Application of Numerical Simulation in Cardiovascular Medicine

Introduction: The purpose of this thesis is to study atherosclerotic risk and thrombotic risk through application of numerical simulation to cardiovascular geometry and morphology. This has been applied to two specific situations, the angle of take-off of the left main coronary artery and the morphology of the left atrial appendage. A. The distribution of atherosclerotic plaque and the plaque rupture rate in isolated left main coronary disease is different to that seen in left main disease with multi-vessel disease, suggesting local biomechanical forces play an important part in governing plaque formation and rupture. The varying vertical left main coronary artery take-off angulation may impact on the wall shear stress. B. Different left atrial appendage morphologies seem to have different risk of thromboembolism, in patients with atrial fibrillation and low CHADS2 VASC score. From this observation, it can be hypothesized that left atrial morphology subtype with a more complex structure can lead to higher volume of blood stagnation. Aim: A. To investigate the effects of vertical take-off angulation of the left main coronary artery from aorta and varying stenosis severities on wall shear stress in the left main coronary artery. B. To investigate the impact of different left atrial appendage morphologies on slow vortical flow estimated by flow dynamics. Methods: A. Artificially created and patient-specific computed tomography-derived 3-dimensional digital models of the left main coronary artery with varying vertical take-off angulation and artery stenoses were generated. These were exported for numerical simulation to calculate the wall shear stress values and mapping in each model set. B. Patient-specific computed tomography-derived 3-dimensional digital model sets of different left atrial appendage morphologies were exported for numerical simulation to calculate the volume and distribution of slow vortical flow. Left atrial appendage emptying was assessed. Results: A. The study of left main take off demonstrated that the preferred development site of atherosclerotic plaques in pathological studies corresponds to regions of low wall shear stress. Both peak wall shear stress and mean wall shear stress increased with more vertical take-off, and this relationship was accentuated by increasing stenosis severity. The more vertically angled LMCA take-off from aorta in the presence of significant stenosis severity was also associated with a larger area of low wall shear stress. These findings may explain the higher atherosclerotic plaque rupture rate and higher percentage of proximally located plaque seen in isolated left main coronary artery disease B. For complex geometry, the Cauliflower left atrial appendage subtype contained the greatest volume of slow vortical flow at low shear rate across a range of different left atrial appendage emptying velocities. This rheological mechanistic observation correlates well with the clinical observation that the highest rate of clinical thromboembolism is seen with the Cauliflower subtype in patients with low CHADS2 VASC score atrial fibrillation. However, in the presence of severely depressed left atrial appendage function differences between left atrial appendage morphology subtypes diminish. Conclusion: A. LMCA angulation may be an additional important factor to be considered in the clinical evaluation of the pathogenesis and progression of LMCA atheromatous disease. B. Stasis of blood, assessed in this study by the volume of slow vortical flow, is shown to depend on left atrial appendage morphology, and also depends on left atrial appendage function/emptying velocity. Under conditions when function is mildly to moderately reduced, then it is likely that morphology is an important variable