Ironing Out the Details: Advancing Diagnosis and Treatment of Iron Deficiency in Patients with Heart Failure with Preserved Ejection Fraction - A Narrative Review.

Iron deficiency (ID) is a highly prevalent and clinically significant comorbidity in heart failure with preserved ejection fraction (HFpEF), affecting 40-60% of patients. Independent of anemia, ID is associated with reduced exercise capacity, diminished quality of life (QoL), and increased healthcare utilization. Although intravenous (IV) iron therapy has demonstrated consistent benefits in HF with reduced ejection fraction (HFrEF), including improvements in symptoms, QoL, functional status, and reductions in hospitalizations, its role in HFpEF remains incompletely defined. This review synthesizes the epidemiology, pathophysiologic mechanisms, and diagnostic challenges of ID in HFpEF, with particular attention to emerging data for IV iron supplementation in this clinical setting. It summarizes recent and ongoing clinical trials, highlights limitations of current diagnostic criteria, and outlines innovative strategies, including pragmatic trial designs, patient-reported outcomes, and wearable technologies, to evaluate therapeutic response in this heterogeneous population. Together, these insights provide a roadmap for improving the diagnosis and management of ID in HFpEF and addressing a significant unmet clinical need in this growing patient population.