The role of atrial pacing support in cardiac resynchronisation therapy in patients without sinus node dysfunction: a non-inferiority randomised trial

Abstract Background The role of atrial pacing support is unclear in patients with cardiac resynchronisation therapy-defibrillator (CRT-D) and no sinus node dysfunction receiving optimised medical therapy. Purpose We conducted a multicentre, randomised, 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 (non-inferiority margin: 4%). Methods Patients with standard CRT-D indication, optimised medical therapy, and resting sinus rate ≥45 beats/min were randomised 1:1 to CRT-DX (VDD mode at 35 beats/min) or CRT-D (DDD, 50 beats/min). The primary endpoint was a 1-year composite of all-cause mortality, cardiovascular hospitalisation, and lead-related complications resulting in loss of functionality that cannot be resolved by device reprogramming. Secondary endpoints included reverse remodelling at 12 months, defined as either ≥5% absolute increase in left ventricular ejection fraction (LVEF) or ≥15% relative decrease in end-diastolic volume, and 6-minute walk test distance increase from baseline to 12 months. Results 636 patients (age: 68 ± 10 years, 71% males, LVEF: 29% ± 6%) were randomised. The primary endpoint occurred in 13.1% of CRT-DX and 15.6% of CRT-D patients, with a hazard ratio of 0.82 (95% CI: 0.54-1.25), confirming non-inferiority at both per-protocol (p=0.039) and intention-to-treat (p=0.044) analyses. Individual components of the primary endpoint showed no significant differences for all-cause mortality (4.1% CRT-DX vs. 3.9% CRT-D; p=0.57), cardiovascular hospitalisations (9.1% vs. 10.4%; p=0.73), right ventricular lead complications (0.9% vs. 2.3%; p=0.21), and left ventricular lead complications (3.5% vs. 2.9%; p=0.68). However, events related to right atrial functionality were significantly less frequent in the CRT-DX arm (1.3% vs. 4.2%; p=0.040). Reverse remodelling responders were 203 (77%) in the CRT-DX and 190 (76%) in the CRT-D group (p=0.83). Walking distance increased by 44 metres (13%) from a baseline of 346 metres, with no difference between groups (p=0.91). Over a median follow-up of 2.4 years (interquartile range: 1.3–3.8 years), the primary endpoint incidence remained similar in the two groups (hazard ratio: 0.87, 95% CI: 0.61–1.24; p=0.45) (Figure). Median atrial pacing percentage in CRT-D patients was 1% (interquartile range: 0%–7%). Only one CRT-DX patient required implantation of a standard atrial lead. Conclusion Two-lead CRT-DX system without atrial pacing is not inferior to conventional three-lead CRT-D, with fewer atrial lead-related complications.Freedom from primary endpoint