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.     

Hydrodynamic effects of compliance mismatch in stented arteries

Cardiovascular diseases are the number one cause of death in the world, making the understanding of hemodynamics and development of treatment options imperative. The most common modality for treatment of occlusive coronary artery diseases is the use of stents. Stent design profoundly influences the postprocedural hemodynamic and solid mechanical environment of the stented artery. However, despite their wide acceptance, the incidence of stent late restenosis is still high (Zwart et al., 2010, "Coronary Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment," Current Treatment Options in Cardiovascular Medicine, 12(1), pp. 46-57), and it is most prevailing at the proximal and distal ends of the stent. In this work, we focus our investigation on the localized hemodynamic effects of compliance mismatch due to the presence of a stent in an artery. The compliance mismatch in a stented artery is maximized at the proximal and distal ends of the stent. Hence, it is our objective to understand and reveal the mechanism by which changes in compliance contribute to the generation of nonphysiological wall shear stress (WSS). Such adverse hemodynamic conditions could have an effect on the onset of restenosis. Three-dimensional, spatiotemporally resolved computational fluid dynamics simulations of pulsatile flow with fluid-structure interaction were carried out for a simplified coronary artery with physiologically relevant flow parameters. A model with uniform elastic modulus is used as the baseline control case. In order to study the effect of compliance variation on local hemodynamics, this baseline model is compared with models where the elastic modulus was increased by two-, five-, and tenfold in the middle of the vessel. The simulations provided detailed information regarding the recirculation zone dynamics formed during flow reversals. The results suggest that discontinuities in compliance cause critical changes in local hemodynamics, namely, altering the local pressure and velocity gradients. The change in pressure gradient at the discontinuity was as high as 90%. The corresponding changes in WSS and oscillatory shear index calculated were 9% and 15%, respectively. We demonstrate that these changes are attributed to the physical mechanism associating the pressure gradient discontinuities to the production of vorticity (vorticity flux) due to the presence of the stent. The pressure gradient discontinuities and augmented vorticity flux are affecting the wall shear stresses. As a result, this work reveals how compliance variations act to modify the near wall hemodynamics of stented arteries.     

Experimental Study of a Starting Vortex Ring Generated by a Thin Circular Disk

The formation process of vortex ring generated by a thin circular disk was studied experimentally in this paper. A thin circular disk installed a linear motion stage was used to generate the vortex rings. Digital Particle Image Velocimetry (DPIV) was used to measure the velocity and vorticity fields. The finite-time Lyapunov exponent field corresponding to the vortex flow was computed to identify Lagrangian coherent structures of the starting vortex. The results reveal the existence of a flux window between repelling Lagrangian Coherent Structures (rLCS) and attracting Lagrangian Coherent Structures (aLCS), through which the shear flow is entrained into the vortex. The flux window is closed gradually during the starting process. Once the flux window shut down, the formation process of the vortex ring finishes, as the shear flow with vorticity cannot be entrained in the vortex ring.     

Delivery and release of nitinol stent in carotid artery and their interactions: a finite element analysis

Carotid angioplasty and stenting (CAS) has emerged as an effective alternative to carotid endarterectomy, and nitinol stents are commonly used in CAS. To evaluate biomechanical properties of nitinol carotid stents and their interactions with carotid arteries, a finite element method (FEM) model was built which is composed of a stenotic carotid tissue, a segmented-design nitinol stent and a sheath. Two different stents were considered to show the influence of stent design on the stent-vessel interactions. Results show that the superelastic stents were delivered into the stenotic vessel lumen through the sheath and self-expanded in the internal and common carotid artery. The stent with shorter struts may have better clinical results and the different stent designs can cause different carotid vessel geometry changes. This FEM can provide a convenient way to test and improve biomechanical properties of existing carotid stents and give clues for new nitinol carotid stent designs.     

Hemodynamic study of overlapping bare-metal stents intervention to aortic aneurysm

To investigate the hemodynamic performance of overlapping bare-metal stents intervention treatment to thoracic aortic aneurysms (TAA), three simplified TAA models, representing, no stent, with a single stent and 2 overlapped stents deployed in the aneurismal sac, were studied and compared in terms of flow velocity, wall shear stress (WSS) and pressure distributions by means of computational fluid dynamics. The results showed that overlapping stents intervention induced a flow field of slow velocity near the aneurismal wall. Single stent deployment in the sac reduced the jet-like flow formed prior to the proximal neck of the aneurysm, which impinged on the internal wall of the aneurysm. This jet-like flow vanished completely in the overlapping double stents case. Overlapping stents intervention led to an evident decrease in WSS; meanwhile, the pressure acting on the wall of the aneurysm was reduced slightly and presented more uniform distribution. The results therefore indicated that overlapping stents intervention may effectively isolate the thoracic aortic aneurysm, protecting it from rupture. In conclusion, overlapping bare-metal stents may serve a purpose similar to that of the multilayer aneurysm repair system (MARS) manufactured by Cardiatis SA (Isnes, Belgium).     

Optimization of cardiovascular stent design using computational fluid dynamics

Coronary stent design affects the spatial distribution of wall shear stress (WSS), which can influence the progression of endothelialization, neointimal hyperplasia, and restenosis. Previous computational fluid dynamics (CFD) studies have only examined a small number of possible geometries to identify stent designs that reduce alterations in near-wall hemodynamics. Based on a previously described framework for optimizing cardiovascular geometries, we developed a methodology that couples CFD and three-dimensional shape-optimization for use in stent design. The optimization procedure was fully-automated, such that solid model construction, anisotropic mesh generation, CFD simulation, and WSS quantification did not require user intervention. We applied the method to determine the optimal number of circumferentially repeating stent cells (N(C)) for slotted-tube stents with various diameters and intrastrut areas. Optimal stent designs were defined as those minimizing the area of low intrastrut time-averaged WSS. Interestingly, we determined that the optimal value of N(C) was dependent on the intrastrut angle with respect to the primary flow direction. Further investigation indicated that stent designs with an intrastrut angle of approximately 40 deg minimized the area of low time-averaged WSS regardless of vessel size or intrastrut area. Future application of this optimization method to commercially available stent designs may lead to stents with superior hemodynamic performance and the potential for improved clinical outcomes.     

冠状动脉内重叠支架置入术的临床研究进展

重叠支架置入术是临床上用来治疗冠状动脉弥漫性长病变的常用方法,以往曾采取重叠裸金属支架置入术,但其临床预后不佳,目前较为常用的重叠药物洗脱支架置入术被认为相对安全、有效,但仍存在许多潜在问题。本文介绍了适合使用重叠支架置入术进行治疗的冠状动脉病变的特点,回顾了重叠裸金属支架的临床应用情况,阐述了近年来药物洗脱支架的发展以及重叠药物洗脱支架置入术的优势,比较了四种负载不同药物的药物洗脱支架同种重叠置入后的临床疗效,观察了异种药物洗脱支架混合重叠置入后的临床特点和支架重叠段对临床预后的影响,分析了重叠支架置入术与几种其它治疗冠状动脉弥漫性长病变方法的应用区别,并对新一代药物支架的重叠应用进行了展望。     

A new stent with streamlined cross-section can suppress monocyte cell adhesion in the flow disturbance zones of the endovascular stent

We proposed a new stent with streamlined cross-sectional wires, which is different from the clinical coronary stents with square or round cross-sections. We believe the new stent might have better hemodynamic performance than the clinical metal stents. To test the hypothesis, we designed an experimental study to compare the performance of the new stent with the clinical stents in terms of monocyte (U-937 cells) adhesion. The results showed that when compared with the clinical stents, the adhesion of U-937 cells were much less in the new stent. The results also showed that, when Reynolds number increased from 180 (the rest condition for the coronary arteries) to 360 (the strenuous exercise condition for the coronary arteries), the flow disturbance zones in the clinical stents became larger, while they became smaller with the new stent. The present experimental study therefore suggests that the optimization of the cross-sectional shape of stent wires ought to be taken into consideration in the design of endovascular stents.     

A novel heart valve stent design: mechanical interaction with the aortic root

Percutaneous aortic valve implantation has become an alternative technique to surgical valve replacement in patients with high risk for open chest surgery. Vascular stents clinically used today for non-invasive aortic valve replacement tend, however, to impede the dimension changes of the compliant aortic root over the cardiac cycle. The purpose of the present work is to assess the influence of a novel heart valve stent, designed specifically to limit the traumatism in tissue, on the compliance of the aortic root. A theoretical approach is adopted to model the mechanical behaviour of the different stent parts and assess the compliance modification induced by the stent. The validity of the model is then tested experimentally. Both approaches show that the specific geometry of the stent makes it possible to keep the compliance of the aortic root close to the native root values.     

Understanding urinary conditioning film components on ureteral stents: profiling protein components and evaluating their role in bacterial colonization

Ureteral stents are fraught with problems. A conditioning film attaches to the stent surface within hours of implantation; however, differences between stent types and their role in promoting encrustation and bacterial adhesion and colonization remain to be elucidated. The present work shows that the most common components do not differ between stent types or patients with the same indwelling stent, and contain components that may drive stent encrustation. Furthermore, unlike what was previously thought, the presence of a conditioning film does not increase bacterial adhesion and colonization of stents by uropathogens. Genitourinary cytokeratins are implicated in playing a significant role in conditioning film formation. Overall, stent biomaterial design to date has been unsuccessful in discovering an ideal coating to prevent encrustation and bacterial adhesion. This current study elucidates a more global understanding of urinary conditioning film components. It also supports specific focus on the importance of physical characteristics of the stent and how they can prevent encrustation and bacterial adhesion.     

Numerical simulation of two-phase non-Newtonian blood flow with fluid-structure interaction in aortic dissection

The behavior of blood cells and vessel compliance significantly influence hemodynamic parameters, which are closely related to the development of aortic dissection. Here the two-phase non-Newtonian model and the fluid-structure interaction (FSI) method are coupled to simulate blood flow in a patient-specific dissected aorta. Moreover, three-element Windkessel model is applied to reproduce physiological pressure waves. Important hemodynamic indicators, such as the spatial distribution of red blood cells (RBCs) and vessel wall displacement, which greatly influence the hemodynamic characteristics are analyzed. Results show that the proximal false lumen near the entry tear appears to be a vortex zone with a relatively lower volume fraction of RBCs, a low time-averaged wall shear stress (TAWSS) and a high oscillatory shear index (OSI), providing a suitable physical environment for the formation of atherosclerosis. The highest TAWSS is located in the narrow area of the distal true lumen which might cause further dilation. TAWSS distributions in the FSI model and the rigid wall model show similar trend, while there is a significant difference for the OSI distributions. We suggest that an integrated model is essential to simulate blood flow in a more realistic physiological environment with the ultimate aim of guiding clinical treatment.     

Anomalous hemodynamic effects of a self-expanding intracranial stent: Comparing in-vitro and ex-vivo models using ultra-high resolution MicroCT based CFD

Previous research on the effects of intracranial stents on arterial hemodynamics has involved computational hemodynamics (CHD) simulations applied to artificially generated stent models. In this study, accurate geometric reconstructions of in-vitro (PTFE tube) and ex-vivo (canine artery) deployed stents based on ultra-high resolution MicroCT imaging were used. The primary goal was to compare the hemodynamic effects of deployment in these two different models and to identify flow perturbations due to deployment anomalies such as stent malapposition and strut prolapse, important adverse mechanics occurring in clinical practice, but not considered in studies using idealized stent models.Ultra-high resolution MicroCT data provided detailed visualization of deployment characteristics allowing for accurate in-stent flow simulation. For stent cells that are regularly and symmetrically deployed, the near wall flow velocities and wall shear stresses were similar to previously published results derived from idealized models. In-stent hemodynamics were significantly altered by misaligned or malapposed stent cells, important effects not realistically captured in previous models. This research shows the feasibility and value of an ex-vivo stent model for MicroCT based CHD studies. It validates previous in-vitro studies and further contributes to the understanding of in-stent hemodynamics associated with adverse mechanics of self-expanding intracranial stents.     

What information do Kármán streets offer to flow sensing?

In this work, we focus on biomimetic lateral line sensing in Kármán vortex streets. After generating a Kármán street in a controlled environment, we examine the hydrodynamic images obtained with digital particle image velocimetry (DPIV). On the grounds that positioning in the flow and interaction with the vortices govern bio-inspired underwater locomotion, we inspect the fluid in the swimming robot frame of reference. We spatially subsample the flow field obtained using DPIV to emulate the local flow around the body. In particular, we look at various sensor configurations in order to reliably identify the vortex shedding frequency, wake wavelength and downstream flow speed. Moreover, we propose methods that differentiate between being in and out of the Kármán street with >70% accuracy, distinguish right from left with respect to Kármán vortex street centreline (>80%) and highlight when the sensor system enters the vortex formation zone (>75%). Finally, we present a method that estimates the relative position of a sensor array with respect to the vortex formation point within 15% error margin.     

Effects of stents under asymmetric inflow conditions

Patient-to-patient variations in artery geometry may determine their susceptibility to stenosis formation. These geometrical variations can be linked to variations in flow characteristics such as wall shear stress through stents, which increases the risk of restenosis. This paper considers computer models of stents in non-symmetric flows and their effects on flow characteristics at the wall. This is a fresh approach from the point of view of identifying a stent design whose performance is insensitive to asymmetric flow. Measures of dissipated energy and power are introduced in order to discriminate between competing designs of stents.     

Influence of stent-induced vessel deformation on hemodynamic feature of bloodstream inside ICA aneurysms

One of the effective treatment options for intracranial aneurysms is stent-assisted coiling. Though, previous works have demonstrated that stent usage would result in the deformation of the local vasculature. The effect of simple stent on the blood hemodynamics is still uncertain. In this work, hemodynamic features of the blood stream on four different ICA aneurysm with/without interventional are investigated. To estimate the relative impacts of vessel deformation, four distinctive ICA aneurysm is simulated by the one-way FSI technique. Four hemodynamic factors of aneurysm blood velocity, wall pressure and WSS are compared in the peak systolic stage to disclose the impact of defamation by the stent in two conditions. The stent usage would decrease almost all of the mentioned parameters, except for OSI. Stenting reduces neck inflow rate, while the effect of interventional was not consistent among the aneurysms. The deformation of an aneurysm has a strong influence on the hemodynamics of an aneurysm. This outcome is ignored by most of the preceding investigations, which focused on the pre-interventional state for studying the relationship between hemodynamics and stents. Present results show that the application of stent without coiling would improve most hemodynamic factors, especially when the deformation of the aneurysm is high enough.

     

Endovascular stent configuration affects intraluminal flow dynamics and in vitro endothelialization

Neointimal hyperplasia influenced by intravascular hemodynamics is considered partly responsible for restenosis after endovascular stenting. To evaluate the effect of stent configuration on fluid flow behavior, we visualized flow near stents, and measured the proliferation of cultured endothelial cells (ECs). A single-coil stent (coil pitch; CP = 2.5, 5, or 10 mm) was inserted into a glass tube and perfused at 30-90 ml/min, while the flow pattern was determined by particle imaging velocimetry. The reduction of the flow velocity near the wall was correlated with the decrease in the coil interval of the stent. In perfusion cultures with stents, the proliferation of ECs was influenced by the local flow velocity distribution. When a stent with a CP value of 10 mm was used, the doubling time of ECs was 30.7 h, while the doubling time was 38.5 h when the CP was 5 mm. The doubling time of ECs was shorter at sites upstream of the stent wire where the velocity was higher than downstream of the wire. In conclusion, a single-coil stent can be used to modify hemodynamic factors, suggesting that improved stent design may facilitate rapid endothelialization after stent implantation.     

Numerical simulation of hemodynamics in stented internal carotid aneurysm based on patient-specific model

There is still a considerable lack of quantitative information concerning the effects of stent structures on blood flow in an aneurismal cavity. In this paper, five virtual stents with different structures and wire cross-sections were designed for incorporation into the same patient-specific aneurysm model. Computational fluid dynamics simulations were performed so as to study how these five types of stents modified hemodynamic parameters. Numerical results demonstrated that the mean flow rate in the aneurismal cavity decreased the most in the model that used a stent with a rectangular wire cross-section, and that the wall shear stresses at the dome and neck of the aneurysm decreased more in models that used a stent with a circular wire cross-section or a spiral stent with a rectangular wire cross-section compared to other models. In addition, the wall pressure on the aneurysm increased slightly after implantation of the stent in all five models. This result differs from that previously published, and may help guide the design and assist clinicians in selecting an appropriate stent for treating cerebral aneurysms.     

Radioisotope stents for the prevention of restenosis: what did we learn from pre-clinical studies?

This article will discuss the lessons learned by using stents implanted with low activities of radioisotopes to prevent in-stent restenosis. A continuous low-dose rate radiation delivered by radioisotope stents has been shown to reduce the proliferative activity of smooth muscle cells and to inhibit neointimal growth. However, the radiation also delays endothelialization of the stents. Both the dose rate and the cumulative dose delivered by radioisotope stents appear to affect outcome. The neointima covering radioactive stents is characterized by a reduced cellularity, increased amounts of fibrin and extracellular matrix proteins. Aneurysm formation or excessive tissue destruction due to the radiation were not observed. Animals studies including up to 1 year follow-up periods suggest that beta-particle-radiation as well as gamma-radiation are effective in reducing neointimal hyperplasia. It is still unknown, however, which range of activities are needed and if a combination of radioisotopes, i.e. with short and long halflives, further reduce neotima formation over the long-term. An appropriate stent design for homogenous dose distribution around the stent may be important, i.e. articulations or large cell sizes may have disadvantages. Augmented neointima formation at the ends of radioactive stents, in particular when using beta-particle emitting stents, has been observed in animal models. Future studies will focus on the effects of increasing activity levels at the stent ends, optimal stent designs, alternative isotopes and different dosing strategies.     

Mechanical properties of coronary stents determined by using finite element analysis.

The mechanical function of a stent deployed in a damaged artery is to provide a metallic tubular mesh structure. The purpose of this study was to determine the exact mechanical characteristics of stents. In order to achieve this, we have used finite-element analysis to model two different type of stents: tubular stents (TS) and coil stents (CS). The two stents chosen for this modeling present the most extreme mechanical characteristics of the respective types. Seven mechanical properties were studied by mathematical modeling with determination of: (1) stent deployment pressure, (2) the intrinsic elastic recoil of the material used, (3) the resistance of the stent to external compressive forces, (4) the stent foreshortening, (5) the stent coverage area, (6) the stent flexibility, and (7) the stress maps. The pressure required for deployment of CS was significantly lower than that required for TS, over 2.8 times greater pressure was required for the tubular model. The elastic recoil of TS is higher than CS (5.4% and 2.6%, respectively). TS could be deformed by 10% at compressive pressures of between 0.7 and 1.3 atm whereas CS was only deformed at 0.2 and 0.7 atm. The degree of shortening observed increases with deployment diameter for TS. CS lengthen during deployment. The metal coverage area is two times greater for TS than for CS. The ratio between the stiffness of TS and that of CS varies from 2060 to 2858 depending on the direction in which the force is applied. TS are very rigid and CS are significantly more flexible. Stress mapping shows stress to be localized at link nodes. This series of finite-element analyses illustrates and quantifies the main mechanical characteristics of two different commonly used stents. In interventional cardiology, we need to understand their mechanisms of implantation and action.     

Bristled shark skin: a microgeometry for boundary layer control?

There exists evidence that some fast-swimming shark species may have the ability to bristle their scales during fast swimming. Experimental work using a water tunnel facility has been performed to investigate the flow field over and within a bristled shark skin model submerged within a boundary layer to deduce the possible boundary layer control mechanisms being used by these fast-swimming sharks. Fluorescent dye flow visualization provides evidence of the formation of embedded cavity vortices within the scales. Digital particle image velocimetry (DPIV) data, used to evaluate the cavity vortex formation and boundary layer characteristics close to the surface, indicate increased momentum in the slip layer forming above the scales. This increase in flow velocity close to the shark's skin is indicative of boundary layer control mechanisms leading to separation control and possibly transition delay for the bristled shark skin microgeometry.