Role of Animal Models in Transcatheter Valve Intervention: A Mechanistic, Age-dep

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DESCRIPTION (provided by applicant): Minimally invasive transcatheter aortic valve (TAV) intervention holds promise for a large number of high- risk patients (advanced age and/or with co-morbidities) who might otherwise have limited or no treatment options. Although significant experience has been gained through animal and human clinical trials, disparity between the results of animal trials and those of human trials often exists. In this proposal, we hypothesize that 1) significant differences in the mechanical properties and the anatomic structure exist between animal and human valve tissues, and 2) the biomechanical interaction between a TAV implant and the hosting aortic tissue is significantly different in an animal than in a human. If the above hypotheses are tested to be true, it will raise questions on the validity of animal trials in transcatheter valve intervention. If either of the hypotheses is tested to be false, the study can provide insight on interpreting differences between animal and human trial results to facilitate device development and clinical trials. In a preliminary study, we have found that significant differences in mechanical properties exist between 6-9 months porcine and ~90 year old human aortic tissues. To further test if the hypothesis 1 is valid for other age groups of pig, sheep and human, in this study, aortic tissues of 1- and 2-year old pigs, 6-9 months, 1- and 2-year old sheep, and 60- and 75-year old humans will be studied. To test both of hypotheses, specifically, we propose the following specific aims: 1) Investigation of mechanical property difference between animal and aged human aortic roots at different age groups; 2) Investigation of anatomic structural difference between animal and aged human aortic roots; 3) Investigation of responses of TAV deployment into animal and aged human aortic roots. Project milestones are to: 1) establish databases (knowledge-bases) of mechanical properties and anatomic structures of porcine, ovine and human aortic roots from different age groups, 2) clarify the role of animal trials in TAV intervention and 3) at the conclusion, have sufficient data to warrant a R01 study of TAV-aortic root interaction with thromboembolic and flow dynamic effects. PUBLIC HEALTH RELEVANC: Aortic stenosis affects many individuals of the elderly population, and its prevalence is increasing with an aging population. Transcatheter aortic valve (TAV) replacement is now being investigated as an alternative endovascular, minimally invasive treatment option. This study is related to the investigation of applicability of animal (porcine and ovine) models in transcatheter aortic valve clinical trials. Age-dependency of animal aortic tissue properties will be quantified. Computational modeling will be utilized to elucidate different interactive responses when a TAV device is deployed into animal and human aortic roots of various age groups.