One-stop measurement of iron deposition in the anterior pituitary, liver, and heart in thalassemia patients.

PURPOSE: To assess the feasibility of one-stop evaluation of iron load of myocardium, liver, and anterior pituitary gland in thalassemia patients. MATERIALS AND METHODS: Fifty thalassemia major patients underwent a breath-hold magnetic resonance imaging (MRI) sequence for assessment of T2* for liver and myocardium, a short axis cine trueFISP sequence covering base to apex to assess the ejection fraction of left ventricle, and a turbo spin echo T2-weighted sequence for the anterior pituitary gland. The MRI parameters were correlated with serum growth hormone, insulin growth factor-1 (IGF-1), insulin growth factor binding protein-3 (IGFBP-3), and endocrine failure. RESULTS: Ferritin was found to be associated with T2* liver (P < 0.005), T2SI (signal intensity) pituitary (P = 0.001), and T2 pituitary/fat (P = 0.001), but not with T2* heart. There was significant correlation of T2SI pituitary with IGF-1 and IGFBP-3. T2* liver (P < 0.001), T2* heart (P < 0.001), pituitary SI (P < 0.001) and pituitary/fat SI (P = 0.002) were also found to be significantly correlated with a history of hypogonadism. T2* heart was also found to be significantly correlated with IGF-1. CONCLUSION: A quick MRI protocol for assessment of T2* liver, T2* heart, and T2SI pituitary is technically feasible. This might form an objective basis to monitor the response to different organs to chelation therapy.

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.

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload.

AIMS: To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops. METHODS AND RESULTS: We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0.93, P<0.0001). Inter-study cardiac reproducibility was 5.0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0.61, P<0.001). All patients with ventricular dysfunction had a myocardial T2* of <20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0.79, P<0.002). CONCLUSIONS: Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.