Cardiovascular manifestations of Marfan syndrome: insights from advanced cardiovascular magnetic resonance

Marfan syndrome (MFS) is the commonest inherited disorder of connective tissue and is associated with a high risk of potentially life-threatening complications, including aortic aneurysm, dissection and rupture, and, perhaps, ventricular disease. This work describes the prospective application of advanced cardiovascular magnetic resonance techniques to the aorta and heart of consecutive, unselected subjects with MFS, and to appropriately matched control populations. Comprehensive 3D visualisation of blood flow in the entire thoracic aorta of subjects with MFS was achieved using a time-resolved phase-contrast magnetic resonance technique with 3-directional velocity encoding (4D flow), demonstrating a high prevalence of major flow disturbance (87 ± 12%), compared to controls (28 ±18%), localising to those regions of the aorta known to be most prone to aortic dissection (sinuses of Valsalva and proximal descending aorta). Wall shear stress, recently identified as a potentially important determinant of aneurysm progression and rupture, was interrogated in these datasets at the sinuses of Valsalva (SOV), ascending aorta (AA), arch, and proximal (PDA) and distal descending aorta (DDA), using the 4D flow datasets, and was shown to be significantly reduced at each location (SOV -15%; AA -12%; Arch -17%; PDA -18%; and DDA -14%, p 4D flow datasets were used to generate relative pressure maps in healthy subjects and in subjects with several aortic diseases. A novel method for the separate evaluation of the components of relative pressure was applied, revealing marked differences in the relative contribution of the components of pressure (unsteady > convective >> viscous), and characteristic differences between subjects in overall relative pressure, and its components. Left ventricular volumes and function were evaluated in subjects with MFS, and did not differ significantly from healthy subjects in the absence of significant valvular regurgitation and / or shunt. Left ventricular end-diastolic volume varied markedly with degree of regurgitation (r=0.75, p=0.0001). The mechanistic implications of these findings, and the potential role of these techniques in the evaluation of cardiovascular disease, are discussed.This thesis is not currently available in ORA