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).
Transmural patterns of LGE distinguished ATTR from AL cardiac amyloidosis with high accuracy in this real-world analysis of CMR. Precise diagnosis of cardiac amyloidosis is crucial given the role of chemotherapy in AL type and with novel therapies for ATTR type currently in development.
Background: Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine. Methods: A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made. Results: Myocardial iron loading (T2 * < 20 ms) was present in 108 (65%) patients, which was severe (T2 * < 8 ms) in 22 (13%). Impaired (<56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p < 0.001), weakly related to serum ferritin (Rs = −0.34, p < 0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = −0.35, p < 0.001) and was abnormal in only 5 patients. Conclusions: Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis.
CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.
Purpose:To assess interscanner reproducibility of tissue iron measurements in patients with thalassemia using gradient echo T2* measurements on two different MRI scanners.
Materials and Methods:Twenty-five patients with thalassemia major had liver and myocardial T2* assessment using a Picker Edge 1.5T Scanner and a Siemens Sonata 1.5T scanner, with similar gradient echo sequences. In a subset of 13 patients, two scans on the Siemens scanner were performed to assess interstudy reproducibility.Results: There was a highly significant, linear correlation between T2* values obtained for both the heart (r ϭ 0.95) and the liver (r ϭ 0.99) between scanners. The mean difference, coefficient of variability, and 95% confidence intervals between scanners were 0.8 msec, 9.4% and -5.0 to 6.7 msec for the heart; and 0.9 msec, 7.9% and -2.0 to 3.9 msec for the liver. The interstudy mean difference and coefficient of variability on the Siemens scanner was 0.3 msec and 4.8% (r ϭ 0.99) for the heart, and 0.04 msec and 1.9% (r ϭ 0.99) for the liver.
Conclusion:The T2* technique for measuring tissue iron is reproducible between the two manufacturers' scanners. This suggests that the widespread implementation of the technique is possible for clinical assessment of myocardial iron loading in thalassemia.
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