Sex Differences in 90-Day Readmission and Mortality Trends in Heart Failure With Preserved Ejection Fraction: Insights From the National Readmissions Database.

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure hospitalizations and disproportionately affects women, who present with distinct risk profiles and pathophysiologies compared to men. Prior studies exploring sex differences have been limited by small sample sizes and have often focused on index hospitalizations. We aimed to examine sex differences in risk factors, causes of readmission, and mortality following HFpEF hospitalization using a large, nationally representative cohort. Methods: We performed a retrospective cohort study using the 2016-2019 National Readmissions Database. Adults hospitalized with a primary diagnosis of HFpEF were included. Patients were followed for 90-day readmissions, and multivariable logistic regression was used to identify predictors of readmission and readmission-related mortality, stratified by sex. The final sample included 353,536 patients (217,354 women and 136,182 men). Results: Women were older at admission, more likely to live in lower-income areas, and more often presented with uncomplicated hypertension, while men had a higher burden of ischemic heart disease. Advancing age was associated with increased risk of readmission in women. Women were more frequently readmitted with respiratory failure, diastolic heart failure, and atrial fibrillation, suggesting a greater burden of vascular stiffness and symptom severity. Chronic kidney disease and diabetes were key predictors of readmission and mortality in both sexes. Conclusions: HFpEF manifests with distinct sex-specific risk factors, clinical trajectories, and outcomes. These findings underscore the need for sex-informed, individualized treatment strategies and equitable resource allocation to reduce disparities and improve outcomes in HFpEF care.