Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial

Abstract

Background Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. Methods This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Findings Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95 center dot 3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43 center dot 4%) of 3617 patients were female and 2049 (56 center dot 6%) were male. Median follow-up was 59 center dot 0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23 center dot 5% [95% CI 21 center dot 3-25 center dot 5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25 center dot 7% [23 center dot 5-27 center dot 8] at 60 months) in the conventional CRT group (hazard ratio 0 center dot 89, 95% CI 0 center dot 78-1 center dot 01; p=0 center dot 077). System-related adverse events were reported in 452 (25 center dot 0%) of 1810 patients in the adaptive CRT group and 440 (24 center dot 3%) of 1807 patients in the conventional CRT group. Interpretation Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Funding Medtronic. Copyright (c) 2023 Elsevier Ltd. All rights reserved.