A multiscale model of vascular function in chronic thromboembolic pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a debilitating disease that includes five main subgroups, but only one is curable: chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is caused by recurrent or unresolved pulmonary thromboemboli, leading to perfusion defects and increased arterial wave reflection. Treatment for CTEPH depends on lesion location and severity, and patients with distal lesions are inoperable by standard surgical intervention. Instead, these patients are treated with balloon pulmonary angioplasty (BPA), a multi-session, minimally invasive surgery that disrupts the thromboembolic material blocking the vessel lumen using a catheter balloon. The goal of BPA is to reduce pulmonary arterial pressure and reestablish adequate blood flow to all regions of the lung. However, there still lacks an integrative, holistic tool for identifying target lesions for an optimal treatment. To address this insufficiency, we provide a proof of concept study simulating CTEPH hemodynamics and BPA therapy using a multiscale, one-dimensional (1D) fluid dynamics model. The large pulmonary arterial geometry is derived from a computed tomography (CT) image, whereas a fractal, structured tree represents the small vessels. We model ring-and web-like lesions, common in CTEPH, using two pressure-loss terms. We simulate normotensive conditions and four CTEPH disease scenarios; the latter includes 20 large artery lesions and introduces both local and global vascular remodeling. BPA therapy is simulated by simultaneously reducing lesion severity in three locations. Our predictions mimic severe CTEPH, manifested by an increase in mean proximal pulmonary arterial pressure above 20 mmHg and prominent wave reflections. Both flow and pressure decrease in vessels distal to the lesions and increase in unobstructed vascular regions. We use the main pulmonary artery (MPA) pressure, a wave reflection index, and a measure of flow heterogeneity to select optimal target lesions for BPA. In summary, this study provides a preliminary multiscale, image-to-hemodynamics pipeline for BPA therapy planning for inoperable CTEPH patients.