Henry Y. Chen

Effects of stent sizing on endothelial and vessel wall stress: potential mechanisms for in-stent restenosis

Stent sizing and apposition have been shown to be important determinants of clinical outcome. This study evaluates the mechanical effects of undersizing and oversizing of stents on endothelial wall shear stress (WSS) and vessel wall stress to determine a possible biomechanical mechanism of in-stent restenosis and thrombosis. Three-dimensional computational models of stents, artery, and internal fluid were created in a computer-assisted design package, meshed, and solved in finite element and computational fluid dynamic packages. The simulation results show that the effects of various degrees of undersizing on WSS, WSS gradient, and oscillatory shear index were highly nonlinear. As the degree of undersizing increased, the heterogeneity of WSS became smaller. The WSS distribution for the 20% undersizing was smooth and uniform, whereas the 5% case was very heterogeneous. The combination of lower WSS and higher WSS gradient and oscillatory shear index in the 5% undersized case may induce neointimal hyperplasia or thrombosis. Additionally, the oversizing simulation results show that the maximum intramural wall stress of the 20% oversizing case is significantly larger than the maximum stress for the 10% and zero oversizing cases. Edge stress concentration was observed, consistent with the restenosis typically observed in this region. This study demonstrates that proper sizing of stent is important for reducing the hemodynamic and mechanical disturbances to the vessel wall. Furthermore, the present findings may be used to improve stent design to reduce endothelial flow disturbances and intramural wall stress concentrations.

Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress

Stent can cause flow disturbances on the endothelium and compliance mismatch and increased stress on the vessel wall. These effects can cause low wall shear stress (WSS), high wall shear stress gradient (WSSG), oscillatory shear index (OSI), and circumferential wall stress (CWS), which may promote neointimal hyperplasia (IH). The hypothesis is that stent-induced abnormal fluid and solid mechanics contribute to IH. To vary the range of WSS, WSSG, OSI, and CWS, we intentionally mismatched the size of stents to that of the vessel lumen. Stents were implanted in coronary arteries of 10 swine. Intravascular ultrasound (IVUS) was used to size the coronary arteries and stents. After 4 wk of stent implantation, IVUS was performed again to determine the extent of IH. In conjunction, computational models of actual stents, the artery, and non-Newtonian blood were created in a computer simulation to yield the distribution of WSS, WSSG, OSI, and CWS in the stented vessel wall. An inverse relation (R(2) = 0.59, P < 0.005) between WSS and IH was found based on a linear regression analysis. Linear relations between WSSG, OSI, and IH were observed (R(2) = 0.48 and 0.50, respectively, P < 0.005). A linear relation (R(2) = 0.58, P < 0.005) between CWS and IH was also found. More statistically significant linear relations between the ratio of CWS to WSS (CWS/WSS), the products CWS × WSSG and CWS × OSI, and IH were observed (R(2) = 0.67, 0.54, and 0.56, respectively, P < 0.005), suggesting that both fluid and solid mechanics influence the extent of IH. Stents create endothelial flow disturbances and intramural wall stress concentrations, which correlate with the extent of IH formation, and these effects were exaggerated with mismatch of stent/vessel size. These findings reveal the importance of reliable vessel and stent sizing to improve the mechanics on the vessel wall and minimize IH.

Impact of main branch stenting on endothelial shear stress: role of side branch diameter, angle and lesion

In-stent restenosis and stent thrombosis remain clinically significant problems for bifurcation lesions. The objective of this study is to determine the haemodynamic effect of the side branch (SB) on main branch (MB) stenting. We hypothesize that the presence of a SB has a negative effect on MB wall shear stress (WSS), wall shear stress gradient (WSSG) and oscillatory shear index (OSI); and that the bifurcation diameter ratio (SB diameter/MB diameter) and angle are important contributors. We further hypothesized that stent undersizing exaggerates the negative effects on WSS, WSSG and OSI. To test these hypotheses, we developed computational models of stents and non-Newtonian blood. The models were then interfaced, meshed and solved in a validated finite-element package. Stents at bifurcation models were created with 30° and 70° bifurcation angles and bifurcations with diameter ratios of SB/MB = 1/2 and 3/4. It was found that stents placed in the MB at a bifurcation lowered WSS dramatically, while elevating WSSG and OSI. Undersizing the stent exaggerated the decrease in WSS, increase in WSSG and OSI, and disturbed the flow between the struts and the vessel wall. Stenting the MB at bifurcations with larger SB/MB ratios or smaller SB angles (30°) resulted in lower WSS, higher WSSG and OSI. Stenosis at the SB lowered WSS and elevated WSSG and OSI. These findings highlight the effects of major biomechanical factors in MB stenting on endothelial WSS, WSSG, OSI and suggests potential mechanisms for the potentially higher adverse clinical events associated with bifurcation stenting.

Fluid–Structure Interaction (FSI) Modeling in the Cardiovascular System

The cardiovascular system experiences strong fluid–structure interaction (FSI). This chapter presents the theoretical formulations for two powerful FSI techniques: the arbitrary Lagrangian Eulerian (ALE) and the immersed boundary (IB) methods. Examples of FSI applications to aortic cross-clamping used during surgical treatment of heart failure and valveless pumping are also presented.

Impact of stent mis-sizing and mis-positioning on coronary fluid wall shear and intramural stress.

Stent deployments with geographical miss (GM) are associated with increased risk of target-vessel revascularization and periprocedural myocardial infarction. The aim of the current study was to investigate the underlying biomechanical mechanisms for adverse events with GM. The hypothesis is that stent deployment with GM [longitudinal GM, or LGM (i.e., stent not centered on the lesion); or radial GM, RGM (i.e., stent oversizing)] results in unfavorable fluid wall shear stress (WSS), WSS gradient (WSSG), oscillatory shear index (OSI), and intramural circumferential wall stress (CWS). Three-dimensional computational models of stents and plaque were created using a computer-assisted design package. The models were then solved with validated finite element and computational fluid dynamic packages. The dynamic process of large deformation stent deployment was modeled to expand the stent to the desired vessel size. Stent deployed with GM resulted in a 45% increase in vessel CWS compared with stents that were centered and fully covered the lesion. A 20% oversized stent resulted in 72% higher CWS than a correct sized stent. The linkages between the struts had much higher stress than the main struts (i.e., 180 MPa vs. 80 MPa). Additionally, LGM and RGM reduced endothelial WSS and increased WSSG and OSI. The simulations suggest that both LGM and RGM adversely reduce WSS but increase WSSG, OSI, and CWS. These findings highlight the potential mechanical mechanism of the higher adverse events and underscore the importance of stent positioning and sizing for improved clinical outcome.

Characterization of a Bioprosthetic Bicuspid Venous Valve Hemodynamics and Implications for Mechanism of Valve Dynamics

of CCSVI. We hypothesize that the BA effect on clinical parameters is mediated by mechanical stimulation of perivascular autonomic fibers and is independent of vascular obstruction. The purpose of this study is to describe Trans-Vascular Autonomic Modulation (TVAM) in multiple sclerosis (MS) patients as a means of improving ANS dysfunction, comparing its safety and efficacy to the traditional BA. Methods: Twenty-one MS patients who presented with symptoms of cardiovascular ANS dysfunction underwent TVAM. These patients were compared with 20 MS patients who presented with CSSVI, and who underwent traditional BA. TVAM deviated from traditional BA in that target veins, bilateral internal jugular, azygos, and left renal veins, were each dilated regardless of the presence of vascular abnormalities. This also included treatment of patients without evidence of abnormality in any of the target veins, eliminating the possibility of vascular effect. The improvement in cardiovascular ANS function was indicated by determining R-R interval variations during deep breathing (MCR, E/I ratio), valsalva maneuver (valsalva ratio), and postural changes (30:15 postural ratio). Results: The safety profile of the TVAM procedure was similar to that of the traditional BA with no adverse events occurring in either group. However, TVAM increased MCR, E/I ratio, and postural ratio more significantly than the traditional BA. Postintervention, improvements were seen in the TVAM group relative to baseline for MCR (3.34 6 0.41 vs 2.44 6 0.48; 36.4%; P 1⁄4 .08), E/I ratio (1.11 6 0.01 vs 1.09 6 0.01; 1.8%; P 1⁄4 .3), valsalva ratio (1.95 6 0.09 vs 1.74 6 0.09; 12%; P 1⁄4 .10), and postural ratio (1.36 6 0.08 vs 1.04 6 0.09; 30.7%; P 1⁄4 .027). The postural ratio response in the TVAM group relative to baseline (1.36 6 0.08 vs 1.04 6 0.09; 30.7%; P 1⁄4 .027) demonstrated the largest change relative to postintervention postural ratio in the control group (1.36 6 0.08 vs 1.167 6 0.03; 16.5%; P 1⁄4 .016). Conclusions: TVAM-mediated deposition of mechanical energy to central veins by balloon dilation, including anatomically normal veins, can improve indicators of ANS dysfunction. The observed safety and efficacy of TVAM is encouraging, paving the way for the treatment of ANS dysfunction in pathological states other than MS. Further studies should investigate the response to TVAM in larger cohort. Characterization of a Bioprosthetic Bicuspid Venous Valve Hemodynamics and Implications for Mechanism of Valve Dynamics W. Tien, H. Chen, Z. Berwick, J. Krieger, S. Chambers, D. Dabiri, G. Kassab. University of Washington, Seattle, Wash; 3DT Holdings, LLC, Indianapolis, Ind; COOK Medical, Bloomington, Ind; Indiana University School of Medicine, Indianapolis, Ind

Computational Modeling of Coronary Stents

Realistic computational modeling can be a very useful tool for medical device design optimization as well as pre-operative simulation of cardiovascular surgery. The fluid and solid stress analysis can provide valuable insights into tissue interaction and response mechanisms This chapter focuses on simulations of coronary stents Methods for fluid and solid modeling associated with stents are discussed in detail. The hemodynamic and mechanical data obtained from the simulations are considered in the context of their implications on vascular health and mechanotransduction. The effects of fluid wall shear stresses and solid wall stresses associated with stent implants on tissue remodeling and thrombosis are discussed.

Fluid-structure interaction in aortic cross-clamping: Implications for vessel injury

Vascular cross-clamping is applied in many cardiovascular surgeries such as coronary bypass, aorta repair and valve procedures. Experimental studies have found that clamping of various degrees caused damage to arteries. This study examines the effects of popular clamps on vessel wall. Models of the aorta and clamp were created in Computer Assisted Design and Finite Element Analysis packages. The vessel wall was considered as a non-linear anisotropic material while the fluid was simulated as Newtonian with pulsatile flow. The clamp was applied through displacement time function. Fully coupled two-way solid-fluid interaction models were developed. It was found that the clamp design significantly affected the stresses in vessel wall. The clamp with a protrusion feature increased the overall Von Mises stress by about 60% and the compressive stress by more than 200%. Interestingly, when the protrusion clamp was applied, the Von Mises stress at the lumen (endothelium) side of artery wall was about twice that of the outer wall. This ratio was much higher than that of the plate-like clamp which was about 1.3. The flow reversal process was demonstrated during clamping. Vibrations, flow and wall shear stress oscillations were detected immediately before total vessel occlusion. The commonly used protrusion clamp increased stresses in vessel wall, especially the compressive stress. This design also significantly increased the stresses on endothelium, detrimental to vessel health. The present findings are relevant to surgical clamp design as well as the transient mechanical loading on the endothelium and potential injury. The deformation and stress analysis may provide valuable insights into the mode of tissue injury during cross-clamping.

Impact of bifurcation dual stenting on endothelial shear stress

Despite advances in percutaneous coronary interventions and the introduction of drug eluding stents, in-stent restenosis and stent thrombosis remain a clinically significant problem for bifurcations. The aim of this study is to determine the effect of dual bifurcation stenting on hemodynamic parameters known to influence restenosis and thrombosis. We hypothesized that double stenting, especially with a longer side branch (SB) stent, likely has a negative effect on wall shear stress (WSS), WSS gradient (WSSG), and oscillatory shear index (OSI). To test this hypothesis, we developed computational models of dual stents at bifurcations and non-Newtonian blood simulations. The models were then interfaced, meshed, and solved in a validated finite-element package. Longer and shorter stents at the SB and provisional stenting were compared. It was found that stents placed in the SB at a bifurcation lowered WSS, but elevated WSSG and OSI. Dual stenting with longer SB stent had the most adverse impact on SB endothelial WSS, WSSG, and OSI, with low WSS region up to 50% more than the case with shorter SB stent. The simulations also demonstrated flow disturbances resulting from SB stent struts protruding into the main flow field near the carina, which may have implications on stent thrombosis. The simulations predict a negative hemodynamic role for SB stenting, which is exaggerated with a longer stent, consistent with clinical trial findings that dual-stenting is comparable or inferior to provisional stenting.

Editor's Choice – Fluid–Structure Interaction Simulations of Aortic Dissection with Bench Validation

INTRODUCTION The blood flow and stresses in the flap in aortic dissections are not well understood. Validated fluid-structure interaction (FSI) simulations of the interactions between the blood flow and the flap will provide insight into the dynamics of aortic dissections and may lead to developments of novel therapeutic approaches. METHODS A coupled, two-way blood flow and flap wall computational model was developed. The Arbitrary Lagrange-Eulerian method was used, which allowed the fluid mesh to deform. Inflow velocity waveforms from a pulse duplicator system were used in the simulations. RESULTS The velocities for true lumen (TL) and false lumen (FL) were not significantly different between bench and simulation. The dynamics of the TL % cross-sectional area (CSA) during the cycle was similar between the bench and computational simulations, with the TL %CSA being most reduced near peak systole of the cycle. The experimental distal measurements had significantly lower velocities, likely due to the spatially heterogeneous flow distally. The conservation of mass and validity of simulations were confirmed. Additionally, regions of stress concentrations were found on the flap leading edge, towards the corners, and through the entire vessel wall. The pressure gradient across the FL results in a net force on the flap. CONCLUSION The FSI flow velocities in the TL and the FL as well as the dynamics of the CSA during the cardiac cycle were validated by bench experiments. The validated FSI model may provide insights into aortic dissection including the stresses on the dissection flap and related flow disturbance, which may be subdued by novel therapeutic approaches. Simulations of more realistic human aortic dissections and the effects of current therapeutic approaches such as stent-graft can be developed in the future using the validated computational platform provided in the present study.