Aortic stenosis is the most common valvular heart disease in the Western world and its prevalence is growing with an aging population. The current preferred method of treatment is complete valve replacement with a surgically implanted prosthetic valve. However, for high-risk patients with advanced age and co- morbidities, operative mortality escalates. Recently, minimally invasive transcatheter aortic valve (TAV) implantation has been investigated as an endovascular alternative to surgical valve replacement. Although significant experience has been gained, TAV implantation clinical trials have been associated with complications such as device migration, paravalvular leakage, coronary obstruction, and access site injury. Furthermore, the long-term durability and safety of TAV prostheses are largely unknown and must be evaluated and studied carefully. To gain a quantitative understanding of the biomechanics involved in TAV intervention, our objectives in this project are to develop probabilistic computational models to investigate aortic tissue-TAV structural interaction and hemodynamics under a variety of patient conditions, and to offer scientific rationale for TAV patient screening and TAV design improvement. To accomplish these goals, the following specific aims are proposed: 1) Investigation of elastic properties and microstructure of the human stenotic aortic root through a series of biomechanical tests performed on 50 human cadaver hearts;2) Image analysis of clinical CT scans, which will yield 60 reconstructed patient-specific aortic valve geometries. Statistical shape models will be developed to facilitate the reconstruction process as well as the description of anatomic geometric variation among the patient population;and 3) Probabilistic computational analysis of aortic tissue-TAV structural interaction and hemodynamics. Deterministic finite element (FE) models and computational fluid dynamics (CFD) models will be developed using 12 actual TAV patient data measured prior to the TAV intervention, and validated by the post-TAV clinical CT scans, flow and pressure measurements. A statistical description of patient material properties and geometric variations will be mapped into the computational models and a probabilistic analysis will be conducted to evaluate aortic tissue-TAV structural interaction and hemodynamics. The fundamental study of the biomechanics involved in TAV intervention and the computational modeling of tissue-implant interaction proposed here could lead to the development of a new knowledgebase that has been previously unavailable to academia, clinicians, and the heart valve industry. The methodologies and computational framework developed in this study will serve as a basis for future studies, which will include more design and environmental variables such as different patient demographics, and could also be utilized to facilitate the development of other novel device designs or pre-operative patient screening techniques for different valve diseases, such as mitral valve regurgitation.

Public Health Relevance

Project Narrative Transcatheter aortic valve implantation could potentially revolutionize current surgical valve replacement procedure, and extend the lives of thousands of frail patients who currently are not considered suitable candidates for open-heart valve surgery. This research is to investigate the biomechanics involved the transcatheter valve procedure using a combined experimental and computational modeling approach, and to provide scientific rationale for patient screening and TAV design improvement.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL104080-01A1
Application #
8187827
Study Section
Special Emphasis Panel (ZRG1-BST-E (90))
Program Officer
Baldwin, Tim
Project Start
2011-08-20
Project End
2016-06-30
Budget Start
2011-08-20
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$421,993
Indirect Cost
Name
University of Connecticut
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
614209054
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269
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Madukauwa-David, Immanuel David; Pierce, Eric L; Sulejmani, Fatiesa et al. (2018) Suture dehiscence and collagen content in the human mitral and tricuspid annuli. Biomech Model Mechanobiol :
Murdock, Kyle; Martin, Caitlin; Sun, Wei (2018) Characterization of mechanical properties of pericardium tissue using planar biaxial tension and flexural deformation. J Mech Behav Biomed Mater 77:148-156
Kong, Fanwei; Pham, Thuy; Martin, Caitlin et al. (2018) Finite Element Analysis of Tricuspid Valve Deformation from Multi-slice Computed Tomography Images. Ann Biomed Eng 46:1112-1127

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