The ability to accurately and in a repeatable fashion, measure aortic valve dimensions during aortic valve repair is critical to the restoration of function in a diseased aortic valve, as for example in aortic insufficiency. Although several methods for measuring aortic valve dimensions have been shown to be feasible, they are approximate and lack the accuracy, robustness, and repeatability one would expect to support aortic valve repair surgery. In addition, they do not allow for the intra-operative measurement of aortic valves under conditions equivalent to the physiological (pressurized) state. A prototype medical device was designed, and 3-D printed at the University of Ottawa that would allow cardiac surgeons performing aortic valve repair to do just that. The prototype was tested for its accuracy and precision at the University of Ottawa Heart Institute using porcine aortic valves. Based on unsatisfactory results of this experimentation, namely, that the device was applying forces that were too large, a numerical simulation study was designed using a commercial finite element software LS-DYNA. This simulation study was used to explore the forces that the prototype device needed to apply to obtain end-diastolic pressurized dimensions of the aortic valve. The simulation study showed that one single device was likely not possible to obtain measurements in an aortic valve. However, a system of two devices could be imagined, one to measure the STJ diameter and free margin length of the aortic valve cusps, and one to measure the cusp height of the same valve, for the purposes of aortic valve repair.

No description available.

Transcatheter aortic valve implantation (TAVI) is an effective alternative treatment option for patients with severe aortic stenosis, who are at a high risk for conventional surgical aortic valve replacement or considered inoperable. Despite the short- and mid-term survival benefits of TAVI, adverse clinical events, such as paravalvular leak, aortic rupture, and coronary occlusion, have been reported extensively. Many of these adverse events can be explained from the biomechanics perspective. Therefore, an in-depth understanding of biomechanical interaction between the device and native tissue is critical to the success of TAVI. The objective of this thesis was to investigate the biomechanics involved in the TAVI procedure using patient-specific finite element (FE) simulations. Patient-specific FE models of the aortic roots were reconstructed using pre-procedural multi-slice computed tomography images. The models incorporated aged human aortic material properties with material failure criteria obtained from mechanical tests, and realistic stent expansion methods. TAV deployment and tissue-device interaction were simulated; and the simulation results were compared to the clinical observations. Additionally, parametric studies were conducted to examine the influence of the model input on TAVI simulation results and subsequently the potential clinical complications such as paravalvular leak, annular rupture, and coronary artery occlusion. The methodology presented in this thesis could be potentially utilized to develop valuable pre-procedural planning tools to evaluate device performance for TAVI and eventually improve clinical outcomes.

Aortic valve disease (AVD) affects millions of people of all ages around the world. Current treatment for AVD consists of valvular replacement with a non-living prosthetic valve, which is incapable of growth, self-repair, or remodeling. While tissue engineering has great promise to develop a living heart valve alternative, success in animal models has been limited. This may be attributed to the fact that understanding of valvular cell biology has not kept pace with advances in biomaterial development. Aortic valve leaflets are exposed to a complex and dynamic mechanical environment unlike any in the vasculature, and it is likely that native endothelial and interstitial cells respond to mechanical forces differently from other vascular cells. The objective of this thesis was to compare valvular cell phenotype to vascular cell phenotype, and assess the influence of steady shear stress on valvular cell biology. This thesis demonstrates that valvular endothelial cells respond differently to shear than vascular endothelial cells, by aligning perpendicular to the direction of steady shear stress, and by the differential regulation of hundreds of genes in both static and fluid flow environments. Valvular interstitial cells expressed a combination of contractile and synthetic phenotypes not mimicked by vascular smooth muscle cells. Two three-dimensional leaflet models were developed to assess cellular interactions and the influences of steady laminar shear stress. Valvular co-culture models exhibited a physiological response profile, while interstitial cell-only constructs behaved more pathologically. Steady shear stress enhanced physiological functions of valvular co-cultures, but increased pathological response of interstitial cell-only constructs. These results showed that valvular cells, whether cultured separately or together, behaved distinctly different from vascular cells. It was also determined that shear stress alone cannot induce tissue remodeling to more resemble native valve leaflets. The leaflet models developed in this thesis can be used in future experiments to explore valvular cell biology, assess the progression of certain forms AVD, and develop targeted diagnostic and therapeutic strategies to hopefully eliminate the need for valvular replacement entirely.

Thesis (M.S.)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references (leaves 67-69).

There is growing interest in using large-scale observational data collected through national disease registries to develop clinical prediction models (CPMs) that use the experiences of past patients to make predictions about risks of outcome in future patients. CPMs are often developed in isolation across different populations, with repetitive de novo development a common modelling strategy. However, this fails to utilise all available information and does not respond to changes in health processes through time/space. Using the UK transcatheter aortic valve implantation (TAVI) registry as motivation, this thesis aimed to develop methods that improve the development of CPMs within local populations. Three research questions (RQs) were considered: (1) what are the challenges of mortality risk prediction in TAVI due to changes in procedure knowledge and the patient population? (2) Can we use a combination of baseline patient characteristics to predict the risk of mortality post TAVI? (3) How can we exploit multi-dimensional information about patients to inform clinical decision-making at a local-level? Chapter 2 demonstrates potential to simplify the procedure by removing pre-dilation of the aortic valve, thereby altering the underlying treatment pathway, and Chapter 3 shows that mortality rates from registries should be reported in the context of the underlying patient population. Despite Chapter 2 and 3 presenting potential challenges to TAVI risk prediction (RQ 1), CPMs are fundamental to support benchmarking/audit analyses. To this end, Chapter 4 found that the performance of existing TAVI CPMs was inadequate for use in UK patients. Through the discovery of new risk factors (e.g. frailty) in Chapter 5, the thesis derived a UK-TAVI CPM for audit analyses within the UK cohort (Chapter 6). While Chapters 4-6 present the classic framework of CPM development (RQ 2), this cannot overcome the challenges of mortality prediction in the TAVI setting (RQ 1) and is not suited to support local healthcare decision-making (RQ 3). Thus, Chapter 7 found that local model development could be supported through aggregating existing models rather than re-development. Existing methods of model aggregation were extended in Chapter 8 to allow prior research and new data to be utilised within the modelling strategy; application of the herein derived method to the UK TAVI registry indicated that it could facilitate the choice between model aggregation and de novo CPM derivation. Generally, this thesis has the potential to improve the implementation of CPMs within local populations by moving away from the iterative process of re-development. Practically, the thesis derived a UK-TAVI CPM for audit analyses, using classic and novel methodology.

OBJECTIVE: This study aims to corroborate recent research demonstrating that patients with low body mass indexes tend to have worse postoperative survival outcomes compared to normal BMI patients. It also intends to compare survival outcomes and postoperative complications in transcatheter and surgical aortic valve replacement patients to determine which procedure, TAVR or SAVR respectively, is better for this challenging low BMI patient population. METHODS: This is a retrospective, single-center study comparing patient data collected from 2000-2013 at New York Presbyterian Hospital/Columbia University Medical Center. Patients were dividing into three groups on the basis of BMI and aortic valve procedure: low BMI SAVR (BMI < 22 kg/m2; n = 148; 20.36%), normal BMI SAVR (22-25 kg/m2; n = 458; 63.00%), and low BMI TAVR (< 22 kg/m2; n = 121; 16.64%). There is a total of 606 SAVR patients and 121 TAVR patients. To corroborate recent research that low BMI patients tend to fare worse than normal BMI patients, an unadjusted comparison were used to compare baseline demographics and postoperative outcomes of 148 low BMI patients who underwent SAVR with 458 normal BMI patients who underwent isolated SAVR. These cohorts were then compared via a Kaplan-Meier survival analysis and the log-rank test for 30 days, 6 months, 1 year and 3 years survival outcomes. The 148 low BMI SAVR patients were then compared to 121 low BMI patients who underwent TAVR on baseline demographics and preoperative risk factors. The two cohorts were compared using the Kaplan-Meier analysis and postoperative complications were compared utilizing a multivariable logistic regression after adjustment for age, gender, BMI and STS Scores. RESULTS: The unadjusted analysis of the low BMI and normal BMI SAVR cohorts displayed similar patient demographics and preoperative risk factors. The normal BMI group demonstrated higher EF (55% vs. 51.5%; p = 0.002) and incidence of HLD (47.68% vs. 37.76%; p = 0.038). Conversely, the low BMI cohort had more females (61.49% vs.42.79%; p < 0.001) and individuals with a history of Afib (27.78% vs.16.96%; p = 0.004). As shown in the Kaplan Meier curve, the normal BMI SAVR patients exhibited superior 6 months, 1 year and 3 years survival rates and low BMI was shown to be a significant independent predictor of mortality (HR 2.56; 95% CI: 1.47 – 4.47; p = 0.0009 at 1 year). The two groups had similar postoperative outcomes, however, the low BMI cohort had longer overall hospital stays (8 vs. 6.5 days; p = 0.0003). The low BMI SAVR and TAVR patient cohorts varied significantly on most patient demographics and preoperative risk factors. The low BMI TAVR patients tend to be older (95.04% vs. 55.41% of patients > 75 years old) and had higher STS Scores (10.41 vs. 3.88; p < 0.0001). They also demonstrated significant increases in all the preoperative risk factors excluding DM and prior CVA. The SAVR patients had significantly longer overall hospital stays (8 vs. 6 days; p < 0.0001), more re-exploration for bleeding (5.41% vs. 0.85%; p = 0.0411) and more patients discharged to home (68.24% vs. 50.85%; p = 0.0039) while the TAVR patients demonstrated higher rates of GI bleed (3.39% vs. 0.00%; p = 0.0240) and new PPM (10.17% vs. 0.68%; p = 0.0004). The low BMI SAVR cohort demonstrated better survival rates at 1 year and 3 years and low BMI TAVR was determined to be a significant independent predictor of mortality (HR 0.51; 95% CI: 0.30 – 0.88; p = 0.0146 at 1 year). After controlling for specific covariates in the multivariate logistic regression analysis, the low BMI SAVR had 1.73 times longer ICU stays, 1.90 times longer hospital stays and the odds of being discharged home was 17% less than the TAVR group (p = 0.0005, <0.0001, 0.5665). CONCLUSION: Although the rates of postoperative complications are fairly similar, patients with low BMIs demonstrated worse survival outcomes when compared to the normal BMI SAVR patients. With the current analysis, low BMI TAVR patients had a significantly worse preoperative profile compared to the corresponding SAVR cohort which explains the worse survival and postoperative outcomes. Despite this, the multivariable analysis showed that the low BMI SAVR patients had longer ICU and hospital stays as well as fewer discharges to home. As this is an ongoing study, steps should be made to balance the preoperative profile such that the low BMI SAVR and TAVR groups are comparable prior to survival and postoperative assessment. However, at the current status, TAVR has proven itself to be the preferred treatment for low BMI patients. / 2018-07-13T00:00:00Z

Made available in DSpace on 2016-07-01T13:10:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-12. Added 1 bitstream(s) on 2016-07-01T13:14:12Z : No. of bitstreams: 1 000866809.pdf: 1747343 bytes, checksum: 1bd62536c1ab61130611dd2e937d842f (MD5) / Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the...

Orientador: Paula Schmidt Azevedo Gaiolla / Coorientador: Marcos Ferreira Minicucci / Banca: Meliza Goi Roscani / Banca: Bertha Furlan Polegato / Banca: Paula Felippe Martinez / Resumo: Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / Abstract: The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the... / Doutor

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13421号 / 論医博第2229号 / 新制||医||1052(附属図書館) / (主査)教授 伊達 洋至, 教授 大鶴 繁, 教授 中山 健夫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM