Quantification of Fontan Obstruction as a Marker for Quality of Life and Exercise Performance

摘要 单心室(SV)畸形是最复杂的先天性心脏病之一， 在美国，大约每1000名新生儿中就有2名受到影响。对于SV患者来说，最常见的姑息方法是分期 方坦手术。这一过程的最终结果是全腔静脉-肺连接术(TCPC)，旨在 串联体循环和肺循环。手术后的即时结果通常是 有利的。然而，各种长期的并发症困扰着丰坦人民，其中许多是 与Fontan梗阻有关。以前的研究将Fontan梗阻定义为血管狭窄或 TCPC中的能量升高；然而，它们往往忽略了患者的脑室表现， 脑室畸形的核心问题。因此，只观察到两者之间的弱相关性。 先前定义的Fontan梗阻和Fontan患者的长期并发症。因此，这 拟议的工作将集中在两个普遍的方坦并发症，生活质量下降(QOL)和 减少运动能力，以(1)确定Fontan梗阻的创新定义，包括 TCPC几何构型和/或TCPC血流动力学与心功能和(2)量化水平 新定义的Fontan梗阻对Fontan患者的最佳生活质量和运动表现的影响。二 具体目标将完成本项目：(1)量化Fontan梗阻作为生活质量的标志。 工作假设是集成了TCPC几何和/或TCPC的障碍度度量 血流动力学与静息状态下的心室功能将提供更好的方坦量化 梗阻，并可作为QOL的标志。(2)量化Fontan梗阻作为运动的标志 性能。该目标假设集成了TCPC几何和/或 TCPC血流动力学与心脏功能(在静息状态、运动状态和/或 休息-运动差值)将更好地量化Fontan梗阻，并作为 运动能力的标志。这两个目标都将使用尖端的、经过验证的计算流体动力学和 流体-结构相互作用模型以获得TCPC血流动力学和心脏性能， 分别进行了分析。拟议的工作具有很大的影响，因为它的目标是更好地量化丰坦阻塞 目的：改善方坦患者的生活质量和运动能力。此外，这项建议将加强 新成立的生物医学工程系的本科生研究与教育 在马萨诸塞大学洛厄尔分校。本科生参与这个项目将允许学生 体验各种最先进的技术，掌握医学影像等技能 处理和基于图像的心血管模拟。此外，学生们还将发展出广阔的 来自国家和国际机构的科学家和临床医生之间的伙伴关系网络。 1

SUMMARY Single ventricle (SV) malformations are among the most complex congenital heart defects (CHDs), affecting about 2 per 1000 births in the United States. Common palliation for SV patients is the staged Fontan procedure. This procedure culminates in a total cavopulmonary connection (TCPC), designed to connect systemic and pulmonary circulations in series. Immediate post-procedural outcomes are usually favorable. However, various long-term complications afflict the Fontan population, and many are associated with Fontan obstruction. Previous studies define Fontan obstruction as vessel narrowing or elevated energetics in the TCPC; however, they often overlook the performance of the patient’s ventricle, the core issue of SV malformations. Consequently, only weak correlations were observed between formerly defined Fontan obstruction and long-term complications in Fontan patients. Therefore, this proposed work will focus on two prevalent Fontan complications, diminished quality of life (QoL) and reduced exercise performance, to (1) identify an innovative definition of Fontan obstruction that integrates TCPC geometry and/or TCPC hemodynamics with ventricular performance and (2) to quantify the level of newly defined Fontan obstruction for optimal QoL and exercise performance in Fontan patients. Two specific aims will accomplish this project: (1) Quantify Fontan obstruction as a marker of quality of life. The working hypothesis is that an obstruction metric that integrates TCPC geometry and/or TCPC hemodynamics with ventricular performance at rest will provide a better quantification of Fontan obstruction and serve as a marker of QoL. (2) Quantify Fontan obstruction as a marker of exercise performance. This aim hypothesizes that an obstruction metric that integrates TCPC geometry and/or TCPC hemodynamics with ventricular performance (under resting conditions, exercise conditions, and/or the rest-exercise difference) will provide a better quantification of Fontan obstruction and serve as a marker of exercise capacity. Both aims will use cutting-edge, validated computational fluid dynamics and fluid-structure interaction modeling to obtain TCPC hemodynamics and ventricular performance, respectively. The proposed work is of great impact due to its goals of better quantifying Fontan obstruction to improve QoL and exercise performance for Fontan patients. Furthermore, this proposal will enhance undergraduate research and education for the recently established biomedical engineering department at the University of Massachusetts at Lowell. Undergraduate involvement in this project will allow students to experience a broad spectrum of state-of-the-art techniques and acquire skills such as medical image processing and image-based cardiovascular simulations. Additionally, the students will develop a vast network of partnerships among scientists and clinicians from national and international institutions. 1