M Biffi, Giovanni Rovaris, Ennio Carmine Luigi Pisanò, Calvi, Antonio Rapacciuolo, Matteo Santamaria, Giampiero Maglia, Gabriele Zanotto, Emanuele Bertaglia, Gerardo Nigro, Andrea Giomi, Francesca Notarangelo, Patrizia Pepi, Giuliano D'Alterio, Davide Castagno, Antonio Dello Russo, Antonino Nicosia, Massimo Zecchin, Matteo Bertini, Antonio Duca, Daniele Giacopelli, Alessio Gargaro, Giovanni Luca Botto, Giuseppe Ammirati, Andrea Angeletti, Giuseppe Campisi, Alessandro Carecci, Maria Carla Casale, Antonio Crocamo, Vincenzo De Simone, Igor Diemberger, Antonio D’Onofrio, Daniele Faccenda, Tommaso Infusino, Maurelio Lauretti, Fulvia Longaro, Elena Marino, Cristian Martignani, Elisabetta Montemerlo, Lorenzo Moschetta, Daniele Nicolis, Luca Panchetti, Alessandro Paoletti Perini, Valerio Pergola, Marcello Piacenti, Francesca Piccinin, Mattia Pozzi, Giulia Rapisarda, Vincenzo Russo, Luca Salvatore, Giovanni Statuto, Martina Testolina, Pietro Turrini, Serena Vaghi, Roberto Verlato, Rosi Vrenozaj, Matteo Ziacchi
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±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 ( 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 versus 13 [4.2%] patients in the CRT-D group; P =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 ( P =0.83). Walking distance did not differ between 2 study arms (404 versus 398 m; P =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.