A systematic literature search and narrative synthesis of economic drivers in hospitalizations for heart failure with preserved or mildly reduced ejection fraction in the United States

BACKGROUND: Heart failure (HF) with mildly reduced ejection fraction (HFmrEF) or preserved EF (HFpEF) constitutes 74% of all HF cases in the US and is associated with significant clinical and economic burdens. Hospitalizations for HFmrEF/HFpEF are a leading contributor to the rising economic burden of HF. This literature review aims to identify key drivers of hospitalization costs for patients with HFmrEF/HFpEF in the US and to inform targeted interventions to reduce health care expenditures. METHODS: A comprehensive search of MEDLINE and Embase was conducted to identify observational studies published between January 2022 and May 2025 that reported on hospitalization-related costs for US adults with HFmrEF/HFpEF (defined as left ventricular ejection fraction ≥ 40%). Eligible studies were those reporting direct costs of hospitalization, readmission rates, time to readmission, length of stay, and number of hospitalizations per person. Data were synthesized narratively, and costs were adjusted to 2025 US$. RESULTS: Of 2624 records identified by the literature searches, 37 studies met inclusion criteria. Total annual costs for HFmrEF/HFpEF were $36,921 to $49,081 per person per year (PPPY), with inpatient hospitalizations accounting for nearly half ($18,844-$20,095 PPPY). Readmissions were a major cost driver, with median all-cause readmission costs ($21,371-$28,615) consistently higher than index admission costs ($13,763-$14,944). Approximately 20% of patients were readmitted within 30 days, with HF-specific readmissions accounting for one-third of 30-day readmissions. Comorbidities such as type 2 diabetes (T2D) and chronic kidney disease (CKD) significantly increased costs, with patients having multiple morbidities incurring nearly double the costs of individuals without comorbidities. Prolonged hospital stay was also linked to higher costs. CONCLUSIONS: HFmrEF/HFpEF hospitalizations represent a significant economic burden that is driven by high inpatient costs, frequent readmissions, and coexisting conditions (eg, T2D, CKD). These findings highlight the need for improved adherence to guideline-directed medical therapy and better management of comorbidities. Policymakers and health care providers should prioritize strategies to reduce HF-related hospitalizations and readmissions to mitigate the growing economic impact of HF.