Regions Of Low Wall Shear Stress Research Articles

Impact of lower limb movements on iliac vein stenting in iliac vein compression syndrome patients: insights from computational modeling.

Purpose: Iliac vein stenting is the primary treatment for patients with iliac vein compression syndrome (IVCS). However, post-stent placement, patients often experience in-stent restenosis and thrombosis. Despite this, the role of lower limb movements in the functioning of stents and veins in IVCS patients remains unclear. This study aimed to address this knowledge gap by developing a computational model using medical imaging techniques to simulate IVCS after stent placement. Methods: This research used a patient-specific model to analyze the effects of lower extremity exercises on hemodynamics post-stent placement. We conducted a comprehensive analysis to evaluate the impact of specific lower limb movements, including hip flexion, ankle movement and pneumatic compression on the hemo-dynamic characteristics within the treated vein. The analysis assessed parameters such as wall shear stress (WSS), oscillatory shear index (OSI), and residence time (RRT). Results: The results demonstrated that hip flexion significantly disrupts blood flow dynamics at the iliac vein bifurcation after stenting. Bilateral and left hip flexion were associated with pronounced regions of low WSS and high OSI at the iliac-vena junction and the stent segment. Additionally, active ankle exercise (AAE) and intermittent pump compression (IPC) therapy were found to enhance the occurrence of low WSS regions along the venous wall, potentially reducing the risk of thrombosis post-stent placement. Consequently, both active joint movements (hip and ankle) and passive movements have the potential to influence the local blood flow environment within the iliac vein after stenting. Conclusions: The exploration of the impact of lower limb movements on hemodynamics provides valuable insights for mitigating adverse effects associated with lower limb movements post iliac-stenting. Bilateral and left hip flexions negatively impacted blood flow, increasing thrombosis risk. However, active ankle exercise and intermittent pump compression therapies effectively improve the patency.

Angiogenic Microvascular Wall Shear Stress Patterns Revealed Through Three-dimensional Red Blood Cell Resolved Modeling.

The wall shear stress (WSS) exerted by blood flowing through microvascular capillaries is an established driver of new blood vessel growth, or angiogenesis. Such adaptations are central to many physiological processes in both health and disease, yet three-dimensional (3D) WSS characteristics in real angiogenic microvascular networks are largely unknown. This marks a major knowledge gap because angiogenesis, naturally, is a 3D process. To advance current understanding, we model 3D red blood cells (RBCs) flowing through rat angiogenic microvascular networks using state-of-the-art simulation. The high-resolution fluid dynamics reveal 3D WSS patterns occurring at sub-endothelial cell (EC) scales that derive from distinct angiogenic morphologies, including microvascular loops and vessel tortuosity. We identify the existence of WSS hot and cold spots caused by angiogenic surface shapes and RBCs, and notably enhancement of low WSS regions by RBCs. Spatiotemporal characteristics further reveal how fluctuations follow timescales of RBC "footprints." Altogether, this work provides a new conceptual framework for understanding how shear stress might regulate EC dynamics in vivo.

Study of Typical Ruptured and Unruptured Intracranial Aneurysms Based on Fluid–Structure Interaction

Most intracranial aneurysms (IAs) will be abnormal bulges on the walls of intracranial arteries that result from the dynamic interaction of geometric morphology, hemodynamics, and pathophysiology. Hemodynamics plays a key role in the origin, development, and rupture of IAs. In the past, hemodynamic studies of IAs were mostly based on the rigid wall hypothesis of computational fluid dynamics, and the influence of arterial wall deformation was ignored. We used fluid-structure interaction (FSI) to study the features of ruptured aneurysms, because it can solve this problem very well and the simulation will be more realistic. A total of 12 IAs, 8 ruptured and 4 unruptured, at the middle cerebral artery bifurcation were studied using FSI to better identify the characteristics of ruptured IAs. We studied the differences in the hemodynamic parameters, including the flow pattern, wall shear stress (WSS), oscillatory shear index (OSI), and displacement and deformation of the arterial wall. Ruptured IAs had a larger low WSS area and more complex, concentrated, and unstable flow. Also, the OSI was higher. In addition, the displacement deformation area at the ruptured IA was more concentrated and larger. A large aspect ratio; a large height/width ratio; complex, unstable, and concentrated flow patterns with small impact areas; a large low WSS region; large WSS fluctuation, high OSI; and large displacement of the aneurysm dome could be risk factors associated with aneurysm rupture. If similar cases are encountered when simulation is used in the clinic, priority should be given to diagnosis and treatment.

Prediction of vortex structures in pulsatile flow through S-bend arterial geometry with different stenosis levels

Arterial stenosis poses a high cardiovascular risk, and clinical intervention is needed when these stenoses grow beyond a specific limit. The study of vortex dynamics in these diseased arteries can be beneficial to understand its severity. Therefore, in the present work, we have investigated the flow structures in an S-bend arterial geometry with different levels of stenosis using a sharp interface immersed boundary method. We have observed an onset of Kelvin-Helmholtz-type vortex roll-up for higher degrees of stenoses. Fluctuations in the wall shear stress are observed for higher stenosis degrees. However, these fluctuations depend on the position and length of the stenosis. Newtonian and non-Newtonian Carreau fluids predict similar vortex structures, although minor differences in the Kelvin-Helmholtz vortex structures and associated fluctuations are observed in the diastolic phase. The Newtonian fluid predicts a slightly longer low time-averaged wall shear stress (≤0.5 Pa) region immediately after the stenosis compared with the Carreau fluid in the 58 % blockage S-bend artery.

Simulation of LDL permeation into multilayer wall of a coronary bifurcation using WSS-dependent model: effects of hemorheology.

Atherosclerosis, due to the permeation of low-density lipoprotein (LDL) particles into the arterial wall, is one of the most common and deadly diseases in today's world. Due to its importance, numerous studies have been conducted on the factors affecting this disease. In this study, using numerical simulation, the effects of Wall Shear Stress (WSS), non-Newtonian behavior of blood, different values of hematocrit and blood pressure on LDL permeation into the arterial wall layers are investigated in a 4-layer wall model of a coronary bifurcation. To obtain the velocity and concentration fields in the fluid domain, the Navier-Stokes, Brinkman, and mass transfer equations are numerically solved in the lumen and wall layers. Results show that it is important to consider the effects of WSS on transport properties of endothelium layer in bifurcations and this leads to completely different concentration profiles compared to the constant properties model. Our computations show that a giant accumulation of LDL in the intima layer of the outer wall of the left anterior descending artery, especially in low WSS regions, may lead to atherosclerosis. It is also, necessary to consider the non-Newtonian behavior of blood in bifurcations due to its direct effect on WSS. A pressure-induced increase in the half-width of leaky junctions may be responsible for the higher risk of atherosclerosis in hypertension. In addition, it is shown that the dominant mechanism in LDL permeation into the wall is convection, and also, hypertension increases the effect of mass transfer by convection mechanism more than the diffusion mechanism. Furthermore, our results are consistent with various clinical studies.

Influence of the flow field and vortex structure of patient-specific abdominal aortic aneurysm with intraluminal thrombus on the arterial wall

ABSTRACT In this study, numerical simulations and experiments were conducted on patient-specific normal abdominal aorta and abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) models, which were reconstructed from computed tomography angiography (CTA) images published online. A scale-adaptive simulation (SAS) of the abdominal aortic aneurysm with a posterior eccentric thrombus was performed and the reliability of the numerical simulation was verified by 2D particle image velocimetry (PIV) experimental results. The distribution of wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) of the normal abdominal aorta and AAA were compared and discussed systematically according to the numerical simulation results under rest and exercise conditions. Numerical results indicated that ILT deposition positions were accompanied by low WSS, high OSI, and high RRT regions and were characterized by small vortex groups, which was due to the fragmentation of large vortex structures. The distribution law of the AAA wall parameters has an obvious correlation with the nearby vortex structure formation, development, fragmentation and dissipation. It was also found that high TAWSS, low OSI, and low RRT regions present in the middle and lower aneurysm walls under exercise condition reduce the risk of ILT formation and development.

EFFECTS OF SAND THERAPY ON FLUID DYNAMICS OF BLOOD IN THE POPLITEAL ARTERY BASED ON THE EULER MULTIPHASE MODEL

The effect of sand therapy on the hemodynamics of the popliteal artery (POA) was investigated to elucidate its mechanism in atherosclerosis physiotherapy. The hemodynamic parameters of the POA before and after sand therapy were obtained from 58 subjects and statistically analyzed. A three-dimensional finite element model of POA bifurcation was established. Blood was regarded as a triple-phase flow composed of plasma, red blood cells (RBCs), and white blood cells (WBCs). Using computational fluid dynamics (CFD), blood flow velocity, wall shear stress (WSS), and blood cell volume distribution before and after sand therapy were calculated. Sand therapy could reduce the vortex and reflux in blood vessels. The maximum increase in blood axial velocity was 34.38%. The maximum WSS increased by 22.82 Pa and the blood cells gradually moved away from the vessel wall and toward the axis of the blood vessel. The reduction in vortex and reflux, and the increase in blood axial velocity after sand therapy are beneficial in reducing the accumulation of cholesterol and other substances, thereby alleviating the formation of atherosclerotic plaques and lipid streaks. The rise in WSS slows the tendency of arterial vascular thickening in regions of low WSS. The movement of blood cells to the axis of blood vessels can reduce the possibility of thrombosis caused by blood cells squeezing on the blood vessel walls. These findings suggest that sand therapy may slow atherosclerosis progression.

Fluid-Structure Interaction Simulations of Repaired Type A Aortic Dissection: a Comprehensive Comparison With Rigid Wall Models.

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS () was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young’s moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.

A Hemodynamic Analysis of the Thrombosis Within Occluded Coronary Arterial Fistulas With Terminal Aneurysms Using a Blood Stasis Model.

Objective: The aim of this study is to numerically evaluate thrombosis risk within occluded coronary arterial fistulas (CAF) with terminal aneurysms, and provide guidance in choosing occlusion positions, with clinical observations as reference. Method: Four patients with CAF were studied, with different occlusion positions in actual treatments. Hemodynamics simulations were conducted, with blood residue predicted using the blood stasis model. Three types of models (untreated model, aneurysm-reserved model and aneurysm-removed model) were studeid for each patient. Four metrics, i.e., proportion of high oscillatory shear index (OSI), area of high OSI, old blood volume fraction (OBVF)) and old blood volume (OBV) was obtained to distinguish the thrombosis risk of different treatments (proximal or distal occlusion), comparing with the follow-up CTA. Results: For all the postopertive models, the high OBVF, high OSI(>0.3) and low time-averaged wall shear stress (TAWSS) regions were mainly at the distal fistula, indicating these regions were prone to thrombosis. The regions where blood residue remains are roughly regions of high OSI, corresponding well with clinical observations. In contrast, TAWSS failed to distinguish the difference in thrombosis risk. Absolute values (area of high OSI, OBV) can better reflect the degree of thrombosis risk between treatment types compared with percentage values (proportion of high OSI, OBVF). By comparing with the actual clinical treatments and observations, the OBV is superior to the area of high OSI in determining treatment type. Conclusion: The OBV, a volumetric parameter for blood stasis, can better account for the CAF thrombosis and reflect the degree of blood stasis compared with OSI or TAWSS, is a more appropriate metric for thrombosis in the fistula. Together with morphological parameters, the OBV could guide clinicians to formulate more appropriate surgical plans, which is of great significance for the preoperative evaluation and treatment prognosis of CAF patients.

Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress

ObjectiveHemodynamics-induced low wall shear stress (WSS) is one of the critical reasons leading to vascular remodeling. However, the coupling effects of WSS and cellular kinetics have not been clearly modeled. The aim of this study was to establish a multiscale modeling approach to reveal the vascular remodeling behavior under the interaction between the macroscale of WSS loading and the microscale of cell evolution.MethodsComputational fluid dynamics (CFD) method and agent-based model (ABM), which have significantly different characteristics in temporal and spatial scales, were adopted to establish the multiscale model. The CFD method is for the second/organ scale, and the ABM is for the month/cell scale. The CFD method was used to simulate blood flow in a vessel and obtain the WSS in a vessel cross-section. The simulations of the smooth muscle cell (SMC) proliferation/apoptosis and extracellular matrix (ECM) generation/degradation in a vessel cross-section were performed by using ABM. During the simulation of the vascular remodeling procedure, the damage index of the SMC and ECM was defined as deviation from the obtained WSS. The damage index decreased gradually to mimic the recovery of WSS-induced vessel damage.Results(1) The significant wall thickening region was consistent with the low WSS region. (2) There was no evident change of wall thickness in the normal WSS region. (3) When the damage index approached to 0, the amount and distribution of SMCs and ECM achieved a stable state, and the vessel reached vascular homeostasis.ConclusionThe established multiscale model can be used to simulate the vascular remodeling behavior over time under various WSS conditions.

Influence of Multi Stenosis on Hemodynamic Parameters in an Idealized Coronary Artery Model

This study explores the influence of tandem stenosis on hemodynamic constraints in idealized coronary artery models with different interspace distance between the stenosis and its severity. The blood was assumed as non-Newtonian, incompressible, and pulsatile fluid. The hemodynamic parameters of blood, such as the oscillatory shear index (OSI), wall shear stress (WSS) and time average wall shear stress (TAWSS) are obtained and compared for various degrees of stenosis and interspacing distance in various blood models. The computed results showed that as the interspacing distance between the stenosis decreases, the low wall shear stress area increases for the model P70_D70, leading to further progression of stenosis in the distal region. No significant variation was observed for the model P70_D90, whereas the low WSS region increases as the interspace distance of proximal and distal stenosis increases for the model P90_D70. The highest TAWSS sites were created across the 90% AS (area stenosis) for all the cases studied. As the higher value of TAWSS is clinically significant since it could damage the endothelial layer. It is well known that the maximum value of OSI is strongly associated with the critical areas of stenosis rupture. The maximum value of OSI was found at the proximal and distal stenosis for all the models simulated.

Non-invasive assessment of intracranial wall shear stress using high-resolution magnetic resonance imaging in combination with computational fluid dynamics technique

In vivo studies on association between wall shear stress (WSS) and intracranial plaque are deficient. Based on the three-dimensional T1-weighted high-resolution magnetic resonance imaging (3DT1 HR-MRI) data of patients with low-grade stenotic (<50%) atherosclerotic middle cerebral artery (MCA) and subjects with normal MCA, we built a three-dimensional reconstructed WSS model by computational fluid dynamics (CFD) technique. Three-dimensional registration of the CFD model to the HR-MRI was performed with projections based on the resolution and thickness of the images. The relationships between the WSS at each side of the vessel wall and plaque location were analyzed. A total of 94 MCA plaques from 43 patients and 50 normal MCAs were analyzed. In the normal MCAs, WSS was lower at the ventral-inferior wall than at the dorsal-superior wall (proximal segment, p < 0.001; middle segment, p < 0.001) and lower at the inner wall than at the outer wall of the MCA curve (p < 0.001). In atherosclerotic MCAs, similar low WSS regions were observed where plaques developed. The WSS ratio of the ventral-inferior wall to the dorsal-superior wall in atherosclerotic MCAs was lower than that in normal MCAs (p = 0.002). The WSSinner-outer ratio in atherosclerotic MCAs was lower than that in normal MCAs (p = 0.002). Low WSS was associated with MCA atherosclerosis formation and occurred mainly at the ventral-inferior wall, which was anatomically opposite the orifices of penetrating arteries, and at the inner wall of the MCA curve. Overall, the results were well consistent with the low WSS theory in atherosclerosis formation. The reconstructed WSS model is a promising novel method for assessing an individualized vascular profile once validated by further studies.

Wall shear stress mapping for human femoral artery based on ultrafast ultrasound vector Doppler estimations.

Wall shear stress (WSS), a type of friction exerted on the artery wall by flowing blood, is considered a crucial factor in atherosclerotic plaque development. Currently, achieving a reliable WSS mapping of an artery noninvasively by using existing imaging modalities is still challenging. In this study, a WSS mapping based on vector Doppler flow velocity estimation was proposed to measure the dynamic WSS on the human femoral artery. Because ultrafast ultrasound imaging was used here, flow-enhanced imaging was also performed to observe the moving blood flow condition. The performance of WSS mapping was verified using both straight (8mm in diameter) and stenosis (70% of stenosis) phantoms under a pulsatile flow condition. A human study was conducted from five healthy volunteers. Experimental results demonstrated that the WSS estimation was close to the standard value that was obtained from maximum velocity estimation in straight phantom experiments. In a stenosis phantom experiment, a low WSS region was observed at a site downstream of an obstruction, which is a high-risk area for plaque formation. Dynamic WSS mapping was accomplished in measurement in the femoral artery bifurcation. In measurements, the time-averaged WSS of the common femoral artery, superficial femoral artery, and deep femoral artery was 0.52± 0.19, 0.44 ± 0.21, and 0.29 ± 0.16Pa, respectively, for the anterior wall and 0.29 ± 0.11, 0.54 ± 0.24, and 0.23 ± 0.10Pa, respectively, for the posterior wall. All results indicated that WSS mapping has the potential to be a useful tool for vessel duplex scanning in the future.

Revisiting Raupach’s Flow-Sheltering Paradigm

In this commentary, we revisit Raupach’s flow-sheltering paradigm that asserts reduced wall-shear stress behind a surface roughness element (MR Raupach in Boundary-Layer Meteorol, 60(4):375–395, 1992). Direct numerical simulations of a turbulent boundary layer over a wall-mounted rectangular roughness are conducted we consider roughness with three different aspect ratios and flows at two Reynolds numbers. A large computational domain is used to study the behaviours of the wall-shear stress in both the near-wake and the far-wake regions. Aside from a low wall-shear stress region in the near-wake as one would expect from the flow-sheltering paradigm, a high-stress region is found in the far-wake. The presence of such a high-stress region challenges the well-established flow sheltering paradigm and is also counter-intuitive. Detailed analysis of the vortical structures shows that the high wall-shear stress region is a consequence of the horse-shoe-vortex-induced downwash motion in the far-wake.

Influence of Stent Flexibility on Artery Wall Stress and Wall Shear Stress in Bifurcation Lesions.

PurposeStent flexibility can influence clinical outcome, especially in bifurcation lesions. For instance, an overly rigid stent can impose mechanical stress on the artery at the stent edges and alter both arterial geometry and blood flow dynamics in bifurcations. This study investigated the influence of stent flexibility on vessel geometry, histology, wall stress, and blood flow dynamics in arterial bifurcations.Materials and MethodsWe compared arterial angulation, stenosis, histopathology, simulated wall shear stress (WSS), and simulated blood flow velocity distribution in swine coronary artery bifurcations following placement of the less flexible Multi-link 8 or more flexible Kaname stent (4.1 ± 0.5 vs 1.5 ± 0.1 mN, p < 0.05, t-test). Stents were implanted into six coronary artery bifurcations each using the single-stent crossover technique without side branch strut dilatation. Outcomes were examined after 28 days.ResultsImplantation of both stents significantly increased site angulation (Multi-link 8: 148° ± 8° to 172° ± 2°, p < 0.05, paired t-test; Kaname: 152° ± 5° to 164° ± 4°, p < 0.05, paired t-test), but the change tended to be greater after Multi-link 8 stent implantation (24° ± 15° vs 11° ± 7°, p = 0.1, t-test), suggesting greater straightening of the bifurcation. The Multi-link 8 stent induced greater neointimal thickness than the Kaname stent (0.53 ± 0.3 mm vs 0.26 ± 0.1 mm, p < 0.05, t-test). The distribution of neointimal hyperplasia following stent implantation as revealed by longitudinal histopathology matched the distribution of WSS simulated using computational fluid dynamics (CFD). The endothelium at low WSS areas exhibited aberrant cell morphology and leukocyte adhesion. A CFD model of a curved bifurcation suggested that the region of low WSS is expanded by artery straightening.ConclusionIn bifurcated lesions, stent flexibility influences not only mechanical stress on the artery but also WSS, which may induce local neointimal hyperplasia.

Effect of intimal flap motion on flow in acute type B aortic dissection by using fluid‐structure interaction

A monolithic, fully coupled fluid-structure interaction (FSI) computational framework was developed to account for dissection flap motion in acute type B aortic dissection (TBAD). Analysis of results included wall deformation, pressure, flow, wall shear stress (WSS), von Mises stress and comparison of hemodynamics between rigid wall and FSI models. Our FSI model mimicked realistic wall deformation that resulted in maximum compression of the distal true lumen (TL) by 21.4%. The substantial movement of intimal flap mostly affected flow conditions in the false lumen (FL). Flap motion facilitated more flow entering the FL at peak systole, with the TL to FL flow split changing from 88:12 in the rigid model to 83:17 in the FSI model. There was more disturbed flow in the FL during systole (5.8% FSI vs 5.2% rigid) and diastole (13.5% FSI vs 9.8% rigid), via a λ2 -criterion. The flap-induced disturbed flow near the tears in the FSI model caused an increase of local WSS by up to 70.0% during diastole. This resulted in a significant reduction in the size of low time-averaged WSS (TAWSS) regions in the FL (113.11 cm2 FSI vs 177.44 cm2 rigid). Moreover, the FSI model predicted lower systolic pressure, higher diastolic pressure, and hence lower pulse pressure. Our results provided new insights into the possible impact of flap motion on flow in aortic dissections, which are particularly important when evaluating hemodynamics of acute TBAD. NOVELTY STATEMENT: Our monolithic fully coupled FSI computational framework is able to reproduce experimentally measured range of flap deformation in aortic dissection, thereby providing novel insights into the influence of physiological flap motion on the flow and pressure distributions. The drastic flap movement increases the flow resistance in the true lumen and causes more disturbed flow in the false lumen, as visualized through the λ2 criterion. The flap-induced luminal pressure is dampened, thereby affecting pressure measures, which may serve as potential prognostic indicators for late complications in acute uncomplicated TBAD patients.

A Hemodynamic Mechanism Correlating with the Initiation of MCA Bifurcation Aneurysms.

Previous studies have reported that MCA bifurcation aneurysms usually emerge on inclined bifurcations; however, the reason is unclear. We designed this study to explore hemodynamic mechanisms that correlate with the initiation of MCA bifurcation aneurysms. Fifty-four patients with unilateral MCA bifurcation aneurysms and 54 control patients were enrolled in this study after propensity score matching, and their clinical and CTA data were collected. We extracted the morphologic features of aneurysmal MCA bifurcations to build a simplified MCA bifurcation model and performed a computational fluid dynamics analysis. The presence of MCA aneurysms correlated with smaller parent-daughter angles of MCA bifurcations (P < .001). Aneurysmal MCA bifurcations usually presented with inclined shapes. The computational fluid dynamics analysis demonstrated that when arterial bifurcations became inclined, the high-pressure regions and low wall shear stress regions shifted from the apexes of the arterial bifurcations to the inclined daughter arteries, while the initial sites of MCA bifurcation aneurysms often overlapped with the shifted high-pressure regions and low wall shear stress regions. Our results suggest that the initiation of MCA bifurcation aneurysms may correlate with shifts of high-pressure regions and low wall shear stress regions that occur on inclined MCA bifurcations.

Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve: A Time-Resolved 3-Dimensional Phase-Contrast Magnetic Resonance Imaging Study.

To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.

P5629The effect of strut protrusion on local shear stress and neointimal hyperplasia

Abstract Objective To evaluate effect of strut protrusion (SP) on wall shear stress (WSS) and neointimal growth (NG) 1 and 5 year after implantation of Absorb scaffold. Method 8 patients were selected from Absorb Cohort B. After 3-dimensional reconstruction of coronaries, WSS was quantified using Newtonian steady flow simulation (Figure). At 1-year neointimal thickness (NT) was measured by optical coherence tomography and correlated to WSS and SP post-procedure. Results Median SP was 112.9 (90.8, 133.1) μm. A logarithmic (log) inverse relationship between SP and post-procedure WSS (r=−0.425 p&lt;0.001 correlation coefficients range: −0.143 to −0.553) was observed whereas a correlation between baseline log transformed WSS and NT (r=−0.451 p&lt;0.001 correlation coefficients range: −0.140 to −0.662) was documented at 1 year. Mixed effects analysis between baseline log transformed WSS and NT at follow up yielded a slope of 30 μm/ln Pascal (Pa) and a y-intercept of 98 μm. As result of NG, flow area decreased from 6.91 (6.53, 7.48) mm2 post-implantation to 5.65 (5.47, 6.02) mm2 at 1 year (p=0.01) and to 5.75±1.37 mm2 at 5 years (p=0.024). Vessel surface with low WSS (&lt;1 Pa) decreased from post-procedure (42%) to 1 year (35.9%) and 5 years (15.2%) (p-overall&lt;0.0001). Conclusion SP disturbs laminar flow, creates region of low WSS that is mechanistically associated with NG and lumen area reduction. This observation would suggest thin strut with effective embedment would reduce NG and improve WSS towards physiological values.

Abstract 736: Increased Cell Death in Regions of Elevated Aortic Wall Shear Stress in Bicuspid Valve Aortopathy

Bicuspid aortic valve (BAV) is a common congenital malformation associated with aortopathy and potential rupture. Identifying those patients at greatest risk for dissection is difficult at present. Abnormal hemodynamics in the ascending aorta creates regions of increased wall shear stress (WSS) which causes extracellular matrix dysregulation and may affect cell death. Dying cells release fragmented DNA into the blood and levels of aorta-specific cell-free DNA (cfDNA), identified by the presence of tissue-specific differentially methylated regions (DMRs), could be leveraged as a biomarker. Our objective was to determine if a relationship between elevated WSS and apoptosis in the ascending aorta existed and identify aorta-specific DMRs in the cfDNA of BAV patients. We hypothesized that areas of increased WSS would demonstrate increased cell death that would correlate with increases in aorta-specific cfDNA from patient blood. BAV patients undergoing 4D-flow cardiac magnetic resonance imaging (CMR) and surgery for ascending aorta dilation (range 36-63 mm) were recruited. Blood was collected from 23 patients at the time of CMR and used for the isolation of plasma cfDNA. Aortic wall samples (n = 30) corresponding to regions of high and low WSS were collected at surgery from 15 patients and stained for cell death using the TUNEL assay. Publicly-available methylomes and Metilene were used to identify aorta-specific DMRs in silico . Regions of elevated WSS were seen in all individuals regardless of absolute aortic dimension. These regions of elevated WSS by CMR showed significantly greater cell death when compared to the region of normal WSS in the ascending aorta (0.14 ± 0.05 vs. 0.08 ± 0.06, p=0.00006). Levels of cell death did not correlate with maximal aortic diameter. Twenty-three aorta-specific DMRs were identified. Of the four that were tested, three were found to be hypomethylated in genomic DNA from the aorta compared to 14 other tissues. Levels of aorta-specific cfDNA based on our DMRs did not correlate with maximal aortic diameter. Increased regional cell death corresponding to elevated WSS may implicate abnormal hemodynamic flow in the progression of aortopathy and provides a biological rationale for the use of cfDNA as a biomarker for aortopathy.