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

BACKGROUND: beta-adrenergic receptor antagonism with drugs like carvedilol slows the progression of heart failure by an undefined mechanism. (123)I-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< or =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.

Efeito do carvedilol na insuficiência cardíaca por cardiomiopatia dilatada: resultado de estudo duplo-cego, randômico, com grupo placebo-controle (estudo CARIBE) / Effects of carvedilol in heart failure due to dilated cardiomyopathy: results of a double-blind randomized placebo-controlled study (CARIBE study)

OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women) with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43ñ9 years), and their left ventricular ejection fraction varied from 8 per cnet to 35 per cent. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016) as well as an increase in left ventricular shortening fraction (p=0.02) and in left ventricular ejection fraction (p=0.017) occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.