Abstract
Background Heart failure patients presenting with iron deficiency can benefit from systemic iron supplementation; however, there is the potential for iron overload to occur, which can seriously damage the heart. Therefore, myocardial iron (M-Iron) content should be precisely balanced, especially in already failing hearts. Unfortunately, the assessment of M-Iron via repeated heart biopsies or magnetic resonance imaging is unrealistic, and alternative serum markers must be found. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism. Methods Left ventricle (LV) myocardial biopsies and serum samples were collected from 33 consecutive HF patients (25 males) with LV dysfunction (LV ejection fraction 22 (11) %; NT-proBNP 5464 (3308) pg/ml) during heart transplantation. Myocardial ferritin (M-FR) and soluble transferrin receptor (M-sTfR1) were assessed by ELISA, and M-Iron was determined by Instrumental Neutron Activation Analysis in LV biopsies. Nonfailing hearts (n = 11) were used as control/reference tissue. Concentrations of serum iron-related proteins (FR and sTfR1) were assessed. Results LV M-Iron load was reduced in all HF patients and negatively associated with M-FR (r = −0.37, p = 0.05). Of the serum markers, sTfR1/logFR correlated with (r = −0.42; p = 0.04) and predicted (in a step-wise analysis, R2 = 0.18; p = 0.04) LV M-Iron. LV M-Iron load (μg/g) can be calculated using the following formula: 210.24–22.869 × sTfR1/logFR. Conclusions The sTfR1/logFR ratio can be used to predict LV M-Iron levels. Therefore, serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients.
Highlights
Iron plays a crucial role in oxygen transport and storage, cardiac and skeletal muscle metabolism, energy production, and protein synthesis [1]
The study group consisted of 33 consecutive, symptomatic heart failure (HF) patients (25 males), with a mean age of 48 years, who were referred for orthotopic heart transplantation (OHT)
myocardial iron (M-Iron) load at the cellular level was recently shown to be reduced in the failing heart, without significant changes in the expression of Myocardial ferritin (M-FR) and M-sTfR1 [13, 14]
Summary
Iron plays a crucial role in oxygen transport and storage, cardiac and skeletal muscle metabolism, energy production, and protein synthesis [1]. European Society of Cardiology (ESC) HF guidelines state that iron replacement therapy should be considered in HF patients with ID [6] This clinical benefit of intravenous (iv) iron supplementation in HF patients seems to be independent of the presence of anemia [1, 7]. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism. Serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients
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