Colchicine for Prevention of Atrial Fibrillation Recurrence Following Catheter Ablation: Identification of Sex-Specific Differences

Introduction Atrial Fibrillation (AF) is a common cardiac arrhythmia, often treated with Catheter Ablation (ABLA), involving cauterization of the left atrium (LA) to isolate arrhythmogenic areas. While studies suggest a lower prevalence in women, females with AF face a higher risk of severe complications. ABLA is associated with atrial inflammation, causing AF recurrence in about 10% of patients within 30 days and over 50% after 12 months.Patients experiencing AF recurrence post-ABLA show elevated levels of inflammatory markers. Colchicine is renowned for its anti-inflammatory and cardioprotective properties. Various clinical trials have yielded inconclusive results, with some indicating that Colchicine starting after the ABLA does not decrease AF recurrence. Objective Exploring the sex-dependent response to preemptive Colchicine intervention before ABLA for treating potential ABLA-induced AF occurrence or recurrence. Method Male and female Wistar rats (225–275g) were randomized into 4 groups: Sham or ABLA, treated or not with colchicine (1mg/kg/day; intraperitoneally) starting 2h before surgery. Sham animals underwent the surgery without ABLA. On days 1 (D1) and D3 post-ABLA, in vivo electrophysiological studies and echocardiography were performed. On D3, ex-vivo optical mapping was performed on Langendorff-perfused hearts, and atrial fibrosis, gene and protein expression were analyzed by Masson's trichrome staining, qPCR, and immunoblotting respectively. Results ABLA animals were significantly more susceptible to atrial arrhythmias compared to Sham. LA from ABLA rats have shown significantly slowed conduction velocity, increased fibrosis areas and inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA, restored the normal P-wave duration, normalized LA conduction, LA fibrosis, and LA inflammation. Preliminary data revealed that female rats were less vulnerable to post-ABLA AF incidence than male. An effect accentuated by Colchicine treatment. Conclusion Colchicine treatment starting before ABLA may reduce LA inflammation and AF incidence. A better understanding of male-female differences in the response to colchicine intervention could offer original insights into the management of post-ABLA AF incidence.