Publication Date
2021
Document Type
Dissertation
Committee Members
Philippe Sucosky, Ph.D. (Advisor); George P.G. Huang, Ph.D. (Committee Member); Zifeng Yang, Ph.D. (Committee Member); K. Jane Grande-Allen, Ph.D. (Committee Member); Sundeep Keswani, M.D. (Committee Member)
Degree Name
Doctor of Philosophy (PhD)
Abstract
Discrete subaortic stenosis (DSS) is an obstructive cardiac disease characterized by the formation of a thin fibromuscular ring of tissue in the left ventricular (LV) outflow tract (LVOT). Although its etiology is unknown, the association between DSS, pediatric age, and morphological LVOT abnormalities points to a potential hemodynamic etiology. Here, altered subaortic flow dynamics, stemming from deviated LVOT anatomy, may promote lesion formation through local fluid shear stress abnormalities triggering membrane formation. The assessment of this hypothetical pathway requires elucidation of the complex LV wall shear stress (WSS) environment. The central hypothesis of this dissertation is that altered LV hemodynamics, generated from LVOT anatomical defects associated with DSS, play a focal role in DSS pathogenesis by promoting WSS abnormalities at the site of lesion formation. The objective, therefore, is to quantify computationally abnormal hemodynamics associated with DSS pathogenesis and characterize the complex WSS environments in normal and DSS-prone LVOT anatomies. Cine cardiac MRI images were segmented to reconstruct a 3D LV geometry, and patient-specific ventricular deformation was imposed via a one-way fluid-structure interaction technique in ANSYS 2019 R3. The hemodynamic results showed good agreement both with patient data and with published LV flow fields and was able to provide in-depth characterization of LVOT blood flow. Then, four geometries with aortoseptal angles (AoSA) varying from 160° to 115° were generated to span the physiologic range reported in the literature. The cycle-averaged LV WSS environments were characterized in terms of cycle-averaged pressure, the temporal shear magnitude (TSM), and oscillatory shear index (OSI). The WSS topological skeleton was also computed to map the complex features of the WSS vector field. The results indicated that progressive AoSA steepening contributed to an increasingly disturbed subaortic flow environment coupled with increasing hemodynamic stress abnormalities preferentially along the inferior LVOT. These were characterized by substantial reductions in pressure and a colocalization between WSS overloads and intense luminal contraction. Finally, echocardiographic data taken from recent DSS resection patients (DSS-prone; n = 40) and healthy individuals (control; n = 40) were used to generate additional LV geometries. Variations in LV and LVOT anatomy were parametrized by segregating the patient data into four age ranges (1-2 y/o, 3-5 y/o, 6-8 y/o, and >9 y/o; n = 8 total cases), from which representative geometries were generated. The averaged location of DSS development was identified and specified as a region of interest as well. The results indicated significant LVOT morphological abnormalities and substantial subaortic hemodynamic alterations in the DSS-prone group, which were acutely impacted by increasing age. In conclusion, this dissertation indicated and thoroughly explored the causality between altered LVOT anatomy and WSS abnormalities. This work, for the first time, provided key mechanistic insights into a disease process that is poorly understood, and gave compelling evidence for (1) the existence of a mechano-etiology for DSS, and (2) the potential role played by abnormal WSS in DSS lesion development.
Page Count
230
Department or Program
Ph.D. in Engineering
Year Degree Awarded
2021
Copyright
Copyright 2021, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may not be modified. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
