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Abstract 1011 Background. CMR was introduced in London to assess myocardial iron loading in 1999 and some of these patients now have 10 years of follow-up, most with contemporary CMR determinations. The impact of long-term monitoring of myocardial iron loading in thalassemia major (TM) on the proportion of patients with increased myocardial iron (cT2* Patients and Methods. All patients regularly attending two London thalassemia centres, who received their first CMR Jan 1999 - Dec 2000 were analyzed as a cohort. Patients underwent initial CMR at the Royal Brompton Hospital and received CMR follow up (FU) either there or at the Heart Hospital (UCLH). 132 patients were identified as having received a CMR in 1999–2000. A minimum 7 years CMR FU was required for inclusion in the long-term CMR analysis. 109 patients had at least 7 years of CMR follow up (range 7.0–10.6 years, median 9.2). The median age at 1st CMR was 27.9 years (range 7.7 – 49.5 years). At baseline, patients were receiving chelation with deferoxamine (DFO) monotherapy (70%), deferiprone (DFP) monotherapy (21%), or a combination of these agents (9%). At latest FU, patients were receiving DFO (32%), deferasirox (DFX) (28%), DFP (22%), or combined DFP and DFO therapy (18%). Results: Improvement in cardiac iron: In 1999–2000, 60% of TM patients had cT2* values ≤20ms and 17% had cT2* values Changes to chelation therapy: 31% of patients stayed on the same chelator; 33% had 1 chelator switch, 26% 2 switches and 11% 3 or more switches. 18 switches in chelation therapy were due to side-effects (12 DFP, 5 DFX, 1 DFO). There were 9 breaks in chelation therapy during pregnancy in 8 different women. The proportions of patients with T2* < 20ms fell significantly for those who remained on DFO or DFP monotherapies throughout, or who changed chelation modalities on only one (p=0.002) or two (p=0.02) occasions. Patients who received had 3 or more switches did not show a improvement in this respect. The latter group was also the only subset that showed significant deterioration in myocardial iron (p Mortality rates: the overall mortality rate for the initial cohort was 1.65 per 1000 patient years (95% CI 0.71 – 3.24); median age at death 35.6 years (range 27.3–48.4). This is a substantial improvement in the mortality index compared with the UK thalassemia registry data, of 4.3 per 1000 patient years during the period 2000–2003 (Modell et al, JCMR, 2008). The incidence rate ratio is 0.387 (95% CI 0.11–0.961), p Causes of death: there were 8 deaths during the FU period: 3 with complications of hepatitis C (all with cT2* > 20ms), 3 with sepsis (2 with cT2* 20ms). Thus in only 2 patients could excessive cardiac iron loading be considered a causal/contributory factor. There was no significant difference in the baseline cT2* between those who died and those currently still alive (p= 0.2), meaning that death as a drop-out cause does not explain iron loading trends over FU. Chelators at death: DFO (4), DFP (2), DFX (1), combination (1). Conclusions: Over a decade we have seen an almost 3 fold fall in the proportion of patients with myocardial iron overload. Mortality has become substantially lower and cardiac iron overload is no longer the leading cause of mortality. In addition to CMR, this decade has seen the advent of two new oral iron chelators and many patients switched chelation regimen, sometimes several times, during the follow up period. Whilst the contribution of the individual components of this practice to the improved outcome cannot be concluded without randomized studies, it is clear that this modern management of TM is associated with reduced TM mortality. Disclosures: Off Label Use: Deferiprone is off label in the USA but licensed in Europe. Shah:Novartis: Honoraria, Speakers Bureau; Apotex/ Swedish Orphan: Honoraria. Pennell:Siemens: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Apotex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cardiovascular Imaging Solutions: Director of CVIS, Equity Ownership. Porter:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract 2012 Poster Board I-1034 Background: Cardiovascular magnetic resonance (CMR) is being increasingly used worldwide for monitoring chelation therapy in transfusion-dependent β-thalassemia patients. The assessment of cardiac iron loading using myocardial T2 star (T2*) is a reliable, quick and non-invasive method which can be combined with highly accurate and reproducible cardiac volume and function measurements. It has previously been noted that myocardial siderosis (T2* Methods: A retrospective analysis was performed of 323 consecutive β-thalassemia patients referred for their first CMR scan from 21 UK hematology centers. Only patients on a single chelating agent (deferoxamine) were included. All had received chelation from the mid-to-late 1970s or from an early age if born since then. Patients were excluded if there was significant cardiac, vascular or lung pathology (such as aortic stenosis, pulmonary artery stenosis, tetralogy of Fallot or pulmonary hypertension). All scans were performed using a 1.5T Sonata (Siemens Medical Systems, Germany). A single breath-hold multi-echo sequence with 8 different echo times (TE = 2.54-17.9ms) was used to measure T2* from a full-thickness region of interest in the septum of a mid-ventricular short axis slice. Myocardial T2* was calculated from the exponential signal intensity decay curve using a truncation method to account for background noise. RV and LV volumes and ejection fraction (EF) were calculated from a series of short axis ventricular slices (7mm thickness with 3mm gap). Results: In patients with normal T2* (>20ms), RV EF was within normal limits in 98% of cases (RV EF [mean ±SD] = 65.0 ±6.1%). In patients with myocardial siderosis (T2*20ms (LV EF = 69.5 ±5.2%). Once again, where T2* fell below 20ms, there was a progressive decline in LV EF (r=0.40, p Conclusions: There is a strong association between increasing myocardial iron loading and RV dysfunction which mirrors the decrease in LV ejection fraction seen with worsening myocardial siderosis. RV impairment may be a significant contributor to the syndrome of heart failure associated with severe myocardial siderosis. Disclosures: Carpenter: Swedish Orphan: Honoraria; Apotex: Honoraria. Porter:Novartis: Consultancy, Research Funding. He:Novartis: Consultancy. Smith:Novartis: Consultancy. Pennell:Siemens: Consultancy; Novartis: Consultancy; Apotex: Honoraria; Cardiovascular Imaging Solutions, London: Equity Ownership.

Background: In β-thalassemia major (TM) myocardial iron toxicity is the dominant cause of ventricular dysfunction, with heart failure responsible for the majority of deaths. Abnormal endothelial function has also been described in these patients and could further contribute to cardiovascular complications. Endothelial function can be determined by measurement of flow mediated dilatation of the brachial artery (FMD). This can be assessed reproducibly by cardiovascular magnetic resonance (CMR). Aims: To report the changes in endothelial function, LV ejection fraction and ferritin from a randomized placebo controlled trial comparing combined chelation therapy (deferiprone and deferoxamine) with deferoxamine monotherapy. Methods: 65 patients (male 27, female 38, age 28.7+/−4.8years) with mild-moderate myocardial iron loading (heart T2* 8–20ms) were randomized to receive either deferoxamine with placebo (placebo group), or deferoxamine with deferiprone (combined group). FMD was assessed at baseline and after 12 months. Results: There were significant improvements in endothelial function in the combined treatment group compared with the placebo group (+8.8% vs 3.1% p=0.013). This was in accord with improvements in the combined group in left ventricular ejection fraction (+2.4% vs +0.6%, p=0.02), and serum ferritin (−870 vs −194 μg/L; p Conclusion: In patients with mild-moderate cardiac iron loading, the combined therapy of deferiprone and deferoxamine is superior to deferoxamine alone in improving endothelial function, cardiac function and ferritin, as well as reducing myocardial iron.