Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial

Abstract

Background and aims: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain.

Methods: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization.

Results: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)].

Conclusions: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

Keywords: Cardiac resynchronization therapy; Heart failure; Pacing-induced cardiomyopathy; Right ventricular pacing; Upgrade.

Structured Graphical Abstract

Main inclusion criteria and randomization by arms showing the result of 360 patients (215 CRT-D vs. 145 ICD) analysed by intention to treat. Primary and secondary outcomes showing a substantial treatment effect of CRT-D compared with ICD alone. Among patients with HF and reduced LVEF with intermittent or permanent RV pacing, CRT-D upgrade resulted in a lower incidence of the composite of all-cause mortality, HF hospitalization, or <15% decrease in LVESV as the primary outcome. Secondary outcome of all-cause mortality and HF hospitalization also proved a substantially lower incidence in CRT-D patients compared with ICD. CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; HF, heart failure; HR, hazard ratio; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; OR, odds ratio; RV, right ventricular.

Figure 1

Event rate of the primary composite outcome in the implantable cardioverter defibrillator and cardiac resynchronization therapy with defibrillator arms and its components: first occurrence of heart failure hospitalization with or without subsequent all-cause death, all-cause death without previous heart failure hospitalization, and <15% reduction in left ventricular end-systolic volume assessed at 12-month visit by echocardiography in patients without previous HF hospitalization. ICD, implantable cardioverter defibrillator; CRT-D, cardiac resynchronization therapy with defibrillator; HF, heart failure; LVESV, left ventricular end-systolic volume.

Figure 2

(A) All-cause mortality and heart failure hospitalization. (B) All-cause mortality. (C) Heart failure hospitalization. Kaplan–Meier estimates for secondary outcomes. (A) The Kaplan–Meier curves for the secondary composite outcome of first occurrence of all-cause mortality or heart failure hospitalization. (B) The Kaplan–Meier curves for death from any cause. (C) The Kaplan–Meier curves for heart failure hospitalization. CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; ICD, implantable cardioverter defibrillator.

Figure 3

Primary composite outcome, according to prespecified subgroups.