Gender-Related Differences in Atrial Substrate in Patients with Atrial Fibrillation

Gender-related differences have been reported in patients who underwent pulmonary vein isolation (PVI). Atrial substrate plays a role in the outcomes after ablation but gender-related differences in atrial substrate have never been described in detail. We sought to analyze gender-related differences in atrial remodeling (spontaneous low-voltage zones [LVZs]) and their clinical relevance after PVI. We conducted a prospective multicenter study, including consecutive patients who underwent first PVI-only atrial fibrillation (AF) ablation. LVZs were analyzed on high-density electroanatomical maps collected with multipolar catheter, before PVI. In total, 262 patients (61 ± 11 years, 31% female, 50% persistent AF) were followed for 28 months. In women, LVZs were larger (10% vs 4% of left atrial surface [p <0.001]) and female gender was independently associated with fourfold higher risk of having advanced (LVZ > 15%) atrial remodeling (odds ratio 4.56, p <0.001). AF recurrence-free survival was not different between men and women (log-rank p = 0.2). Although LVZs were independently associated higher AF recurrences at multivariate analysis (hazard ratio [HR] 1.2, p = 0.038), female gender was not (HR 1.4, p = 0.211). Specifically, the LVZ cutoff to predict outcomes was different in men and women: >5% in men (HR 3.0, p <0.001), >15% in women (HR 2.7, p = 0.02). In conclusion, women have more widespread LVZ in all left atrial regions. Despite more extensive atrial remodeling, the AF recurrence rate is similar in men and women, and LVZs become prognostic in women only at high burden (>15%). LVZs seem to have a different prognostic role in men and women.