| Summary: | The end product of the numerous cellular, electrical and mechanical processes within the normal heart is the generation of blood flow. Blood flow within the cardiac chambers exerts forces upon the myocardium, which creates a continuous remodelling process. In heart failure pathological cardiac remodelling occurs; this is a complex process involving numerous transcriptional, molecular, cellular and architectural changes within both the cardiac myocytes and surrounding extracellular structures. Intra-cardiac blood flow can now be visualised in vivo using three-directional, three-dimensional time resolved velocity encoding cardiac magnetic resonance imaging (4D flow). The interactions between intra-cardiac blood flow patterns and cardiovascular disease processes using 4D flow were determined. The relationship between atypical right atrial flow patterns and embolic stroke across a patent foramen ovale (PFO) were explored, as were the flow parameter changes in heart failure patients. It was found that in the presence of a PFO, participants with atypical flow patterns were more likely to have had an embolic event than those with classical vortical flow. Left ventricular 4D flow parameters were demonstrated to be highly repeatable and stable within a normal study population over time. In dilated (DCM) and ischaemic (IHD) cardiomyopathy patients, inefficient blood flow patterns and deranged kinetic energy profiles were found. The derangement in kinetic energy was demonstrated to correlate with worsening myocardial function, dilatation, Brain-type natriuretic peptide (BNP) levels, six minute walk test (6MWT) and patient symptoms. These findings suggest that derangements in flow parameters are novel biomarkers of disease severity in heart failure patients, which may become useful in monitoring novel heart failure therapies and predicting prognosis. An association between impairment of cardiac energetics and derangement of intra-cardiac blood flow kinetic energy was demonstrated for the first time using phosphorus magnetic resonance spectroscopy (31P MRS). The work on field strength effects on cardiac 31P-MRS has shown that 7T is feasible in a patient cohort with increased precision of metabolite quantification and increased signal to noise compared to 3T. In summary, the work in this thesis demonstrates the powerful role of 4D flow in elucidating the detrimental effects of cardiovascular disease upon intra-cardiac blood flow parameters.
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