Left atrial appendage occlusion: On the need of a numerical model to simulate the implant procedure.

Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention.

Investigating Balloon-Vessel Contact Pressure Patterns in Angioplasty: In Silico Insights for Drug-Coated Balloons.

Drug-Coated Balloons have shown promising results as a minimally invasive approach to treat stenotic arteries, but recent animal studies have revealed limited, non-uniform coating transfer onto the arterial lumen. In vitro data suggested that local coating transfer tracks the local Contact Pressure (CP) between the balloon and the endothelium. Therefore, this work aimed to investigate in silico how different interventional and device parameters may affect the spatial distribution of CP during the inflation of an angioplasty balloon within idealized vessels that resemble healthy femoral arteries in size and compliance. An angioplasty balloon computational model was developed, considering longitudinal non-uniform wall thickness, due to its forming process, and the folding procedure of the balloon. To identify the conditions leading to non-uniform CP, sensitivity finite element analyses were performed comparing different values for balloon working length, longitudinally varying wall thickness, friction coefficient on the balloon-vessel interface, vessel wall stiffness and thickness, and balloon-to-vessel diameter ratio. Findings indicate a significant irregularity of contact between the balloon and the vessel, mainly affected by the balloon's unfolding and longitudinal thickness variation. Mirroring published data on coating transfer distribution in animal studies, the interfacial CP distribution was maximal at the middle of the balloon treatment site, while exhibiting a circumferential pattern of linear peaks as a consequence of the particular balloon-vessel interaction during unfolding. A high ratio of balloon-to-vessel diameter, higher vessel stiffness, and thickness was found to increase significantly the amplitude and spatial distribution of the CP, while a higher friction coefficient at the balloon-to-vessel interface further exacerbated the non-uniformity of CP. Evaluation of balloon design effects revealed that the thicker tapered part caused CP reduction in the areas that interacted with the extremities of the balloon, whereas total length only weakly impacted the CP. Taken together, this study offers a deeper understanding of the factors influencing the irregularity of balloon-tissue contact, a key step toward uniformity in drug-coating transfer and potential clinical effectiveness.

The impact of modeling choices on the assessment of Ni-Ti fatigue properties through surrogate specimens.

The implant of self-expandable Ni-Ti stents for the treatment of peripheral diseases has become an established medical practice. However, the reported failure in clinics highlights the open issue of the fatigue characterization of these devices. One of the most common approaches for calculating the Ni-Ti fatigue limit (commonly defined in terms of mean and alternate strain for a fixed number of cycles) consists of using surrogate specimens which replicate the strain distributions of the final device but in simplified geometries. The main drawback lies in the need for computational models to determine the local distribution and, hence, interpret the experimental results. This study aims at investigating the role of different choices in the model preparation, such as the mesh refinement and the element formulation, on the output of the fatigue analysis. The analyses show a strong dependency of the numerical results on modeling choices. The use of linear reduced elements enriched by a layer of membrane elements is successful to increase the accuracy of the results, especially when coarser meshes are used. Due to material nonlinearity and stent complex geometries, for the same loading conditions and element type, (i) different meshes result in different couples of mean and amplitude strains and (ii) for the same mesh, the position of the maximum mean strain is not coincident with the maximum amplitude, making difficult the selection of the limit values.

Epistemic and Non-epistemic Values in Earthquake Engineering.

The importance of epistemic values in science is universally recognized, whereas the role of non-epistemic values is sometimes considered disputable. It has often been argued that non-epistemic values are more relevant in applied sciences, where the goals are often practical and not merely scientific. In this paper, we present a case study concerning earthquake engineering. So far, the philosophical literature has considered various branches of engineering, but very rarely earthquake engineering. We claim that the assessment of seismic hazard models is sensitive to both epistemic and non-epistemic values. In particular, we argue that the selection and evaluation of these models are justified by epistemic values, even if they may be contingently influenced by non-epistemic values. By contrast, the aggregation of different models into an ensemble is justified by non-epistemic values, even if epistemic values may play an instrumental role in the attainment of these non-epistemic values. A careful consideration of the different epistemic and non-epistemic values at play in the choice of seismic hazard models is thus practically important when alternative models are available and there is uncertainty in the scientific community about which model should be used.

Relevant Choices Affecting the Fatigue Analysis of Ni-Ti Endovascular Devices.

Ni-Ti alloys are widely used for biomedical applications due to their superelastic properties, which are especially convenient for endovascular devices that require minimally invasive insertion and durable effects, such as peripheral/carotid stents and valve frames. After crimping and deployment, stents undergo millions of cyclic loads imposed by heart/neck/leg movements, causing fatigue failure and device fracture that can lead to possibly severe consequences for the patient. Standard regulations require experimental testing for the preclinical assessment of such devices, which can be coupled with numerical modeling to reduce the time and costs of such campaigns and to obtain more information regarding the local state of stress and strain in the device. In this frame, this review aimed to enlighten the relevant choices that can affect the outcome of the fatigue analysis of Ni-Ti devices, both from experimental and numerical perspectives.

An in silico trials platform for the evaluation of stent design effect in post-implantation outcomes.

Bioresorbable Vascular Scaffolds (BVS), developed to allow drug deliver and mechanical support, followed by complete resorption, have revolutionized atherosclerosis treatment. InSilc is a Cloud platform for in silico clinical trials (ISCT) used in the design, development and evaluation pipeline of stents. The platform integrates beyond the state-of-the-art multi-disciplinary and multiscale models, which predict the scaffold's performance in the short/acute and medium/long term. In this study, a use case scenario of two Bioabsorbable Vascular Stents (BVSs) implanted in the same arterial anatomy is presented, allowing the whole InSilc in silico pipeline to be applied and predict how the different aspects of this intervention affect the success of stenting process.

Patient-specific multi-scale design optimization of transcatheter aortic valve stents.

BACKGROUND AND OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for a wide range of patients with aortic stenosis. Although some of the TAVI post-operative complications are addressed in newer designs, other complications and lack of long-term and durability data on the performance of these prostheses are limiting this procedure from becoming the standard for heart valve replacements. The design optimization of these devices with the finite element and optimization techniques can help increase their performance quality and reduce the risk of malfunctioning. Most performance metrics of these prostheses are morphology-dependent, and the design and the selection of the device before implantation should be planned for each individual patient. METHODS: In this study, a patient-specific aortic root geometry was utilized for the crimping and implantation simulation of 50 stent samples. The results of simulations were then evaluated and used for developing regression models. The strut width and thickness, the number of cells and patterns, the size of stent cells, and the diameter profile of the stent were optimized with two sets of optimization processes. The objective functions included the maximum crimping strain, radial strength, anchorage area, and the eccentricity of the stent. RESULTS: The optimization process was successful in finding optimal models with up to 40% decrease in the maximum crimping strain, 261% increase in the radial strength, 67% reduction in the eccentricity, and about an eightfold increase in the anchorage area compared to the reference device. CONCLUSIONS: The stents with larger distal diameters perform better in the selected objective functions. They provide better anchorage in the aortic root resulting in a smaller gap between the device and the surrounding tissue and smaller contact pressure. This framework can be used in designing patient-specific stents and improving the performance of these devices and the outcome of the implantation process.

Reliable Numerical Models of Nickel-Titanium Stents: How to Deduce the Specific Material Properties from Testing Real Devices.

The current interest of those dealing with medical research is the preparation of digital twins. In this frame, the first step to accomplish is the preparation of reliable numerical models. This is a challenging task since it is not common to know the exact device geometry and material properties unless in studies performed in collaboration with the manufacturer. The particular case of modeling Ni-Ti stents can be highlighted as a worst-case scenario due to both the complex geometrical features and non-linear material response. Indeed, if the limitations in the description of the geometry can be overcome, many difficulties still exist in the assessment of the material, which can vary according to the manufacturing process and requires many parameters for its description. The purpose of this work is to propose a coupled experimental and computational workflow to identify the set of material properties in the case of commercially-resembling Ni-Ti stents. This has been achieved from non-destructive tensile tests on the devices compared with results from Finite Element Analysis (FEA). A surrogate modeling approach is proposed for the identification of the material parameters, based on a minimization problem on the database of responses of Ni-Ti materials obtained with FEA with a series of different parameters. The reliability of the final result was validated through the comparison with the output of additional experiments.

An experimental investigation into the physical, thermal and mechanical degradation of a polymeric bioresorbable scaffold.

This study presents a comprehensive evaluation of the mechanical, micro-mechanical and physical properties of Reva Medical Fantom Encore Bioresorbable Scaffolds (BRS) subjected to a thermally-accelerated degradation protocol. The Fantom Encore BRS were immersed in phosphate buffered saline solution at 50 °C for 112 days with radial compression testing, nanoindentation, differential scanning calorimetry, gel permeation chromatography and mass loss characterisation performed at consecutive time points. In the initial stages of degradation (Days 0-21), the Fantom Encore BRS showed increases in radial strength and stiffness, despite a substantial reduction in in molecular weight, with a slight increase in the melt temperature also observed. In the second phase (Days 35-54), the radial strength of the BRS samples were maintained despite a continued loss in molecular weight. However, during this phase, the ductility of the stent showed a reduction, with stent fracture occurring earlier in the crimp process and with lower amounts of plastic deformation evident under visual examination post-fracture. In the final phase (Days 63-112), the load-bearing capacity of the Fantom Encore BRS showed continued reduction, with decreases in radial stiffness and strength, and drastic reduction in the work-to-fracture of the devices. Throughout each phase, there was a steady increase in the relative crystallinity, with limited mass loss until day 112 and only minor changes in glass transition and melt temperatures. Limited changes were observed in nano-mechanical properties, with measured local elastic moduli and hardness values remaining largely similar throughout degradation. Given that the thermally-accelerated in vitro conditions represented a four-fold acceleration of physiological conditions, these results suggest that the BRS scaffolds could exhibit substantially brittle behaviour after âˆ¼ one year of implantation.

An in silico trials platform for the evaluation of effect of the arterial anatomy configuration on stent implantation.

The introduction of Bioresorbable Vascular Scaffolds (BVS) has revolutionized the treatment of atherosclerosis. InSilc is an in silico clinical trial (ISCT) platform in a Cloud-based environment used for the design, development and evaluation of BVS. Advanced multi-disciplinary and multiscale models are integrated in the platform towards predicting the short/acute and medium/long term scaffold performance. In this study, InSilc platform is employed in a use case scenario and demonstrates how the whole in silico pipeline allows the interpretation of the effect of the arterial anatomy configuration on stent implantation.

A computational optimization study of a self-expandable transcatheter aortic valve.

Developing an efficient stent frame for transcatheter aortic valves (TAV) needs thorough investigation in different design and functional aspects. In recent years, most TAV studies have focused on their clinical performance, leaflet design, and durability. Although several optimization studies on peripheral stents exist, the TAV stents have different functional requirements and need to be explicitly studied. The aim of this study is to develop a cost-effective optimization framework to find the optimal TAV stent design made of Ni-Ti alloy. The proposed framework focuses on minimizing the maximum strain occurring in the stent during crimping, making use of a simplified model of the stent to reduce computational cost. The effect of the strut cross-section of the stent, i.e., width and thickness, and the number and geometry of the repeating units of the stent (both influencing the cell size) on the maximum strain is investigated. Three-dimensional simulations of the crimping process are used to verify the validity of the simplified representation of the stent, and the radial force has been calculated for further evaluation. The results suggest the key role of the number of cells (repeating units) and strut width on the maximum strain and, consequently, on the stent design. The difference in terms of the maximum strain between the simplified and the 3D model was less than 5%, confirming the validity of the adopted modeling strategy and the robustness of the framework to improve the TAV stent designs through a simple, cost-effective, and reliable procedure.

Comprehensive computational analysis of the crimping procedure of PLLA BVS: effects of material viscous-plastic and temperature dependent behavior.

Recently, researchers focused their attention on the use of polymeric bioresorbable vascular scaffolds (BVSs) as alternative to permanent metallic drug-eluting stents (DESs) for the treatment of atherosclerotic coronary arteries. Due to the different mechanical properties, polymeric stents, if compared to DESs, are characterized by larger strut size and specific design. It implies that during the crimping phase, BVSs undergo higher deformation and the packing of the struts, making this process potentially critical for the onset of damage. In this work, a computational study on the crimping procedure of a PLLA stent, inspired by the Absorb GT1 (Abbott Vascular) design, is performed, with the aim of evaluating how different strategies (loading steps, velocities and temperatures) can influence the results in terms of damage risk and final crimped diameter. For these simulations, an elastic-viscous-plastic model was adopted, based on experimental results, obtained from tensile testing of PLLA specimens loaded according to ad hoc experimental protocols. Furthermore, the results of these simulations were compared with those obtained by neglecting strain rate and temperature dependence in the material model (as often done in the literature), showing how this lead to significant differences in the prediction of the crimped diameter and internal stress state.

Validation of the computational model of a coronary stent: a fundamental step towards in silico trials.

The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico clinical trials. When dealing with a coronary stenting procedure, the virtual scenario should be able to replicate the real device, passing through the different stages of the procedure, which has to maintain the atherosclerotic vessel opened. Nevertheless, most of the published studies adopted commercially resembling geometries and generic material parameters, without a specific validation of the employed numerical models. In this work, a workflow for the generation and validation of the computational model of a coronary stent was proposed. Possible sources of variability in the results, such as the inter-batches variability in the material properties and the choice of proper simulation strategies, were accounted for and discussed. Then, a group of in vitro tests, representative of the device intended use was used as a comparator to validate the model. The free expansion simulation, which is the most used simulation in the literature, was shown to be only partially useful for stent model validation purposes. On the other hand, the choice of proper additional experiments, as the suggested uniaxial tensile tests on the stent and deployment tests into a deformable tube, could provide further suitable information to prove the efficacy of the numerical approach.

From the real device to the digital twin: A coupled experimental-numerical strategy to investigate a novel bioresorbable vascular scaffold.

The purpose of this work is to propose a workflow that couples experimental and computational activities aimed at developing a credible digital twin of a commercial coronary bioresorbable vascular scaffold when direct access to data about material mechanical properties is not possible. Such a situation is be faced when the manufacturer is not involved in the study, thus directly investigating the actual device is the only source of information available. The object of the work is the Fantom® Encore polymeric stent (REVA Medical) made of Tyrocore™. Four devices were purchased and used in mechanical tests that are easily reproducible in any mechanical laboratory, i.e. free expansion and uniaxial tension testing, the latter performed with protocols that emphasized the rate-dependent properties of the polymer. Given the complexity of the mechanical behaviour observed experimentally, it was chosen to use the Parallel Rehological Framework material model, already used in the literature to describe the behaviour of other polymers, such as PLLA. Calibration of the material model was based on simulations that replicate the tensile test performed on the device. Given the high number of material parameters, a plan of simulations was done to find the most suitable set, varying each parameter value in a feasible range and considering a single repetitive unit of the stent, neglecting residual stresses generated by crimping and expansion. This strategy resulted in a significant reduction of computational cost. The performance of the set of parameters thus identified was finally evaluated considering the whole delivery system, by comparing the experimental results with the data collected simulating free expansion and uniaxial tension testing. Moreover, radial force testing was numerically performed and compared with literature data. The obtained results demonstrated the effectiveness of the digital twin development pipeline, a path applicable to any commercial device whose geometric structure is based on repetitive units.

Analytical methods for braided stents design and comparison with FEA.

Braiding technology is nowadays commonly adopted to build stent-like devices. Indeed, these endoprostheses, thanks to their typical great flexibility and kinking resistance, find several applications in mini-invasive treatments, involving but not limiting to the cardiovascular field. The design process usually involves many efforts and long trial and error processes before identifying the best combination of manufacturing parameters. This paper aims to provide analytical tools to support the design and optimization phases: the developed equations, based on few geometrical parameters commonly used for describing braided stents and material stiffness, are easily implementable in a worksheet and allow predicting the radial rigidity of braided stents, also involving complex features such as multiple twists and looped ends, and the diameter variation range. Finite element simulations, previously validated with respect to experimental tests, were used as a comparator to prove the reliability of the analytical results. The illustrated tools can assess the impact of each selected parameter modification and are intended to guide the optimal selection of geometrical and mechanical stent proprieties to obtain the desired radial rigidity, deliverability (minimum diameter), and, if forming processes are planned to modify the shape of the stent, the required diameter variations (maximum and minimum diameters).

Finite Element Simulations of the ID Venous System to Treat Venous Compression Disorders: From Model Validation to Realistic Implant Prediction.

The ID Venous System is an innovative device proposed by ID NEST MEDICAL to treat venous compression disorders that involve bifurcations, such as the May-Thurner syndrome. The system consists of two components, ID Cav and ID Branch, combined through a specific connection that prevents the migration acting locally on the pathological region, thereby preserving the surrounding healthy tissues. Preliminary trials are required to ensure the safety and efficacy of the device, including numerical simulations. In-silico models are intended to corroborate experimental data, providing additional local information not acquirable by other means. The present work outlines the finite element model implementation and illustrates a sequential validation process, involving seven tests of increasing complexity to assess the impact of each numerical uncertainty separately. Following the standard ASME V&V40, the computational results were compared with experimental data in terms of force-displacement curves and deformed configurations, testing the model reliability for the intended context of use (differences < 10%). The deployment in a realistic geometry confirmed the feasibility of the implant procedure, without risk of rupture or plasticity of the components, highlighting the potential of the present technology.

Multimodal Loading Environment Predicts Bioresorbable Vascular Scaffolds' Durability.

Bioresorbable vascular scaffolds were considered the fourth generation of endovascular implants deemed to revolutionize cardiovascular interventions. Yet, unexpected high risk of scaffold thrombosis and post-procedural myocardial infractions quenched the early enthusiasm and highlighted the gap between benchtop predictions and clinical observations. To better understand scaffold behavior in the mechanical environment of vessels, animal, and benchtop tests with multimodal loading environment were conducted using industrial standard scaffolds. Finite element analysis was also performed to study the relationship among structural failure, scaffold design, and load types. We identified that applying the combination of bending, axial compression, and torsion better reflects incidence observed in-vivo, far more than tranditional single mode loads. Predication of fracture locations is also more accurate when at least bending and axial compression are applied during benchtop tests (>60% fractures at connected peak). These structural failures may be initiated by implantation-induced microstructural damages and worsened by cyclic loads from the beating heart. Ignoring the multi-modal loading environment in benchtop fatigue tests and computational platforms can lead to undetected potential design defects, calling for redefining consensus evaluation strategies for scaffold performance. With the robust evaluation strategy presented herein, which exploits the results of in-vivo, in-vitro and in-silico investigations, we may be able to compare alternative designs of prototypes at the early stages of device development and optimize the performance of endovascular implants according to patients-specific vessel dynamics and lesion configurations in the future.

How to Validate in silico Deployment of Coronary Stents: Strategies and Limitations in the Choice of Comparator.

This study aims at proposing and discussing useful indications to all those who need to validate a numerical model of coronary stent deployment. The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico trials. Recently, the ASME V&V Standard Committee for medical devices prepared the V&V 40 standard document that provides a framework that guides users in establishing and assessing the relevance and adequacy of verification and validation activities performed for proving the credibility of models. To the knowledge of the authors, only a few examples of the application of the V&V 40 framework to medical devices are available in the literature, but none about stents. Specifically, in this study, the authors wish to emphasize the choice of a relevant set of experimental activities to provide data for the validation of computational models aiming to predict coronary stent deployment. Attention is focused on the use of ad hoc 3D-printed mock vessels in the validation plan, which could allow evaluating aspects of clinical relevance in a representative but controlled environment.

Nickel-Titanium peripheral stents: Which is the best criterion for the multi-axial fatigue strength assessment?

Ni-Ti stents fatigue strength assessment requires a multi-factorial complex integration of applied loads, material and design and is of increasing interest. In this work, a coupled experimental-numerical method for the multi-axial fatigue strength assessment is proposed and verified for two different stent geometries that resemble commercial products. Particular attention was paid to the identification of the material fatigue limit curve. The common approach for the Ni-Ti stents fatigue assessment based on the von Mises yield criterion was proven unsuitable for a realistic fatigue strength assessment. On the other hand, critical plane-based criteria were more representative of the experimental outcomes regardless of stent design.