A cohort study showing correspondence of low wall shear stress and cephalic arch stenosis in brachiocephalic arteriovenous fistula access

Background: A brachiocephalic fistula is frequently placed for hemodialysis; unfortunately, cephalic arch stenosis commonly develops, leading to failure. We hypothesized that a contribution to brachiocephalic fistula failure is low wall shear stress resulting in neointimal hyperplasia leading to venous stenosis. The objective of this investigation is to determine correspondence of low wall shear stress and the development of cephalic arch stenosis. Methods: Forty subjects receiving hemodialysis with a primary brachiocephalic fistula access were followed from time of placement for 3 years or until cephalic arch stenosis. Venogram, Doppler, and viscosity were performed at time of fistula maturation, annually for 3 years or to time of cephalic arch stenosis. Computational hemodynamics modeling was performed to determine location and percent low wall shear stress in the arch. The relationship between wall shear stress at time of maturation and location of cephalic arch stenosis were estimated by correlating computational modeling and quadrant location of cephalic arch stenosis. Results: In total, 32 subjects developed cephalic arch stenosis with 26 displaying correspondence between location of low wall shear stress at time of maturation and subsequent cephalic arch stenosis, whereas 6 subjects did not (p = 0.0015). Most subjects with correspondence had low wall shear stress areas evident in greater than 20% of the arch (p = 0.0006). Low wall shear stress was associated with a higher risk of cephalic arch stenosis in the 23-to-45 age group (p = 0.0029). Conclusions: The presence and magnitude of low wall shear stress in the cephalic arch is a factor associated with development of cephalic arch stenosis in patients with brachiocephalic fistula. Attenuation of low wall shear stress at time of maturation may help prevent the development of cephalic arch stenosis which is difficult to treat once it develops.

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Increase of wall shear stress caused by arteriovenous fistula reduces neointimal hyperplasia after stent implantation in healthy arteries

Vascular ◽

10.1177/1708538120913748 ◽

2020 ◽

Vol 28 (4) ◽

pp. 396-404

Author(s):

Chong Dong Liu ◽

Feng Chen

Keyword(s):

Shear Stress ◽

Carotid Artery ◽

Wall Shear Stress ◽

Arteriovenous Fistula ◽

Common Carotid Artery ◽

Stent Implantation ◽

Neointimal Hyperplasia ◽

Stent Group ◽

Wall Shear ◽

Endothelial Nitric Oxide

Background and objectives Wall shear stress plays a critical role in neointimal hyperplasia after stent implantation. It has been found that there is an inverse relation between wall shear stress and neointimal hyperplasia. This study hypothesized that the increase of arterial wall shear stress caused by arteriovenous fistula could reduce neointimal hyperplasia after stents implantation. Methods and results Thirty-six male rabbits were randomly divided into three groups: STENT, rabbits received stent implantation into right common carotid artery; STENT/arteriovenous fistula, rabbits received stent implantation into right common carotid artery and carotid-jugular arteriovenous fistula; Control, rabbits received no treatment. After 21 days, stented common carotid artery specimens were harvested for histological staining and protein expression analysis. In STENT group, wall shear stress maintained at a low level from 43.2 to 48.9% of baseline. In STENT/arteriovenous fistula group, wall shear stress gradually increased to 86% over baseline. There was a more significant neointimal hyperplasia in group STENT compared with the STENT/arteriovenous fistula group (neointima area: 0.87 mm2 versus 0.19 mm2; neointima-to-media area ratio: 1.13 versus 0.18). Western blot analysis demonstrated that the protein level of endothelial nitric oxide synthase in STENT group was significantly lower than that in STENT/arteriovenous fistula group, but the protein levels of proliferating cell nuclear antigen, vascular cell adhesion molecule 1, phospho-p38 mitogen-activated protein kinase (Pp38), and phospho-c-Jun N-terminal kinase in STENT group were significantly higher than that in the STENT group. Conclusion High wall shear stress caused by arteriovenous fistula as associated with the induction in neointimal hyperplasia after stent implantation. The underlying mechanisms may be related to modulating the expression and activation of endothelial nitric oxide synthase, vascular cell adhesion molecule 1, p38, and c-Jun N-terminal kinase.

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Computational modeling of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis

PLoS ONE ◽

10.1371/journal.pone.0254016 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254016

Author(s):

Mary Hammes ◽

Andres Moya-Rodriguez ◽

Cameron Bernstein ◽

Sandeep Nathan ◽

Rakesh Navuluri ◽

...

Keyword(s):

Blood Flow ◽

Shear Stress ◽

Wall Shear Stress ◽

Computational Modeling ◽

Arteriovenous Fistula ◽

Low Flow ◽

Flow Measurements ◽

Stress Profiles ◽

Wall Shear ◽

Brachiocephalic Fistula

Background The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. Methods Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shear stress profiles generated. Results Our models generated from imaging and flow measurements at 3 and 12 months offer snapshots of the patient’s cephalic arch at a precise time point, although the remodeling of the vessel downstream of an arteriovenous fistula in patients undergoing regular dialysis is a dynamic process that persists over long periods of time (~ 5 years). The velocity and pressure increase at the cephalic bend cause abnormal hemodynamics most prominent along the inner wall of the terminal cephalic arch. The topology of the cephalic arch is highly variable between subjects and predictive of pathologic stenosis at later time points. Conclusions Low flow velocity and wall pressure along the inner wall of the bend may provide possible nidus of endothelial activation that leads to stenosis and thrombosis. In addition, 3D modelling of the arch can indicate areas of stenosis that may be missed by venograms alone. Computational modeling reconstructed from 3D radiologic imaging and Doppler flow provides important insights into the hemodynamics of blood flow in arteriovenous fistula. This technique could be used in future studies to determine optimal flow to prevent endothelial damage for patients with arteriovenous fistula access.

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Arteriovenous fistula maturation and the influence of fluid dynamics

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1177/0954411920926077 ◽

2020 ◽

Vol 234 (11) ◽

pp. 1197-1208 ◽

Cited By ~ 1

Author(s):

Eamonn Colley ◽

Anne Simmons ◽

Ramon Varcoe ◽

Shannon Thomas ◽

Tracie Barber

Keyword(s):

Fluid Dynamics ◽

Shear Stress ◽

Wall Shear Stress ◽

Arteriovenous Fistula ◽

Computational Studies ◽

Disease Development ◽

Vascular Remodelling ◽

Maturation Period ◽

Fistula Maturation ◽

Arteriovenous Fistula Maturation

Arteriovenous fistula creation is the preferred vascular access for haemodialysis therapy, but has a large failure rate in the maturation period. This period generally lasts 6 to 8 weeks after surgical creation, in which the vein and artery undergo extensive vascular remodelling. In this review, we outline proposed mechanisms for both arteriovenous fistula maturation and arteriovenous fistula failure. Clinical, animal and computational studies have not yet shown a definitive link between any metric and disease development, although a number of theories based on wall shear stress metrics have been suggested. Recent work allowing patient-based longitudinal studies may hold the key to understanding arteriovenous fistula maturation processes.

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Longitudinal Effect of Wall Shear Stress on the Amount of Intimal-Medial Thickening of Venous Wall in Arteriovenous Fistula

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80806 ◽

2012 ◽

Author(s):

Ehsan Rajabi-Jaghargh ◽

Prabir Roy-Chaudhury ◽

Mahesh K. Krishnamoorthy ◽

Yang Wang ◽

Rupak K. Banerjee

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Arteriovenous Fistula ◽

Hemodynamic Parameters ◽

Temporal Gradient ◽

Post Surgery ◽

Venous Stenosis ◽

Venous Diameter ◽

Consistent Increase ◽

Wall Shear

Arteriovenous fistula (AVF) maturation failure is mainly due to venous stenosis characterized by significant amount of intima-media thickening (IMT). Although hemodynamic endpoints are believed to play a crucial role in pathogenesis of venous stenosis, the exact mechanism behind this is unclear. Our hypothesis is that longitudinal (temporal) changes of hemodynamic parameters, specifically wall shear stress (WSS), influences amount of IMT in maturation process of AVF. AVFs were created in curved (C-AVF) and straight (S-AVF) configurations between femoral artery and vein of 3 pigs. CT-scans and ultrasound were utilized to calculate WSS at 2D (D: days), 7D, and 28D post-surgery. IMT was measured at 4 histological blocks along the vein of AVFs. It was found that C-AVF underwent outward remodeling characterized by consistent increase in venous diameter and larger IMT. This remodeling process was governed by negative temporal gradient of WSS (τ′) [−0.99 ± 0.60 dyn/cm2/day]. In contrast, S-AVF underwent inward remodeling characterized by temporal decrease in venous diameter and relatively smaller IMT. This remodeling process was governed by positive τ′ (0.42 ± 0.6 dyn/cm2/day). In summary, temporal gradient of WSS influences IMT. Temporal decrease of WSS in C-AVF resulted in vasodilation and outward growth of wall (favorable to maturation). However, temporal increase in WSS in S-AVF leaded to vasoconstriction and inward growth of wall (detrimental to maturation). Thus, clinically it can be of great importance to surgeons to create AVF in a configuration that can result in favorable hemodynamic parameters and histological end-points.

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Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00123.2014 ◽

2015 ◽

Vol 309 (7) ◽

pp. H1130-H1140 ◽

Cited By ~ 3

Author(s):

Hongfeng Wang ◽

Dorothee Weihrauch ◽

Judy R. Kersten ◽

Jeffrey M. Toth ◽

Anthony G. Passerini ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Vascular Resistance ◽

Transforming Growth Factor ◽

Oxidized Ldl ◽

Neointimal Hyperplasia ◽

Ldl Receptor ◽

Transforming Growth Factor Β ◽

Age Related ◽

Wall Shear

Mechanisms of restenosis in type 2 diabetes mellitus (T2DM) are incompletely elucidated, but advanced glycation end-product (AGE)-induced vascular remodeling likely contributes. We tested the hypothesis that AGE-related collagen cross-linking (ARCC) leads to increased downstream vascular resistance and altered in-stent hemodynamics, thereby promoting neointimal hyperplasia (NH) in T2DM. We proposed that decreasing ARCC with ALT-711 (Alagebrium) would mitigate this response. Abdominal aortic stents were implanted in Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. Blood flow, vessel diameter, and wall shear stress (WSS) were calculated after 21 days, and NH was quantified. Arterial segments (aorta, carotid, iliac, femoral, and arterioles) were harvested to detect ARCC and protein expression, including transforming growth factor-β (TGF-β) and receptor for AGEs (RAGE). Downstream resistance was elevated (60%), whereas flow and WSS were significantly decreased (44% and 56%) in ZD vs. ZL rats. NH was increased in ZO but not ZD rats. ALT-711 reduced ARCC and resistance (46%) in ZD rats while decreasing NH and producing similar in-stent WSS across groups. No consistent differences in RAGE or TGF-β expression were observed in arterial segments. ALT-711 modified lectin-type oxidized LDL receptor 1 but not RAGE expression by cells on decellularized matrices. In conclusion, ALT-711 decreased ARCC, increased in-stent flow rate, and reduced NH in ZO and ZD rats through RAGE-independent pathways. The study supports an important role for AGE-induced remodeling within and downstream of stent implantation to promote enhanced NH in T2DM.

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Accurate Prediction of Wall Shear Stress in a Stented Artery: Newtonian Versus Non-Newtonian Models

Journal of Biomechanical Engineering ◽

10.1115/1.4004408 ◽

2011 ◽

Vol 133 (7) ◽

Cited By ~ 16

Author(s):

Juan Mejia ◽

Rosaire Mongrain ◽

Olivier F. Bertrand

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Linear Model ◽

Newtonian Fluid ◽

Nonlinear Model ◽

Numerical Models ◽

Neointimal Hyperplasia ◽

Computational Cost ◽

Arterial Segment ◽

Wall Shear

A significant amount of evidence linking wall shear stress to neointimal hyperplasia has been reported in the literature. As a result, numerical and experimental models have been created to study the influence of stent design on wall shear stress. Traditionally, blood has been assumed to behave as a Newtonian fluid, but recently that assumption has been challenged. The use of a linear model; however, can reduce computational cost, and allow the use of Newtonian fluids (e.g., glycerine and water) instead of a blood analog fluid in an experimental setup. Therefore, it is of interest whether a linear model can be used to accurately predict the wall shear stress caused by a non-Newtonian fluid such as blood within a stented arterial segment. The present work compares the resulting wall shear stress obtained using two linear and one nonlinear model under the same flow waveform. All numerical models are fully three-dimensional, transient, and incorporate a realistic stent geometry. It is shown that traditional linear models (based on blood’s lowest viscosity limit, 3.5 Pa s) underestimate the wall shear stress within a stented arterial segment, which can lead to an overestimation of the risk of restenosis. The second linear model, which uses a characteristic viscosity (based on an average strain rate, 4.7 Pa s), results in higher wall shear stress levels, but which are still substantially below those of the nonlinear model. It is therefore shown that nonlinear models result in more accurate predictions of wall shear stress within a stented arterial segment.

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