Background Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance (CMR) relaxation parameter R2* (assessed clinically via its reciprocal T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans is limited. Methods and Results Twelve human hearts were studied from transfusion dependent patients following either death (heart failure n=7, stroke n=1) or transplantation for end-stage heart failure (n=4). After CMR R2* measurement, tissue iron concentration was measured in multiple samples of each heart using inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean (±SD) global myocardial iron causing severe heart failure in 10 patients was 5.98 ±2.42mg/g dw (range 3.19–9.50), but in 1 outlier case of heart failure was 25.9mg/g dw. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R2=0.910, p<0.001) leading to [Fe]=45.0•(T2*)−1.22 for the clinical calibration equation with [Fe] in mg/g dw and T2* in ms. Mid-ventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. Conclusions These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for CMR R2* against myocardial iron concentration. The iron values are of considerable interest with regard to the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in-vivo by CMR of the mid septum.

SummaryHeart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron-induced cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5AE1 ± 1AE9 to 8AE1 ± 2AE8 ms, P ¼ 0AE003), liver iron (9AE6 ± 4AE3 to 2AE1 ± 1AE5 mg/g, P ¼ 0AE001), LV ejection fraction (52 ± 7AE1% to 63 ± 6AE4%, P ¼ 0AE03), LV volumes (end diastolic volume index 115 ± 17 to 96 ± 3 ml, P ¼ 0AE03; end systolic volume index 55 ± 16 to 36 ± 6 ml, P ¼ 0AE01) and LV mass index (106 ± 14 to 95 ± 13, P ¼ 0AE01). Iron cleared more slowly from myocardium than liver (5AE0 ± 3AE3% vs. 39 ± 23% per month, P ¼ 0AE02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver.

Purpose:To assess tissue iron concentrations by the use of a gradient echo T2* multiecho technique. Materials and Methods:We compared the results of measurements of heart T2* from 32 patients using the established multiple breath-hold variable TR technique with a new multiecho sequence that acquires all images within a single breath-hold with constant TR. Results:There was good agreement of myocardial T2* values between both methods in the abnormal range of T2* Ͻ 20 msec (mean difference 0.2msec, 95% CI -1.3 to 0.9 msec, r ϭ 0.97, P Ͻ 0.0001). The coefficient of variability between the methods was 3.5%. The interstudy reproducibility using the multiecho sequence had a variability coefficient of 2.3% in the abnormal T2* range and 5.8% over all T2* values. There was good agreement between the techniques for the liver T2* values. Conclusions:The use of the single breath-hold, multiecho acquisition allowed reliable quantification of myocardial T2*. The good reproducibility, speed, and T1 independence of this technique allows greater accuracy, faster patient throughput, and, therefore, reduced costs (which is important in developing countries where thalassemia is most prevalent).