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 ―

Abstract

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.

Personalized Target Heart Rate for Patients with Heart Failure and Reduced Ejection Fraction

“…In HFrEF, a lower HR was associated with lower mortality [2]. HR reduction after β-blocker introduction was associated with more favorable outcomes such as lower mortality [3], which was evident especially in HFrEF patients with sinus rhythm (SR) [4,5]. In systolic heart failure treatment in the If inhibitor ivabradine (SHIFT) trial, which examined the safety and efficacy of the sinus node inhibitor ivabradine in patients with HFrEF and SR, ivabradine reduced the primary composite endpoint of cardiovascular death or admission for acute decompensated heart failure (ADHF) compared to the placebo group [6].…”