The Left Atrial Appendage, once thought to be "a relatively insignificant portion of cardiac anatomy," has currently been realized to possess "important pathological associations [1a]" particularly in its role in promoting serious, frequent thromboembolic events common in individuals suffering from Atrial Fibrillation. Prior approaches to mitigating these events have either required invasive procedures, proved less than fully effective, or presented with problematic sequelae of their own. This work will present a new procedure that addresses both the prevention of the thromboembolic events and the correction of the shortcomings of the major prior methods utilized. A compliant hydrogel that can conform to the geometry of the appendage is proposed as a more effective method of occluding the chamber. This material would be transported to the LAA in liquid form via a multi-lumen catheter, and then solidify within the chamber to form a solid plug. Previous research has identified a candidate hydrogel, comprised of PEG-tetra-thiol and Dextran vinyl sulfone as a candidate hydrogel for this application. Experimental work has investigated fluid properties of the material, as well as degradation and swelling properties of the material. Results from this experimentation were used for fluid transport analysis, and for evaluation of anchoring force of the hydrogel within the chamber. Finally, subfunctions of the occlusion procedure were modeled and tested. During the actual procedure, a catheter balloon will isolate the appendage from the rest of the heart. A model was developed to study interactions between the appendage and this balloon. Additionally, due to fast solidification time, hydrogel components in the surgical procedure will be mixed in a mixing chamber at the tip of the catheter. Potential mixing chamber designs were modeled, and a ternary diffusion model was developed to better understand hydrogel mixing. Prototypes for both these subfunctions were built and tested as well. Additional analysis looked at the overall occlusion procedure, and how various subfunctions interacted with each other. / text

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Understanding the hemodynamics of the cardiovascular system and associated diseases is important for mitigating health risks. We applied flow diagnostic techniques to investigate pulsatile flow characteristics past sidewall cavities, which have implications to two biomedical problems in the cardiovascular system: sidewall aneurysms and the left atrial appendage. Superhydrophobically-coated mesh diverters and synthetic slippery surfaces were studied for their effects on flow diversion and cavity flow enhancements. The study of pulsatile flow over a coated mesh diverter showed that the formation of the primary vortex was prevented which prevents flow stagnation and downwash flow in the cavity. The second study indicates that the healthy heart cycle is essential to reducing flow stasis inside the left atrial appendage. After applying a synthetic slippery surface to the interior of a side wall cavity model, this surface reduced the wall shear stress and allowed vortical flow to reach deeper into the cavity.

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<p>Stroke is a devastating event for a patient. Patients undergoing cardiac surgery are at risk of both peri-operative and delayed stroke. This thesis comprises 8 chapters that highlight the rate of stroke in cardiac surgery patients and its risk predictors. It justifies the need for a randomized controlled trial of left atrial appendage (LAA) occlusion on top of usual antithrombotic therapy for stoke prevention in patients with atrial fibrillation or flutter.</p> <p>Chapter 1 is a preface that provides the rationale for undertaking each of the studies included within this thesis.</p> <p>Chapter 2 presents a large cohort study that examines the predictors of early and long-term stroke in patients undergoing cardiac surgery with emphasis on the impact of atrial fibrillation as well as the CHADS₂ score.</p> <p>Chapter 3 has been published in the journal <em>Circulation </em>in a modified form. A review of the current literature is presented, highlighting that although LAA occlusion holds promise for stroke prevention in AF, there is currently insufficient evidence that it can replace the gold standard of oral anticoagulation.</p> <p>Chapter 4 is a long-term follow-up study of the first Left Atrial Appendage Occlusion Study. This trial included patients undergoing coronary artery bypass grafting with or without AF. By performing a long-term follow-up of these patients, an estimate of stroke risk and risk of developing new AF was obtained.</p> <p>In Chapter 5, the results of LAAOS II are presented. This registry and pilot trial was used to assess the rate of recruitment into a novel design of a trial comparing LAA occlusion to antithrombotic therapy, LAA amputation safety, and the rate of a composite outcome of death, myocardial infarction, stroke, non-cerebral systemic emboli, and major bleeding.</p> <p>Chapter 6 presents the design for the LAAOS III trial. The data presented in the previous chapters is used to create the definitive trial of LAA occlusion on top of usual antithrombotic therapy using a prospective, randomized open trial with blinded end-point study (i.e., PROBE) design.</p> <p>Chapter 7 presents the health economic analysis plan for LAAOS III.</p> <p>Finally, Chapter 8 presents the conclusion, limitations, and implications of the research presented in my PhD thesis</p> / Doctor of Philosophy (PhD)

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The data obtained from computational fluid dynamics (CFD) simulations of blood flow in the heart is plentiful, and processing this data takes time and the procedure for that is not straightforward. This project aims to develop a tool that can semi-automatically process CFD simulation data, which is based on 4D flow computed tomography (CT) data, with minimal user input. The tool should be able to time efficiently calculate flow parameters from the data, and automatically create overview images of the flow field while doing so, to aid the user's analysis process. The tool is coded using Python programming language, and the Python scripts are inputted to the application ParaView for processing of the simulation data.  The tool generates 3 chamber views of the heart by calculating three points from the given patient data, which represent the aortic and mitral valves, and the apex of the heart. A plane is generated that pass through these three points, and the heart is sliced along this plane to visualize 3 chambers of the heart. The camera position is also manipulated to optimize the 3 chamber view. The maximum outflow velocity over the cardiac cycle in the left atrial appendage (LAA) is determined by searching in a time range around the maximum outflow rate of the LAA in a cardiac cycle, and finding the highest velocity value that points away from the LAA in this range. The flow component analysis is calculated in the LAA and left ventricle (LV) by seeding particles in each at the start of the cardiac cycle, and tracking these particles forwards and backwards in time to determine where the particles end up and come from, respectively. By knowing these two aspects, the four different flow components of the blood can be determined in both the LAA and LV.  The tool can successfully create 3 chamber views of the heart model from three semi-automatically determined points, at a manipulated camera location. It can also calculate the maximum outflow velocity of the flow field over a cardiac cycle in the LAA, and perform a flow component analysis of the LAA and the LV by tracking particles forwards and backwards in time through a cardiac cycle. The maximum velocity calculation is relatively time efficient and produces results similar to those found manually, yet the output is dependent on the user-defined inputs and processing techniques, and varies between users. The flow component analysis is also time efficient, produces results for the LV that are comparable to pre-existing research, and produces results for the LAA that are comparable to the LVs' results. Although, the extraction process of the LAA sometimes includes part of the left atrium, which impacts the accuracy of the results. After processing each part, the tool creates a single file containing each part's main results for easier analysis of the patient data. In conclusion, the tool is capable of semi-automatically processing CFD simulation data which saves the user time, and it has thus met all the project aims