Differential Response to Heart Rate Reduction by Carvedilol in Heart Failure and Reduced Ejection Fraction Between Sinus Rhythm and Atrial Fibrillation ― Insight From J-CHF Study ―

Background: Heart rate (HR) reduction by β-blocker might not benefit patients with heart failure and reduced ejection fraction (HFrEF) with atrial fibrillation (AF). Methods and Results: The J-CHF study was a prospective randomized multicenter trial that assigned 360 HFrEF patients to a 2.5 mg/5 mg/20 mg target dose of carvedilol. Carvedilol was uptitrated over 8 weeks and then the dose was fixed. Of 321 patients available for analysis, AF was identified in 65 (20%). Using the median absolute change in HR at 32 weeks (∆HR), the subjects were further divided into group A (∆HR >-6 beats/min) and B (∆HR ≤-6 beats/min). Both in sinus rhythm (SR) and AF, baseline characteristics and achieved carvedilol dose were similar between groups A and B. In SR, the time-dependent change in left ventricular EF (LVEF) and LV end-diastolic dimension (LVEDD) over 56 weeks was more favorable in B compared with A (∆LVEF, P=0.036; ∆LVEDD, P=0.047), and ∆HR was independently associated with ∆LVEF (P=0.040). Group B had a lower rate of the primary endpoint, defined as a composite of death and hospitalization due to cardiovascular causes including acute decompensated HF at 3 years (P=0.002). ∆HR was an independent predictor of the primary endpoint (P=0.01), but this was not observed in AF. Conclusions: Response to the carvedilol HR reduction might differ in HFrEF between SR and AF.