RESUMO
BACKGROUND: Skeletal muscle dysfunction is a feature of heart failure (HF). Iron deficiency (ID) is prevalent in patients with HF associated with exercise intolerance and poor quality of life. Intravenous iron in iron deficient patients with HF has attenuated HF symptoms, however the pathomechanisms remain unclear. The aim of study was to assess whether intravenous iron supplementation as compared to placebo improves energy metabolism of skeletal muscles in patients with HF. METHODS: Men with heart failure with reduced ejection fraction (HFrEF) and ID were randomised in 1:1 ratio to either intravenous ferric carboxymaltose (IV FCM) or placebo. In vivo reduction of lactates by exercising skeletal muscles of forearm was analyzed. A change in lactate production between week 0 and 24 was considered as a primary endpoint of the study. RESULTS: There were two study arms: the placebo and the IV FCM (12 and 11 male patients with HFrEF). At baseline, there were no differences between these two study arms. IV FCM therapy as compared to placebo reduced the exertional production of lactates in exercising skeletal muscles. These effects were accompanied by a significant increase in both serum ferritin and transferrin saturation in the IV FCM arm which was not demonstrated in the placebo arm. CONCLUSIONS: Intravenous iron supplementation in iron deficient men with HFrEF improves the functioning of skeletal muscles via an improvement in energy metabolism in exercising skeletal muscles, limiting the contribution of anaerobic reactions generating ATP as reflected by a lower in vivo lactate production in exercising muscles in patients with repleted iron stores.
RESUMO
BACKGROUND: Skeletal and respiratory muscle dysfunction constitutes an important pathophysiological feature of heart failure (HF). We assessed the relationships between respiratory muscle function, skeletal muscle mass, and physical fitness in men with HF with reduced left ventricular ejection fraction (HFrEF), and investigated the hypothesis of whether iron deficiency (ID) contributes to respiratory muscle dysfunction in these patients. METHODS: We examined 53 male outpatients with stable HFrEF without asthma or chronic obstructive pulmonary disease (age: 64 ± 10 years; New York Heart Association [NYHA] class I/II/III: 36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction ≤40%) and 10 middle-aged healthy men (control group). We analysed respiratory muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was measured using dual-energy X-ray absorptiometry), physical fitness (components of Functional Fitness Test for Older Adults), and iron status. RESULTS: MIP, MEP, and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs. healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower in men with HFrEF with vs. without ID. In a multivariable linear regression model lower serum ferritin (but not transferrin saturation) was associated with lower MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In multivariable linear regression models, lower MIP was associated with worse results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and haemoglobin concentration). CONCLUSIONS: In men with HFrEF, low ferritin reflecting depleted iron stores is associated with inspiratory muscle weakness independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates with worse physical fitness independently of either skeletal muscle mass or disease severity.