부산대학교 도서관

Hypertrophic cardiomyopathy (HCM) is the commonest inherited heart muscle disease. Both diagnosis and risk stratification can be challenging and although the majority of patients experience a benign clinical course, a significant number are at increased risk of sudden cardiac death (SCD) and progressive heart failure. On histology, HCM is characterised by hypertrophy, fibrosis, microvascular abnormalities, and disarray. This thesis examines the application of cardiovascular magnetic resonance (CMR) to the assessment of HCM with respect to its principal histological features. The prognostic significance of replacement fibrosis, as detected by late gadolinium enhancement (LGE) imaging was assessed through clinical follow-up of a large cohort of patients. For the first time, we were able to demonstrate that neither the presence nor the amount of fibrosis predicted SCD risk independent of confounding variables and that left ventricular ejection fraction was the most powerful predictor of outcome. Although LGE-CMR detects replacement fibrosis, it cannot resolve interstitial fibrosis which is thought to be an early feature of HCM. Novel extracellular volume mapping techniques were applied to determine whether CMR can identify interstitial changes in HCM. These techniques reliably identified replacement fibrosis but did not appear able to detect significant interstitial fibrosis. Microvascular abnormalities are an important histological feature of HCM and a potential driver of fibrosis. The prevalence of perfusion abnormalities in HCM is unknown. Through the study of a large consecutive cohort, this was found to be 80%. Novel pixel mapping techniques were then applied to quantify the severity of ischaemia and to study its relationship to hypertrophy and fibrosis. For the first time, we found severe microvascular steal in a subset of patients, a finding which may be of prognostic value. We also found that the relationship with fibrosis was not independent of wall thickness. Finally, novel diffusion tensor imaging sequences were applied to image myocardial fibre architecture in-vivo. These were not able to detect compelling evidence of disarray, but marked differences in diffusivity were found between patients and controls, which may signify interstitial expansion. In conclusion, CMR is able to provide valuable insights into the pathogenesis of HCM which may be of diagnostic and potential prognostic value. However, further work is required to refine the application of CMR to clinical practice.