Iron deficiency in heart failure and cardiovascular diseases – from pathophysiology to modern strategies

Abstract

Iron deficiency affects 40-80% of heart failure patients – across reduced, mid-range, and preserved ejection fraction subtypes – worsening exercise intolerance, frailty, quality of life, hospitalization rates, and mortality, regardless of anemia presence. This review examines iron deficiency’s central role in oxygen metabolism, mitochondrial energy production (adenosine triphosphate), and cellular respiration; its strong links to coronary artery disease (around 60% prevalence, raising ischemic events and impairing heart muscle remodeling after infarction) and pulmonary hypertension (40-60% prevalence, shortening six-minute walk distance, elevating pulmonary pressures, and harming right heart function); diagnostic hurdles during inflammation; and evidence-driven treatment strategies. Inflammation boosts hepcidin, a hormone that traps iron inside cells by breaking down ferroportin, starving heart muscle cells of energy and forcing reliance on inefficient anaerobic metabolism. Intravenous iron, such as ferric carboxymaltose, consistently delivers gains: better left ventricular ejection fraction, New York Heart Association symptom class, six-minute walk distance (plus 45 meters versus placebo), and quality-of-life scores (EQ-5D or Minnesota questionnaires), alongside 20-30% drops in heart failure hospitalizations from major trials like FAIR-HF, IRONMAN, HEARTFID, and FAIR-HF2. Oral iron falls short due to poor uptake in inflamed conditions. European Society of Cardiology 2023 guidelines urge routine screening and intravenous iron for symptomatic reduced or mid-range ejection fraction heart failure (strongest recommendation, high-quality evidence), with growing support for preserved ejection fraction and pulmonary hypertension cases.