Anker SD, Comin Colet J, Filippatos G, et al. . N Engl J Med. 2009;361:2436-48.
Ferric carboxymaltose in patients with heart failure and iron deficiency
 

In our usual practice of clinical hematology, we frequently deal with excess iron in the hearts of patients with thalassemia, hemoglobinopathies, or transfusional iron overload. Today oral and intravenous iron chelation therapy can markedly improve cardiac function, preventing irreversible cardiomyopathy and heart failure. It is ironic for hematologists to think about giving intravenous iron to improve cardiac function, but that is exactly what Anker et al. demonstrated in their recent New England Journal of Medicine article.

Patients with NYHA class II or III heart failure with left ventricular ejection fraction <40 percent and iron deficiency defined by a low serum ferritin, transferrin iron saturation <20 percent, and hemoglobin between 9.5 and 13.5 gram/dL were randomized in a 2-1 ratio to receive intravenous ironor saline. The patients received “total” iron replacement by infusion of 200 mg ferric carboxymaltose weekly until replaced, then every four weeksfor maintenance. After 24 weeks, patients receiving intravenous iron reported improvement in a Global Assessment survey, distance walked oversix minutes, and improvement in quality-of-life assessments. Improvements in iron-treated patients occurred both in those who were anemic and nonanemic; adverse event and death rates were similar.

Unfortunately, there are several limitations to this provocative study, including a high drop-out rate, subjective endpoints (questionnaire-derived primarily with few objective measures such as ejection fraction), the method of iron replacement (intravenous vs. oral), unknown causes of iron deficiency in the patients, and lack of long-term follow-up on patients.1  Despite this, the study reminds me of Finch’s classic study2  on work capacity in rats made iron-deficient. He showed that despite similar hemoglobin levels, rats that were iron-deficient did not run on a treadmill as long as iron-replete rats. Concentrations of cytochromes, myoglobin, and rates of mitochondrial oxidative phosphorylation were reduced in iron-deficient skeletal muscle, with iron dextran reversing the effects. Is the subjective improvement in Anker’s study just due to better skeletal muscle health? In patients with heart failure and iron deficiency, iron may improve skeletal muscle function and possibly cardiac muscle function.3  Toblli et al. showed that iron replacement could decrease C-reactive peptide (CRP), N-terminal pro-brain natriuretic peptide, ejection fraction, and walking distance in six minutes.

In light of the recent work by Anker and colleagues, hematologists may play a greater role in evaluating and treating patients with heart failure for iron deficiency. Thorough assessments for the causes of low iron stores including source of blood loss, use of aspirin or anticoagulants, or absorption/diet are required. Appropriate decisions regarding oral or parenteral iron therapies with their potential side effects necessitate collaboration with cardiologists and primary-care physicians.

2.
Finch CA, Miller LR, Inamdar AR, et al. Iron deficiency in the rat. Physiological and biochemical studies of muscle dysfunction. J Clin Invest. 1976;58:447-53.

Competing Interests

Dr. Vercellotti indicated no relevant conflicts of interest.