The Role of Atrial Pacing Support in Cardiac Resynchronization Therapy: A Non-Inferiority Randomized Trial.

Abstract

The role of atrial pacing support is unclear in cardiac resynchronization therapy-defibrillator (CRT-D) patients without sinus node dysfunction. We conducted a randomized, parallel-group, non-inferiority trial to evaluate whether a two-lead CRT-DX system capable of atrial sensing (but no pacing) via a floating dipole on the right ventricular lead is not inferior to a three-lead CRT-D with conventional atrial lead. Between October 17, 2018, and March 5, 2024, 636 patients (68 ± 10 years old, 28.6% females) with standard CRT-D indication, optimized medical therapy, and resting sinus rate ≥45 beats/min were randomized 1:1 to CRT-DX (VDD 35 beats/min) or CRT-D (DDD 50 beats/min) at 23 Italian sites. A centralized block randomization procedure stratified by site was used, with patients and primary outcome assessors blinded to treatment assignment. The primary endpoint was a 1-year composite of all-cause mortality, cardiovascular hospitalization, and lead-related complications (loss of functionality not correctable by device reprogramming). Key secondary endpoints were each component, echocardiographic reverse remodeling, and 6-minute walk test distance at 12 months. The primary endpoint occurred in 41 (13.1%) patients in the CRT-DX group and 47 (15.6%) patients in the CRT-D group, corresponding to a hazard ratio of 0.82 (95% CI, 0.54-1.25). This confirmed non-inferiority (pre-specified relative margin of 1.20) in both the per-protocol (p=0.039) and intention-to-treat (p=0.044) analyses. Individual components showed no significant differences, except for lead complications related to right atrial functionality (4 [1.3% ] patients in the CRT-DX group vs. 13 [4.2%] patients in the CRT-D group; p=0.040). Reverse remodeling responders were 203 (77.5% of 262) CRT-DX patients and 190 (76.3% of 249) CRT-D patients (p=0.83). Walking distance did not differ between two study arms (404 vs. 398 m; p=0.62). After median follow-up of 2.4 years, only one CRT-DX patient required implantation of a standard atrial lead. Two-lead CRT-DX system without atrial pacing is non-inferior to conventional three-lead CRT-D, with fewer atrial lead-related complications.