of AF in patients with HF.
PMID: 24874201 [PubMed - as supplied by publisher]