Dobutamine stress testing in patients with Fontan circulation augmented by biomechanical modeling

Understanding (patho)physiological phenomena and mechanisms of failure in patients with Fontan circulation—a surgically established circulation for patients born with a functionally single ventricle—remains challenging due to the complex hemodynamics and high inter-patient variations in anatomy and function. In this work, we present a biomechanical model of the heart and circulation to augment the diagnostic evaluation of Fontan patients with early-stage heart failure. The proposed framework employs a reduced-order model of heart coupled with a simplified circulation including venous return, creating a closed-loop system. We deploy this framework to augment the information from data obtained during combined cardiac catheterization and magnetic resonance exams (XMR), performed at rest and during dobutamine stress in 9 children with Fontan circulation and 2 biventricular controls. We demonstrate that our modeling framework enables patient-specific investigation of myocardial stiffness, contractility at rest, contractile reserve during stress and changes in vascular resistance. Hereby, the model allows to identify key factors underlying the pathophysiological response to stress in these patients. In addition, the rapid personalization of the model to patient data and fast simulation of cardiac cycles make our framework directly applicable in a clinical workflow. We conclude that the proposed modeling framework is a valuable addition to the current clinical diagnostic XMR exam that helps to explain patient-specific stress hemodynamics and can identify potential mechanisms of failure in patients with Fontan circulation.

探究方坦循环（Fontan circulation）患者的病理生理现象与衰竭机制——方坦循环是为先天性功能性单心室（functionally single ventricle）患者建立的外科循环通路——目前仍因复杂的血流动力学特征、解剖与功能层面显著的个体间差异而颇具挑战。本研究构建了一套心脏与循环系统的生物力学模型（biomechanical model），用于辅助早期心力衰竭方坦患者的诊断评估工作。所提出的框架采用降阶心脏模型（reduced-order model），结合包含静脉回流的简化循环系统，构建闭环系统。我们将该框架应用于辅助分析联合心脏导管与磁共振检查（XMR）所获数据，该检查在静息及多巴酚丁胺负荷（dobutamine stress）状态下完成，受试者包括9名方坦循环患儿与2名双心室对照患儿。研究结果证实，本建模框架可实现针对患者个体的心肌僵硬度（myocardial stiffness）、静息状态下收缩能力、负荷状态下收缩储备（contractile reserve）以及血管阻力变化的个性化分析。借此，该模型可识别此类患者对应激产生病理生理反应的关键影响因素。此外，该模型可快速适配患者个体数据并快速完成心动周期模拟，使其可直接应用于临床工作流程（clinical workflow）。综上，本研究所提出的建模框架可作为当前临床XMR诊断检查的有效补充，有助于阐释患者个体的应激血流动力学特征，并可助力探明方坦循环患者心力衰竭的潜在机制。