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Title: Characterising metabolic mechanisms of disease in cardiomyopathies using multiparametric cardiovascular magnetic resonance imaging
Author: Suttie, Joseph
ISNI:       0000 0004 2721 6629
Awarding Body: Oxford University
Current Institution: University of Oxford
Date of Award: 2011
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In addition to pathological ventricular remodeling, the failing heart is characterised by impaired myocardial energetics and profound alterations in glucose and fatty acid metabolism. Understanding these complex metabolic pathways is crucial to improving clinical risk stratification and developing targeted therapeutic interventions. Cardiac magnetic resonance imaging (CMR) and magnetic resonance spectroscopy (MRS) are powerful tools in the interrogation of cardiac disease. Although technically challenging, the assessment of myocardial energetics by 3'p MRS has been possible for several decades. More recent techniques have allowed for the rapid assessment of cardiac steatosis using 'H MRS. The relationship between cardiac steatosis and other parameters of myocardial function such as myocardial energetics, contractility, fibrosis and perfusion have not been previously investigated. I assessed these parameters in patients with dystrophinopathy, a cause of inherited dilated cardiomyopathy in which disease pathways have not been well described. This study found myocardial contractility is strongly correlated with the myocardial PCr/ATP ratio, and that in those patients with impaired myocardial energetics there is significant cardiac steatosis. These changes were independent of body mass index and occurred in patients with normal glucose and lipid profiles. In order to further elucidate the phenotype, we investigated these markers of myocardial dysfunction in dystrophinopathic patients with and without prior exposure to Coxsackie B infection, an acquired cause of dystrophinopathy. Previous Coxsackie B exposure predicts worsening myocardial fibrosis, but was not associated with parameters of metabolic dysfunction. 17 - Suttie J.J. In order to further investigate the significance of cardiac steatosis in inborn errors of metabolism, I phenotyped a cohort of patients with mitochondrial myopathy. Mitochondrial myopathies are associated with profound cardiac steatosis, impaired myocardial energetics, inflammation and fibrosis. Furthermore, we report cardiac steatosis also occurs in patients with impaired myocardial energetics due to hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy and asymptomatic aortic stenosis. Finally, even higher spatial resolution imaging may be achieved be achieved at higher field strength, and I therefore undertook the first validation of CMR cardiac functional imaging at 7 T. This work significantly expands our understanding of cardiac steatosis in the energetically failing heart and supports its potential role as a novel biomarker in a range of cardiomyopathies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available