Sex-based differences in bi-atrial structure, function, and electrophysiology in atrial fibrillation

Background Differences in atrial voltage have been reported amongst male and female patients with atrial fibrillation (AF). However, it is unclear whether these changes reflect physiological variation or pathological remodelling. Purpose To examine sex-based differences in bi-atrial structure, function, and electrophysiology using pre-procedural magnetic resonance imaging (MRI) and intra-procedural electrophysiological assessment. Methods A multicentre, prospective observational cohort study was conducted in patients undergoing first-time AF ablation. Structural, functional, and electrophysiological parameters, including bi-atrial volume, ejection fraction, MRI-defined fibrosis, bipolar voltage, conduction velocity, wave collision percentage, and effective refractory period (ERP), were quantified. Following ablation, an AF induction protocol was performed, and receiver operating characteristic (ROC) analysis was used to determine sex-specific optimal mean left atrial voltage thresholds for distinguishing inducible from non-inducible atrial arrhythmia. Propensity score matching based on CHA2DS2-VA score, body mass index and atrial fibrillation type was performed to adjust for baseline differences. Results A total of 70 patients (62±12 years; 31% female) were included. Female patients demonstrated significantly lower mean bipolar voltages in both atria (left: 1.67±0.70mV versus 2.30±0.77 mV, p=0.003; right: 1.80±0.49 mV versus 2.35±0.61mV, p=0.0003) (Figure 1). After propensity score matching (n=32), voltage differences persisted (left: 1.57±0.73mV versus 2.30±0.77mV, p=0.015; right: 1.83±0.54mV versus 2.37±0.57mV, p=0.011). There were no significant differences in bi-atrial volume, ejection fraction, MRI-defined fibrosis burden, conduction velocity, wave collision percentage, or ERP after propensity score matching. ROC analysis identified lower optimal voltage thresholds for post-procedural AF inducibility in women (1.90 mV) compared with men (2.22 mV) (Figure 2). Conclusions Women with AF exhibit lower bi-atrial bipolar voltages despite comparable atrial structural, functional, and electrophysiological properties. These findings suggest that observed voltage differences primarily reflect physiological variation rather than pathological remodelling. The adoption of sex-specific voltage thresholds may improve the accuracy of substrate assessment and support a more individualised approach to AF management.