Physical bench top experiments are performed to validate and complement ongoing computational fluid dynamics (CFD) analyses of ventricular assist device (VAD) circulation. VADs are used in patients whose hearts do not function to their maximum potential due advanced stages of heart disease and, consequently, are unable to adequately supply blood to the systemic circulation. VADs are commonly utilized as a bridge-to-transplantation, meaning that they are implanted in patients while waiting for a heart transplant. In such cases of long term utilization of VADs, it has been reported in the literatures that thrombo-embolic cerebral events occur in 14-47% of patients over the period of 6 to 12 months. This is a result of thrombus forming despite the use of anticoagulants and advances in VAD design. Accepting current rates of thrombo-embolisms, the main objective of the project is to identify and propose an optimal surgical cannula implantation orientation aimed at reducing the rate of thrombi reaching the carotid and vertebral arteries and thus reduce the morbidity and mortality rate associated with the long term use of VADs to patients suffering from advanced heart failure. The main focus of the experiment is on the physical aspect using a synthetic anatomically correct model constructed by rapid prototyping of the human aortic arch and surrounding vessels. Three VAD cannula implantation configurations are studied with and without bypass to the left carotid artery or to the Innominate artery with ligation of the branch vessel at its root. A mixture of water and glycerin serves to match blood viscosity measured with a rotating cone-plate viscometer. The Reynolds number in the ascending aorta is matched in the flow model. A closed loop mock circulatory system is then realized. In order to match the Reynolds number in the ascending aorta and LVAD cannula with that of the CFD model, a volumetric flow rate of 2.7 liters per minute is supplied through the synthetic VAD cannula and 0.9 liter per minute is supplied to the ascending aorta. Flow rates are measured using rotary flow meters and a pressure sensor is used to ensure a mean operating pressure of 100 mmHg is maintained. Synthetic acrylic blood iv clots are injected at the inlet of the VAD cannula and they are captured and counted at the vertebral and carotid arteries. The sizes of the thrombi simulated are 2, 3.5 and 5 mm which are typical of the range of diameters encountered in practice. Nearly 300 particles are released over 5 separate runs for each diameter, and overall embolization rates as well as individual embolization rates are evaluated along with associated confidence levels. The experimental results show consistency between CFD and experiment. Means comparison of thromboembolization rates predicted by CFD and bench-top results using a Z-score statistic with a 95% confidence level results in 22 of 24 cases being statistically equal. This study provides confidence in the predictive capabilities of the bench-top model as a methodology that can be utilized in upcoming studies utilizing patient-specific aortic bed model.

Aortic aneurysms are the 14th leading cause of death in the United States. Annually, abdominal aortic aneurysm (AAA) ruptures are responsible for 4500 deaths. There are another 45,000 repair procedures performed to prevent rupture, and of these approximately 1400 lead to deaths. With proper detection, the aneurysm may be treated using endovascular aneurysm repair (EVAR). Understanding how the flow of the blood within the artery is affected by the aneurysm is important in determining the growth of the aneurysm, as well as how to properly treat the aneurysm. The goal of this project was to develop a physical construct of the AAA, and use this construct to validate a computational model of the same aneurysm through flow visualization. The hypothesis was that the fluid velocities within the physical construct would accurately mimic the fluid velocities used in the computational model. The physical model was created from a CT scan of an AAA using 3D printing and polymer casting. The result was a translucent box containing a region in the shape of the aneurysm. Fluid was pumped through the construct to visualize and quantify the velocity of the fluid within the aneurysm. COMSOL Multiphysics® was used to create a computational model of the same aneurysm, as well as obtain velocity measurements to statistically compare to those from the physical construct. There was no significant difference between the velocity values for the physical construct and the COMSOL Multiphysics® model, confirming the hypothesis. This study used a CT scan to create an anatomically accurate model of an AAA that was used to validate a computational model using a novel technique of flow visualization. As EVAR technologies continue to progress, it will become increasingly important to understand how the blood flow within the aneurysm affects the growth and treatment of AAAs.

Ischemia caused by particles becoming dislodged during transcatheter aortic valve replacement (TAVR) is a possible complication of TAVR. The particles that become dislodged can travel out of the aortic valve, into the aortic arch, and then into either the brachiocephalic artery, the left common carotid artery, the left subclavian artery or continue into the descending aorta. If the particles continue into the descending aorta it poses no risk of causing ischemia however if it travels into the other arteries then it increases the possibility of the particle causing an ischemic event. The goal of this study is to determine what parameters cause the particle to enter one artery over another. The parameters analyzed are the particle diameter, the particle density, the blood pressure, and the diameter of the catheter used in the surgery. This was done by creating a finite element model in COMSOL Multiphysics® to track the particles flowing through a scan of an actual aortic arch. It was determined that the particle diameter, particle density, and the blood pressure affect which artery the particles take to exit the aortic arch. However the diameter of the surgical catheter used in a transaortic approach is not statistically significant when determining which artery the particles will exit. The study shows that larger diameter particle would lead to a higher transmissions probability into the brachiocephalic artery, the left common carotid artery, and the left subclavian artery while a smaller diameter particle would have a higher transmission probability for the descending aorta. Averaging all particle diameters, densities and blood pressure found that 54.95 ± 13.66% of the particles released will travel into the cerebral circulatory system.

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Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6–62.0) v/s 45.4 (32.6–58.1), p = 0.207) and STS-PROM (1.8 (1.6–2.1) v/s 1.9 (1.4–2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort

Heart valve disease is currently one of the leading forms of heart disease. Current literature has shown that endothelin I, angiotension II and 5-HT are vasoactive agents which cause concentration dependent contractions in aortic valve leaflet tissue. This study tested the mechanical properties of leaflets cut in the radial direction after they were exposed to the agents at varied concentrations or for 0.5, 6 or 24 hours. The elastic modulus, ultimate tensile strength and the yield strength were calculated. In the time trials the elastic modulus and the ultimate tensile strength both showed a significant increase at 24-hours. However, there were no significant differences found between the concentrations. Indicating the amount of vasoactive agent is not as significant as the length of exposure.

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京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第23819号 / 社医博第119号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 湊谷 謙司, 教授 永井 純正, 教授 波多野 悦朗 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM