Changes in Heart Rate Variability Are Correlated to Hemodynamic Improvement With Chronic CARVEDILOL Therapy in Heart Failure

Abstract

Background Reduced heart rate variability (HRV) has been shown to predict mortality in heart failure (CHF). The relationship between improved cardiac function and improvement in HRV has not been previously studied. Methods and Results This was substudy of a randomized, placebo-controlled, double-blinded trial of carvedilol of four months duration. Analysis of HRV was performed on 24-hour Holter monitors obtained at baseline and completion of study. All subjects had symptomatic CHF and an left ventricular ejection fraction (LVEF) <0.35. Study medication was titrated over 1 month to 50 mg/day (≤75 kg) or 100 mg/day (<75 kg). A total of 17 subjects were randomized to carvedilol and 12 to placebo. Treatment with carvedilol was associated with significant increases in total frequency power, very low frequency power, high frequency power, SDNN, the root-mean square of difference of successive RRs, and pNN50. Change in time and frequency domain measures of HRV had a positive correlation with change in LVEF and negative correlation with change in coronary sinus norepinephrine levels. Conclusion Carvedilol therapy in patients with CHF significantly increased HRV. Change in HRV correlates to improved hemodynamics. This suggests that carvedilol therapy partially normalizes autonomic modulation of heart rate in patients with CHF.