Myocardial and Systemic Iron Depletion in Heart Failure: Implications for Anemia Accompanying Heart Failure

Objectives This study sought to determine the potential pathophysiological link between anemia and disease severity, and adverse outcome in heart failure (HF). Background Anemia frequently accompanies advanced HF; however, the pathophysiological mechanism responsible for the association between anemia and more severe HF remains uncertain. We hypothesized that a depletion of myocardial iron content may provide the biological link. Methods Complementary clinical and basic studies were performed. Hemodynamic, biochemical, and echocardiographic investigations were performed in 9 healthy controls and 25 patients with advanced HF (left ventricular ejection fraction: 23 ± 10%). Tissue iron content and type 1 transferrin receptor (Tfr1) expression were assessed in human myocardial tissue, and the regulation of Tfr1 expression was studied in isolated cardiomyocytes. Results HF patients displayed evidence of iron deficiency as measured by lower serum iron (p Conclusions This study suggests the presence of iron depletion in the failing human heart, providing a potential link for the association between anemia and adverse prognosis in HF.