Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major.

BACKGROUND: The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major. METHODS AND RESULTS: We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P<0.001) or serum ferritin (0.629; P<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P<0.001) or serum ferritin (0.518; P<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia. CONCLUSIONS: Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.

A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance.

BACKGROUND: Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. METHODS AND RESULTS: Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001). CONCLUSIONS: In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.

Myocardial iron loading in patients with thalassemia major on deferoxamine chelation.

BACKGROUND: Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine. METHODS: A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made. RESULTS: Myocardial iron loading (T2* < 20 ms) was present in 108 (65%) patients, which was severe (T2* < 8 ms) in 22 (13%). Impaired (< 56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p < 0.001), weakly related to serum ferritin (Rs = -0.34, p < 0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = -0.35, p < 0.001) and was abnormal in only 5 patients. CONCLUSIONS: Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis.