Dose-dependent prognostic effect of carvedilol in patients with chronic heart failure--special reference to transcardiac [corrected] gradient of norepinephrine.

BACKGROUND The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF). METHODS AND RESULTS To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (<10 mg/day, n=41) and group II: high dose (>or=10 mg/day, n=66)]. There was no difference between the 2 groups for the hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE, but was significantly correlated with the transcardiac increase in NE. During a median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox stepwise multivariate analyses, a high level of transcardiac increase in NE (P<0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of carvedilol (P=0.012) were significant independent predictors. CONCLUSION The carvedilol dose is important for the management of CSA and prognosis in patients with systolic CHF.