Characterisation of the bi-atrial electrical substrate in males and females with atrial fibrillation

Abstract Background The prevalence of atrial fibrillation is greater amongst male patients but there is an increased risk of arrhythmia recurrence following ablation in females. Some studies suggest that females have more advanced left atrial remodelling, which may contribute to disparate ablation outcomes. However, the influence of sex on the right atrial electrical substrate remains incompletely understood. An improved understanding of sex differences in the bi-atrial electrical substrate could enhance our understanding of the clinical variability of atrial fibrillation in males and females. Purpose To study differences in the bi-atrial electrical substrate in males and females with atrial fibrillation. Methods Bi-atrial electrical substrate characterisation was performed in 34 patients (29% female) undergoing atrial fibrillation ablation. Electroanatomic maps of the left and right atria were created in sinus rhythm under coronary sinus pacing (500 ms). EP workbench was used to calculate bipolar voltage, conduction velocity, and wave collision points (percentage of points with conduction velocity field divergence values < -1.5) (Figure 1). Left and right atrial refractoriness were assessed by pacing with S1 set at 600 ms and S2 at 400ms, decreasing by 10ms increments to determine atrial effective refractory period (ERP). Results Mean bipolar atrial voltages were significantly greater in males versus females in both atria (left atrium: 2.15±0.16mV versus 1.59±0.20mV (p=0.04); right atrium: 2.19±0.13mV versus 1.78±0.15mV (p=0.04)) (Figure 2A). There were no significant differences in mean conduction velocity between males and females, with values of 0.69±0.02m/s in males and 0.65±0.03m/s in females for the left atrium (p = 0.25) and 0.63±0.01m/s versus 0.64±0.03m/s for the right atrium (p = 0.61) (Figure 2B). Similarly, wave collision points showed no differences, with mean values of 5.95±0.59% and 6.62±0.82% (p = 0.51) in the left atrium for males and females, and 6.09±0.56% and 5.94±0.51% (p = 0.85) in the right atrium (Figure 2C). Mean left atrial ERP was 230±9ms versus 268±16ms (p =0.07) and mean right atrial ERP was 243±7ms versus 256±15ms (p=0.48) in males versus females, respectively. Conclusion Our results demonstrate consistent sex-based differences in bipolar voltage across the left and right atria, despite no significant differences in conduction velocity, divergence or refractoriness. These findings could indicate more advanced bi-atrial substrate remodelling in females, potentially explaining the poorer response to catheter ablation. Alternatively, the differences may suggest physiologically lower bipolar voltages in females. These findings have significant clinical implications, as current voltage threshold values may fail to accurately reflect the underlying atrial substrate in women. Further research is urgently required to clarify whether sex-based differences in bi-atrial voltages are physiological or pathological.