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A multimodal approach to investigate the effects of respiration on Fontan flow to inform strategies for circulatory support
The prevalence of single ventricle physiology is estimated to be 1/3000. Fontan physiology is the final palliative stage for a series of congenital heart diseases resulting in a single ventricle. Resulting hemodynamics are not well characterized and remain poorly understood. Hence, mid-term survival rates remain high and suitable circulatory support strategies are undetermined. At the core of this clinical problem lies a limited understanding of the interactions of respiration, hemodynamics, and tissue damage. Respiration has been identified to govern flow fluctuation including retrograde flow in the Fontan IVC but bench top simulators and animal models fail to recreate the interaction of breathing and venous flow adequately.
The goal of this dissertation is to develop and validate a suit of bench top and computational models which recapitulate the interaction of respiratory biomechanics and Fontan flow, to leverage the simulator platform and a clinical study to characterize the respiratory impact on Fontan hemodynamics and retrograde flow, and to design and evaluate promising approaches for the circulatory support.
First, we develop and validate a biomimetic respiratory simulator with integrated circulatory Fontan flow that shows high physiological fidelity. Then we leverage the cardiorespiratory simulator and a clinical study of 20 patients to characterize the impact of breathing and other physiological parameters. Thereby, we identify and characterize new physiological drivers of retrograde flow in the Fontan circulation.
Finally, we design and test circulatory support strategies and establish the importance to tailor them to the unique flow patterns of the Fontan flow. We show potential benefits of valve implantation in the Fontan IVC and optimize the device design.
In summary, this work provides a multimodal simulator platform paired with a clinical trial to provide deeper understanding of the Fontan physiology. The platform is a valuable tool for circulatory support development as we demonstrate here.
Thesis Supervisor:
Ellen Roche, PhD
W.M. Keck Career Development Professor in Biomedical Engineering; Associate Professor of Mechanical Engineering and of the Institute for Medical Engineering & Science, MIT
Thesis Committee Chair:
Thomas Heldt, PhD
Associate Professor of Electrical and Biomedical Engineering, Department of Electrical Engineering & Computer Science; Core faculty member, Institute for Medical Engineering and Science, MIT
Thesis Committee Member:
Pedro J. del Nido, MD
William E. Ladd Professor of Child Surgery, HMS; Chairman, Department of Cardiac Surgery, Boston Children’s Hospital
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Topic: Markus Horvath PhD Thesis Defense
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