Sex-related differences in clinical outcomes of patients with atrial fibrillation and heart failure with preserved ejection fraction
Authors: Rattka M , Jungen C , Rudolph I , Mavrakis E , Vlachopoulo D , Kohn C , Bohnen J , Yahsaly L , Rassaf T , Mathew S 
Published: May 2024

Abstract

Background
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are both highly prevalent diseases that commonly coexist, sharing clinical features and pathomechanisms. While prevalence of AF is higher in men compared to women with HFpEF, outcomes appear to be worse in women. However, there are no studies systematically examining gender-specific differences.

Purpose
Aiming for deeper insights into the effects of gender on clinical outcomes of patients with AF and HFpEF.

Methods
AF patients with HFpEF were included. HFpEF was diagnosed according to the current ESC guideline. Outcomes of men and women were compared. The primary endpoint was the time to heart failure hospitalization. Secondary endpoints were maintenance of sinus rhythm, as well as clinical and functional parameters. Factors related to a primary endpoint event were assessed.

Results
A total of 161 patients were included in our study (69 male patients, 92 female patients). Assessment of patient characteristics at baseline showed that male patients suffered more often from coronary artery disease (male: 45/69 patients (65%); female: 45/92 patients (49%); p=0.039), and OSAS (male: 14/69 patients (20%); female: 5/92 patients (5%); p=0.004). After a follow-up of 3 years, occurrence of the primary endpoint event was less frequent in women than in men (Hazard Ratio (HR): 0.61; 95% Confidence Interval (CI): 0.38-0.97; p=0.36; Figure A). By logistic regression analysis, we identified female sex (HR 0.48; 95%CI: 0.23-0.97; p=0.041), AF ablation (HR: 0.26; 0.13-0.53; p&lt;0.001), and decrease in Left Ventricular Mass Index (LVMI) (HR:0.66; 95%CI: 0.44-0.98; p=0.041) as preventive factors with regard to heart failure hospitalization. Subgroup analysis for AF ablation versus medical therapy showed that patients who underwent ablation had lower hospitalization events (AF (HR: 0.49; 95% CI: 0.25-0.98; p=0.45). Additionally, left ventricular reverse remodeling, as assessed by the decrease of LVMI had a "dose-dependent" protective effect on heart failure hospitalizations (p=0.024, Figure B). Evaluation of functional HFpEF parameters revealed that only in women LVMI (baseline: 111 [99; 133] g/m2; follow-up: 105 [93; 127] g/m2; p=0.006), E/E’ ratio (baseline: 13.0 [10.2; 15.3]; follow-up: 11.5 [8.6; 14.7]; p=0.046), and NT-pro BNP serum levels (baseline: 1367 [352; 3605]; follow up: 987 [438; 2579]; p=0.039) improved.

Discussion
Our study suggests that women with AF and HFpEF have better outcomes as compared to men regarding heart failure hospitalization. LVMI and AF ablation are ssociated with fewer heart failure hospitalizations. Assessment of LVMI and further markers of HFpEF (E/E’ ratio and NT-pro BNP) only improved in women, suggesting that the gender-difference in heart failure hospitalization might be mediated by left ventricular induced remodeling following AF ablation. Further studies are necessary to verify this hypothesis generating results.Kaplan-Meier Analysis