Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

Abstract

Iron is an essential micronutrient for a myriad of physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF), with a prevalence reaching up to 59% even in non-anaemic patients. ID impairs exercise capacity, reduces the quality of life, increases hospitalisation rate and mortality risk regardless of anaemia. Intravenously correcting ID has emerged as a promising treatment in HF as it has been shown to alleviate symptoms, improve quality of life and exercise capacity and reduce hospitalisations. However, the pathophysiology of ID in HF remains poorly characterised. Recognition of ID in HF triggered more research with the aim to explain how correcting ID improves HF status as well as the underlying causes of ID in the first place. In the past few years, significant progress has been made in understanding iron homeostasis by characterising the role of the iron-regulating hormone hepcidin, the effects of ID on skeletal and cardiac myocytes, kidneys and the immune system. In this review, we summarise the current knowledge and recent advances in the pathophysiology of ID in heart failure, the deleterious systemic and cellular consequences of ID.

Novel Phenotyping for Acute Heart Failure—Unsupervised Machine Learning-Based Approach

“… Iron deficiency is a frequent comorbidity in heart failure, present in approximately 30–50% of patients and is associated with worse long-term outcomes [ 23 , 24 , 25 ].…”

Fluctuating iron levels in heart failure: when and where to look at?

“…Although our understanding of iron deficiency (ID) in heart failure (HF) has been evolving from merely a prevalent comorbidity that is associated with worse clinical course to an important player in disease progression that can be modified, many questions remain to be answered 1 . In the most recent HF guidelines of the European Society of Cardiology (ESC) of 2021, it is suggested that haemoglobin and iron status should be checked periodically in all HF patients 2 .…”

“…The mechanisms of the spontaneous resolution could be explained by the initial aetiology of ID. For this several hypotheses have been proposed, including reduced dietary intake, decreased iron uptake due to inflammation and impaired intestinal function, and increased loss of iron as a result of occult gastrointestinal bleeding 1 . Some of these might alter over time, while others are persistent in nature.…”

“…These observations are likely attributed to the dependence on ferritin. Although ferritin provides a useful indirect estimate of iron stores in otherwise healthy individuals, ferritin is an acute‐phase reactant that increases in inflammatory conditions such as HF 1 . In fact, ferritin levels significantly correlate with inflammatory markers, while correlating poorly with iron indices in HF 4,5,15 .…”

“…Although ferritin provides a useful indirect estimate of iron stores in otherwise healthy individuals, ferritin is an acute-phase reactant that increases in inflammatory conditions such as HF. 1 In fact, ferritin levels significantly correlate with inflammatory markers, while correlating poorly with iron indices in HF. 4,5,15 The authors report that at baseline, 81% (n = 568) of iron deficient patients as per the ESC criteria had a serum ferritin <100 μg/L.…”