Atrial Fibrillation in Heart Failure with Preserved Left Ventricular Systolic Function: Distinct Elevated Risk for Cardiovascular Outcomes in Women Compared to Men

Background: Heart failure with preserved ejection fraction (HFpEF) is prevalent in women and is associated with atrial fibrillation (AF). However, sex associations in AF-related HFpEF are not well explored. Aim: We studied differences between men and women with and without AF-related HFpEF symptoms on left ventricular (LV) geometry and diastolic dysfunction (DD) and their effect on cardiovascular events. Methods: Retrospectively, HFpEF patients with and without a history of AF referred for echocardiography were studied. Echocardiographic assessments were focused on LV geometry and diastolic functions. Patients were followed for the occurrence of cardiac events defined as death and cardiac hospitalization. Results: We studied 556 patients [age: 66.7 ± 17 years, 320 (58%) women, 91 (16%) AF]. Compared to HFpEF without AF (HFpEF-AF), HFpEF with AF patients (HFpEF+AF) were older (76 ± 13.8 vs. 64.9 ± 17.3 years, p < 0.001), had more risk factors, comorbidities, left ventricular hypertrophy (32 vs. 13%, p < 0.001), higher relative wall thickness (0.50 ± 0.14 vs. 0.44 ± 0.15, p < 0.001), and DD (56 vs. 30%, all p < 0.001). HFpEF+AF women had the worst clinical, LV geometric, and diastolic functional profiles and highest rates of cardiovascular outcomes compared to HFpEF+AF men and were the only group to predict outcomes (HR: 2.7, 95%CI: 1.4–5.1), while HFpEF-AF women were a low-risk group; HFpEF+AF and HFpEF-AF men had intermediate cardiovascular outcomes which were confirmed after propensity score matching. Conclusions: Among patients with HFpEF, women with AF had more abnormal LV geometry and diastolic function and had an increased risk of adverse cardiovascular outcomes independent of traditional risk factors, comorbidities, and baseline diastolic function.