5222Muscle-derived follistatin and decorin levels in men with heart failure with reduced ejection fraction and different iron status

Abstract

Background: The functioning of skeletal muscle in heart failure (HF) patients is impaired upon disturbed iron status. Thanks to its secretory capacity skeletal muscle produces various, mainly contraction‐induced proteins (myokines). These bioactive factors trigger local responses, affecting energy metabolism, hypertro‐phy and regeneration of the muscle. Purpose: We aimed to determine whether patients with HF and iron deficiency (ID) had the altered the production of decorin which exerts pro‐hypertrophic effect, and follistatin, a myokine promoting muscle regenerative potential. Further, we investigated whether the intravenous iron repletion influenced the exercise‐induced production of these myokines. Methods: Study population comprised of 53 men with heart failure with reduced ejection fraction (LVEF <40%; mean age: ±64 years; NYHA class I‐II: 87%) and of 15 middle‐aged healthy men. We assessed follistatin and decorin levels in plasma samples from peripheral blood from all patients by ELISA. Further, we analyzed samples taken from antecubital veins draining the forearm muscle be‐fore and after physical local exercise (standardized 5‐minute handgrip exercise) for the myokines. Additionaly iron‐deficient HF patients (serum ferritin<100(xg/L or serum ferritin 100‐300 (xg/L with Tsat<20%) and were randomized in a 1:1 fashion (double‐blind scheme) to receive either intravenous ferric carboxymaltose (FCM) or saline (comparator) (24‐week dosing protocol according to CONFIRM‐HF trial). Results: We observed no differences in concentrations of both myokines mea‐sured in peripheral samples between HF patients and controls, and between HF patients with and without ID. There were no correlations between myokine levels in peripheral and forearm samples. In forearm samples levels of decorin and follistatin assessed both before and after handgrip were significantly lower in HF patients with ID as compared to those with preserved iron status (all p<0.001). Moreover, both before and after exercise the lower levels of decorin in forearm samples of men with HF were associated with lower mean handgrip strength (R=0.45, p<0.01; R=0.46, p<0.01). In HF patients during exercise there was a correlation between a reduced netto decorin and higher netto lactate formation in forearm samples (R=‐0.38, p<0.01). Notably, the netto muscle production of follistatin in forearm samples was significantly increased in men with HF and ID treated with FCM as compared to those who received saline (p<0.01). Conclusions: In patients with HF and ID decreased decorin and follistatin secretion assessed in forearm blood, but not in peripheral blood, reflects the lower pro‐hypertrophic and regenerative potential. Lower secretion of decorin in HF patients during exercise is associated with altered muscle metabolic activity. In patients with HF and ID iron repletion therapy partially restitutes the follistatin production during exercise. Funding Acknowledgements: This research was financially supported by National Science Centre (Poland) grant no: SONATA 2012/05/E/NZ5/00590.