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. We develop a biomimetic respiratory simulator with integrated circulatory Fontan flow loop that shows high physiological fidelity. Vascular models with physiological compliance values interact with the respiratory mechanics to recreate characteristic Fontan flow. We characterize the simulator and validate the system with a computational lumped parameter model and a pilot clinical trial. We then extend the platform a computational fluid dynamics model of the Fontan shunt. We leverage the cardiorespiratory simulator to characterize the impact of breathing and other physiological parameters. We conduct a clinical trial to evaluate respiratory effects Fontan retrograde flow. Thereby, we identify and characterize new physiological drivers. Subsequently, we conduct a retrospective study to evaluate clinical effects this flow reversal. Finally, we design and test circulatory support strategies and establish the importance to tailor them to the unique flow patterns. We 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.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Harvard-MIT Program in Health Sciences and Technology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2022

Author dc:creator

• Horvath, Markus Attila

Advisor dc:contributor.advisor

• Roche, Ellen T.

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright MIT

Licence dc:rights.uri

• http://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/144552

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/144552