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Thalassaemia and iron-induced cardiac failure: Development of a method to quantify myocardial iron and its application for clinical management

Anderson, Lisa Judith; (2002) Thalassaemia and iron-induced cardiac failure: Development of a method to quantify myocardial iron and its application for clinical management. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Background: Iron-induced heart failure is the commonest cause of death in thalassaemia major. The cardiomyopathy is reversible when treated early, but once heart failure is established it is often rapidly progressive, and unresponsive to treatment. Our aim was to develop and validate a non-invasive measurement of myocardial iron in order to allow earlier diagnosis and treatment. Methods and Results: We have developed and validated a new magnetic resonance (MR) T2* technique for the measurement of tissue iron. There was a highly significant, inverse correlation between iron concentration by liver biopsy and liver T2* (r=0.93, p<0.0001). Inter-study reproducibility was 5.0% in the heart and 3.3% in the liver. As myocardial iron increased, there was a progressive decline in ejection fraction (r= 0.61, P<0.0001), associated with a progressive increase in left ventricular mass and end systolic volume. Myocardial iron content cannot be predicted from serum ferritin or liver iron, the conventional markers of tissue iron deposition, and assessments of cardiac function alone detect only those with advanced disease. Multivariate analysis to relate left ventricular ejection fraction to clinical parameters including age, liver iron and serum ferritin identified myocardial T2* as the only independent predictor (odds ratio 7.0, p<0.0001). In a small, prospective study of patients with cardiac involvement we demonstrated that intensification of iron-chelation therapy leads to removal of iron from the heart and reversal of the cardiomyopathy. A controlled comparison study of the iron-chelating agents, deferiprone and desferrioxamine, suggests that deferiprone is more effective in removing iron from the heart than standard treatment with desferrioxamine. Conclusions: This MR T2* technique provides a simple, robust assessment of myocardial iron deposition. Early identification and treatment of patients with myocardial iron overload should reduce the excess mortality and morbidity from this reversible cardiomyopathy.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Thalassaemia and iron-induced cardiac failure: Development of a method to quantify myocardial iron and its application for clinical management
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Heart failure; Iron concentration
URI: https://discovery.ucl.ac.uk/id/eprint/10102010
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