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.
Background-The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major. Methods and Results-We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values Ͻ10 ms (compared with Ͼ10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* Ͻ6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; PϽ0.001) or serum ferritin (0.629; PϽ0.001). Cardiac T2* was Ͻ10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values Ͻ20 ms (compared with Ͼ20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of Ͻ6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; PϽ0.001) or serum ferritin (0.518; PϽ0.001). The cardiac T2* was Ͻ20 ms in 83% of scans in patients who developed arrhythmia. Conclusions-Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration-URL: http://www.clinicaltrials.gov.
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