Our findings suggest a protective role of oral ranolazine when administered in a moderate dose preoperatively in patients undergoing on-pump CABG surgery. Future studies based on a wider sample of patients will eventually support our conclusions.
Ranolazine is a relatively novel antiischemic/antianginal compound with antiarrhythmic properties. We investigated its ability to shorten the time to conversion of postoperative atrial fibrillation (POAF) when added to amiodarone after coronary artery bypass graft (CABG) surgery. In this prospective, randomized, allocation-concealed, single-blind, single-site clinical trial, we enrolled consecutive eligible patients who developed POAF after elective on-pump CABG surgery. Participants were randomized to receive either ranolazine 375 mg twice daily orally plus intravenous amiodarone (active group) or intravenous amiodarone alone (control group). We enrolled 41 patients; 20 in the active and 21 in the control group. There were no significant differences between the groups in terms of age, procedural duration, extracorporeal circulation time, and aortic cross-clamp time. Mean time of conversion was significantly shorter in the active group (19.9 ± 3.2 vs 37.2 ± 3.9 hours, P < .001), suggesting that compared to amiodarone alone, the ranolazine-amiodarone combination had a superior antiarrhythmic effect against POAF.
Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. There exist consistent experimental and clinical data suggesting that aldosterone antagonists (AAs) may exert beneficial effects regarding electrical and structural remodeling in failing myocardium. Recently, eplerenone (EPL) has been found to reduce the incidence of nonsurgical AF when added to guideline-recommended therapy in patients with systolic heart failure. Based on these findings, we primarily aimed to evaluate by retrospective analysis the impact of the two AAs, EPL and spironolactone (SPL), given at standard therapeutic doses in preventing new-onset POAF in patients the majority of which had a preoperative ejection fraction (EF) below 40%. A total of 332 patients (298 men/34 women, mean age 64.3 ± 9 years) without history of AF were included in this analysis; 132 of these patients received long-term EPL or SPL in addition to beta-blockade/statins therapy and 200 patients received neither EPL nor SPL. All patients underwent on-pump coronary artery bypass graft (80%) and/or valvular surgery (20%). In the nonAA group (EF = 35.8 ± 6%) 90/200 patients (45%) had POAF, while in the AA group (EF = 36.2 ± 5%) only 40/132 patients (30.3%) developed POAF (P < 0.01, χ (2) test). Multivariate logistic regression analysis revealed that only AAs and left atrial diameter significantly affected the development of POAF even when adjusted for other clinical variables (P < 0.05). In conclusion, AAs significantly reduced the incidence of POAF when added to standard heart failure therapy in patients undergoing on-pump cardiac surgery.
Ranolazine (Ran) is a novel anti-ischemic agent with electrophysiologic properties mainly attributed to the inhibition of late Na(+) current and atrial-selective early Na(+) current. However, there are only limited data regarding its efficacy and mechanism of action against atrial flutter (Afl) and atrial fibrillation (AF) in intact animals. Therefore, we aimed to investigate the electrophysiologic mechanism of Ran in a rabbit model of inducible atrial tachyarrhythmias elicited by acetylcholine (ACh). Arrhythmias were produced in 19 rabbits by rapid atrial burst pacing during control, after intravenous ACh and after Ran + ACh administration. Recording of right atrial monophasic action potentials (MAPs) and programmed stimulation were utilized to determine the duration of atrial repolarization at various cycle lengths and voltage levels of action potential, including 75% of total MAP duration (MAPD75), effective refractory period (ERP), and postrepolarization refractoriness (PRR = ERP - MAPD75) prior to and after Ran. Control stimulation yielded no arrhythmias or maximal nonsustained runs of Afl/AF. Upon ACh, 17 of 19 rabbits exhibited sustained Afl and AF as well as mixed forms of Afl/AF, while 2 animals revealed none or short runs of nonsustained arrhythmias and were excluded from the study. High-frequency burst pacing during the first 30 minutes after Ran + ACh failed to induce any arrhythmia in 13 of 17 rabbits (76%), while 2 animals displayed sustained Afl/AF and 2 other animals nonsustained Afl/AF. At basic stimulation cycle length of 250 milliseconds, Ran prolonged baseline atrial ERP (80 ± 8 vs 120 ± 9 milliseconds, P < .001) much more than MAPD75 (65 ± 7 vs 85 ± 7 milliseconds, P < .001), leading to atrial PRR which was more pronounced after Ran compared with control measurements (35 ± 11 vs 15 ± 10 milliseconds, P < .001). This in vivo study demonstrates that Ran exerts antiarrhythmic activity by suppressing inducibility of ACh-mediated Afl/AF in intact rabbits. Its action may predominantly be related to a significant increase in atrial PRR, resulting in depressed electrical excitability and impediment of arrhythmia initiation.
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