Heart failure is a prevalent cause of mortality, especially in aging populations, often accompanied by comorbidities such as iron deficiency. Iron deficiency, affecting around 2 billion people globally, negatively impacts hospitalization and mortality rates in heart failure patients and hence there is a need for increased attention to managing iron deficiency in heart failure care to enhance patient outcomes and quality of life.

The current definitions of heart failure (HF) vary and emphasize different aspects, ranging from hemodynamic and physiologic components to clinical diagnostic elements. In 2021, a revised definition was proposed jointly by the Japanese Heart Failure Society (JHFS), the Heart Failure Association of the European Society of Cardiology (HFA/ESC), and the Heart Failure Society of America (HFSA). HF is considered a clinical syndrome, lacking specific pathognomonic histological or biochemical signs and arising from various clinical disease states. It ranks among the leading causes of mortality in industrialized nations, with a prevalence of 1%–2% in adults, increasing with age. HF patients often have multiple comorbidities that influence their clinical care, quality of life, and prognosis, including iron deficiency (ID), a prevalent nutritional deficiency affecting approximately 2 billion people worldwide.

This review addresses the prevalence, clinical implications, ongoing trials related to ID treatment in HF, and explores how iron therapy can potentially enhance exercise capacity, functional status, and quality of life in HF patients.

Several clinical trials are investigating intravenous (IV) iron therapy in patients with heart failure (HF), primarily focusing on outcomes like cardiovascular (CV) death or HF hospitalization.

FAIR-HFpEF: Evaluating IV iron therapy’s impact on exercise capacity in HFpEF patients with iron deficiency, with secondary endpoints including quality of life and NYHA class.

HEART-FID: A double-blind trial comparing IV iron to a placebo, assessing the composite endpoint of death and HF hospitalization at 12 months.

FAIR-HF2: Investigating IV iron’s effect on reducing recurrent HF hospitalizations and CV death in HFrEF patients.

IRONMAN: Differs from other trials by using IV iron isomaltose (IIM) instead of ferric carboxymaltose (FCM) and aims to determine IV IIM’s impact on CV mortality or hospitalization for worsening HF.

RESAFE-HF: An open-label registry trial assessing IV FCM’s effects on various parameters in HFrEF patients.

ESC Guidelines: The 2021 ESC guidelines stress the importance of diagnosing iron deficiency (ID) in HF patients, recommending regular screening for anemia and ID. IV FCM supplementation is considered for recently hospitalized HFrEF patients to reduce rehospitalizations.

Conclusion: ID significantly affects HF patients, negatively impacting prognosis, physical performance, and quality of life. However, ID management remains suboptimal in clinical practice. Mechanistic research is ongoing to understand IV iron’s cardiovascular benefits and its broader role in circulation. Addressing ID in HF care can improve patient outcomes and quality of life.

Source: Deichl A, Edelmann F. Improvement of exercise and functional capacity and quality of life in patients with heart failure by iron therapy. Frontiers in Cardiovascular Medicine. 2023 May 22;10:1025957.

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