The effect of altering heart rate on ventricular function in patients with heart failure treated with β-blockers

Background β-Blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect. Methods A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving β-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up. Results Forty-nine patients were randomized. Mean age was 74 ± 6 years and with LV ejection fraction of 26% ± 9% at baseline. During 14 ± 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 ± 104 mL vs lower rate −65 ± 92 mL, P = .03) and systolic (higher rate +29 ± 83 mL vs lower rate −60 ± 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate −4.2% ± 4.4% vs lower rate +2.2% ± 5.4%, P = .002). Conclusion Reversal of β-blocker–induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.