Key Points:
- Cardiac resynchronization therapy defibrillators (CRT-Ds) are routinely implanted with a dedicated atrial lead to enable atrial pacing, yet the clinical benefit of routine atrial pacing in patients without sinus node dysfunction is uncertain.
- The CRT-NEXT trial randomized 636 patients with standard CRT-D indications and no sinus node dysfunction to either a two-lead CRT-DX system or a conventional three-lead CRT-D system, with a median follow-up of 2.4 years.
- CRT-DX was non-inferior to conventional CRT-D for the composite primary endpoint of all-cause mortality, cardiovascular hospitalization, and lead-related complications at 12 months, with significantly fewer atrial lead.
Cardiac resynchronization therapy (CRT) has become a cornerstone treatment for those with reduced ejection fraction and left bundle branch block. Standard CRT-Ds are implanted with three leads — right ventricular, left ventricular, and right atrial. However, multiple prior studies have shown that atrial support and rate-adaptive pacing in patients with left ventricular systolic dysfunction do not improve exercise tolerance or clinical outcomes compared with simple atrial tracking. Meanwhile, the majority of CRT candidates maintain adequate sinus node function even on rate-lowering guidelines directed medical therapy. Whether atrial pacing is necessary for patients with CRT remains unknown.
The CRT-NEXT trial was a prospective, multicenter, randomized, non-inferiority trial. Conducted at 23 centers in Italy between October 2018 and March 2024, the study enrolled 636 patients with standard indications for CRT-D implantation, no sinus node dysfunction (and either a resting sinus rate ≥45 beats/min or a maximum heart rate ≥85 beats/min during the 6-minute walk test) on optimized medical therapy. Patients were randomized 1:1 to receive a two-lead CRT-DX system — which incorporates a floating atrial dipole on the right ventricular lead to enable atrial sensing and tracking without atrial pacing — or a conventional three-lead CRT-D. The primary endpoint was a 12-month composite of all-cause mortality, cardiovascular hospitalization, and lead-related complication resulting in loss of functionality not correctable by device reprogramming. The results were presented at the American College of Cardiology Scientific Sessions on March 30, 2026 and simultaneously published in Circulation.
Among the 625 patients in the intention-to-treat analysis, baseline characteristics were well balanced: mean age 68 years, 71% male, mean left ventricular ejection fraction 29%, and 89% with left bundle branch block. The primary endpoint occurred in 13.1% of CRT-DX patients and 15.6% of CRT-D patients at 12 months (hazard ratio 0.82; 95% CI 0.54–1.25, p=0.36), confirming non-inferiority in both the per-protocol (p=0.039) and intention-to-treat (p=0.044) analyses. There were no significant differences in all-cause mortality (4.1% vs. 3.9%) or cardiovascular hospitalizations (9.1% vs. 10.4%). Atrial lead complications were significantly less frequent with CRT-DX (1.3% vs. 4.2%; p=0.040), driven primarily by atrial lead dislodgements. Procedure times were significantly shorter with CRT-DX (92 vs. 107 minutes; p=0.028). At 12 months, reverse remodeling rates were nearly identical between groups (77% vs. 76%), as were 6-minute walk test distances, left ventricular volumes, and ejection fraction. Crucially, no ventricular arrhythmia was triggered by a short-long-short sequence or by bradycardia, and only one CRT-DX patient (0.3%) required late implantation of a conventional atrial lead — after 4.5 years — due to a newly developed need for atrial pacing.
When interviewed, the lead investigator Dr. Mauro Biffi concluded that for appropriately selected CRT candidates without sinus node dysfunction, “reliable atrial sensing is sufficient, and routine atrial pacing support may be unnecessary.” He emphasized that the CRT-DX approach not only simplifies the implant procedure and reduces lead-related risk, but also maintains the same robust clinical benefit — including high rates of reverse remodeling and functional improvement — as the conventional three-lead system.