The findings of the present work are very relevant and unique since this is the first time it has been shown that, in patients with HF without systemic ID according to the standard criteria, raised sTfR levels as a marker of increased iron demand may be indicative of an early stage of subtle iron insufficiency at the tissue level, promoting early impairments in submaximal exercise capacity and self-perceived health status. Here, TFRC is linked to hydrops fetalis.