Closed Loop Stimulation reduces the incidence of atrial high-rate episodes compared to conventional rate-adaptive pacing in patients with sinus node dysfunctions

Background and aims: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, Closed Loop Stimulation (CLS) integrated into the circulatory control system through intracardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared to conventional DDDR pacing. Methods: Patients with sinus node dysfunctions (SND) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n=612) or accelerometer-based DDDR pacing (n=598) and followed for 3 years. The primary endpoint was time to the composite endpoint of first AHRE lasting ≥6 minutes, stroke, or transient ischemic attack (TIA). All AHREs were independently adjudicated using intracardiac electrograms. Results: The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 hours and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS versus DDDR was 0.84 (95%-CI, 0.72-0.99; p=0.035). After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95%-CI, 0.71-0.99; p=0.033). In subgroup analyses, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.76; p=0.006) and in patients without AF history (HR, 0.73; p=0.010). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. Conclusions: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.