Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstructs flow and increases pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the small pulmonary arteries due to CTEPH are not easily measurable. Using previously published hemodynamic measurements and imaging from a large animal model of CTEPH, we applied a subject-specific one-dimensional (1D) computational fluid dynamic (CFD) approach to investigate the impact of CTEPH on pulmonary artery stiffening, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) in extralobar (main, right, and left) pulmonary arteries and intralobar (distal to the extralobar) arteries. Our results demonstrate that CTEPH increases pulmonary artery wall stiffness and decreases TAWSS in extralobar and intralobar arteries. Moreover, CTEPH increases the percentage of the intralobar arterial network with both low TAWSS and high OSI, quantified by the novel parameter \(\varphi\), which is related to thrombogenicity. Our analysis reveals a strong positive correlation between increases in mean pulmonary artery pressure (mPAP) and \(\varphi\) from baseline to CTEPH in individual subjects, which supports the suggestion that increased \(\varphi\) drives disease severity. This subject-specific experimental–computational framework shows potential as a predictor of the impact of CTEPH on pulmonary arterial hemodynamics and pulmonary vascular mechanics. By leveraging advanced modeling techniques and calibrated model parameters, we predict spatial distributions of flow and pressure, from which we can compute potential physiomarkers of disease progression. Ultimately, this approach can lead to more spatially targeted interventions that address the needs of individual CTEPH patients.

慢性血栓栓塞性肺动脉高压 (CTEPH) 是由于肺血管系统中血凝块积聚阻碍血流并增加压力而引起的。驱动 CTEPH 进展的机械生物学因素尚不清楚，部分原因是 CTEPH 引起的小肺动脉的机械和血流动力学变化不易测量。利用先前发表的 CTEPH 大型动物模型的血流动力学测量和成像，我们应用特定于受试者的一维 (1D) 计算流体动力学 (CFD) 方法来研究 CTEPH 对肺动脉硬化、时间平均壁剪切的影响叶外（主、右、左）肺动脉和叶内（叶外远端）动脉的应力（TAWSS）和振荡剪切指数（OSI）。我们的结果表明，CTEPH 增加肺动脉壁硬度并降低叶外和叶内动脉的 TAWSS。此外，CTEPH 增加了具有低 TAWSS 和高 OSI 的叶内动脉网络的百分比，通过新参数\(\varphi\)进行量化，该参数与血栓形成有关。我们的分析显示，个体受试者中平均肺动脉压 (mPAP) 与从基线到 CTEPH的 varphi增加之间存在很强的正相关性，这支持了varphi增加会导致疾病严重程度的建议。这种针对特定主题的实验计算框架显示出作为 CTEPH 对肺动脉血流动力学和肺血管力学影响的预测因子的潜力。通过利用先进的建模技术和校准的模型参数，我们预测流量和压力的空间分布，从中我们可以计算疾病进展的潜在生理标志物。最终，这种方法可以带来更具空间针对性的干预措施，满足个别 CTEPH 患者的需求。