Impact of Downregulated Inflammation via the IL6R Asp358Ala Variant on Atrial Fibrillation Recurrence Following Ablation.

BACKGROUND: Elevated interleukin (IL)-6 levels are associated with the development of atrial fibrillation (AF). Whether downregulation of IL-6 mediated inflammation reduces AF recurrence following ablation is uncertain. OBJECTIVES: Using a common variant in the IL-6 receptor gene, IL6R Asp358Ala, as a genetic proxy for IL-6 receptor blockade, we evaluated the effect of impaired IL-6 signaling on AF recurrence following ablation. METHODS: We identified patients undergoing AF ablation with genomic data in the All of Us Research database. Patients were stratified based on the presence of the IL6R Asp358Ala allele. The primary outcome was AF recurrence, defined as a composite of repeat AF ablation, cardioversion, or new class I/III antiarrhythmic drug, following a 3-month blanking period after ablation. RESULTS: Of the 1,540 patients undergoing AF ablation, 707 patients carried 1 copy of the Asp358Ala variant and 226 carried 2 copies. At a median follow-up of 1,317 days, the AF recurrence rate was 14.2 per 100 patient-years for carriers of Asp358Ala as compared to 15.9 for noncarriers (adjusted HR: 0.93, 95% CI: 0.79-1.10). No difference in recurrence was observed when using an additive model (2 vs 1 vs no variant allele), suggesting no dose-response with the variant. In subgroup analysis of patients with heart failure (n = 312), there was a potential beneficial effect of Asp358Ala on recurrence (adjusted HR: 0.72, 95% CI: 0.52-1.00; interaction P = 0.049). CONCLUSIONS: Targeted IL-6 inhibition may have little impact on long-term AF recurrence in the general AF population undergoing ablation, although there may be potential benefit in heart failure patients.