Clinical outcomes after pulmonary vein isolation for atrial fibrillation in men versus women; insights from a contemporary large-scale population study

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of stroke and mortality. Pulmonary vein isolation (PVI) is the most effective treatment to reduce AF burden and is associated with a reduced risk of stroke and death. Differences in long-term clinical outcomes following PVI between sexes are debatable. PURPOSE: We aimed to explore the sex differences in outcomes following PVI in a contemporary population of AF patients. METHODS: This is a historical population-based study including all adult patients of the largest health maintenance organization in Israel who were first diagnosed with AF between January 1st, 2010, and January 1st, 2020. Patients with congenital heart disease, significant mitral stenosis, or who underwent valvular surgery were excluded. The primary outcomes were stroke and all-cause death after PVI. Early (30-day) outcomes were compared using logistic regression, and late (3-year) outcomes were assessed using multivariable survival analyses with Cox regression. RESULTS: Of 94,612 patients diagnosed with incident AF during the study period, 4593 (4.85%) underwent PVI, of whom 1892 (38.2%) were women. Women were older (65±12 vs. 63±13) and less likely to be smokers (15.0% vs. 33.0%). Women had higher body-mass-index (30.26±6.58 vs. 29.14±4.86) and higher rates of hypertension (66.4% vs. 63.2%) but had lower rates of known coronary or peripheral vascular disease and congestive heart failure (p<0.05 for all). The CHA2DS2-VASc score was higher among women compared to men [median 3 (IQR 2-4) vs. median 2 IQR (1-3), p<0.001). Compared to men, women were treated more often with beta-blockers (74.5% vs. 69.4%), non-dihydropyridine calcium channel blockers (6.5% vs. 3.0%), and class 1c antiarrhythmic drugs (19.4% vs. 12.8%; p<0.001 for all), but were treated less with amiodarone (14.2% vs. 18.1%, p<0.001). In the 30 days following CA, stroke occurred in 8 (0.2%) patients, and 26 (0.6%) patients died (p>0.1 for both). Three-year mortality was lower in women than in men (6.2%% vs. 8.6%, p=0.003), while stroke rates were similar in women (1.0%) and men (1.5%, p>0.1). In multivariable survival models, adjusting for potential confounders, women had a lower risk of mortality [aHR 0.72 95%CI (0.56-0.92), p=0.009]. Conversely, the risk of stroke was similar in women and men [aHR 0.62 95%CI (0.33-1.12), p=0.114]. The results were similar in propensity-adjusted models accounting for all differences between men and women. CONCLUSIONS: In this contemporary AF population, short-term stroke and mortality rates after PVI were very low and similar in men and women. The risk of long-term stroke following PVI was relatively low and similar across sex criteria. Women had a lower risk of long-term mortality than men following PVI despite undergoing the procedure at an older age and after adjusting for comorbidities and background medical therapy, suggesting possible sex differences in long-term mortality after PVI. [Figure: see text]