Association of Sodium-Glucose Cotransporter-2 Inhibitors With Atrial High-Rate Episodes in Patients With Cardiac Implantable Electronic Devices

Background and objective Atrial high-rate episodes (AHREs) are subclinical atrial tachyarrhythmias detected by cardiac implantable electronic devices (CIEDs). Identifying strategies to reduce AHRE occurrence is clinically relevant. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are commonly prescribed for cardiometabolic conditions, and their potential role in subclinical atrial arrhythmias remains to be clarified. The objective of this study is to compare the incidence of AHREs and major adverse cardiovascular events (MACE) between SGLT2i users and nonusers among CIED patients. Methods This retrospective cohort study included CIED recipients from January 2020 to December 2024. Patients were categorized into two groups based on SGLT2i exposure. Clinical characteristics, device parameters, and AHRE data were collected and analyzed. MACE were also recorded. Multiple imputation was applied for missing left ventricular ejection fraction and left atrial volume index data. Propensity score overlap weighting was used to balance baseline covariates. Cox proportional hazards models estimated HRs for AHREs and MACE. Results A total of 123 patients with CIEDs were included, with a mean age of 73.3 ± 13.1 years, and 46.3% were male. Of these, 15 patients received SGLT2i. Overlap propensity score weighting was applied. During follow-up, AHREs occurred in three patients (SGLT2i group) and 54 patients (non-SGLT2i group), corresponding to weighted incidence rates of 40.8 and 1304.9 per 1,000 person-years, respectively. SGLT2i use was associated with a significantly lower risk of AHRE occurrence (HR 0.32, 95% CI 0.10-0.98, p = 0.03). For MACE, three events were observed in the SGLT2i group and 20 in the non-SGLT2i group, yielding a weighted HR of 1.10 (95% CI 0.25-4.96, p = 0.10). Kaplan-Meier survival analysis demonstrated significantly higher AHRE-free survival among patients receiving SGLT2i (log-rank p = 0.03), whereas MACE-free survival did not differ significantly between the groups (p = 0.10). The duration of the longest single AHRE episode was numerically shorter among SGLT2i users, although the difference was not statistically significant. Conclusions SGLT2i use was associated with a significantly lower risk of AHRE occurrence among CIED recipients, suggesting a potential reduction in subclinical atrial arrhythmia burden. However, no significant difference in MACE was observed. These findings highlight a possible antiarrhythmic benefit beyond established cardiovascular effects. Larger prospective studies are warranted to confirm these results.