Clinical Research
Heart Failure
Myocardial and Systemic Iron Depletion in Heart Failure: Implications for Anemia Accompanying Heart Failure

https://doi.org/10.1016/j.jacc.2011.01.059Get rights and content
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Objectives

This study sought to determine the potential pathophysiological link between anemia and disease severity, and adverse outcome in heart failure (HF).

Background

Anemia frequently accompanies advanced HF; however, the pathophysiological mechanism responsible for the association between anemia and more severe HF remains uncertain. We hypothesized that a depletion of myocardial iron content may provide the biological link.

Methods

Complementary clinical and basic studies were performed. Hemodynamic, biochemical, and echocardiographic investigations were performed in 9 healthy controls and 25 patients with advanced HF (left ventricular ejection fraction: 23 ± 10%). Tissue iron content and type 1 transferrin receptor (Tfr1) expression were assessed in human myocardial tissue, and the regulation of Tfr1 expression was studied in isolated cardiomyocytes.

Results

HF patients displayed evidence of iron deficiency as measured by lower serum iron (p < 0.05) and transferrin saturation (TFS) (p < 0.05). When subclassified according to the presence of anemia, TFS was lower in anemic compared with nonanemic HF patients, whereas TFS in nonanemic HF patients was intermediate. In association, myocardial iron content was reduced in HF versus non-HF samples (0.49 ± 0.07 μg/g vs. 0.58 ± 0.09 μg/g, p < 0.05), and there was a significant reduction (p < 0.05) in the myocardial mRNA expression of Tfr1, which plays a key role in cellular iron transport. In the context of HF, catecholamines and aldosterone both down-regulated Tfr1 expression in isolated cardiomyocytes.

Conclusions

This study suggests the presence of iron depletion in the failing human heart, providing a potential link for the association between anemia and adverse prognosis in HF.

Key Words

anemia
heart failure
iron

Abbreviations and Acronyms

eGFR
estimated glomerular filtration rate
Hb
hemoglobin
HF
heart failure
hs-CRP
high-sensitivity C-reactive protein
IQR
interquartile range
LVEF
left ventricular ejection fraction
PCR
polymerase chain reaction
Tfr1
type 1 transferrin receptor
TFS
transferrin saturation

Cited by (0)

Dr. Maeder was supported by the Swiss National Science Foundation. Prof. Kaye is supported by a Program Grant from the National Health and Medical Research Council of Australia. All other authors have reported that they have no relationships to disclose.