Iron Deficiency and Anaemia in Heart Failure: Understanding the FAIR-HF Trial

José González-Costello; Josep Comín-Colet


Eur J Heart Fail. 2010;12(11):1159-1162. 

In This Article

Diagnosis of Iron Deficiency

Diagnosing ID in CHF patients is important, as iron plays a key role in oxygen uptake, transport, and storage, in the oxidative metabolism of the skeletal muscle and in erythropoiesis.[22] The evaluation of iron metabolism must include the determination of serum iron, transferrin, TSAT, and ferritin (see Table 1). In the FAIR-HF trial, true ID was defined as ferritin <100 µg/L, normally accompanied by high transferrin and low TSAT. In these patients, overt bleeding and poor dietary intake need to be evaluated, and it seems logical that these patients will respond to IV iron. Patients with functional ID defined as ferritin between 100 and 299 µg/L, and a TSAT <20% also benefited from IV iron. But what does this functional ID mean? If we consider anaemia of CHF as anaemia of chronic disease, then there will be increased uptake and retention of iron in the cells of the reticuloendothelial system. This is achieved by the expression of DMT1, which is up-regulated by cytokines. Divalent metal transporter 1 mediates iron transport into the intestinal mucosal cells and into the activated macrophages, but the export of iron from these cells is inhibited by down-regulation of the expression of ferroportin by means of an increase in hepcidin. This protein also inhibits iron absorption from the gut, and hepcidin levels seem to reflect iron load and response to EPO rather than inflammation and EPO resistance.[26] Thus, this will imply normal or increased ferritin with low serum iron, low transferrin, low TSAT and thus poor availability of iron at the bone marrow.[25] In a recent study of 546 patients with systolic CHF, ID (absolute or functional) was found in 37% of patients and ID, but not anaemia, was related to an increased risk of death or heart transplantation in multivariable analysis, reinforcing its importance as an independent predictor of unfavourable outcome.[27]