Iron status, catabolic/anabolic balance, and skeletal muscle performance in men with heart failure with reduced ejection fraction

BACKGROUND: Metabolic derangements related to tissue energetics constitute an important pathophysiological feature of heart failure. We investigated whether iron deficiency and catabolic/anabolic imbalance contribute to decreased skeletal muscle performance in men with heart failure with reduced ejection fraction (HFrEF), and whether these pathologies are related to each other. METHODS: We comprehensively examined 23 men with stable HFrEF (median age [interquartile range]: 63 [59–66] years; left ventricular ejection fraction: 28 [25–35]%; New York Heart Association class I/II/III: 17/43/39%). We analyzed clinical characteristics, iron status, hormones, strength and fatigability of forearm flexors and quadriceps (surface electromyography), and exercise capacity (6-minute walking test). RESULTS: None of the patients had anemia whereas 8 were iron-deficient. Flexor carpi radialis fatigability correlated with lower reticulocyte hemoglobin content (CHR, p < 0.05), and there was a trend towards greater fatigability in patients with higher body mass index and lower serum ferritin (both p < 0.1). Flexor carpi ulnaris fatigability correlated with lower serum iron and CHR (both p < 0.05). Vastus medialis fatigability was related to lower free and bioavailable testosterone (FT and BT, respectively, both p < 0.05), and 6-minute walking test distance was shorter in patients with higher cortisol/FT and cortisol/BT ratio (both p < 0.05). Lower ferritin and transferrin saturation correlated with lower percentage of FT and BT. Men with HFrEF and iron deficiency had higher total testosterone, but lower percentage of FT and BT. CONCLUSIONS: Iron deficiency correlates with lower bioactive testosterone in men with HFrEF. These two pathologies can both contribute to decreased skeletal muscle performance in such patients.