Abdel-Gadir, Amna; (2024) Detection of iron and cobalt by cardiovascular magnetic resonance. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Heart failure remains the leading cause of significant morbidity and mortality in patients with iron or cobalt overload or toxicity, resulting from accumulation of metal in the heart. Survival of patients with iron overload from primary and secondary haemochromatosis has improved with the introduction of the cardiovascular magnetic resonance (CMR) T2* technique allowing a personalised approach to chelator dosing, but this diagnostic test is limited to services with access to the necessary resources. Additionally, limitations have been identified with this technique, which may impact patient outcomes. An alternative MRI measure, T1 mapping, promises major advantages of time and cost over this gold standard. In a single short breath-hold an instant colour map demonstrates the iron content without the need for complex analysis. More recently, the increasing number of case reports describing fatal cardiomyopathy secondary to high circulating cobalt and chromium from metalon- metal (MoM) hips has provoked great public concern, strong media coverage, and well profiled litigation cases. Patients are currently risk stratified and monitored for toxicity with crude assessments including measurement of blood levels and echocardiographic assessment of cardiac function, but a diagnostic tool to measure tissue deposition does not exist. Diagnosis depends on invasive myocardial biopsies or post-mortem examinations. As cobalt exhibits similar magnetic properties to iron, CMR has the potential to noninvasively detect tissue deposition of metal ions and act as a screening tool for patients at risk of systemic toxicity and thus guide management. The work described in this thesis demonstrates the relationship between the gold standard CMR T2* measurement with T1 mapping. In the largest single centre study for iron overload, 300 adults and 21 paediatric patients at risk of iron overload underwent CMR scans involving both techniques allowing insights into the disease. T1 mapping correlated well with T2* in all patients with iron loading, and potentially diagnosed iron in approximately 50% of patients with a normal T2* value. The utility and ease of the T1 mapping method was further demonstrated in Thailand where 128 scans performed in 2 days demonstrated previously undiagnosed cardiac and liver iron in almost all patients. Scan duration was 4 times faster than a standard non-contrast CMR. These findings had great clinical and cost implications. Finally, I have shown, in a blinded study involving 90 patients recruited from the UK’s national hip prosthesis retrieval service, that patients with high levels of circulating cobalt did not develop heart failure or features suggestive of cardiomyopathy using advanced CMR techniques. In this study, there were no significant differences in ventricular function or tissue characterisation between patients with MoM and non-MoM. Although the results were negative this unique study may provide reassurance to patients and surgeons.

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