Discussion
Our study aimed to unravel the long-term outcomes of AF ablation in relation to gender differences, focusing on the recurrence of AF and the incidence of MACCE in a representative Chinese cohort. The main findings of this study include: gender differences are a significant risk factor for AF recurrence after catheter ablation in patients with AF; gender differences are also present in patients with early ablation treatment; there is no significant difference in the incidence of MACCE between men and women; the risk factors for AF recurrence and MACCE after the procedure are not the same in males and females. The findings have significant implications as they reinforce and expand our comprehension of gender disparities in clinical outcomes following catheter ablation treatment for AF.
The collection of sex-specific data has expanded in areas such as myocardial infarction21, heart failure, stroke22, sudden cardiac death, and AF4,5,23,24. Women with AF who are treated with warfarin therapy may face a higher risk of stroke compared to men3. However, studies indicate that there is no significant gender difference in the primary outcomes when undergoing left atrial appendage occlusion25. Gender differences in recurrence rates following catheter ablation for AF have been observed over an extended period. The meta-analysis including 19 observational studies found the rate of freedom from AF recurrence was lower in women than men at the 2.4-year follow-up9. Our research revealed that throughout an extended follow-up period (50.36 ± 19.65 months), women exhibited a significantly higher rate of recurrence following catheter ablation compared to men. This finding was consistent in the population matched by PSM, and gender remained an independent predictor of recurrence in multivariate regression analysis. Some studies suggest that there is no significant difference in recurrence after catheter ablation between genders. These studies have noted that women are typically older and have smaller left atrial dimensions11,26. Meanwhile, Ma and colleagues, through a study utilizing a 1:1 propensity-matched cohort, reported no significant difference in arrhythmia recurrence rates between genders, with the duration of AF being the lone predictor for its recurrence27.
Early intervention has been posited to slow the progression of AF-induced alterations in the heart’s electrical and structural integrity, vascular endothelium, and metabolic functions28,29. As demonstrated by Masuda et al., women show a higher prevalence of left atrial low-voltage areas which are associated with more frequent AF recurrences30. Consequently, it is worth investigating whether similar gender differences in prognosis exist for patients undergoing early catheter ablation. In our present study, the gender differences in AF recurrence post-catheter ablation were evident regardless of whether the intervention was early or late. When analyzing the recurrence risk factors following catheter ablation for AF in different genders, distinct factors emerge for men and women; however, LAD emerged as a common risk factor across genders. Research has also highlighted that in women, other predominant risk factors include left atrial size and AF type26,30. Thus, it is important to incorporate gender differences into clinical evaluations, taking a comprehensive approach to assess the AF burden and the degree of left atrial remodeling.
The sex-based difference of long-term outcomes including death, stroke, acute coronary syndrome etc. were main concerns for clinicians. In the CABANA trial, the primary composite outcome (death, disabling stroke, serious bleeding, or cardiac arrest) was comparable between genders31. Our research also suggests that gender differences are not a statistically significant factor affecting MACCE. In the EAST-AFNET 4 study, the primary outcome showed no significant difference between the sexes31. Kang and colleagues conducted a study by drawing on data from the National Health Insurance Service database to identify patients who received treatment for AF within one year of their diagnosis. Their research findings indicated that a rhythm control strategy was associated with a reduced risk of primary composite outcomes when compared to rate control in both male and female patients. The study further suggests that initiating treatment at an earlier stage—specifically within six months of diagnosis—may offer enhanced effectiveness in female patients32. The observation that there was no significant difference in the incidence of MACCE between the genders may appear counterintuitive given the established increase in stroke risk in women with AF22. However, it is imperative to understand that this lack of difference might be reflecting the effectiveness of the therapeutic interventions (including catheter ablation and oral anticoagulation) which could potentially neutralize the inherent gender-related risk for MACCE seen in AF populations.
While the gender-based disparities in AF care are notable—ranging from symptom burden to the effectiveness of treatment interventions—the findings of this study highlight the necessity for gender-informed management strategies for AF. This implies that healthcare providers might consider adjusting their therapeutic approach considering the greater likelihood of AF recurrence in women, despite similar rates of MACCE compared to men.
Limitations of the current study include its observational nature, potential for residual confounding despite PSM, and the fact that data were sourced from a single center, which may influence the generalizability of the findings. It is also crucial to acknowledge the dynamic nature of AF management guidelines and treatment innovations that continue to influence outcomes over time. Furthermore, the study participants received inconsistent medication regimens following their operations, exhibiting a reduced frequency of anticoagulant administration and a limited use of agents aimed at preventing atrial remodeling. These factors could introduce biases in the reported outcomes.
In conclusion, our research offers valuable evidence that gender differences do influence long-term outcomes post-catheter ablation for AF—particularly regarding AF recurrence rates—with important implications for the customization of treatment plans. As we move toward a more personalized medicine approach, factoring in gender-based risk nuances might enhance clinical decision-making and, ultimately, patient outcomes.