The effect of β-adrenergic receptor antagonism in cardiac sympathetic neuronal remodeling in patients with heart failure

Abstract

Background β-adrenergic receptor antagonism with drugs like carvedilol slows the progression of heart failure by an undefined mechanism. 123I-metaiodobenzylguanidine (MIBG) is an analog of norepinephrine used to study cardiac sympathetic function. Methods and results In this double-blind randomized, placebo-controlled study, we used MIBG imaging to evaluate the effect of carvedilol ( n = 15) or placebo ( n = 7) on neuronal norepinephrine reuptake in patients with heart failure due to idiopathic dilated cardiomyopathy, with LVEF less than 35% and functional class II or III. The drug was begun at 6.25 mg b.i.d. and titrated up to 25 mg t.i.d, as tolerated. Thorax planar scintigraphy images were obtained 15 min (Initial) and 4 h (Late) after MIBG injection at baseline ( t 0) as well as 2 months ( t 1) and 6 months ( t 2) after drug initiation. The multifarious statistical technique of profile analysis was applied and p ≤ 0.05 was considered significant. The heart/mediastinum MIBG uptake (H/M ratio) was calculated from these images. On the Initial images, the H/M ratio was 1.64 ± 0.24 ( t 0), 1.71 ± 0.21 ( t 1), and 1.87 ± 0.34 ( t 2) in the carvedilol group and 1.68 ± 0.42 ( t 0), 1.81 ± 0.45 ( t 1), and 1.69 ± 0.44 ( t 2) in controls ( p = 0.0455). On the Late images, the H/M ratio was 1.39 ± 0.24 ( t 0), 1.53 ± 0.23 ( t 1), and 1.64 ± 0.36 ( t 2) in the carvedilol group, and 1.49 ± 0.45 ( t 0), 1.53 ± 0.47 ( t 1), and 1.47 ± 0.41 ( t 2) in controls ( p = 0.0513). Conclusion Compared with placebo, the addition of carvedilol to existing heart failure treatment incites the reverse remodeling of cardiac sympathetic nervous system function.