Background: Altough T2* cardiovascular magnetic resonance (CMR) represents the non-invasive gold standard for myocardial iron overload (MIO) assessment, native myocardial T1 mapping was demonstrated more sensitive in presence of small amounts of iron. The myocardial extracellular volume (ECV) by CMR has been introduced as a surrogate marker of diffuse interstitial myocardial fibrosis, significantly associated with MIO. Aims: We explored the clinical impact of ECV mapping for detecting heart failure in thalassemia major (TM). Methods: 108 β-TM patients (62 females, 40.16±8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, underwent CMR. T2* and native and post-contrast T1 values were assessed in all 16 myocardial segments. Segmental ECV values were calculated with input of native and post-contrast myocardial segmental and blood pool T1 values and same-day hematocrit. Global value was the mean of all segmental values. Results: Patients without and with at least one cardiovascular risk factor showed comparable global ECV values (31.89±5.65% vs 33.00±7.46%; P=0.404). N-terminal pro-BNP levels, a proven diagnostic biomarker for the diagnosis and prognosis of patients with heart failure, were significantly correlated with global ECV values (R=0.237; P=0.016) but not with global heart T2* or T1 values. Significant MIO (global heart T2*<20 ms) was found in 9 (8.3%) patients. Global ECV values were significantly higher in patients with significant MIO than in patients without significant MIO (40.07±10.62% vs 31.85±5.71%; P=0.049). Ten (9.3%) patients had a history of heart failure. Compared to patients without heart failure, patients with a history of heart failure showed significantly lower global heart T1 values (882.68±125.46 ms vs 962.66±81.90 ms; P=0.047) and significantly higher global heart ECV values (36.63±9.41 vs 32.12±6.14 ms; P=0.039) (Figure). Global heart T2* values tended to be lower in patients with heart failure than in patients free of heart failure, but the difference was not significant (30.44±14.53 vs 38.24±8.63 ms; P=0.077). Image:Summary/Conclusion: In our population of well treated patients, generally not heavily loaded at the cardiac level, native T1 and ECV values turned out to be a associated with heart failure, more strongly than global heart T2* values. So, when possible, the ECV assessment should be included in the routine CMR of TM patients. Longitudinal prospective studies are needed to clarify the temporal association between MIO and diffuse fibrosis. Moreover, the potential of treatments targeted at interstitial fibrosis to reduce the risk of heart failure should be investigated, especially in TM patients refractory to iron chelating therapy.

Background:Patients with non‐transfusion dependent thalassaemia (NTDT) can be placed on regular transfusional therapy either for the prevention or for the management of different complications.Aims:We retrospectively evaluated the effects of blood transfusions (BT) in the real‐life and quite extensive context of the Myocardial Iron Overload in Thalassaemia (MIOT) network where most of biochemical, cardiac, hepatic parameters and morbidities typical of the NTDT patients could be analysed and compared in a chronologically manner.Methods:147 NTDT patients (46.49 ± 12.27 years; 92 females) who started regular BT at the mean age of 21.84 ± 17.85 years were considered. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2∗ technique) and biventricular morphological and functional parameters (cine sequences).Results:For the 40% of the patients there were more than two indications for the transition to regular BT, with anemia being present in the 92.5% of the cases. The patients reached a pre‐transfusion hemoglobin of 9.64 ± 0.72 g/dl.The percentage of chelated patients increased significantly after starting regular BT (52.5% vs 91.7%; P < 0.00001).Table 1 shows the changes (6 months before vs 6 months after starting regular BT) in the haematochemical and iron‐overload parameters. A down‐regulation of all erythropoietic and/or haemolysis indices and a drop‐in platelets and white blood cell count were detected. No changes in serum ferritin, MRI liver iron concentration (LIC) and global heart T2∗ values were detected.There was a significant decrease of the left ventricular end‐diastolic volume index (101.58 ± 19.67 ml/m2 vs 91.65 ± 20.99; P = 0.050).After the start of regular BT, patients were followed‐up for 24.08 ± 15.62 years. There was a significant increase in the frequency of endocrinopathies (diabetes, hypogonadism, hypothyroidism and osteopenia), bone pain, infections, and alloimunization, but their prevalence remained lower than 20%.A positive impact on patients’ health‐related quality of life was detected, with the sense of well‐being passing from 16.4% to 73.0% (P < 0.0001).Summary/Conclusion:Following the use of regular BT and chelation therapy, only a mild increase in most of the complications evaluated in the analysis was recorded; we cannot exclude that it could be ascribable to aging per se, as it happens for general population. No increase in iron overload parameters was detected and conversely, we recorded a positive cardiac remodelling. Therefore, in the Italian context, the decision to regularly transfuse patients with NTDT, despite sometimes complex and problematic, may represent a way to prevent or slow down the natural progression of the disease and improve the patients overall quality of life.image