Heart Failure with Preserved Ejection Fraction: Challenges and Current Approaches
Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with substantial morbidity, mortality, and impaired quality of life. Despite its rising prevalence, particularly among older adults and women, HFpEF has historically been characterized as a “therapeutic graveyard” because of decades of inconclusive or neutral clinical trials.
Methods: A secondary qualitative analysis of the literature indexed in PubMed, Scopus, and Embase from January 2018 through June 2025 was conducted. Randomized controlled trials, systematic reviews, meta-analyses, guideline statements, and high-quality observational studies were included. Data were extracted and synthesized thematically across five domains: epidemiology, pathophysiology, diagnostic strategies, therapeutic approaches, and future directions.
Results: Epidemiological data confirm increasing global prevalence, driven by aging demographics and clustering of comorbidities such as obesity, hypertension, diabetes, and atrial fibrillation. Pathophysiological insights highlight a complex, multiorgan syndrome with distinct phenotypes. Diagnostic accuracy remains hampered by overlapping comorbidities, limited biomarker sensitivity in obese or renally impaired patients, and heterogeneity in imaging findings. Artificial intelligence and machine learning approaches are emerging but not yet established in clinical care. Therapeutically, sodium–glucose cotransporter-2 (SGLT2) inhibitors represent the first pharmacologic agents to consistently reduce hospitalization and improve outcomes in HFpEF, while lifestyle modification, rehabilitation, and device-based interventions offer complementary benefits. Emerging strategies emphasize precision medicine, digital health, and biomarker-driven stratification.
Conclusion: HFpEF remains a major unexplained challenge in cardiovascular management. The efficacy of sodium–glucose cotransporter-2 inhibitors can mark a paradigm shift; however, significant weaknesses persist in diagnostic and therapeutic areas. Further progress depends on phenotype-specific, multimodal, and patient-centered strategies that combine clinical care, digital innovation, and molecular research.
