A Systematic Review on Cardiovascular Stent and Stenting Failure: Coherent Taxonomy, Performance Measures, Motivations, Open Challenges and Recommendations

Cardiovascular stenting is a mature topic but it is still being developed in the research community because of its importance. To provide worthy information about cardiovascular stenting environments and to give support to the researchers, attention must be given to understand the obtainable choices and gaps in this research field. This work aims to examine and examine the literature of each work related to the placement of cardiovascular stents, the failure of the stents and the models of stent designs to provide a good understanding through the investigation of articles published in various contextual aspects, such as motivations, open-challenges and recommendations to improve the field of stent placement. A systematic review is carried-out to map and examine the articles related to cardiovascular stents, the failure of the stents and the models of stent designs through a coherent-taxonomy used in three well-known scientific databases: ScienceDirect, IEEE Explore, and Web of Science. These databases involve literature that highlight arterial stenting. Based-on our inclusion and exception, a total of 90 articles composed the final set that offer various classes and sub-classes. The first class includes the development studies with (42/90) of experimental, computational and combined experimental and computational studies related to stent models performance and stent failure, the second class discussed studies that have been performed on stent design with (32/90), the third class is focused on the framework studies with (10/90), and the fourth class includes problems of stenting long-term with (6/90). The performance of stent designs, which is a research area that requires periodic controls, tools and procedures that could provide a stent design with good mechanical performance, reduce restenosis in the stent and increase fatigue resistance and durability. There have been numerous studies on stent performance that could promise good results in this field. The fields of research in stent designs vary, but all fields are fundamental equally. The expectation of this work could help to emphasize present research chances and, therefore, expand and make further research fields

Characterization of the Deformation Behavior and Mechanical Response of the Femoro-popliteal Arterial Tract after Stent Placement

The femoro-popliteal (FP) segment is the most commonly diseased artery of the peripheral circulation. Obstructions of these lower-limb arteries are frequent and even with the new generation Nitinol stents (drug-eluting or otherwise), long-term restenosis rates following endovascular procedures range from 15 to 40% and are much higher compared with the long-term outcomes after coronary artery interventions. The major difference between peripheral and coronary arteries concerns their mechanical environments, with the FP arterial segments being subjected to repeated external deformations during leg flexion. It has been widely hypothesized that the high distortion of the tissues due to the un-physiological deformations of the arteries following stent implantation is the main cause for restenosis. However, there is very limited information on the FP artery deformations of patients with Peripheral Arterial Disease (PAD). Furthermore, the effects of endovascular therapy on the deformation behavior of the PAD-afflicted FP arteries are currently unknown. As such, further research on the deformations of the FP arteries is warranted to not only improve existing stent designs, but to also determine the correct interventional procedure. The main objectives of this thesis were to characterize the deformation behavior and mechanical response of the FP arterial tract through clinical and numerical investigations. The former was achieved by, first, investigating the pre-angioplasty deformations of the FP arteries during leg flexion in a pilot study of five patients with PAD and utilizing 3D rotational angiography. The methodology was then adapted to perform a clinical study of 35 patients with PAD, in which X-ray angiography was used to image the FP arteries in straight and flexed positions prior to endovascular therapy and following either Percutaneous Transluminal Angioplasty (PTA) or primary Nitinol stent implantation. The 3D models of the FP arteries were reconstructed from the 2D X-ray angiograms and the deformations of axial deformation and curvature were quantified. Both studies showed that the PAD-afflicted FP arterial segment undergoes significant shortening and an increase in curvature with leg flexion. Comparisons between the pre- and post-treatment deformations, as well as between the different treatment methods, suggested that the choice of the treatment method significantly affects the post-interventional axial deformations of the FP arteries (post-balloon: 7.6% ± 4.9%; post-stent: 3.2% ± 2.9%; P: 0.004). As such, while PTA results in a more flexible artery, stents restrict the arteries’ shortening capabilities. Depending on the anatomical position of the stents, this axial stiffening of the arteries may lead to chronic kinking, which may cause occlusions and, consequently, impact the long-term success of the procedure. As current stent designs were found to conform to the curvature behavior of the FP arterial tract, improvements should be focused on reproducing the native axial stiffness of the artery to reduce the risk of restenosis for patients that will have to undergo stent implantation. The complexities caused by leg flexion are further exacerbated by controversial clinical practices, such as Nitinol stent oversizing. The procedure is frequently performed in peripheral arteries to ensure a desirable acute lumen gain and strong wall apposition, and to prevent stent migration. However, the increased radial force exerted onto the arterial walls by the oversized stents could lead to significant arterial damage and, in turn, restenosis. The contradictory findings between animal and clinical studies, in conjunction with the majority of the numerical studies focusing on balloon-expandable stents, suggests that the efficacy of the procedure remains as an issue to be answered. The mechanical behavior of the FP artery under Nitinol stent oversizing was investigated by creating a validated finite element (FE) framework, which included numerical models of healthy FP arteries with patient-specific geometries and idealized arteries with clinically relevant levels of PAD. Based on the artery model, either only stent implantation or the complete endovascular therapy (PTA + stent implantation) was simulated. Four different stent-to-artery ratios ranging from 1.0 to 1.8 were used in the simulations. For the healthy arteries, additional analyses, in the form of computational fluid dynamics (CFD) analyses and fatigue behavior of the stents, were performed to observe the hemodynamic behavior of the arteries with respect to increased oversizing ratios. For the calcified arteries, three different plaque types were modeled to report the influence of the plaque behaviors on the outcomes of endovascular therapy and stent oversizing. Regardless of the presence of a plaque tissue, results showed that Nitinol stent oversizing was found to produce a marginal lumen gain in ix contrast to a significant increase in arterial stresses. For the lightly and moderately calcified arteries, oversizing was found to be non-critical; whereas for healthy and heavily calcified arteries, the procedure should be avoided due to a risk of tissue failure. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, the studies showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure. In order to predict the possibility of restenosis through mechanical markers that are associated with the effects of leg movement following stent implantation, clinical investigations should be complimented with patient-specific numerical analyses. Combining intra-arterial imaging methodologies with in-vivo arterial deformations, which can be translated to FE simulations as boundary conditions, and building upon the numerical framework that is introduced in the 2nd part of this thesis, it’s possible to generate accurate patient-specific models. These models, evaluated in conjunction with clinical follow-ups, are expected to provide a deeper understanding of the mechanical background of restenosis in peripheral arteries

Stents for transcatheter aortic valve replacement

Rheumatic heart disease (RHD) is the leading cause of aortic valve disease in the world. Surgery to repair or replace the diseased valves is the only means to save a patient's life once the disease becomes symptomatic. Transcatheter aortic valve replacement (TAVR) has revolutionised the treatment of age-related degenerative aortic valve disease, but is currently not suitable for the majority of RHD sufferers due to the rapid degeneration of flexible leaflet valves in younger patients, contraindications of commercial devices to regurgitant or non-calcific aortic valve disease, and also due to resource or funding limitations. The current research project aimed to develop and test novel compressible balloon-expandable stents suitable for patients with symptomatic rheumatic aortic valve disease, and which would allow for a percutaneous polymeric valve to be manufactured, be crimped onto balloon-based devices, and be expanded into a compliant or non-calcific native aortic valve. Several stent concepts were developed and evaluated using Finite Element Analysis (FEA) and two favoured concepts were selected for more complex FEA, in which the balloon was simulated using an Ogden material model, and rigorous testing. The stent material, a nickel-cobalt-chromium alloy, was modelled as an isotropic elasto-plastic material with isotropic hardening. The novel stent designs incorporated a native leaflet-mimicking crown shape for continuous leaflet attachment and mechanisms to anchor the stented valve within compliant aortic roots. The first of the favoured designs provided tactile location during delivery and anchored using self-expanding arms on a balloon-expandable frame of the same material ("self-locating stents"). The second design anchored using arms that protruded during deployment as a consequence of plastic deformation incurred during crimping ("expanding arm stents"). Prototypes were successfully manufactured through laser cutting and electropolishing and showed good surface quality. In vitro testing included determination of crimping and expansion behaviour and measurement of mechanical properties such as resistance to migration in the anatomy. Valve performance was evaluated through in vitro haemodynamics in a pulse duplicator and durability was tested in a high-cycle fatigue tester. Simulated use testing was performed using cadaveric animal hearts. Finally, valves were also implanted into the aortic valve position of pigs (in acute termination experiments) through a transapical approach in order to verify valve deployment behaviour and function in vivo, and determine the stent's ability to anchor in the native anatomy. Stents could be crimped to diameters below 6mm and deployed using commercial balloons and proprietary non-occlusive deployment devices. FEA simulations of stent crimping and deployment matched experimental behaviour well and provide a tool to optimise stent performance. Peak Von Mises stresses during deployment (1437 MPa and 1633 MPa for self-locating and expanding arm stents, respectively) were comparable to a "zig-zag" stent simulated for control purposes (1650 MPa). Radial strength, evaluated for expanding arm stents, was lower than the Control stent (116 N vs. 347 N). This design, although predicted to be safe under fatigue loading, had a lower fatigue safety factor than the Control stent. Stents resisted migration to forces of at least 22 N, which is four times greater than physiological loading on the valves. Polymeric valves incorporating the stents were constructed and demonstrated good in vitro haemodynamic performance (Effective Orifice Areas ≥2.0cm², ΔP<9 mmHg, regurgitation <6%) and durability of over 400 million cycles. Designs functioned as intended in simulated use tests. Valves constructed using self-locating stents could be successfully deployed without rapid pacing in eight of nine pigs, and valve position was correct in seven of these. Valves of expanding arm stents remained anchored in six of eight attempted implants in pigs. This study has demonstrated proof of concept for a novel balloon-expandable stent for a polymeric transcatheter heart valve that is capable of anchoring in a compliant native aortic valve

Computational methods in cardiovascular mechanics

The introduction of computational models in cardiovascular sciences has been progressively bringing new and unique tools for the investigation of the physiopathology. Together with the dramatic improvement of imaging and measuring devices on one side, and of computational architectures on the other one, mathematical and numerical models have provided a new, clearly noninvasive, approach for understanding not only basic mechanisms but also patient-specific conditions, and for supporting the design and the development of new therapeutic options. The terminology in silico is, nowadays, commonly accepted for indicating this new source of knowledge added to traditional in vitro and in vivo investigations. The advantages of in silico methodologies are basically the low cost in terms of infrastructures and facilities, the reduced invasiveness and, in general, the intrinsic predictive capabilities based on the use of mathematical models. The disadvantages are generally identified in the distance between the real cases and their virtual counterpart required by the conceptual modeling that can be detrimental for the reliability of numerical simulations.Comment: 54 pages, Book Chapte

Finite Element Analysis to Study Percutaneous Heart Valves

Communications engineering / telecommunication

Computational modelling of stent deployment and mechanical performance inside human atherosclerotic arteries

Atherosclerosis is the obstruction of blood stream caused by the formation of fatty plaques (stenosis) within human blood vessels. It is one of the most common cardiovascular conditions and the primary cause of death in developed countries. Nowadays stenting is a standard treatment for this disease and has been undergoing a rapid technological development. The aim of this PhD is to simulate the deployment of stents within atherosclerotic arteries in order to understand the mechanical performance of these devices. To this purpose, specific objectives were identified to study: (i) the effects of stent design, material and coating on stent deployment; (ii) the influence of balloon type, arterial constraints and vessel constitutive models in stenting simulation; (iii) the importance of plaque thickness, stenosis asymmetry and vessel curvature during the process of stent deployment; (iv) the necessity of considering vessel anisotropy and post-deployment stresses to assess stents mechanical behaviour; (v) the performance of biodegradable polymeric stents in comparison with metallic stents. Finite element (FE) analyses were employed to model the deployment of balloon-expandable stents. The balloon-stent-artery system was generated and meshed using finite element package Abaqus. Individual arterial layer and stenosis were modelled using hyperelastic Ogden model, while elastic-plastic behaviour with nonlinear hardening was used to describe the material behaviour of stents. The expansion of the stent was obtained by application of pressure inside the balloon, with hard contacts defined between stent, balloon and artery. The FE model was evaluated by mesh sensitivity study and further validated by comparison with published work. Comparative study between different commercially available stents (i.e. Palmaz-Schatz, Cypher, Xience and Endeavor stents) showed that open-cell design tends to have easier expansion and higher recoiling than closed-cell design, with lower stress level on the plaque after deployment. Also, stents made of materials with lower yield stress and weaker strain hardening experience higher deformation and recoiling, but less post-deployment stresses. Folded balloon produces sustained stent expansion under a lower pressure when compared to rubber balloon, with also increased stress level on the stent and artery. Simulations with different arterial constraints showed that stress on the plaque-artery system is higher for a free artery as a result of more severe stretch. Study of arterial constitutive models showed that saturation of expansion could not be noticed for models that neglect the second stretch invariant in the strain energy potential. Stent expansion is highly affected by plaque thickness, and stresses and recoiling increased considerably with the increasing level of stenosis. Asymmetry of the plaque causes non-uniform stent expansion and high levels of vessel wall stresses are developed in the regions covered by thin layer of plaque. Also, a reduction in stent expansion is observed with the increase of artery curvature, accompanied by an elevation of stresses in the plaque and arterial layers. Vessel anisotropic behaviour reduces the system expansion at peak pressure, and also lowers recoiling effect significantly. The post-deployment stresses caused by stent expansion increase the system flexibility during in-plane bending and radial compression. Comparative study of a PLLA stent (Elixir) and a Co-Cr alloy stent (Xience) showed that polymeric stent has a lower expansion rate and a reduction in final expansion than metallic stent

Finite element analysis of idealised cardiovascular stents : understanding the influence of artery material models on stent stress distribution

Stent fracture (SF) is thought to be a major contributor to in-stent restenosis and other adverse clinical events. It has been linked to angulated vessels and bifurcations, where there is often a hinge-motion movement throughout the cardiac cycle. Finite element (FE) analysis of stented arteries can be utilised to assess stent stresses and predict the likelihood of SF.An idealised tubular stent model was initially created and validated for use as a design- independent representation of stent devices. The stent model was idealised to a cylindrical tube to eliminate the device artifacts and ensure the resulting stent stress analysis was not distorted by highly localised areas of higher stress. The idealised model was based on the 3-point-bend test of a cardiovascular stent, and the FE model created to represent the mechanical behaviour of the device.Human arteries have previously been represented using a variety of mathematical models ranging from simple linear isotropic models to more complex hyperelastic models. As there has been little comparative work to qualify the necessity of using the more complex constitutive models for analysis of stresses in the stent, this study employed a variety of mathematical models used to represent human arteries to allow direct comparison of the sensitivity of model variation. The idealised stent model was used to represent an angulated stented vessel undergoing hinge-motion bending. Six different artery models from the literature were used to define the artery in the FE model and the resulting stent stresses were assessed.The results of the sensitivity study were varied and indicated little sensitivity to the artery model in terms of the stress distribution pattens, however the maximum stress values were more diverse. Overall, the likely location of SF was determined to be on the inside of the hinge-point of the stented bifurcation lesion. The model was determined to be useful as a comparative model to assess different stents devices and materials for those most likely to fracture

A computational study of mechanical behavior of bioresorbable polymeric stents

Coronary artery disease (CAD) is a leading killer of human life worldwide. Clinically, stent implantation with percutaneous coronary intervention has become a standard and effective method to treat coronary artery disease. A large amount of research work has been carried out to investigate the mechanical, degradation and fatigue behavior for permanent metallic stents, but not for bioresorbable polymeric stents. Such research gaps are urgently required to be addressed, as bioresorbable polymeric stents are regarded as the next generation medical devices, even replacing metallic stents. In this thesis, pioneering efforts have been made to systematically study the mechanical behavior of polymeric stents using finite element method, which are novel and have not been reported in literature yet. [Continues.

The development of a transcatheter mitral valve

Transcatheter heart valve replacements avoid the main risks associated with conventional open heart surgery and so is the preferred replacement technique for high-risk patients with aortic stenosis. Due to technical challenges, adaptation for the mitral position is still in early stages of research. The aim of this project was to develop the novel UCL transcatheter mitral valve (TMV) based on a prior conceptual design. The UCL TMV is designed to treat mitral regurgitation (MR) and is based on the UCL transcatheter aortic valve (TAV) which is retrievable, repositionable and has enhanced anchoring and sealing. The UCL TMV leaflets, which ensure unidirectional blood flow, are novel because they mimic native mitral valve morphology by having two leaflets, being D-shaped and conical. Their optimal design criterion and two key design parameters were identified using a failure mode and effects analysis and numerical simulations were used to select a design with acceptable stress levels and maximum coaptation area. The optimal leaflets were prototyped as a surgical valve to evaluate their performance against available commercial device designs and were then incorporated in TMV prototypes, and assessed for hydrodynamic performance, both of which exceeded international standard requirements. Durability assessment of the TMV is ongoing and very encouraging; currently withstanding > 80 million cardiac cycles. In conclusion, the results presented and ongoing durability assessments for the UCL TMV indicate it could be a new and effective treatment option for severe MR in high-risk patients whom are declined surgical interventions