Abstract 17668: Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model
Introduction: Chronic tachycardia is a well-known cause of non-ischemic cardiomyopathy. We hypothesized that nebivolol, a beta-blocker with nitric oxide activity, would be superior to a pure beta-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model.
Method: Fifteen healthy Yucatan pigs were randomly assigned in 6-6-3 fashion to receive nebivolol 10 mg daily, metoprolol 25 mg daily, or placebo. All pigs underwent dual-chamber pacemaker implantation (Medtronic Inc, Minneapolis, MN). The medication was started the day after the pacemaker implantation. On day 7 after implantation, the pacemaker was set at A-V pace (rate, 170 bpm), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed.
Results: All pigs remained hemodynamically stable and survived to the end of the study. All pigs developed left ventricular cardiomyopathy. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups (p = 0.51). Echocardiographic and chemistry findings (Table) showed changes in inflammatory and autonomic response blood markers from baseline in each group, but these changes were not significantly different among the groups. There was mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 pigs (6 nebivolol, 5 metoprolol, and 3 placebo). One pig in the metoprolol group had severe multifocal inflammatory changes, including extensive myocardial fibrosis and necrosis in the left ventricle.
Conclusion: Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state.
- © 2013 by American Heart Association, Inc.