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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.

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

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.

Background In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Purpose Our aim was to detect if the presence of a β°/β° homozygous genotype was associated to different rate of cardiac findings by Cardiovascular Magnetic Resonance (CMR) and cardiac complications. Methods We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project. CMR was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All cardiac complications were classified according to international guidelines. Results Two groups of patients were identified: non homozygous β°/β° genotype (N=61) and homozygous β°/β° genotype (N=20.) No significant differences for sex and age were found between the groups. Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060). No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table). Frequencies of heart failure and arrhythmias were comparable between the groups. Non-β0/β0 homozygous genotype β0/β0 homozygous genotype P Left Atrial Area (cm2/m2) 13.87±2.59 16.63±2.59 0.001 LV EDVI (ml/m2) 94.88±15.59 112.94±21.52 0.003 LV ESVI (ml/m2) 35.22±9.55 41.88±9.70 0.018 LV SVI (ml/m2) 61.98±12.57 69.81±11.20 0.029 LV mass index (g/m2) 61.26±10.15 68.63±15.89 0.030 RV EDVI (ml/m2) 91.27±23.50 107.53±23.87 0.019 RV ESVI (ml/m2) 33.93±17.55 40.81±15.20 0.043 Conclusions Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. These data can support the knowledge of different phenotypic groups in the management of NTDT patients.

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 prospectively assessed by magnetic resonance imaging (MRI) the advantages of desferrioxamine (DFO) with respect to the absence of chelation therapy in non transfusion-dependent thalassaemia (NTDT) patients. We considered 18 patients non-chelated and 33 patients who received DFO alone between the two MRI scans. Iron overload was assessed by the T2* technique. Biventricular function parameters were quantified by cine sequences. No patient treated with DFO had cardiac iron. At baseline, only one non-chelated patient showed a pathological heart T2* value (

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.

Aims Cardiovascular magnetic resonance (CMR) has dramatically changed the clinical practice in thalassemia major (TM), lowering cardiac complications. We prospectively reassessed the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM. Methods and results We considered 481 white TM patients (29.48 ± 8.93 years, 263 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. Mean follow-up was 57.91 ± 18.23 months. After the first CMR scan 69.6% of the patients changed chelation regimen. We recorded 18 episodes of HF. In the multivariate analysis the independent predictive factors were myocardial fibrosis (HR = 10.94, 95% CI = 3.28-36.43, P

Background: In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Our aim was to detect if the presence of a β°/β° homozygous genotype is associated to increased iron overload and rate of complications. Methods: We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All complications were classified according to international guidelines. Results: Two groups of patients were identified: non homozygous β°/ β° genotype (N=61) and homozygous β°/ β° genotype (N=20.) No significant differences for sex and age were found between the groups. The frequency of non chelated patients was significantly lower in the homozygous β°/β° group (17.6% vs 49.1%; P=0.026) and the frequency of desferrioxamine therapy was 70.6 in the homozygous β°/β° group and 43.4 in the non homozygous β°/β° group (P=0.051). Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060). Serum ferritin levels, liver transaminases and MRI liver iron concentarion (LIC) values were comparable between the groups. No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table). Frequencies of heart failure and arrhythmias were comparable between the groups. No patient showed diabetes or hypoparathyroidism and there was no difference between groups in terms of frequency of hypogonadism or hypothyroidism. Conversely, patients with homozygous β°/β° genotype had a significant higher frequency of osteoporosis (50.0% vs 16.7%; P=0.003). Among patients with osteoporosis, 75% were treated with DFO therapy. Conclusions: Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. Osteoporososis was significantly more frequent in patients with homozygous β°/β° genotype, treated for more than two-thirds with DFO therapy. These data support the knowledge of different phenotypic groups in the management of NTDT patients. Table Table. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Multiecho gradient-echo T*2 magnetic resonance imaging is a well-established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*2 values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51±17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient-echo T*2 sequence. T*2 measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*2 values was feasible in all subjects. For the T*2 global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*2 values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*2 values. No significant correlation was found between T*2 and patient age or gender. In conclusion, pancreatic T*2 measurements appear to be feasible, reproducible, nontime-consuming and reliable. Gender- and age-related differences concerning pancreatic T*2 were not found.

Results Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO mean dosage 37.52±8.69 mg/kg/ die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFPdosage 71.70 ±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73 ±15.89 years. At baseline in DFO group two patients (7.4%) showed a global heart T2*

Introduction. We aimed to prospectively assess if the male gender was associated with an higher risk of progressive cardiac iron accumulation, development of biventricular dysfunction and myocardial fibrosis assessed by CMR, and development of cardiac complications including heart failure (HF), arrhythmias and pulmonary hypertension (PH). Methods. We considered 1711 TM patients (899 females, 31.09±9.08 years), consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis. Results. Although having a similar risk of accumulating iron, males showed a significant higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications globally considered (Table 1). Figure 1 shows the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator. Until 20-30 years of follow-up the two lines (male and female sex) were almost overlapping while after they clearly diverged. So, patients were divided in two groups based on the follow-up duration. A significant gender-specific difference in the frequency of ventricular dysfunction and cardiac complications appeared for patients followed for at least 20 years. So, two subgroups of patients were identified: patients followed for less than 20 years and patients followed for more than 20 years. In the first subgroup males and females had a comparable risk of developing cardiac iron overload, ventricular dysfunction and cardiac complications. Conversely, if a follow-up longer than 20 years was considered, males exhibited a significant higher risk of having ventricular dysfunction, heart failure, arrhythmias, and cardiac complications. Conclusion. Females seem to tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress. According to the International Guidelines, TM patients should perform a complete cardiac evaluation every year. Our study suggested that in females older than 20 years the follow-up may be performed every 24 months, thus reducing health care costs. Table 1 Table 1. Figure 1 Figure 1. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.. De Franceschi:F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Funding.

Background T2* multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). This study aimed to determine if a preferential pattern of MIO was preserved between two CMR scans in thalassemia major (TM) patients. Methods

Introduction: Recently, the ability of LIC (liver iron concentration) and serum ferritin in predicting myocardial iron overload (MIO) has been challenged by magnetic Resonance Imaging (MRI) monitoring which demonstrated no or weak correlation between serum ferritin or LIC and MIO. Anyway, the role of this traditional markers could result particularly useful in pediatric population, where MRI assessment is difficult to carry out, because of early age, scarce collaboration or limited availability. So, we derived objective thresholds for these markers for predicting cardiac T2* Methods: From the 2171 patients with hemoglobinopathies enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we retrospectively selected 107 paediatric patients with thalassemia major (TM) (61 boys, median age 14.4 years). MIO was assessed using a multislice multiecho T2* approach. Hepatic T2* values were assessed in a homogeneous tissue area and converted into LIC. Results: Twenty-three patients (21.5%) showed an abnormal global heart T2* value and none of them was under 7.9 years of age. Serum ferritin was negatively correlated with global heart T2* values (r=-0.425; P There was a significant negative correlation between global heart and MRI LIC values (P=-0.436; P Conclusion: A weak connection between serum ferritin levels or hepatic iron and cardiac iron was demonstrated in our pediatric population. Anyway, MRI LIC≥14 mg/g/dw and serum ferritin levels≥2000 ng/ml were found to be significant risk factors for a global heart T2* value Figure 1. Figure 1. Disclosures Pepe: Novartis: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Chiesi: Speakers Bureau.

Background. Impairment of the endocrine and exocrine function of the pancreas is a common complication in thalassemia major (TM). Multiecho T2* Magnetic Resonance Imaging (MRI) allows the reproducible and noninvasive assessement of pancreatic iron overload. However, there are no prospective studies describing the changes of pancreatic T2* values. So, our aim was to describe the changes in pancreatic T2* values over a follow-up (FU) of 18 months and to evaluate prospectively the effectiveness of the three iron chelators in monotherapy. Methods. We selected 22 TM patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who had received only one chelator in monotherapy between the two MRI scans. Pancreatic iron burden was measured using a T2* gradient-echo multiecho sequence. The images were analyzed using a previously validated, custom-written software (HIPPO-MIOT®). Results. Three groups of patients were identified: 9 patients (5 females, mean age 32.8±8.6 years) treated with desferioxamine (DFO – mean dosage 44.8±3.8 mg/kg/die), 6 patients (2 females, mean age 36.3±6.5 years) treated with deferiprone (DFP– dosage 75mg/kg/die) and 7 patients (6 females, mean age 30.4±9.1 years) treated with deferasirox (DFX – mean dosage 28.2±4.6 mg/kg/die). The percentage of patients with a excellent/good compliance was comparable among the groups. All patients under DFO therapy showed at the baseline MRI pancreatic iron overload (T2* In the DFP group at baseline 5 patients showed pancreatic iron and none recovered at the follow up (Figure 1, center). The patient with a normal baseline pancreatic T2* value, maintained it at the FU. For the subgroup with pancreatic iron at the baseline, there was a significant increment in the pancreatic T2* values (mean difference: 3.99±2.05; P=0.043). In the DFX group 5 patients showed at the baseline pancreatic iron and although the pancreatic T2* increased for all of them, the normal value was not reached at the follow up (Figure 1, right). Both the patients who showed no pancreatic iron overload at the baseline maintained at the FU the same status. For the subgroup with pancreatic iron at the baseline, there was a significant increment in the pancreatic T2* values (mean difference: 2.48±3.06; P=0.043). Conclusion: Prospectively in TM patients at the dosages used in the clinical practice all three chelators in monotherapy allowed a significant reduction in pancreatic iron. Further prospective studies involving more patients are needed to establish which is the most effective drug. Figure 1 Figure 1. Disclosures Pepe: Novartis: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Chiesi: Speakers Bureau.

Epidemiologic as well as clinical studies confirm a close link between diabetes mellitus (DM) and heart failure (HF) in the general population. In a retrospective historical thalassemia major (TM) cohort, DM was demonstrated to lead to an higher frequency of cardiac complications also independently of cardiac iron status, but not prospective data are available. So, we determined prospectively the predictive value of DM for HF, arrhythmias and cardiac complications (HF, arrhythmias and pulmonary hypertension) in TM. We followed prospectively 537 patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Fifty-six patients were excluded because a cardiac complication was present at the time of the first Cardiovascular Magnetic Resonance (CMR), representing our starting point. All the considered 481 TM patients were white (29.48±8.93 years, 263 females). Mean follow-up was 57.91±18.23 months. DM was present in the 9.8% of patients. Cardiac events were recorded in 36 patients (7.5%). There were 18 episodes of HF, 16 arrhythmias and 2 pulmonary hyperthension. DM was a significant predictive factor for HF (hazard ratio-HR=5.62, 95%CI=2.08-15.22; P DM remained a significant prognosticator for HF and cardiac complications also in a multivariate model including cardiac iron. In conclusion, DM was found to be a strong predictor for HF, arrhythmias and cardiac complications. Our findings are relevant for the prevention of glucose disorder metabolism and they stress the need to intensify the chelation therapy in patients in whom excess pancreatic iron is found by MR, where available, or when patients develop glucose metabolism disorders. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Magnetic Resonance Imaging (MRI) provides unique insight regarding tissue characterization in the heart. We reported the baseline MRI findings at the end of the recruitment in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study. In particular, we evaluated the distribution of iron overload in the whole left ventricle (LV) and he presence of myocardial fibrosis in patients with myelodysplastic syndromes (MDS); the association with LV function was also investigated. No data are available in the literature about this issue. Methods MIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam. Mean age was 71.7±8.5 years and 17 patients were females. MIO was assessed using a multislice multiecho T2* approach. Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement acquisitions. Results We found 27 (56.3%) patients with no MIO (all 16 segmental T2* values >20 ms). The remaining patients showed an heterogeneous MIO (some segments with T2* values >20 ms and other segments with T2* values Myocardial fibrosis was detected in the 35.9% of the patients. Three patients showed an ischemic pattern and one of them had a transmural fibrosis in the LV apical region. Out of the 3 patients with an ischemic pattern, only one patient had a positive history for a previous myocardial infarction. The majority of the patients had two or more foci of myocardial fibrosis, involving more frequently the septal segments. Patients with myocardial fibrosis were significantly older (75.4±7.9 vs 68.9±7.6 yrs; P=0.019). Global heart T2* and LV volumes were not significantly different between patients with and without fibrosis. The LV EF was lower in fibrotic patients but the statistical significance was not reached (58.4±11.7 vs 64.8±8.9 %; P=0.067). Conclusions Although a significant heart iron was found only in two cases, nearly half the patients had abnormal T2* values in at least one myocardial segment. This finding underlines the importance to use a multislice approach in order to perform an early diagnosis and prevent a more diffuse iron distribution by chelation therapy. This goal could be critical in patients with myocardial fibrosis that seems to be a relative common findings in the old MDS patients. In fact, an underlying heart damage as represented by fibrosis could make the hearts of the old MDS patients more sensitive to lower levels of accumulated iron. Disclosures: No relevant conflicts of interest to declare.

Poster: "ECR 2014 / C-1269 / Movement abnormalities in the left ventricle of Thalassemia Major patients" by: "C. Tudisca1, A. Meloni2, E. Grassedonio1, C. Argento3, G. Restaino4, G. Giannotti5, M. Lombardi2, M. Midiri1, A. Pepe2; 1Palermo/IT, 2Pisa/IT, 3Agrigento/IT, 4Campobasso/IT, 5Paterno (CT)/IT"

Background: Due to the limited data available in literature, the aim of this multi-centre study was to prospectively compare in thalassemia major (TM) patients the efficacy of combined deferiprone (DFP) and deferoxamine (DFO) regimen versus either DFP and DFO in monotherapy by cardiovascular magnetic resonance (CMR) over a follow up of 18 months. Methods: Among the first 1135 TM patients in the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated those who had received either combined regimen (DFO + DFP, N=51) or DFP (N=39) and DFO (N=74) monotherapies between the two CMR scans. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: The percentage of patients that maintained a normal global heart T2* value was comparable between DFP+DFO versus both monotherapy groups. Among the patients with myocardial iron overload at baseline, the changes in the global heart T2* and in biventricular function were not significantly different in DFP+DFO compared with the DFP group. The improvement in the global heart T2* was significantly higher in the DFP+DFO than the DFO group, without a difference in biventricular function. Among the patients with hepatic iron at baseline, the decrease in liver iron concentration values was significantly higher with combination therapy than with either monotherapy group. Conclusions: In TM patients at the dosages used in the real world, the combined DFP+DFO regimen was more effective in removing cardiac iron than DFO, and was superior in clearing hepatic iron than either DFO or DFP monotherapy. Combined therapy did not show an additional effect on heart function over DFP.

Abstract 2123 Background. The leading cause of death in thalassemia major patients remains the heart failure, but impairment of the endocrine and exocrine function of the pancreas is a common complication. Multiecho T2* Magnetic Resonance Imaging (MRI) is a well established technique for heart and liver iron overload assessment. Little is known about the relationship between myocardial iron burden and cardiac function with pancreatic siderosis. Aim of our study was to investigate using quantitative MRI the correlation between heart iron overload and function with pancreatic siderosis in thalassemia major patients. Methods. We studied 147 thalassemia major patients (233 males, mean age 31±9 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia network where MRI (1.5 T) was performed using standardized and validated procedures. Myocardial iron overload was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Pancreatic iron burden was measured using a T2* gradient-echo multiecho sequence. The images were analyzed using a previously validated, custom-written software (HIPPO-MIOT IFC-CNR®). Results. Significant positive correlations of the global pancreas T2* values were demonstrated for global heart T2* values (r=0.355, P Pancreatic T2* values were positively related with left ventricular (r=0.21, P=0.028; Figure 2A) and right ventricular (r=0.23, P=0.015; Figure 2B) ejection fractions. No significant correlation was found between pancreatic T2* values and biventricular volumes. Conclusions. Pancreatic iron overload is positively correlated to myocardial iron overload and negatively correlated to bi-ventricular systolic function. Disclosures: No relevant conflicts of interest to declare.

Abstract 3194 Introduction: Using T2* Magnetic Resonance (MR) a randomized placebo controlled study from Sardinia demonstrated combination therapy with deferiprone and desferrioxamine (DFP+DFO) significantly more effective than DFO in improving myocardial iron. One non-randomized study from Sardinia and one observational study from Greece seem to confirm for DFP+DFO therapy the most rapid clearance of cardiac iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. The aim of our multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in TM patients by quantitative MR. Methods: Among the 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans We evaluated prospectively the 51 patients treated with DFP+DFO versus the 39 patients treated with DFP and the 74 patients treated. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: The dosages were: combined therapy DFP 61.9±24.3 mg/kg per 6.1±1.4 days/week and DFO 40.7±6.0 per 3.5±1.1 days/week; DFP 73±13 mg/kg per 6.1±1.4 days/week; DFO 40.7±6.5 per 5.4±0.93 days/week. Excellent/good levels of compliance were comparable in the DFP+DFO (90.2%) versus DFP (94.9%) and DFO (95.9%) groups. The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP+DFO (96%) versus (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload at baseline (global heart T2* Conclusions: Prospectively in TM patients at the dosages used in the clinical practice combined DFP+DFO showed superior reduction in myocardial iron only versus the DFO in monotherapy and it did not show better improvement in biventricular function in comparison to DFO and DFP monotherapy. On the other hand, combined DFP+DFO was significantly more effective in the reduction of the liver iron versus DFO and DFP in monotherapy. Disclosures: Pepe: Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy.

ss Open Acce Poster presentation MRI assessment of correlation between cardiac biventricular function, myocardial iron overload and pancreatic iron overload in a large cohort of thalassemia major patients Gennaro Restaino*1, Antonella Meloni2,3, Vincenzo Positano2, Massimiliano Missere1, Caterina Borgna Pignatti4, Aurelio Maggio5, Marcello Capra6, Antongiulio Luciani7, Gianluca Valeri8, Giuseppina Sallustio1 and Alessia Pepe2