Longitudinal prospective comparison of pancreatic iron by magnetic resonance in thalassemia patients transfusion-dependent since early childhood treated with combination deferiprone-desferrioxamine vs deferiprone or deferasirox monotherapy.

BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.

Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Left ventricular global function index is associated with myocardial iron overload and heart failure in thalassemia major patients.

PURPOSE: The left ventricular global function index (LVGFI) is a comprehensive marker of cardiac performance, integrating LV morphology with global function. We explored the cross-sectional association of LVGFI with myocardial iron overload (MIO), LV ejection fraction (LVEF), myocardial fibrosis, and heart failure (HF) in ß-thalassemia major (TM) patients. METHODS: We considered 1352 adult TM patients (708 females, 32.79 ± 7.16years) enrolled in the Myocardial Iron Overload in Thalassemia Network and 112 healthy subjects (50 females, 32.09 ± 6.08years). LVGFI and LVEF were assessed by cine images and MIO by multislice multiecho T2* technique. Replacement myocardial fibrosis was detected by late gadolinium enhancement technique. RESULTS: LVGFI and LVEF were significantly lower in patients with significant MIO (global heart T2*<20ms) than in patients without MIO and in healthy subjects but were comparable between TM patients without MIO and healthy subjects. In TM, LVGFI was significantly associated with LVEF (R = 0.733; p < 0.0001). Global heart T2* values were significantly associated with both LVGFI and LVEF, but the correlation with LVGFI was significantly stronger (p = 0.0001). Male sex, diabetes mellitus, significant MIO, and replacement myocardial fibrosis were the strongest predictors of LVGFI. Eighty-six patients had a history of HF and showed significantly lower global heart T2* values, LVEF, and LVGFI than HF-free patients. A LVGFI ≤ 44.9% predicted the presence of HF. The LVGFI showed a diagnostic performance superior to that of LVEF (area under the curve: 0.67 vs. 0.62; p = 0.039). CONCLUSION: In TM patients the LVGFI correlates with MIO and provides incremental diagnostic value for HF detection compared with LVEF.

Multicenter validation of the magnetic resonance T2* technique for quantification of pancreatic iron.

OBJECTIVES: To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for pancreatic iron overload assessment. METHODS: Multiecho T2* sequences were installed on ten 1.5-T MRI scanners of the three main vendors. Five healthy subjects (n = 50) were scanned at each site. Five patients with thalassemia (n = 45) were scanned locally at each site and were rescanned at the reference site within 1 month. T2* images were analyzed using a previously validated software and the global pancreatic T2* value was calculated as the mean of T2* values over the head, body, and tail. RESULTS: T2* values of healthy subjects were above 26 ms and showed inter-site homogeneity. The T2* values measured in the MRI sites were comparable to the correspondent values observed in the reference site (12.02 ± 10.20 ms vs 11.98 ± 10.47 ms; p = 0.808), and the correlation coefficient was 0.978 (p < 0.0001). Coefficients of variation (CoVs) ranged from 4.22 to 9.77%, and the CoV for all the T2* values independently from the sites was 8.55%. The intraclass correlation coefficient (ICC) for each MRI site was always excellent and the global ICC was 0.995, independently from the sites. The mean absolute difference in patients with pancreatic iron (n = 39) was -0.15 ± 1.38 ms. CONCLUSION: The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron and may be transferred among MRI scanners by different vendors in several centers. KEY POINTS: • The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron. • The gradient-echo T2* MRI technique for the quantification of pancreatic iron may be transferred among MRI scanners by different vendors in several centers. • Pancreatic iron might serve as an early predictor of cardiac siderosis and is the strongest overall predictor of glucose dysregulation.