Sex differences in atrial fibrillation-related atrial remodelling assessed by electroanatomic mapping and biopsy

Background and Aims Histopathological sex differences in atrial structural remodelling in patients with non-valvular atrial fibrillation (AF) require further investigation. Methods Right atrial biopsy was performed on 282 patients undergoing AF ablation and high-density voltage mapping (66 ± 12 years; 81 women). Of the 58 patients without AF undergoing supraventricular tachycardia ablation included, 26 underwent atrial biopsy and 41 underwent voltage mapping. The voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and histopathological parameters (fibrosis, intercellular space, myofibrillar loss, myocardial nuclear density, and cardiomyocyte diameter) were evaluated. Results Vbiopsy (7.4 ± 2.6 vs 9.3 ± 3.2 mV, P < .001) and VGLA (4.9 ± 1.8 vs 6.7 ± 2.2 mV, P < .001) were significantly lower in women with AF. A similar relationship was observed in patients without AF: Vbiopsy (7.8 ± 2.7 vs 10.9 ± 2.6 mV, P < .001) and VGLA (7.3 ± 1.7 vs 9.4 ± 1.4 mV, P < .001) were lower in women. Vbiopsy and VGLA positively correlated in both groups (r = 0.70 and 0.60, P < .001), supporting an integrated interpretation of the voltage and histopathological data. No significant sex differences were observed among the histopathological parameters. In 34 patients with minimal histological change, small cardiomyocytes (<10 μm) were more frequent in women (37% ± 23% vs 20% ± 19%, P = .029). Conclusions Despite consistently lower voltage in women, no significant histopathological sex differences were identified in non-valvular cases, likely due to their inherently smaller atrial mass.