Sex-Related Differences in Atrial Remodeling in Patients With Atrial Fibrillation: Relationship to Ablation Outcomes

Abstract

Background: Population studies have demonstrated a range of sex differences including a higher prevalence of atrial fibrillation (AF) in men and a higher risk of AF recurrence in women. However, the underlying reasons for this higher recurrence are unknown. This study evaluated whether sex-based electrophysiological substrate differences exist to account for worse AF ablation outcomes in women. Methods: High-density electroanatomic mapping of the left atrium was performed in 116 consecutive patients with AF. Regional analysis was performed across 6 left atrium segments. High-density maps were created using a multipolar catheter (Biosense Webster) during distal coronary sinus pacing at 600 and 300 ms. Mean voltage and conduction velocity was determined. Complex fractionated signals and double potentials were manually annotated. Results: Overall, 42 (36%) were female, mean age was 61±8 years and AF was persistent in 52%. Global mean voltage was significantly lower in females compared with males at 600 ms (1.46±0.17 versus 1.84±0.15 mV, P <0.001) and 300 ms (1.27±0.18 versus 1.57±0.18 mV, P =0.013) pacing. These differences were seen uniformly across the left atrium. Females demonstrated significant conduction velocity slowing (34.9±6.1 versus 44.1±6.9 cm/s, P =0.002) and greater proportion of complex fractionated signals (9.9±1.7% versus 6.0±1.7%, P =0.014). After a median follow-up of 22 months (Q1–Q3: 15–29), females had significantly lower single-procedure (22 [54%] versus 54 [75%], P =0.029) and multiprocedure (24 [59%] versus 60 [83%], P =0.005) arrhythmia-free survival. Female sex and persistent AF were independent predictors of single and multiprocedure arrhythmia recurrence. Conclusions: Female patients demonstrated more advanced atrial remodeling on high-density electroanatomic mapping and greater post-AF ablation arrhythmia recurrence compared with males. These changes may contribute to sex-based differences in the clinical course of females with AF and in part explain the higher risk of recurrence.

Sex Differences in Epicardial Adipose Tissue: Association With Atrial Fibrillation Ablation Outcomes

“…Some reports found sex differences in the AF recurrence ( 7 , 8 , 39 ). Consistent with the above results, this study demonstrated that women experienced a higher incidence of post-ablation AF recurrence.…”

“…Matrix metalloproteinases, a vital modulator of extracellular matrix turnover that contributes to atrial fibrosis, were upregulated in the AF period, and their secretion increased within EAT ( 37 , 38 ). An existing study reported that female patients with AF had more advanced atrial remodeling compared with male patients ( 39 ).…”

Do Elderly Patients with Atrial Fibrillation Have Comparable Ablation Outcomes Compared to Younger Ones? Evidence from Pooled Clinical Studies

“…Multiple risk factors, including unmodifiable risk factors (e.g., gender, age, and genetics) and modifiable risk factors (e.g., hypertension, DM, and obesity), played a significant role in contributing to the initiation and progression of AF. A growing number of clinical studies have suggested that female patients have a higher risk of AF recurrence than male patients after ablation, owing to more advanced atrial remodeling [ 44 , 45 ]. The recurrent AF subanalysis in the CABANA trial (NCT00911508) proved that the efficacy of ablation in the female subgroup was significantly inferior to that in the male subgroup when compared with the efficacy of drug therapy (HR: 0.64 vs. 0.46, p for interaction = 0.035) [ 46 ].…”

Catheter ablation of symptomatic atrial fibrillation: Sex, ethnicity, and socioeconomic disparities

“… 37 More advanced atrial remodeling and a greater number of recurrences have been shown after AF ablation in females despite AF duration similar to males. 38 In contrast, a systematic review reported that none of the more than 20 included studies found female sex to be a predictor of AF recurrence after AF ablation. 39 Furthermore, the AXAFA-AFNET 5 study showed similar improvement in quality of life in both sexes after ablation.…”