ABSTRACT
Multiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed. The framework replicates the 2-month arterial wall remodeling in response to the PTA-induced injury and altered hemodynamics, by combining three modules: (i) the PTA module, consisting in a finite element structural mechanics simulation of PTA, featuring anisotropic hyperelastic material models coupled with a damage formulation for fibrous soft tissue and the element deletion strategy, providing the arterial wall damage and post-intervention configuration, (ii) the hemodynamics module, quantifying the post-intervention hemodynamics through computational fluid dynamics simulations, and (iii) the tissue remodeling module, based on an agent-based model of cellular dynamics. Two scenarios were explored, considering balloon expansion diameters of 5.2 and 6.2 mm. The framework captured PTA-induced arterial tissue lacerations and the post-PTA arterial wall remodeling. This remodeling process involved rapid cellular migration to the PTA-damaged regions, exacerbated cell proliferation and extracellular matrix production, resulting in lumen area reduction up to 1-month follow-up. After this initial reduction, the growth stabilized, due to the resolution of the inflammatory state and changes in hemodynamics. The similarity of the obtained results to clinical observations in treated SFAs suggests the potential of the framework for capturing patient-specific mechanobiological events occurring after PTA intervention.
Subject(s)
Femoral Artery , Hemodynamics , Models, Cardiovascular , Humans , Femoral Artery/physiopathology , Femoral Artery/injuries , Angioplasty , Patient-Specific ModelingABSTRACT
The transaortic valvular pressure gradient (TPG) plays a central role in decision-making for patients suffering from severe aortic stenosis. However, the flow-dependence nature of the TPG makes the diagnosis of aortic stenosis challenging since the markers of cardiac performance and afterload present high physiological interdependence and thus, isolated effects cannot be measured directly in vivo. We used a validated 1D mathematical model of the cardiovascular system, coupled with a model of aortic stenosis, to assess and quantify the independent effect of the main left ventricular performance parameters (end-systolic (Ees) and end-diastolic (Eed) elastance) and principal afterload indices (total vascular resistance (TVR) and total arterial compliance (TAC)) on the TPG for different levels of aortic stenosis. In patients with critical aortic stenosis (aortic valve area (AVA) ≤ 0.6 cm2), a 10% increase of Eed from the baseline value was associated with the most important effect on the TPG (-5.6 ± 0.5 mmHg, p < 0.001), followed by a similar increase of Ees (3.4 ± 0.1 mmHg, p < 0.001), in TAC (1.3 ±0.2 mmHg, p < 0.001) and TVR (-0.7 ± 0.04 mmHg, p < 0.001). The interdependence of the TPG left ventricular performance and afterload indices become stronger with increased aortic stenosis severity. Disregarding their effects may lead to an underestimation of stenosis severity and a potential delay in therapeutic intervention. Therefore, a comprehensive evaluation of left ventricular function and afterload should be performed, especially in cases of diagnostic challenge, since it may offer the pathophysiological mechanism that explains the mismatch between aortic severity and the TPG.
