Role of Atrial Pacing Support in Cardiac Resynchronization Therapy: A Noninferiority Randomized Trial.

Abstract (English)

BACKGROUND: The role of atrial pacing support is unclear in patients receiving cardiac resynchronization therapy-defibrillator (CRT-D) without sinus node dysfunction. METHODS: We conducted a randomized, parallel-group, noninferiority trial to evaluate whether a 2-lead CRT-D capable of atrial sensing (but no pacing) by a floating dipole on the right ventricular lead (CRT-DX) is not inferior to a 3-lead CRT-D with a conventional atrial lead. Between October 17, 2018, and March 5, 2024, a total of 636 patients (68&#xb1;10 years old, 28.6% women) with standard CRT-D indication, optimized medical therapy, and resting sinus rate ≥45 beats/min were randomized 1:1 to CRT-DX (atrial tracking without atrial pacing mode 35 beats/min) or CRT-D (atrial tracking with atrial pacing mode 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 end point was a 1-year composite of all-cause mortality, cardiovascular hospitalization, and lead-related complications (loss of functionality not correctable by device reprogramming). Secondary end points included each individual component of the primary end point separately, echocardiographic reverse remodeling, and 6-minute walk test distance at 12 months. RESULTS: The primary end point 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 noninferiority (prespecified relative margin of 1.20) in both the per-protocol (<i>P</i>=0.039) and intention-to-treat (<i>P</i>=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 versus 13 [4.2%] patients in the CRT-D group; <i>P</i>=0.040). Reverse remodeling responders were 203 (77.5% of 262) patients receiving CRT-DX and 190 (76.3% of 249) patients receiving CRT-D (<i>P</i>=0.83). Walking distance did not differ between 2 study arms (404 versus 398 m; <i>P</i>=0.62). After a median follow-up of 2.4 years, only 1 patient receiving CRT-DX required implantation of a standard atrial lead. CONCLUSIONS: The 2-lead CRT-DX system without atrial pacing is noninferior to conventional 3-lead CRT-D, with fewer atrial lead-related complications. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03587064.