Atheroprone sites of coronary artery bifurcation: Effect of heart motion on hemodynamics-dependent monocytes deposition

https://doi.org/10.1016/j.compbiomed.2021.104411Get rights and content

Highlights

  • The heart motion, and real velocity profile at the inlet are applied.

  • Monocyte deposition is calculated using Lagrangian method since it is correlated with the LDL deposition.

  • The deposition of monocytes increases near the LAD-D1 bifurcation and myocardial wall due to heart motion.

Abstract

Atherosclerosis as a common cardiovascular disease is a result of both adverse hemodynamics conditions and monocyte deposition within coronary arteries. It is known that the adhesion of monocytes on the arterial wall and their interaction with the vascular surface are one of the main parameters in the initiation and progression of atherosclerosis. In this work, hemodynamic parameters and monocyte deposition have been investigated in a 3D computational model of the Left Anterior Descending coronary artery (LAD) and its first diagonal branch (D1) under the heart motion. A one-way Lagrangian approach is performed to trace the monocyte particles under different blood flow regimes and heart motion conditions. The hemodynamic results show that the myocardial wall, and also the flow divider wall can be candidates for atheroprone sites. The dynamic movement and pulsatile inlet changed the flow rate between branches about 21% compared to the static case and steady inlet. On the other hand, the calculation of monocytes' depositional behavior illustrates that they settle down downstream the LAD-D1 bifurcation and on the myocardial wall. The deposition rate is closely associated with the inlet type and changing the steady inlet to the sinusoidal and real physiologic profile showed a 150% increase in the deposition rate. These results ensure that the myocardial wall and LAD-D1 bifurcation are the desirable locations for atherosclerosis. These results are in good agreement with the clinical observations.

Introduction

Coronary Artery Disease (CAD) is correlated with atherosclerosis plaque formation in the coronary artery wall. Atherosclerosis usually occurs at the bifurcations where minimum Wall Shear Stress (WSS) and maximum oscillating WSS and flow division occur [1]. Hemodynamics of blood flow in the coronary artery and wall shear stress to determine the high-risk region has been numerically and experimentally studied in many studies [[2], [3], [4]]. Researches show that cardiac motion affects the hemodynamics of coronary arteries. Ramaswamy et al. [5] showed that the velocity profiles in stenosis location and the peripheral distribution of the axial WSS in the artery alter with the wall motion by using CFD. Also, their results show that the WSS is different in static and dynamic cases in which its value decreased in dynamic cases. Weydahl et al. [6] investigated the effects of dynamic deformation of coronary artery bifurcation on wall shear rate patterns. Their results indicate that the low WSS value and its highest variations respectively occur in the myocardial wall and the outer wall. Also, the static geometry results are different from dynamic geometry, and heart motion should be considered to identify regions with the lowest strain rate. Zeng et al. [7] performed a study on the effects of cardiac-induced motion on the blood hemodynamics in the right coronary arteries. They found that Right Coronary Arteries (RCA) motion has little effect on Time-Averaged Wall Shear Stress (TAWSS), and it had a more significant effect on the temporal variation of WSS. As such, the hemodynamics investigation of the consequent stenotic coronary arteries studied by Liu et al. [8] and Hoque et al. [9]. TAWSS are calculated in the stenotic branches, and their variations along the branches are also studied. The pressure difference and virtual Fractional Flow Reserve (vFFR) results allowed them to distinguish the un-stenosed and stenosis arterial models for diagnosis in clinical application. Doutel et al. [10], analyzed flows in the Left Coronary Artery (LCA) bifurcation experimentally and numerically. Their results predicted a significant swirling in both branches as the flow distribution deviates from Murray's law, and investigating this secondary flow and its interaction to the wall can lead to the diagnosis of regions propitious to atherosclerosis formation. Pakravan et al. [11] used a multiscale approach to examine the morphology of endothelial cells and susceptible sites of atherosclerosis in the left main coronary artery (LMA) and its bifurcation to the left circumflex artery (LCX) and left anterior descending coronary artery (LAD). They used fluid-structure interaction in their simulation. Their results predicted that one of the three factors, low TAWSS, high WSS angle and high longitudinal strain are effective in atherosclerotic disease. Besides, they indicated dynamic curvature of cardiac motion increases the risk of atherosclerosis. Biglarian et al. [12] numerically investigated the shear stress variations in an artery with 30 and 50% stenosis. In their simulation, the inlet flow was similar to the actual cardiac pulse, and the dynamic changes of the artery were also applied sinusoidally. The lowest amount of WSS in all cases occurred downstream the stenosis on the inner wall (myocardial) and decreased with decreasing the blood flow rate.

It is known that the adhesion and interaction of monocytes to the surface of arterial walls are the main parameters in the initiation and progression of atherosclerosis. Hence, their deposition plays a significant role in that [[13], [14], [15], [16]]. Also, some studies [17] illustrated that monocyte adhesion to endothelium takes place from the local hemodynamics of blood flow. Chen et al. [18] studied the effect of swirling flow on the adhesion of monocyte to the wall. Their results showed that increasing the swirling flow reduces monocytes deposition. They also illustrated swirling flow enhances WSS and thus, washes the monocytes from the wall. Hardman et al. [13] investigated the monocytes deposition and residency time in Abdominal Aortic Aneurysms (AAA) by Large Eddy Simulation (LES) and Discrete Phase Model (DPM).

They considered an ideal and two patient-specified aneurysms geometries and the effect of different parameters such as geometrical characteristics of aneurysm and dynamics of flow in inlet studied. They found that vorticity can significantly influence on AAA hemodynamics, and predicted monocytes deposition is in close association with aneurysm diameter. They identified there is a critical size beyond that, near-wall particle residency time and wall degradation increase significantly. Longest and Kleinstreuer [19] studied the monocytes deposition and platelet in unparalleled flow, considering reattachment stagnation and recirculation of flow. To identify prone regions of significant particle–wall interactions, they evaluated models such as WSS correlations, multicomponent mixture approach and Lagrangian particle tracking in two conditions (with and without hydrodynamic particle-wall interaction) and compared the results. Their results demonstrated that increasing wall shear stress causes an increment in the deposition and diffusion of the monocyte particles. The deposition of monocyte particles in a 3-D geometry of the carotid artery is investigated by Hyun et al. [20]. For the validation of the computational results, the velocity profiles in different cross-sections are compared with the experimental data. Their results predicted that the areas with a high WSS gradient and regions with low oscillatory WSS values are the most prone and important regions for monocyte depositions. Jung et al. [21] investigated a multi-phase and non-Newtonian blood flow in an idealized coronary artery. Their results revealed that there is a direct correlation between the low wall shear stress and Red Blood Cells (RBCs) buildup on the artery wall. They claimed that this result could be generalized for the monocytes deposition on the inside curvature as the prone regions for the formation of atherosclerosis plaque. Buchanan et al. [22] performed a study on the monocyte deposition in the rabbit abdominal artery as a suitable sample for atherosclerosis plaque disease. Their study indicated that the percentage of the deposited monocytes has a significant correlation with the blood hemodynamic parameters and by enhancing the Wall Shear Stress Gradient (WSSG) and Wall Shear Stress Angle Gradient (WSSAG), the percentages of the deposited monocyte increased.

In the previous studies, the effects of the inlet pulse and the heart's dynamic motion on blood flow hemodynamic parameters have been studied. However, the simultaneous effect of the heart motion along with the effect of each one of these parameters has not yet been carried out on the hemodynamics and monocytes deposition. The purpose of the present work is to model and analyze the hemodynamic variables of the flow and monocyte deposition in a three-dimensional model of the left anterior descending coronary artery and its first diagonal branch (LAD-D1) bifurcation using the CFD. Monocytes are considered as spherical particles exposed to the drag, weight, buoyancy, lift forces and pressure gradient as well as virtual mass in the Lagrangian approach. Also, our simulations are performed with the sinusoidal and physiological inlet flow conditions for both static and dynamic geometry as well as the deposition of monocytes was calculated. The significant contribution of this study is to investigate the plaque formation sites in atherosclerosis disease through the correlation between the monocytes deposition and the hemodynamics parameters during the heart motion, including (TAWSS), Oscillatory Shear Index (OSI) and Relative Residence Time (RRT).

Section snippets

Computational geometry and mesh regeneration

The computational domain of LAD-D1 bifurcation with heart-curvature has been shown in Fig. 1a. The whole parts of LAD and its bifurcation are situated on a hypothetical sphere through which the heart's periodic movement can be applied. In the dynamic case, the heart motion simulated by periodically changing the sphere radius, R(t) (Eq. (1)) [6,23]; in which, R0 considered as the average radius in the static case, and equal to 56.25 mm δ considered as the changes in the heart dynamic movement

Grid independency

Three different structural hexahedral grids (1.10×106,1.60×106,1.90×106) have been investigated to achieve a grid size having the optimum computational cost. The Normalized myocardial Wall Shear Stress (NWSS) for three generated mesh is shown in Fig. 4b. Based on Fig. 4a, the second grid size with 1.60×106 cells has been chosen for modeling process.

Validation

For validation of the numerical procedure, the geometry with the same boundary conditions of Santamarina et al. [23] has been used (Fig. 5). Wall

Conclusion

Hemodynamic variables of the flow and Monocytes deposition have been investigated in a three-dimensional model from coronary artery bifurcation. To calculate the deposition of monocyte in the coronary wall which is the most factor in atherosclerosis, considered them as spherical, the Lagrangian approach is applied in this simulation. For simulating monocyte motion, weight, buoyancy, pressure gradient, virtual mass and Saffman lift forces are considered. One of the most important limitations in

Declaration of competing interest

The authors declare no conflict of interest.

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