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Title: Aortic stenosis : a myocardial disease : insights from myocardial tissue characterisation
Author: Treibel, Thomas Alexander
ISNI:       0000 0004 7226 6190
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Aortic stenosis (AS) is a disease of not just the valve, but also of the myocardium. Patient symptoms and outcome are determined by the myocardial response; a crucial but poorly understood process. Diffuse and focal myocardial fibrosis play a key role. Until recently, both could only be assessed using invasive histology, but now cardiovascular magnetic resonance (CMR) offers late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) techniques. In this thesis, I developed new methods to quantify ECV by synthetic ECV and cardiac CT. I then explored myocardial remodelling and fibrosis in patients with severe AS undergoing aortic valve replacement (AVR) using myocardial biopsy, CMR, biomarkers and a wide range of clinical parameters. Prior to AVR, CMR in patients with severe AS revealed important differences in myocardial remodelling between sexes, otherwise missed on echocardiography alone. Given apparently equal valve severity, the myocardial response to AS appeared unexpectedly maladaptive in men compared to women. Intra-operative myocardial biopsy revealed three pattern of fibrosis: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Biopsy best captured the transmural gradient of fibrosis and microscars, while on CMR, LGE captured mainly microscars and ECV captured mid-myocardial related functional changes beyond LGE. Combining LGE and ECV allowed better stratification of AS patients. Incidentally, I found that 6% of AS patients older then 65 years had wild-type transthyretin amyloid deposits on cardiac biopsy, which was associated with poor outcome. This is now the basis of a BHF research fellowship. Following AVR, I demonstrated for the first time non-invasively that diffuse fibrosis regresses (focal fibrosis did not), which is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target.
Supervisor: Moon, J. C. ; Taylor, S. A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available