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Aim To assess the prevalence and prognostic significance of NI-LGE in patients undergoing stress-CMR. Methods Stress-CMR with either dipyridamole or adenosine was performed in 283 patients (228 men, 81%) including perfusion imaging, wall motion evaluation and LGE. Follow-up was completed in all enrolled patients (median time: 1850 days; interquartile range: 1225-2705 days). Composite endpoint included cardiac death, ventricular tachycardia, myocardial infarction, stroke, hospitalization for cardiac cause and coronary revascularization performed beyond 90 days from stress-CMR scans. Results One hundred and twelve patients (40%) had negative LGE (no-LGE), 140 patients (49%) I-LGE and 31 patients (11%) NI-LGE. Twenty-five events occurred in the no-LGE group, 68 in I-LGE and 11 in the NI-LGE group. On survival curves, patients with NI-LGE had worse prognosis than patients with no-LGE regardless of the presence of inducible perfusion defects. No significant prognostic differences were found between I-LGE and NI-LGE. Conclusion NI-LGE can be detected in 11% of patients during stress-CMR providing a diagnosis of nonischemic cardiac disease. Patients with NI-LGE have worse prognosis than those with no-LGE.

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

A retrospective magnetic resonance imaging (MRI) study on a large cohort of children with thalassemia major (TM) showed cardiac involvement by early childhood; 21% of children presented with abnormal cardiac T2* and 16% with cardiac fibrosis. Moreover, moderate and/or severe liver iron overload (IO

Objectives Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. Methods The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0–1.4) year was generated. Results Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. Conclusion T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

We determined the prevalence of incidental extracardiac findings (IEF) at Magnetic Resonance Imaging (MRI) potentially related to anemia and hypoxia in age- and sex-matched populations (N = 318) with thalassemia major (TM) and thalassemia intermedia (TI) enrolled in the Myocardial Iron Overload in Thalassemia network. Overall, IEFs were detected in 33.3% and 25.8% of patients with TI and TM, respectively (P = 0.114). TI and TM patients had elevated but comparable prevalence of renal, splenic and liver cysts, and vertebral hemangiomas while TI patients had a significant higher frequency of extramedullary hematopoiesis (EMH) (15.1% vs 4.4%; P = 0.002). The prevalence of total IEFs increased with advancing age. TI non-transfusion-dependent patients had a significantly lower frequency of renal cysts than TI transfusion-dependent patients (8.8% vs 26.4%; P = 0.005). The prevalence of renal cysts in the thalassemic population was significantly higher than that in the general population (19.2% vs 1.9%; P

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project received “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.). Background Cardiovascular magnetic Resonance (CMR) has dramatically changed the clinical practice and improved the prognosis in thalassemia major (TM). Aim This is the first study evaluating the predictive value of changes in CMR parameters (myocardial iron, function, and fibrosis) for cardiac complications in TM. Methods We followed prospectively 709 TM patients (374 females; 29.77 ± 8.53 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who performed a baseline and a 1st follow up CMR scan after 18 months. Myocardial iron overload (MIO) was measured by multislice multiecho T2* technique and atrial dimensions and biventricular function by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Risk classes were defined based on the 4 patterns of MIO from worst to normal. For patients with baseline MIO (at least one segmental T2* The percentage change was used for continuous variables. For biventricular ejection fractions, improvement was a %change > 10%, stabilization a %change between -10% and 10%, and worsening a %change 10%. Myocardial fibrosis was considered absent if not detected in any of the two CMRs and present if detected in at least one examination. Results During a mean follow-up of 89.4 ± 33.3 months, cardiac events were recorded in 50 (7.1%) patients: 24 (48%) episodes of heart failure, 24 (48%) arrhythmias (23 supraventricular and 1 hypokinetic), and 2 (4.0%) pulmonary hypertension. Mean time from the 1st follow up CMR to the development of a cardiac complication was 75.31 ± 35.35 months. In the univariate Cox regression analysis, cardiac iron cleareance and myocardial fibrosis were identified as univariate prognosticators (Table 1). In the multivariate analysis only myocardial fibrosis remained an independent predictor factor. Conclusion The presence of myocardial fibrosis at the baseline CMR or developed within 18 months emerges as the strongest long-term predictor for cardiac complications in TM. Our data demonstrate the importance in using the contrast medium for CMR scans in thalassemia patients.

Background. Cardiac function indices in patients with hemoglobinopathies are different from those in healthy population, mainly due to chronic anemia. Normal reference values specific for SCD patients are not available by CMR. Aim. We aimed to define the normal cut-off value in SCD patients for bi-atrial and biventricular cardiac magnetic resonance (CMR) parameters. Methods. We considered forty-eight adult SCD patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2*≥20 ms, consecutively enrolled in the MIOT network (Myocardial iron overload in thalassemia). SCD patients were compared with ninety-six healthy controls and 96 thalassemia major (TM) patients without cardiac damage, both matched for age and gender. Nine pediatric SCD patients were also analysed in comparison with 9 TM patients and 9 healthy subjects matched for age and gender. Cine images were acquired to quantify biventricular function parameters: LV and RV end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) were normalized for body surface area (EDVI, ESVI, SVI), as well as biventricular mass and atrial areas. Myocardial iron overload was assessed by segmental T2* technique. Late gadolinium enhancement (LGE) images were acquired for evaluation of macroscopic myocardial fibrosis. Results. In all three groups males showed higher biventricular volumes and mass indexes than females. SCD male patients had significantly higher LVEDVI (p SCD and TM patients showed comparable values of bi-atrial and biventricular volumes and function. When compared to TM, SCD patients showed a larger LV (p No significant differences in MR parameters were found among the pediatric groups. Conclusions. Normal reference ranges of bi-atrial and biventricular MR parameters for adult males and females SCD patients were established. The use of these reference values will prevent possible misdiagnosis of cardiomyopathy in patients with SCD. Figure 1 Figure 1. Disclosures Pepe: Chiesi Farmaceutici S.p.A: Other: no profit support; Bayer S.p.A.: Other: no profit support. Quarta: Sanofi - Genzyme: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Blue Bird Bio: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Celgene: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Takeda: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; speaker at conferences; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at conferences. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

We prospectively evaluated changes in cardiac and hepatic iron overload (IO) and in morpho-functional cardiac parameters and myocardial fibrosis by magnetic resonance imaging (MRI) in patients with low-risk and intermediate-1-risk myelodysplastic syndromes (MDS). Fifty patients enrolled in the Myocardial Iron Overload in MyElodysplastic Diseases (MIOMED) study were followed for 12 months. IO was quantified by the T2* technique and biventricular function parameters by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Twenty-eight patients (71.89±8.46 years; 8 females) performed baseline and follow-up MRIs. Thirteen patients had baseline hepatic IO, with a higher frequency among transfusion-dependent patients. Out of the 15 patients with a baseline MRI liver iron concentration

BACKGROUND Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (β-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE Retrospective/cohort study. POPULATION In all, 251 β-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS Compared to controls, males with β-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between β-TM patients and healthy subjects in all the age groups. In the male β-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In β-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P

Objectives: Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff’s criteria and of the CMR findings in predicting adverse cardiovascular events (CE). Methods: We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni’s echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff’s criteria (global Grothoff’s criteria). Late gadolinium enhancement (LGE) images were acquired to detect the presence of replacement myocardial fibrosis. Results: Petersen’s CMR criterion for LVNC (NC/C ratio > 2.3 in at least one myocardial segment) was fulfilled in the whole population. Twenty-six patients fulfilled the global Grothoff’s criteria (four out of four). The mean duration of the follow-up was 44.2 ± 27.4 months and 28 CE were registered: 10 ventricular tachycardias, 12 episodes of heart failure (HF), four strokes, and two cardiac deaths. In the multivariate analysis, the independent predictive factors for CE were positive global Grothoff’s criteria (hazard ratio, HR = 3.33, 95% CI = 1.52–7.29; p = 0.003) and myocardial fibrosis (HR = 2.41, 95% CI = 1.08–5.36; p = 0.032). Conclusions: Positive global Grothoff’s criteria and myocardial fibrosis were powerful predictors of CE in patients with a diagnosis of LVNC by CMR Petersen’s criterion. Thus, we strongly suggest a step approach confirming the diagnosis of LVNC by using the global planimetric Grothoff’s criteria, which showed a prognostic impact. Key Points: • Positive global Grothoff’s criteria and replacement myocardial fibrosis were powerful predictors of cardiovascular events in patients with a diagnosis of LVNC by CMR Petersen’s criterion. • Positive global Grothoff’s criteria were associated with a higher frequency of ventricular arrhythmias in patients with a diagnosis of LVNC by CMR Petersen’s criterion.

Aim: to evaluate the relationship between uric acid (UA), hepatic and cardiac iron overload (T2*-MRI), ferritin, endocrinological diseases and cardiac complications in a large thalassemia major (TM) cohort. Methods: A total of 369 TM patients (187 men; 33 ± 6 years) were retrospectively studied, from the myocardial iron overload in thalassemia (MIOT) electronic databank. Results: Multiple regression model identified male sex (p 3 mg/g/dw), heart failure, endocrinopathies, ferritin (>2000 ng/l), alanine transaminase (>40 UI/l) and/or aspartate transaminase (>35 UI/l) and/or glutamyl transferase (>64 UI/l). Discussion: UA appears directly associated to T2* and inversely with derivatives of reactive oxygen species, and as such reduced according to increased oxidative stress and cardiac iron overload in TM patients.

Introduction. Pancreatic iron deposition is a common finding in thalassemia major, being detected in more than one third of patients undergoing their first T2* Magnetic Resonance Imaging scan (MRI) for this purpose. However, no longitudinal studies on pancreatic iron are available in literature. Aim: The aim of this multicenter study was to evaluate the changes in pancreatic iron overload in TM patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) Network who performed a baseline and a follow-up (FU) MRI scan at 18 months. Methods. We considered 416 TM patients (37.77±10.46 years; 220 females) consecutively enrolled. Iron overload was quantified by the T2* technique. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. Results. Pancreatic iron overload (global pancreas T2* A significant inverse association was detected between % change in global pancreas T2*and baseline global pancreas T2* values (R=-0.369; P Changes (%) in global pancreas T2* were not associated with baseline serum ferritin levels or MRI liver iron concentration (LIC) values but were inversely correlated with % changes in serum ferritin levels (R=-0.199; P At baseline MRI, 169 patients showed an alteration of glucidic metabolism: 32 had impaired fasting glucose, 65 impaired glucose tolerance, and 72 diabetes mellitus. These patients showed significantly higher % changes in global pancreas T2* than patients with a normal glucidic metabolism (33.06±79.48% vs 11.93±59.47%; P=0.003). Conclusions. Our data showed that it is difficult to remove the iron from the pancreas and higher improvements were detected in more heavily loaded patients, with alterations of glucidic metabolism. The reduction in pancreatic iron was paralleled by a decrease in hepatic and cardiac iron. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

This study analysed the impact of liver steatosis (LS) on the parameters of iron overload in 110 patients with non-transfusion dependent thalassaemia (NTDT). LS was diagnosed by ultrasound. Liver iron concentration (LIC) measurements were available for 64 patients who underwent a magnetic resonance imaging (MRI) scan. LS was frequent (35·5%) and was significantly more prevalent in males than in females (49·0% vs. 24·6%, P = 0·008). Patients with LS had significant higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST ratio and ferritin than those without, but LIC values were comparable. An ALT/AST ratio0·89 predicted the presence of LS with a sensitivity of 0·872 and a specificity of 0·901 (P 0·0001). Ferritin levels correlated with LIC values (R = 0·558, P 0·0001) but the correlation was stronger in patients without LS (R = 0·656, P 0·0001) than in patients with LS (R = 0·426, P = 0·05). LS is a frequent issue in NTDT patients and should be suspected in the presence of an ALT/AST ratio0·89. Recently, serum ferritin thresholds that predict clinically relevant LIC for guiding iron chelation therapy when MRI is unavailable have been determined. Our data show that LS may cause increase in ferritin levels and may be responsible for anticipating/exceeding chelation treatment in NTDT patients in the absence of LIC evaluation.

Non-transfusion-dependent thalassemia includes a variety of phenotypes and genotypes that rarely require regular transfusions. However, these patients can experience a wide range of complications. The objective of this retrospective study was to verify whether there is a significant difference in non-transfusion-dependent thalassemia-related complications and treatment among males and females.We performed a re-analysis of samples evaluated in a previously published cross-sectional study, regarding 96 non-transfusion-dependent thalassemia patients followed at the 'UOSD Malattie Rare del Globulo Rosso' Centre of the Cardarelli Hospital in Naples, Italy.We found that females were more anemic than males, but there was no significant difference in prevalence of common complications among genders, except for hypogonadism. Furthermore, the transitory regular transfusions regimen in women who had been pregnant does not seem to have a significant impact on overall prognosis.In non-transfusion-dependent thalassemia patients, the lower levels of hemoglobin found in females do not seem to indicate a higher prevalence of complications.This data should be considered in studies with experimental treatments aiming to correct anemia in patients with non-transfusion-dependent thalassemia. It should probably also be taken into account in order to set up different transfusion regimens among genders in transfusion-dependent patients.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular dysfunction and excessive fibrosis, involving internal organs including the heart. The estimated prevalence of cardiac involvement in SSc is high and remains subclinical until the late stages. It is either primary, related to myocardial inflammation and fibrosis, or secondary, due to pulmonary arterial hypertension (SSc-PAH) or systemic hypertension, in those patients with renal involvement. Cardiovascular magnetic resonance (CMR) is a useful tool for the early assessment of cardiac involvement in SSc. It is the gold standard technique to assess ventricular volumes,ejection fraction, and in particular is very useful to reliably and non-invasively detect myocardial inflammation, early perfusion defects, and myocardial fibrosis. However, the CMR evaluation in SSc may be problematic, because of cardiac and respiratory artefacts, commonly found in these patients. Therefore, a high level of expertise is necessary for both acquisition and interpretation of CMR images in SSc.

Cardiac magnetic resonance (CMR) has emerged as a reliable and accurate diagnostic tool for the evaluation of patients with cardiac disease in several clinical settings and with proven additional diagnostic and prognostic value compared with other imaging modalities. This document has been developed by the working group on the 'application of CMR' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical applications of CMR and to inform cardiologists on how to implement their clinical and diagnostic pathways with the inclusion of this technique in clinical practice. The writing committee consisted of members of the working group of the Italian Society of Cardiology and two external peer reviewers with acknowledged experience in the field of CMR.

The current document was developed by the working group on the 'application of cardiac magnetic resonance' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical cardiac magnetic resonance applications and to inform cardiologists how to implement their clinical and diagnostic pathway with the introduction of this technique in the clinical practice. Appropriateness criteria were defined using a score system: score 1-3 = inappropriate (test is not generally acceptable and is not a reasonable approach for the indication), score 4-6 = uncertain (test may be generally acceptable and may be a reasonable approach for the indication but more research and/or patient information is needed to classify the indication definitively) and score 7-9 = appropriate (test is generally acceptable and is a reasonable approach for the indication).

Background.The T2* cardiovascular magnetic resonance (CMR) is the gold standard for the non invasive detection of myocardial iron overload (MIO). The native myocardial T1 mapping has been proposed as a complementary tool, thanks to its higher sensitivity in presence of small amounts of iron, but no data are available in literature about its clinical impact. Objective:To explore the clinical impact of T1 mapping for detecting cardiac complications in thalassemia major (TM). Methods.We considered 146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Three parallel short-axis slices of the left ventricle (LV) were acquired with the Modified Look-Locker Inversion recovery (MOLLI) sequence. The native T1 values in all 16 myocardial segments were obtained and the global value was the mean. Results.Twenty-one patients had an history of cardiac complications: 11 heart failure, 8 arrhythmias (7 supraventricular and 1 ventricular), and 2 pulmonary hyperthension. Patients with cardiac complications had significantly lower global heart T1 values (879.3±121.9 ms vs 963.2±98.5 ms; P Conclusion:We found out a significant association between decreased native global heart T1 values and a history of cardiac complications, suggesting that an early detection of myocardial iron burden by native T1 can support the clinicians in modifing chelation therapy earlier. Figure Disclosures Pepe: ApoPharma Inc.:Other: no profit support;Bayer:Other: no profit support;Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

Background Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect a wide spectrum rather than a dichotomy, and may actually be interchangeable at many parts of the disease journey. Thus, an evaluation of alternate clusters to classify TS patients remains of merit. Aims The aim of this study was to cluster TS patients on the basis of possible clinical indicators of phenotype severity (IPhS) using suitable algorithms and to determine whether these are able to detect cohorts with different clinical phenotypes. Methods Representatives from thirteen international centers from seven countries agreed on 19 IPhS to be collected for a retrospective study. Data from 7910 TS patients were collected. NbClust R Packagewas performed for exploring the existence of a substructure inside the studied TS population, determining the best number of clusters. Unsupervised Random Forest (RF)clustering and the Partitioning Around Medoids (PAM)algorithms were performed to define the clusters. The most important IPhS in defining clusters were selected according to the Gini index. Kaplan-Meier (K-M) survival curves of the identified clusters, defined by the selected IPhS, were used to represent the risk of death for these clusters. Results NbClust method showed the existence of three possible clusters. The RF-PAM procedure defined three distinct clusters with a classification error rate of 4.3% (Fig 1). Moreover, the most important IPhS were patient age, mean serum ferritin level, age at diagnosis, age at first transfusion, age at first iron chelation, and number of complications. K-M curves showed statistically significant differences in survival among the three clusters (p Conclusions The observation of statistically significant differences in survival between the three newly identified clusters but not the original TDT-NTDT classification confirms that the latter classification is interchangeable, and a new triad classification system is required. These findings warrant further evaluation in prospective studies to determine specific thresholds for IPhs indicators that can aid physicians in assigning classes and tailoring care, in order to improve survival in TS patients. Disclosures Meloni: Chiesi Farmaceutici S.p.A.: Other: speakers' honoraria. Pistoia:Chiesi Farmaceutici S.p.A.: Other: speakers' honoraria. Vichinsky:Novartis: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding.

Introduction.The presence of iron deposits results in a significant reduction in all magnetic resonance imaging (MRI) relaxation times (T1, T2 and T2*). In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with hemoglopinopathies. Purpose.To compare myocardial T2 against T2* in patients with thalassemia major (TM) for myocardial iron characterization. Methods.133 TM patients (79 females, 38.4±11.3 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered. T2 and T2* images were acquired, respectively, with multi-echo fast-spin-echo and gradient-echo sequences. Global heart T2 and T2* values were obtained by averaging the values in all 16 myocardial segments. The normal T2 range was established as mean±2 standard deviations on data acquired on 80 healthy volunteers (males: 48-56 ms and females: 50-57 ms). The lower limit of normal for global heart T2*, established on the same healthy population, was 32 ms. Results.A significant correlation was detected between global heart T2 and T2* values (R=0.577; P Out of the 113 (84.9%) patients with a normal global heart T2* value, none had a decreased global heart T2 value, while 58 (51.3%) had an increased T2 value. Out of the 20 patents with a decreased global heart T2* value, only 10 (50%) had also a reduced T2 value. Conversely, 9 (45.0%) had a normal global heart T2 value and one (4.5) showed an increased T2 value. The 59 patients with increased global heart T2 value were significantly older than the remaining patients (40.8±10.5 vs 36.4±11.6 years; P=0.019) Conclusion.All patients with decreased T2 value had also a decreased T2* value and in half of the patients iron load was undetected by T2, suggesting that T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment. However, more than half of TM patients had an increased T2 value, thus may be caused by the presence of myocardial inflammation and/or edema. So, T2 mapping could reveal subclinical myocardial involvement in TM patients. Figure Disclosures Pistoia: Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

Background.Cardiovascular magnetic resonance (CMR) is the only available technique for the non-invasive quantification of MIO. The native T1 mapping has recently been proposed as an alternative to the universally adopted T2* technique, due to the higher sensitivity for detection of changes associated with mild or early iron overload. Objective.To study the association between T1 values and left ventricular (LV) function in thalassemia major (TM) and to evaluate for the first time if T1 measurements quantifying MIO are influenced by macroscopic myocardial fibrosis. Methods.146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent CMR. Native T1 values were obtained by Modified Look-Locker Inversion recovery (MOLLI) sequence in all 16 myocardial segments and the global value was the mean. LV function parameters were quantified by cine images. Late gadolinium enhancement (LGE) technique was used to detect macroscopic myocardial fibrosis. Results.No correlation was detected between global heart T1 values and LV volume indexes, LV mass index, or LV ejection fraction. Foourteen (9.6%) patients had an abnormal LV motion (13 hypokinesia and 1 dyskinesia) and they showed significantly lower global heart T1 values than patients without LV motion abnormalities (883.8±139.7 ms vs 959.0±91.3 ms; P=0.049). LGE images were acquired in 88 patients (60.3%) and macroscopic myocardial fibrosis was detected in 36 patients (40.9%). The 72.2% of patients had two or more foci of fibrosis. Patients with macroscopic myocardial fibrosis had significantly lower global heart T1 values (921.3±100.3 ms vs 974.5±72.7 ms; P=0.027) (Figure 1A). Data about the LGE was present for 1408 segments (88 patients x 16 segments) and 105 (7.5%) were positive. Segments with LGE had significantly lower T1 values than segments LGE-negative (905.6±110.6 ms vs 956.9±103.8 ms; P Conclusion.No correlation between T1 values and LV function parameters was detected, probably because the majority of the patients had normal or mild abnormal LV parameters. TM patients with macroscopic myocardial fibrosis showed significantly lower T1 values suggesting that T1 measurements for quantifying MIO are not influenced by macroscopic myocardial fibrosis and an association between myocardial iron and macroscopic fibrosis, previously detected only in pediatric TM patients. Figure Disclosures Pepe: Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria;Bayer:Other: no profit support;ApoPharma Inc.:Other: no profit support.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

OBJECTIVE We systematically explored the link of pancreatic iron with glucose metabolism and with cardiac complications in a cohort of 1,079 patients with thalassemia major (TM) enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. RESEARCH DESIGN AND METHODS MRI was used to quantify iron overload (T2* technique) and cardiac function (cine images) and to detect macroscopic myocardial fibrosis (late gadolinium enhancement technique). Glucose metabolism was assessed by the oral glucose tolerance test (OGTT). RESULTS Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with impaired fasting glucose, impaired glucose tolerance, and diabetes. A pancreas T2* CONCLUSIONS Pancreatic iron is a powerful predictor not only for glucose metabolism but also for cardiac iron and complications, supporting the close link between pancreatic iron and heart disease and the need to intensify iron chelation therapy to prevent both alterations of glucose metabolism and cardiac iron accumulation.

We differentiated the left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to a negative remodeling in thalassemia intermedia (TI) patients applying linear and planimetric criteria and comparing the cardiovascular magnetic resonance (CMR) findings. CMR images were analyzed in 181 TI patients enrolled in the Myocardial Iron Overload in Thalassemia Network and 27 patients with proved LVNC diagnosis. The CMR diagnostic criteria applied in TI patients were: a modified linear CMR Petersen’s criterion based on a more restrictive ratio of diastolic NC/C > 2.5 at segmental level and the combination of planimetric Grothoff’s criteria (percentage of trabeculated LV myocardial mass LV–MM ≥ 25% of global LV mass and total LV–MMI NC ≥ 15 g/m2). Seventeen TI patients showed at least one positive NC/C segment. Compared to LVNC patients, these patients showed a lower frequency of segments with non-compaction areas (2.41 ± 1.33 vs 5.48 ± 2.26; P < 0.0001), significantly lower LV–MM NC percentage (10.99 ± 4.09 vs 28.20 ± 4.27%; P < 0.0001), LV–MMI (7.58 ± 4.86 vs 19.88 ± 5.02 g/m2; P < 0.0001) and extension of macroscopic fibrosis (0.44 ± 0.18 vs 4.65 ± 2.89; P = 0.004), and significantly higher LV ejection fraction (61.29 ± 5.17 vs 48.50 ± 17.55%; P = 0.016) and cardiac index (4.80 ± 1.49 vs 3.46 ± 1.11 l/min/m2; P = 0.002). No TI patient fulfilled the Grothoff’s criteria. All TI patients with an NC/C ratio > 2.5 showed morphological and functional CMR parameters significantly different from the patients with a proved diagnosis of LVNC. Differentiation of LVNC from hypertrabeculated LV in β-TI patients due to a negative heart remodeling depends on the selected CMR criterion. We suggest using planimetric Grothoff’s criteria to improve the specificity of LVNC diagnosis.

Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.

Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.

Background: Cardiac involvement is frequent in patients with systemic sclerosis (SSc). It is often subclinical, but significantly affects the prognosis of the disease. Cardiovascular magnetic resonance (CMR) is the non-invasive gold standard to quantify biventricular functional parameters and to perform a myocardial tissue characterization. Objectives: To evaluate the prognostic value of CMR for cardiac events in SSc. Methods: Two hundred and seventy-three SSc patients with a thorough clinical assessment underwent a CMR exam using a 1.5 T GE scanner. We quantified biventricular function parameter by SSFP cine images, oedema by STIR T2 images, and macroscopic fibrosis by late gadolinium enhancement (LGE) technique. Patients were followed-up and cardiac events were recorded as new onset of pulmonary arterial hypertension (PAH), new onset of heart failure (HF), or at least sustained ventricular tachycardia. Results: Mean follow-up was 23.9 ± 17.0 months. During the follow-up a total of 14 events occurred (3 new onset PAH, 5 new onset HF, 6 ventricular tachycardia). CMR predictors of cardiac events by univariate analysis were left and right ventricular ejection fractions, indexed left and right atrial areas, and LGE (see Table). Myocardial fibrosis by LGE was the only independent predictor at multivariate analysis (hazard ratio 3.175; 95% C.I. 1.021-9.870, see Figure). Conclusion: Cardiac magnetic resonance anatomical and functional parameters of both the left and right heart have significant prognostic value in patients with SSc. Disclosure of Interests: Cosimo Bruni: None declared, Luna Gargani: None declared, Alessia Pepe: None declared, Antonella Meloni: None declared, Daniele De Marchi: None declared, Giancarlo Todiere: None declared, Fabio Fulgenzi: None declared, Yacob Ghebru: None declared, Serena Guiducci: None declared, Raffaele De Caterina: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen

Background in SSc, cardiac involvement either primary or secondary, is frequently subclinical. In myocardial diseases, CMR is considered the non-invasive gold standard to diagnose myocardial tissue involvement and LGE has a significant impact on prognosis. Objectives: to identify the predictors of the presence of LGE in SSc patients. Methods: patients fulfilling the 2013 ACR/EULAR classification criteria were assessed with CMR (1.5 T GE scanner) when clinically indicated. Data on demographics, clinical SSc features, laboratory and instrumental tests for cardio-pulmonary, microvascular and renal involvements were recorded at the time of CMR evaluation. Binary regression analysis was performed with SPSS version 20.0. Results: 317 SSc patients (284 women, mean age 52±14) were enrolled in the study. LGE-CMR was present in 32.9% and Myocardial edema (ME-CMR) in 6.1% of patients. On univariate regression analysis,%DLco values, NYHA functional class, history of DU (hDU), TAPSE and couples of ventricular premature beats (VPBc) were predictors of LGE-CMR or ME-CMR. At multivariate analysis,TAPSE (OR 0.832, 95% CI 0,727-0,951, p=0.007), hDU (OR 3.893, 95% CI 1.614-9.387, p=0.002) and VPBc (OR 4.238, 95%CI 0.959-18.738, p=0.057) were independent predictors for LGE-CMR. Presence of pericardial effusion was the only predictor for ME-CMR (OR 3.379, 95% CI 1.018-12.988, p=0.047). Conclusion: DU history, ventricular ectopic beats on 24 hours ECG, TAPSE impairment and pericardial effusion on echocardiography may predict myocardial LGE. More studies are necessary to further verify and validate these “red flags” to refer the patients to CMR. Disclosure of Interests: Cosimo Bruni: None declared, Luna Gargani: None declared, Alessia Pepe: None declared, Antonella Meloni: None declared, Daniele De Marchi: None declared, Giancarlo Todiere: None declared, Gennaro D’Angelo: None declared, Alberto Moggi Pignone: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen

In patients with TM, uncontrolled iron overload has serious clinical consequences with considerable morbidity and mortality. Complications include liver damage, cardiac disease and endocrine dysfunction. Diabetes is an important complication of TM. The mechanisms of abnormal glucose homeostasis are complex and multifactorial. This review updates the current knowledge about glycemic abnormalities in TM patients and directs the attention to an early diagnosis and proper management.

Background: Classification of phenotype severity in patients with beta-thalassaemia has so far relied mainly on expert opinion using parameters of genotype, clinical features at diagnosis, and transfusion requirement. The aim of this study was to use a large dataset of patients with beta-thalassaemia and evaluate a classification system based on onset variables agreed on by an international expert group, including age at diagnosis, at first transfusion, and at first iron chelation. Methods: A retrospective dataset of 7910 patients with homozygous or compound heterozygous beta-thalassaemia was used and subjected to cluster and classification analysis starting with the onset variables. Results: Cluster analysis suggested that three clusters with minimal overlapping exist. Three phenotype severity classes (mild, moderate, severe) were accordingly assigned which showed statistically significant descending variation of age at diagnosis and start of transfusion and iron chelation. The estimated classification error rate was only 3.07% with an accuracy of 96.93%. It was evident that severe patients had higher blood requirement and iron overload levels and showed a younger age for mortality especially from heart disease. Although mild and moderate patients showed the opposite in gradual severity, they still showed evidence of high morbidity rate for complications that require longer time to manifest (eg liver damage and hepatocellular carcinoma). Conclusion: Age of diagnosis and start of transfusion and iron chelation distinguish three classes of phenotype severity in beta-thalassaemia that carry unique clinical profiles. Further prospective studies are recommended to validate these findings. Funding Statement: The authors state: "None" Declaration of Interests: The authors state: " None to disclose." Ethics Approval Statement: An International Health Repository (IHR) protocol, approved on May 25th, 2017 by the Italian Ethical Committee (EudraCT and Sponsor's Protocol Code Numbers were 2017-004457-17 and 143AOR2017) was established to allow collection of relevant data.

Beta thalassemia major (β-TM) displays a great deal of phenotypic heterogeneity, not fully investigated in terms of cause-effect. We aimed to detect if different genotypic groups could be related to different levels of cardiac impairment, evaluated by cardiovascular magnetic resonance (CMR). We considered 671 β-TM patients (age 30.1 years, 52.9% females) consecutively enrolled in the Myocardial Iron Overload (MIO) in Thalassemia network. MIO was assessed by T2* technique. Biventricular function was quantified by cine images. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Three groups of patients were identified: heterozygotes β+/β° (N = 279), homozygotes β + (N = 154), homozygotes β° (N = 238). Transfusional needs resulted significantly lower in homozygous β + TM patients when compared to the other groups. The homozygous β + group versus the heterozygous and homozygous β° groups showed higher global heart T2* values (P The β+/β + TM patients showed less MIO and a concordant better systolic heart function. These data support the knowledge of different genotypic groups in the management of β-TM patients.

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for pancreatic iron overload assessment. 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. 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

We prospectively assessed the efficacy of deferasirox versus deferiprone or desferrioxamine as monotherapy in thalassaemia major (TM) patients by magnetic resonance imaging (MRI). We selected the patients enrolled in the Myocardial Iron Overload in Thalassaemia network who received only one chelator between two MRIs (deferasirox = 235, deferiprone = 142, desferrioxamine = 162). Iron overload was measured by T2* technique and biventricular function by cine images. Among the patients with baseline myocardial iron, in all three groups there was a significant improvement in global heart T2* values. The deferiprone and desferrioxamine groups showed a significant improvement in left ventricular ejection fraction (LVEF). Only the deferiprone group showed a significant improvement in right ventricular ejection fraction (RVEF). The improvement in global heart T2* was significantly lower in the deferasirox versus the deferiprone group. The improvement in the LVEF was significantly higher in the deferiprone and desferrioxamine groups than in the deferasirox group and the improvement in the RVEF was significantly higher in the deferiprone than in deferasirox group. Among the patients with baseline hepatic iron, the changes in hepatic iron were comparable in deferasirox versus the other groups. Deferasirox monotherapy was less effective than deferiprone in improving myocardial siderosis and biventricular function and less effective than desferrioxamine in improving the LVEF.

Cardiac involvement in systemic sclerosis (SSc) is frequent and significantly affects the prognosis. Myocardial fibrosis is the pathological hallmark and has been reported in >50% of necropsies [(1)][1]. Given the low sensitivity of transthoracic echocardiography (TTE) in detecting myocardial

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P

We aimed to evaluate the role of two-dimensional speckle tracking imaging (2DSTI) in detecting early changes of myocardial deformation in patients affected by thalassemia major (TM) and its relation with myocardial iron overload (MIO) detected by T2* cardiovascular magnetic resonance (CMR). We studied 28 TM patients (15 males, 37.4 ± 10 years). All patients underwent CMR and echocardiography in the same day. Segmental and global T2* values were measured. Values of global longitudinal strain (GLS) were derived from the three apical views, while radial and circumferential strain were obtained as average strain from the short axis views at basal, mid and apical level. Six patients (21.4%) showed significant MIO (global heart T2*

We assessed whether male gender was associated with a higher risk of cardiac iron accumulation and fibrosis, heart dysfunction and complications in a large, multicentre cohort of thalassaemia major (TM) patients, in order to optimize the timing in cardiac follow-up. We considered 1711 TM patients (899 females, 31·09 ± 9·08 years), enrolled in the Myocardial Iron Overload in Thalassaemia Network. Clinical/instrumental data are recorded from birth to the first Cardiovascular Magnetic Resonance Imaging scan. Although having a similar risk of accumulating iron, males showed a significantly higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications overall, when compared to females (P < 0·0001). Up to 20-30 years of follow-up, the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator almost overlapped, whereas they clearly diverged after this period. In patients with follow-up longer than 20 years, males exhibited a significantly higher risk of ventricular dysfunction, heart failure, arrhythmias, and cardiac complications. Female patients may have an intrinsically better tolerance for iron toxicity. International guidelines suggest annual cardiac evaluation for thalassaemia patients. It is possible that female patients can be evaluated at longer intervals, thus reducing health costs.

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients.

Chronically transfused sickle cell disease (SCD) patients have lower risk of myocardial iron overload (MIO) than comparably transfused thalassemia major (TM) patients. However, cardioprotection is incomplete. We present the clinical characteristics of six patients who have prospectively developed MIO, to identify potential risk factors for cardiac iron accumulation. From 2002 to 2011, cardiac, hepatic, and pancreatic iron overload were assessed by R2 and R2 * magnetic resonance imaging techniques in 201 chronic transfused SCD patients as part of their clinical care. At the time, they developed MIO, five of six patients had been on chronic transfusion for more than 11 years; only one was on exchange transfusion. The time to MIO was correlated with reticulocyte and hemoglobin S percentages. All patients had qualitatively poor chelation compliance ( 4600 ng/ml and liver iron concentration >22 mg/g. Pancreatic R2 * was >100 Hz in every patient studied (5/6). Cardiac iron rose proportionally to pancreas R2 *, with all patients having pancreas R2 *>100 Hz when cardiac iron was present. MIO had a threshold relationship with liver iron that was higher than observed in TM patients. In conclusion, MIO occurs in a small percentage of chronically transfused SCD patients and is only associated with exceptionally poor control of total body iron stores. Duration of chronic transfusion is clearly important but other factors, such as levels of effective erythropoiesis, appear to contribute to cardiac risk. Pancreas R2 * can serve as a valuable screening tool for cardiac iron in SCD patients.

Introduction. A prospective magnetic resonance imaging (MRI) study demonstrated a good control of myocardial iron overload (MIO) in terms of prevention and treatment in children with thalassemia major (TM). The aim of the present study was to evaluate if changes in MIO were related to baseline hepatic iron or changes in hepatic iron overload (HIO). Methods. We considered 68 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) project with less than 18 years at the first MRI scan and who performed a follow-up (FU) study at 18±3 months. Myocardial and hepatic iron burdens were quantified by the T2* technique. The value of 20 ms was used as conservative normal value for the global T2* value. Liver T2* values were converted into liver iron concentration (LIC) values. A LIC Results. Thirty-six patients were females and mean age at the time of the baseline MRI was 13.74±3.09 years. Baseline global heart T2* values were 29.72±11.21 ms and 16 (23.5%) patients showed significant baseline MIO. The percentage changes in global heart T2* values per month in the whole patient population were 0.66±1.70 and they resulted significantly higher in the 16 patients with significant baseline MIO versus the patients with no baseline MIO (1.99±2.53% vs 0.25±1.09% ms; P=0.002). Percentage changes in global heart T2* values per month were not influenced by initial MRI LIC values (R=0.048; P=0.695) (Figure 1A) and were comparable among the 4 groups of patients identified on the basis of baseline MRI LIC values (14 no HIO: 0.29±1.12% vs 21 mild HIO: 0.75±1.56% vs 15 moderate HIO: 0.82±2.03% vs 18 severe HIO: 0.71±2.00%; P=0.876). Percentage changes in global heart T2* values per month were not associated to final MRI LIC values (R=-0.134; P=0.277) (Figure 1B). The correlation between % changes in global heart T2* and MRI LIC values did not reach the statistical significance (R=-0.244; P=0.067) (Figure 1C). In patients with baseline MIO no correlation was found between % changes in global heart T2* values per month and initial MRI LIC values (R=-0.325; P=0.219) or % changes in MRI LIC values per month (R=-0.353; P=0.180). Conclusion. In pediatric TM patients changes in cardiac iron are not correlated to baseline MRI LIC values and changes in hepatic iron. So, our data seem not supporting the hypothesis for which it is necessary to clean the liver before removing iron from the heart. Figure 1 Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher & Saliba, 2017). Several factors, independently by genotype and globin chain unbalance, modulate the severity of ineffective erythropoiesis (Rivella et al, 2015). Considering the complexity of this pathophysiology, one tool to evaluate patients on an individual basis is needed. The aim of this study was to develop a severity scoring system with a view to initiate timely interventions that would prevent any further complications. Methods An International Health Repository (IHR) protocol was approved on May 25th, 2017 by the Italian Ethical Committee (EudraCT Code Numbers 2017-004457-17 and 143AOR2017). Subsequently, an International Working Group (IWG) on Thalassemia was formed and it met in Palermo, Italy, on September 15th and 16th, 2017. Indicators of phenotype severity thought to be most pertinent in defining disease severity were shared among the IWG based on their expertise as well as on expert opinion reported on literature. These data were collected and stored on IHR platform (www.sanitasicilia.eu/IWG ). In order to define the prognostic score (PS) a retrospective multicenter case-control study was carried ahead. Overall, clinical findings of 7910 patients who attended the IWG centres from 1976 to 2018 were collected (Tab. 1). The study was based on 5657 cases that developed complications and 2253 controls that didn't develop any complications. The term "patient" was used both for cases and for controls. The variables used for the scoring system development were reported in Table 2. The PS was built using a Conditional Logistic Regression Model (CLRM) (DW. Hosmer, Jr., 2013). The full data-set was split into two data-set containing Group A and Group B patients. Group A included transfused TDT and NTDT patients, while Group B included only no transfused NTDT patients. This was necessary because of the variable "age at first transfusion" was absent in no transfused patients. The two PS will refer as Score A and Score B, respectively. The Stata 12 (StataCorp, College Station, TX, USA) was used for all analyses. Results Overall, the analysis was performed on 5657 cases (2812 Females, age at follow up 34.7±12.9) with a mortality of 8.5% and 2253 controls (1136 Females, age at follow up 22.1±12.8) with a mortality of 1.9%. Table 3 shows complications and deaths in the full data set. Moreover, it even suggests, as single patient may have more than one complication and that the cardiac complications followed by the cancer and infection were the most common. Table 4 shows the statistically significant variables for the calculation of the score. The age of the patient and at first diagnosis, the mean Hb, AST, ALT and the Left Ventricular Ejection Fraction (LVEF) were the statistically significant variables at CLRM analysis, for the Group A. The formula for the Score A=1.1x(Age)+0.9x(Age at first diagnosis)+1.3x(Hb mean)+1.006x(AST)+1.02x(ALT)+ 0.9x(EF). The age of the patient, the mean Hb and the LVEF were the statistically significant variables at CLRM analysis for the Group B. The formula for the Score B= 1.05x(Age)+1.001x(Hb mean) +0.9x(EF). Finally, Table 5 shows the application of these formulas to the full data set, defining five well-distinguished prognostic categories (Very low, Low, Intermediate, High, Very high). Conclusions Following appropriate validation, we propose that the severity scoring system described here could be developed into a practical tool for widespread clinical application, not only to evaluate patient status and classify disease subgroups, but also to inform treatment decisions and monitor patient progress in response to therapy. Finally, the use of this scoring system may help to select appropriate candidate for innovative treatment. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support. Vichinsky:bluebird bio: Consultancy, Research Funding; GBT: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding.