Effect of sacubitril/valsartan and SGLT2 inhibitors on arrhythmia burden in ICD patients

Background: This study aimed to examine whether the use of sodium–glucose co-transporter 2 inhibitors (SGLT2i) and/or sacubitril/valsartan in individuals with an implantable cardioverter-defibrillator (ICD) was associated with differences in pathological rhythm burden, specifically atrial fibrillation (AF), ventricular tachycardia (VT), and ventricular fibrillation (VF), during follow-up. Methods: Data from 275 patients who underwent ICD implantation between 2022 and 2025 were analyzed retrospectively. The primary endpoint was change in device-detected arrhythmic burden, categorized as unchanged/increased, 0–50% reduction, 50–100% reduction, or arrhythmia-free status during 12-month follow-up. The secondary endpoint was change in LVEF (ΔEF). Associations between medical therapies and EF change were assessed using multivariable linear regression models adjusted for demographic and clinical covariates. Results: Overall, mean LVEF increased significantly during follow-up (ΔEF 9.7 ± 8.7%, p < 0.001). In adjusted analyses, ARNI use was independently associated with greater EF improvement (B = 10.647, p < 0.001), whereas SGLT2i therapy alone was not significantly associated with ΔEF. In unadjusted analyses, both ARNI and SGLT2i therapies were associated with a higher likelihood of substantial reduction in arrhythmic burden and arrhythmia-free status (p < 0.001 for both). Patients receiving combined ARNI and SGLT2i therapy demonstrated the highest proportion of arrhythmia-free status during follow-up. Conclusion: In this retrospective cohort of ICD recipients with HFrEF, ARNI therapy was independently associated with greater improvement in LVEF, while both ARNI and SGLT2i use were associated with lower device-detected arrhythmic burden in unadjusted analyses. Prospective studies are required to determine causality and clarify the independent antiarrhythmic effects of contemporary guideline-directed therapies in ICD populations.