Sex-related disparities in elderly patients with heart failure with mildly reduced or preserved ejection fraction

INTRODUCTION: Heart failure with preserved or mildly reduced ejection fraction (HFmrEF/HFpEF) is a complex syndrome common in elderly patients with multiple comorbidities. Age and sex affect the clinical phenotypes and outcomes of this condition. This study aimed to identify age- and sex-specific factors influencing prognosis in elderly patients with HFmrEF/HFpEF to improve risk stratification and guide personalized treatment. METHODS: This observational, ambispective study was conducted at Papa Giovanni XXIII Hospital, Bergamo, from June 2017 to August 2022, enrolling patients >65 years with HFmrEF/HFpEF [New York Heart Association (NYHA) Class II-IV] according to ESC guidelines. Data collected included demographics, medical history, echocardiograms, and lab tests. Follow-up lasted at least 1 year, with outcomes defined as a composite of all-cause death, urgent heart transplant, HF hospitalization, and emergency department referral for decompensated HF. Findings were validated using the Swedish HF registry with a similar cohort. RESULTS: Among 2263 HF patients, 971 HFmrEF/HFpEF patients (56.8% males, mean age 79.2 years) were analysed. Males had a higher prevalence of cardiovascular risk factors (e.g. diabetes, obesity, coronary artery disease). The composite outcome occurred more frequently in males (20.6 vs 17.14 per 100 patient years; IRR = 1.20, P = .035). Multivariable analysis identified male sex (HR 1.40, 95% CI 1.13-1.73), age >80 years (HR 1.91, 95% CI 1.22-3.00), higher NYHA class, chronic kidney disease, and severe valvular heart disease as independent predictors of worse outcomes. Males had a 40% higher risk of the outcome compared with women (HR 1.40, 95% CI 1.13-1.73), while patients >80 years old had nearly double the risk compared with those aged 65-70 (HR 1.91, 95% CI 1.22-3.00). The validation analysis in the SwedeHF, adapting the same multiple Cox regression model on 20 950 selected patients, median age 79 years and 57.8% men, and observed between January 2017 and August 2022, showed similar independent risk factors for the composite outcome. CONCLUSION: This study highlights significant sex disparities in elderly HFmrEF/HFpEF patients, with higher age and male sex being an independent predictor for poor outcomes. These findings emphasize the need for personalized treatment strategies based on these demographic factors.