Mitochondrial Function, Skeletal Muscle Metabolism, and Iron Deficiency in Heart Failure

ron deficiency is one of the most prevalent comorbidities in chronic heart failure (HF), affecting more than half of all HF patients. The detrimental clinical and prognostic consequences of iron deficiency have been stressed by numerous studies. 1 However, the pathophysiology of iron deficiency in HF is largely unclear. Although anemia, as a consequence of iron deficiency, may seem a reasonable explanation for the adverse effects, iron deficiency without anemia was also strongly and independently associated with impaired quality of life, exercise intolerance, and mortality. 1 Furthermore, the beneficial effects of intravenous iron in iron-deficient HF patients (ie, improvement in exercise tolerance, New York Heart Association Functional Classification, and quality of life) were irrespective of attained hemoglobin levels. 2,3 These findings shifted the focus from hemoglobin toward more direct effects of iron itself on nonhematopoietic tissues that are important for exercise capacity, such as skeletal and cardiac muscle. It has also been acknowledged that the exercise intolerance of chronic HF patients is not solely explained by peripheral muscle underperfusion associated with cardiac dysfunction. 5] A more direct way to study the effects of iron status on exercise tolerance is to analyze mitochondrial respiratory function in skeletal muscle biopsies. 7 However, this method provides static results and is associated with excessive burden to the patients, especially when multiple biopsies are taken.