The Role of Atrial Pacing Support in Cardiac Resynchronization Therapy: A Non-Inferiority Randomized Trial
M BiffiGiovanni RovarisEnnio Carmine Luigi PisanòCalviAntonio RapacciuoloMatteo SantamariaGiampiero MagliaGabriele ZanottoEmanuele BertagliaGerardo NigroAndrea GiomiFrancesca M. NotarangeloPatrizia PepiGiuliano D'AlterioDavide CastagnoAniello RussoAntonino NicosiaMassimo ZecchinMatteo BertiniAntonio DucaDaniele GiacopelliAlessio GargaroGiovanni Luca Botto
Key result
The two-lead CRT-DX system without atrial pacing was non-inferior to conventional three-lead CRT-D for the primary composite endpoint of mortality, hospitalization, and lead complications (HR 0.82).
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Why the study?
The role of atrial pacing support in CRT-D patients without sinus node dysfunction is unclear.
Does a two-lead CRT-DX system without atrial pacing reduce or prevent adverse clinical outcomes and lead complications compared to a conventional three-lead CRT-D system in patients without sinus node dysfunction?
Key Points
- To assess whether a two-lead CRT-DX system providing atrial sensing without pacing is non-inferior to a conventional three-lead CRT-D system in patients without sinus node dysfunction.
- A randomized, parallel-group, non-inferiority trial enrolled 636 patients (68 ± 10 years old, 28.6% females) with standard CRT-D indications and resting sinus rate ≥45 beats/min across 23 Italian sites between October 17, 2018, and March 5, 2024.
- Patients were randomized 1:1 using centralized block randomization stratified by site to CRT-DX (VDD 35 beats/min) or CRT-D (DDD 50 beats/min), with patients and primary outcome assessors blinded to treatment assignment.
- The primary composite endpoint of 1-year all-cause mortality, cardiovascular hospitalization, and lead-related complications occurred in 41 (13.1%) patients in the CRT-DX group and 47 (15.6%) patients in the CRT-D group (HR 0.82; 95% CI, 0.54–1.25), confirming non-inferiority with a pre-specified relative margin of 1.20 in both per-protocol (P=0.039) and intention-to-treat (P=0.044) analyses.
- Right atrial lead-related functionality complications occurred in 4 (1.3%) CRT-DX patients versus 13 (4.2%) CRT-D patients (P=0.040).
- Echocardiographic reverse remodeling response rates (77.5% in CRT-DX vs. 76.3% in CRT-D; P=0.83) and 6-minute walk test distance (404 vs. 398 m; P=0.62) did not differ significantly between arms at 12 months.
Study Design
Type
RCT (n=636)
Blinding
Double-blind
Randomization
1:1 centralized block randomization stratified by site
Multicenter
Yes
Structured PICO
Does a two-lead CRT-DX system without atrial pacing reduce or prevent adverse clinical outcomes and lead complications compared to a conventional three-lead CRT-D system in patients without sinus node dysfunction?
P
Population
636 adults (mean age 68, 28.6% female) with standard CRT-D indications and no sinus node dysfunction, followed for 12 months.
I
Intervention
Two-lead CRT-DX system capable of atrial sensing (but no pacing) via a floating dipole on the right ventricular lead, programmed to atrial tracking without atrial pacing mode at a base rate of 35 beats/min.
C
Comparator
Conventional three-lead CRT-D system with a conventional atrial lead, programmed to atrial tracking with atrial pacing mode at a base rate of 50 beats/min.
O
Outcome
12-month composite of all-cause mortality, cardiovascular hospitalization, and lead-related complications (loss of functionality of atrial, RV, or LV lead not correctable by device reprogramming requiring surgical intervention).composite
Main Result
Hazard Ratio: 0.82 (95% CI 0.54–1.25)
Absolute Event Rate: 13.1% vs 15.6%
p-value: p=0.039 for noninferiority
A two-lead CRT-DX system without atrial pacing is non-inferior to a conventional three-lead CRT-D system in heart failure patients without sinus node dysfunction, significantly simplifying the procedure and reducing atrial lead-related complications.
Limitations
- Conducted exclusively in Italian centers, which may limit generalizability
- Predominantly White European ancestry cohort
- May be underpowered to detect small differences in individual components or rare safety events
- Greater structural complexity of the RV-DX lead design could theoretically predispose to higher long-term failure rates
- COVID-19 pandemic prolonged the enrollment phase
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These results confirm what early pilot studies suggested—that, for the vast majority of CRT candidates, atrial pacing is not needed in the long term. By removing the atrial lead, CRT‑DX offers meaningful advantages in safety and procedure simplification without compromising clinical performance.”
DHDavid HayesChief Medical Officer, Biotronik
“Biotronik's CRT-DX system is the only two-lead CRT‑D solution on the market. The CRT‑NEXT results clearly demonstrate the system's distinct advantages for both clinicians and patients. These data reinforce our leadership in CRT innovation and offer strong clinical support for a significant evolution in CRT treatment.”
GSGreg ShockeyChief Strategy Advisor, Pointward Inc.
“Important findings for device therapy. A two lead CRT DX system being non inferior to three lead CRT D could have real implications for procedural complexity and lead related complications. Looking forward to more detailed outcomes from CRT NEXT.”
Implication
Simplifies CRT-D implantation and reduces atrial lead complications in eligible patients; confirms non-inferiority and extends evidence for two-lead systems.
Abstract
BACKGROUND: The role of atrial pacing support is unclear in cardiac resynchronization therapy-defibrillator (CRT-D) patients without sinus node dysfunction. METHODS: 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. RESULTS: 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. CONCLUSIONS: Two-lead CRT-DX system without atrial pacing is non-inferior to conventional three-lead CRT-D, with fewer atrial lead-related complications.
Cite This Study
Biffi et al. (2026) conducted an RCT in Standard CRT-D indication without sinus node dysfunction (n=636). Two-lead CRT-DX system without atrial pacing vs. Three-lead CRT-D with conventional atrial lead (DDD 50 beats/min) was evaluated on 1-year composite of all-cause mortality, cardiovascular hospitalization, and lead-related complications (HR 0.82, 95% CI 0.54-1.25, p=0.039 for noninferiority). The two-lead CRT-DX system without atrial pacing was non-inferior to conventional three-lead CRT-D for the primary composite endpoint of mortality, hospitalization, and lead complications (HR 0.82).