Effect of sex on atrial fibrillation ablation in heart failure: a post hoc analysis of the RAFT-AF Trial

Background Women with atrial fibrillation (AF) benefit from catheter ablation, but often have worse outcomes compared to men. It is unknown if this holds true in women with AF and heart failure(HF). A post hoc analysis of the RAFT AF trial was performed to determinate whether sex is an important determinant of response to ablation-based rhythm control in patients with AF and HF. Methods The RAFT AF study was a randomized trial of 411 patients with blinded endpoint adjudication. Patients with AF, HF, NYHA II-II and an elevated NT-proBNP were randomized to ablation-based rhythm control or rate control. The primary outcome was a composite of all cause mortality and HF events. Secondary outcomes included left ventricular ejection fraction, change in NTproBNP, six minute walk test and quality of life. This analysis focused on sex as a determinant of the primary and secondary outcomes. Unadjusted Kaplan Meier curves for the primary outcome by sex and assigned therapy were calculated; a multivariable Cox model was constructed to adjust for potential confounders. Results There were 106 women and 305 men included in the study. Women had lower rates of coronary disease (16.8% vs 36.0%), alcohol use (45.6% vs 63.0%) but more symptoms (92% vs 81%). There were no differences amongst any other comorbidities or CHADS2 score. Women had fewer primary outcome events (n=28/106) than men (n=86/305); when compared by treatment assignment, women had a statistically significant reduction in events with ablation-based rhythm control (HR 0.42 95%CI 0.19,0.92; p=0.02) compared to men (HR 0.86 95%CI 0.56,1.32;p=0.55).(interaction p value 0.077)(Figure). When adjusted in a Cox model, the p-value for the interaction term for treatment with sex was 0.06; NYHA III, elevated NT-proBNP and diabetes were associated with worse outcomes.(Table) The adjusted hazard ratio for women was 0.38 (95%CI 0.17-0.83, p=0.015) in favour of ablation-based rhythm control while for men there was no difference (HR 0.88 95%CI 0.57,1.35; p=0.552). Conclusion In this post hoc analysis of the RAFT AF study, women with AF and HF had improved outcomes with ablation-based rhythm control as compared to men. This study underscores the importance of sex differences in response to therapy and calls for increased enrolment of women into clinical trials of ablation-based strategies, particularly with AF and HF.