Effects of carvedilol on heart rate dynamics in patients with congestive heart failure.

Abstract

Patients with congestive heart failure (CHF) have alterations in the traditional and nonlinear indices of heart rate (HR) dynamics, which have been associated with an increased risk of mortality. This study was designed to test the effects of carvedilol, a nonselective beta-blocker with alpha-1 blocking properties, on HR dynamics in patients with CHF. We studied 15 patients with CHF secondary to ischemic or idiopathic cardiomyopathy who met the following inclusion criteria: NYHA functional class II-III, optimal conventional medical therapy, normal sinus rhythm, left ventricular ejection fraction (LVEF) of < 40%, and resting systolic blood pressure greater than 100 mmHg. The 6-minute corridor walk test, estimation of LVEF, and 24-hour Holter recording were performed at baseline and after 12 weeks of therapy with carvedilol. Traditional time and frequency domain measures and short-term fractal scaling exponent of HR dynamics were analyzed. After 12 weeks of therapy with carvedilol, the mean LVEF improved significantly (from 0.27 +/- 0.08 to 0.38 +/- 0.08, P < 0.001). The average HR decreased significantly (from 86 +/- 11 to 70 +/- 8 beats/min, P < 0.001). The mean distance traveled in the 6-minute walk test increased significantly (from 177 +/- 44 to 273 +/- 55 m, P < 0.01). The frequency-domain indices (HF and LF), the time domain indices (rMSSD and PNN5 ), and the short-term fractal scaling exponent increased significantly. The scaling exponent increased particularly among the patients with the lowest initial values (< 1.0), and the change in the fractal scaling exponent correlated with the change in ejection fraction (r = 0.63, P < 0.01). Carvedilol improves time and frequency domain indices of HR variability and corrects the altered scaling properties of HR dynamics in patients with CHF. It also improves LVEF and functional capacity. These specific changes in HR behavior caused by carvedilol treatment may reflect the normalization of impaired cardiovascular neural regulation of patients with CHF.