Abstract 12958: Temporal Association of Systemic Inflammatory Biomarkers With Incidence of Postoperative Atrial Fibrillation After Botulinum Toxin Type A Administration in Epicardial Fat Pads

Abstract

Background: A one-time injection of botulinum toxin type A (BoNT/A) in epicardial fat pads was evaluated for post-operative atrial fibrillation (POAF) in patients undergoing open-chest cardiac surgery in the Ph2 NOVA trial. Treatment with 125U BoNT/A numerically reduced the incidence of POAF in the mITT (36.5% vs 46.1%) and CABG populations (28.4% vs 40.0%), with statistical significance observed in the CABG + ≥65 years subgroup (27.5% vs 56.4%; P <0.01). No significant reduction was observed in the 250U group vs placebo. Purpose: Explore systemic inflammatory biomarker changes after treatment with BoNT/A and the temporal relation to incidence of POAF. Methods: This analysis included 308 patients who received 125U BoNT/A (n=103), 250U BoNT/A (n=103), or placebo (n=102). Subgroup analysis was done for CABG (n=198), age ≥65 years (n=185), and CABG + ≥65 years (n=118). Serum samples were collected preoperatively prior to dosing on Day 1, then post-treatment on Days 2-4 to test for IL-6, IL-10, and hsCRP. A 2-sample t test was used for mean concentrations and a linear mixed model was used for fold change (FC) from baseline. Results: Baseline levels of IL-6, IL-10, and hsCRP were similar between treatment groups. Reduction of IL-6 (45.7 ± 4.4 vs 62.4 ± 5.8 pg/mL, P <0.05; 10.8 vs 15.9 FC, P <0.01) and IL-10 (1.49 ± 0.13 vs 2.04 ± 0.24 pg/mL, P <0.05; 1.96 vs 2.66 FC, P <0.01) was most significant on Day 2 in CABG patients treated with 125U vs placebo, which aligns with the highest rate and risk of POAF (Figure 1). Mean hsCRP was most significantly reduced on Day 4 in the 250U group among CABG patients (193 ± 8 vs 227 ± 10 mg/dL, P <0.01) followed by 125U vs placebo (196 ± 10 vs 227 ± 10 mg/dL, P <0.05); a similar dose-dependent reduction was observed by FC analysis. Conclusions: Treatment with 125U BoNT/A in cardiac surgery patients lowered the incidence of POAF vs placebo and reduced postoperative systemic IL-6 and IL-10 on Day 2, most significantly in the CABG population.