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Iron deficiency as therapeutic target in heart failure: a translational approach

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Abstract

Heart failure (HF) is a potentially debilitating condition, with a prognosis comparable to many forms of cancer. It is often complicated by anemia and iron deficiency (ID), which have been shown to even further harm patients’ functional status and hospitalization risk. Iron is a cellular micronutrient that is essential for oxygen uptake and transportation, as well as mitochondrial energy production. Iron is crucially involved in electrochemical stability, maintenance of structure, and contractility of cardiomyocytes. There is mounting evidence that ID indeed hampers the homeostasis of these properties. Animal model and stem cell research has verified these findings on the cellular level, while clinical trials that treat ID in HF patients have shown promising results in improving real patient outcomes, as electromechanically compromised cardiomyocytes translate to HF exacerbations and arrhythmias in patients. In this article, we review our current knowledge on the role of iron in cardiac muscle cells, the contribution of ID to anemia and HF pathophysiology and the capacity of IV iron therapy to ameliorate the patients’ arrhythmogenic profile, quality of life, and prognosis.

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Abbreviations

ACE:

Angiotensin converting enzyme

EPO:

Erythropoietin

FCM:

Ferric carboxymaltose

HF:

Heart failure

HFrEF:

Heart failure with reduced ejection fraction

ID:

Iron deficiency

IREs:

Iron-responsive elements

IRP:

Iron regulatory proteins

IV:

Intravenous

LVEF:

Left ventricle ejection fraction

mID:

Myocardial iron deficiency

OXPHOS:

Oxidative phosphorylation

Tfr1:

Transferrin receptor 1

TSAT:

Transferrin saturation

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  1. Constantinos Bakogiannis and Alexandros Briasoulis contributed equally to this work.

Authors and Affiliations

  1. 3rd Department of Cardiology Hippocration Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54 352, Thessaloniki, Greece

    Constantinos Bakogiannis, Dimitrios Mouselimis, Anastasios Tsarouchas, Christodoulos Papadopoulos, Nikolaos Fragakis & Vassilios Vassilikos

  2. Division of Cardiovascular Medicine, Section of Heart Failure and Transplantation, University of Iowa, Iowa City, IA, USA

    Alexandros Briasoulis

  3. Electrophysiology Department, Barts Heart Centre, St. Bartholomew’s Hospital, London, UK

    Nikolaos Papageorgiou

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Bakogiannis, C., Briasoulis, A., Mouselimis, D. et al. Iron deficiency as therapeutic target in heart failure: a translational approach. Heart Fail Rev 25, 173–182 (2020). https://doi.org/10.1007/s10741-019-09815-z

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