Accurate Noninvasive Assessment of Myocardial Iron Load in Advanced Heart Failure Patients

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, $R^2=0.18$ ; $p=0.04$ ) LV M-Iron. LV M-Iron load (μg/g) can be calculated using the following formula: $210.24–22.869\times \text{sTfR}1/\text{logFR}$ . 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.