Cardiac magnetic resonance imaging assessment of aortic stenosis to improve clinical care
Everett, Russell James
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Background Aortic stenosis is the commonest valve disease requiring intervention in the developed world. Current guideline-based management strategies are based on historical observational data or expert opinion and may leave many patients with irreversible myocardial damage and adverse outcomes following valve intervention. The aims of this thesis are to investigate novel cardiac magnetic resonance techniques and how they can be applied to improve our decision making around the timing of valve intervention. Methods and Results Cardiac magnetic resonance imaging can detect two forms of myocardial fibrosis non-invasively; diffuse fibrosis using T1 mapping and replacement fibrosis with the late gadolinium enhancement technique. I devised a novel measure of diffuse fibrosis, the indexed extracellular volume (iECV) and showed that these techniques can be used to divide patients into three categories according to the type and amount of fibrosis present: no fibrosis, diffuse fibrosis and replacement fibrosis. Moreover, I demonstrated that there was evidence of increasing left ventricular decompensation across these three groups. How fibrosis and left ventricular hypertrophy change over time has not been well studied in patients with aortic stenosis. Using serial imaging scans, I showed that hypertrophy and diffuse fibrosis gradually progress over time, whilst replacement fibrosis accumulates rapidly once first established. Following valve replacement, cellular hypertrophy regresses faster than diffuse fibrosis, but replacement fibrosis appears permanent and irreversible. I then proceeded to investigate T1 mapping measures in a large international multicentre cohort of patients with aortic stenosis scheduled for valve replacement. I showed that extracellular volume-based T1 mapping measures were comparable across centres and therefore confirmed that multicentre studies are feasible. Extracellular volume fraction was associated with a decompensating ventricle and emerged as a powerful independent predictor of all-cause mortality in this group. Finally, I investigated the use of novel hybrid magnetic resonance and positron emission tomography imaging in patients with aortic stenosis, showing that this technique is feasible and well-tolerated. I tested novel attenuation correction and motion correction methods and showed that this technique can offer multiparametric imaging of valve, myocardium and coronary arteries in a single scan. Conclusion I have defined the longitudinal changes in hypertrophy and myocardial fibrosis in aortic stenosis and validated extracellular volume measures as prognostic markers in this group. Moreover, I have described novel magnetic resonance and positron emission tomography techniques and their potential to aid the clinical assessment of patients with aortic stenosis.