Introduction. T2* measurement of myocardial iron overload (MIO) is presently the gold standard for monitoring and tailoring the chelation in thalassemia patients. Native T1 mapping has been proposed also for the MIO quantification because it is known that iron can reduce native T1 values. No data are available in literature comparing T1 and T2* mapping using a segmental approach including the whole left ventricle. The goal of our study was to assess the relationship between T1 and T2* values using a segmental approach.

Background: The analysis of cine cardiovascular magnetic resonance (CMR) images allows the quantification of the myocardial contraction fraction (MCF), a volumetric analog of myocardial deforming, that is calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume. Aims: We verified the association of this new marker with myocardial iron overload and cardiac events (heart failure, arrhythmias and pulmonary hypertension) in thalassemia major (TM) patients. Methods: We considered 1492 TM patients (771 females, 31.06 ± 8.95 yrs) enrolled in the MIOT network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2∗ technique and biventricular morphological and functional parameters by cine sequences. Results: MCF values were significantly lower in males (0.94 ± 0.22 vs 1.01 ± 0.22; P < 0.0001) and decreased with increasing age (R = −0.129 P < 0.0001). Patients with MIO (global heart T2∗ < 20 ms; N = 400) showed significant lower MCF values than patients without MIO (0.91 ± 0.20 vs 1.00 ± 0.22; P < 0.0001). The patient population was randomly divided in two groups of equal size (N = 746). In the first group 99 patients had at least one cardiac complication and at receiver‐operating characteristic (ROC) curve analysis a MCF ≤ 0.87 was the best predictor of cardiac complications (area under the curve 0.659, 95% CI 0.64 to 0.69; sensitivity 60%, specificity 67%). In order to validate the result, the obtained value was tested in the remaining 746 patients (group 2). One hundred and thirty‐five patients had a cardiac complication and patients with a MCF ≤ 0.87 were more likely to have cardiac complications (odds ratio – OR = 2.73, 95%CI = 1.86‐4.01; P < 0.0001), also adjusting for cardiac iron (see Figure). Summary/Conclusion: Contractile function is reduced in patients with MIO. A MCF ≤0.87 can help to identify patients with a significant higher risk of adverse cardiovascular events, independently by the presence of MIO. image

Background: Non-transfusion-dependent thalassemia (NTDT) is a term used to indicate patients who do not require lifelong regular transfusions for survival. Morbidity in NTDT patients is more common and serious than previously recognized. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in NTDT patients.

Abstract Introduction In thalassemia major (TM) three iron chelators in monotherapy are available to treat chronic iron overload due to blood transfusions: subcutaneous desferrioxamine (DFO) introduced in the 1960s, oral deferiprone introduced in 1999 and oral deferasirox (DFX) licensed in 2006. Nowadays pharmacoeconomics analysis are frequently required by the health authorities due to the actual economic crisis. The aim should be to ensure to the whole community the sustainability for health care of proved quality. The objective of this study was to determine the costs of the three chelators in monotherapy in a cohort of 193 TM patients followed prospectively for 18 ± 3 months. Methods Within the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated prospectively 193 TM patients who had been received one chelator alone between the 2 Magnetic Resonance scans and we calculated the direct costs (drug, administration and monitoring) for each patient treated with DFX, DFO and DFP. We used the cost values for the year 2007. For the drugs we considered the cost ex-factory. For the oral chelators the administration cost was considered null. For the DFO we calculated the costs for the administration (pump, infusion set, syringes and gauzes) using the tariffs applied in Veneto Region, Italy. For the monitoring costs we considered the exams suggested in the technical sheet for each drug; we considered the tariffs by the Veneto Region, Italy. In Italy Veneto Region was proved to be one of the most upright region in the health costs management. In the analysis we considered the drug cost for the standard dosage reported in the technical sheet: 40 mg/kg/d for DFO, 75 mg/kg/d for DFP and 30 mg/kg/d for DFX. Based on the mean weight of the patients we referred the drug cost to a patient of 60 Kg. Results In the clinical practice the dose of DFX was 26±7 mg/kg/d, DFP was 73±13 mg/kg/d and DFO was 41±6 mg/kg for 5.5 d/wk. Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P=0.6). The cost/mg was € 0.006 for Generic DFO, € 0.003 for Ferriprox® (DFP) and € 0.047 for Exjade® (DFX). For 18 months of treatment the total costs for DFO were € 10.465,8 (administration and monitoring costs € 3.965,1 + drug cost 6.500,7), for DFP were € 8.292,9 (administration and monitoring costs € 460,8 + drug cost 7.832,2), for DFX were € 46.461,2 (administration and monitoring costs € 211,14 + drug cost 46.249,8). The details about the administration and monitoring costs for DFO, DFP and DFX are reported in the table. Conclusion In this analysis, for managing chronic iron overload the direct costs for oral DFP appeared to be the less expensive. The limit of this study is that a cost-utility analysis taking into account efficacy, adverse events and route of administration was not performed. Disclosures: Pepe: ApoPharma inc, Novartis, Chiesi: Speakers Bureau.

Background T2* Magnetic Resonance Imaging (MRI) technique allows noninvasive quantification of organ-specific iron burden, playing a key role in the management of thalassemia major (TM) patients. There are few data on the incidence of heart failure and arrhythmias in TM patients according to baseline T2* values. So, the aim of this study was to establish prospectively the risk of cardiac complications in a large cohort of well-treated TM patients. Methods We considered 527 TM patients (252 males, mean age 30±9) for who clinical data relative to a period of 5 years after the first MRI were collected in a central data base. At time of the first scan mean ferritin levels were1653±1559 ng/l, global heart was 27±13 ms, and excellent/good level of compliance were present in the 96% of the study population. Results At 5 years of follow-up, we recorded 24 cardiac events: 4 episodes of cardiac failure, 15 of arrhythmia, 1 of pulmonary hypertension and 4 of other cardiac complications. The majority of these events (21/24) happened within the first 24 months subsequent to the MRI, so we considered this follow-up period. At the first MRI scan, in patients with cardiac complications the global heart T2* was 22.5 ±12.4 ms. In comparison with global heart T2* values ≥20 ms, there was not a significantly increased risk of cardiac complications associated with global heart T2* values <20 ms (HR= 2.028 P=0.09).

Abstract Abstract 3197 Background: The prognosis for thalassemia major (TM) has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop secondary iron overloading, and eventually death, particularly from cardiac disease. The possibility of detecting easily and earliest the patients at risk of cardiac death is so far the main challenge of clinical management of these patients. Therefore, the mean reduction of Left Ventricular Ejection Fraction (LVEF), determined by echocardiography, was evaluated over the time. Methods: Among the 413 observed patients only 188 had complete records for LVEF measurements during, at least, five considered consecutive years. Included patients were divided into two cohorts: the not alive and the alive-group with 22 and 166 patients, respectively. Generalized Estimating Equations (GEE) model was used to show the reduction of the mean of LVEF (Hedeker & Gibbons, 2006). This approach was implemented in the 'xtgee' procedure of Stata 11 software (StataCorp, College Station, TX, USA). The logistic regression model was used to evaluate the risk of death (Collet D. 2003). In this analysis, the mean reduction of LVEF was categorized into three levels: the baseline category including all patients with an increase greater than 0%, the category 1 including all patients with a reduction greater than 0% but less than 7% and the category 2 including all patients with a reduction higher or equal to 7%. All of the statistical analyses were performed under code at the Department for Mathematical and Statistical Sciences 'S. Vianelli', University of Palermo (Italy) by A.V. Results: Baseline findings are shown on Table I. Figure 1 shows the proÞles of the GEE model for the mean LVEF between the two groups. The regression coefficient of Status×Time shows a statistically significant linear decrease over the time of 1,51 per year of the mean LVEF between not alive versus alive patients (Coeff. −1.51, CI (−2,31;−0,71), p-value<0,0001,Fig. 1). Patients with a mean reduction of LVEF greater or equal to 7% over the time had a statistical significant higher risk of death from heart failure (OR= 4,93,95% CI 1,61;15,11, p-value = 0,005). Discussion: Recently, Kirk et al. 2009 suggested as cardiac T2* magnetic resonance is able to detect patients at high risk of heart failure and arrhythmia from myocardial siderosis. However, other studies showed the presence of patients with abnormal heart function and normal heart T2* and did not suggest lower heart T2* for patients suffering from arrhythmia (Pepe et al., 2006; Marsella et al.,2011). Moreover, although the use of T2* is spreading, its availability is so far limited. Instead, availability of echocardiography is surely greater. Moreover, interobserver and intraobserver reliability for the visual assessment of the global LVEF measurements have been extensively shown even in comparison with Magnetic Resonace Imaging (Hoffmann et al. 2005; Gimelli et al. 2008; Blondheim et al., 2008; Sjzli et al. 2011). Therefore, repeated measurements of LVEF may be a strong and more accessible tool for detecting at risk of heart failure TM population. Disclosures: No relevant conflicts of interest to declare.

Abstract 1089 This icon denotes a clinically relevant abstract