Aims Iron deficiency (ID) is a common co-morbidity in heart failure (HF). Intravenous iron therapy improves outcomes. Several mechanisms have been proposed, including myocardial iron repletion. However, it is unknown if clinical iron markers predict the extent of this repletion. The aim of this study is to address this question by harnessing data from two clinical studies that evaluated changes in myocardial iron using cardiac magnetic resonance (CMR).

Methods and Results We performed a post-hoc analysis of two previously published trials. The Myocardial-IRON trial measured change in myocardial iron, denoted by a decrease in CMR T1-mapping, at 7 and 30 days after FCM in patients with ID and HF. The STUDY trial measured myocardial and spleen iron at multiple timepoints after FCM in patients with ID without HF. In this post-hoc analysis, we examined the association between baseline iron markers (Tsat and ferritin) and change in myocardial iron in the weeks after FCM therapy. Changes in spleen iron were also examined, due its role as an intermediary in the redistribution of iron from iron-carbohydrate complexes such as FCM. In patients with or without HF, higher plasma ferritin at baseline predicted lower rise in myocardial iron in the weeks after therapy with FCM. In contrast, higher plasma ferritin at baseline predicted a greater rise in spleen iron.

Conclusions These data point towards the hypothesis that functional ID, which is characterized by elevated ferritin, could limit myocardial iron repletion after IV iron therapy, by favoring iron trapping in the spleen.

S.L.-L. reports receipt of previous research funding from Vifor Pharma, personal honoraria on a lecture from Pharmacosmos and consultancy fees from Disc Medicine and ScholarRock.

NCT03398681 NCT05609318

JN was supported by an unrestricted grant from Vifor Pharma, CIBER Cardiovascular [grant numbers 16/11/00420], Unidad de Investigacion Clinica y Ensayos Clinicos INCLIVA Health Research Institute, Spanish Clinical Research Network (SCReN; PT13/0002/0031 and PT17/0017/0003), cofounded by Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III, and Proyectos de Investigacion de la Seccion de Insuficiencia Cardiaca 2017 from Sociedad Espanola de Cardiologia. S.L.-L, MVA and SNK were funded by a Medical Research Council Senior Research Fellowship awarded to S.L-L (MR/V009567/1/) and the British Heart Foundation Centre for Research Excellence (HSR00031 and RE/18/3/34214).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of Agencia Espanola del Medicamento y Productos sanitarios (AEMPS), Comite Etico de Investigacion Clinica (CEIC) del Hospital Clinico Universitario de Valencia, NHS Ethics Committee in the UK (North West-Liverpool Central Research Ethics Committee Ref: 22/NW/0172), and the Health Research Authority gave ethical approval for this work.

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