Intravenous Iron Therapy in Very Old Adults with Heart Failure: A Frailty-Oriented Therapeutic Perspective

Iron deficiency is common in heart failure (HF) and particularly frequent in older adults, in whom it may contribute to fatigue, exercise intolerance, impaired quality of life and functional decline, even without overt anaemia. In HF, intravenous iron has shown consistent benefits on symptoms, functional capacity and health-related quality of life in selected populations, mainly with reduced ejection fraction, and some studies have suggested a reduction in recurrent HF hospitalisations. However, more recent large trials have shown less consistent effects on hard clinical outcomes and a mortality benefit remains unproven. Importantly, the evidence underpinning current recommendations is derived predominantly from younger and highly selected HF populations, creating a major evidence-to-practice gap for patients who are very old and multimorbid. Although some pivotal trials included meaningful numbers of chronologically older participants, frailty, cognitive impairment, functional dependency, multimorbidity severity and treatment burden remain poorly characterised. Diagnostic criteria used in HF are also more difficult to interpret in older adults because of chronic inflammation, renal dysfunction, malnutrition and other age-related comorbidities that influence ferritin and transferrin saturation. Preliminary evidence in HF with preserved ejection fraction suggests a possible functional benefit, but available data remain insufficient to establish effects on clinical events or applicability to frail older populations. In this structured, clinically oriented review, we examine the pathophysiology, diagnostic challenges and trial evidence for iron deficiency management in older adults with HF, with particular emphasis on the mismatch between available evidence and real-world data on patients who are older and multimorbid. We also propose an illustrative frailty-informed framework integrating conventional biomarker thresholds, expected symptomatic and functional benefit, adverse-effect risk, cognition, treatment burden and patient goals, without using frailty as an automatic exclusion criterion.