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.

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.

Global stiffness and residual stresses in spinal fixator systems: A validated finite element study on the interconnection mechanism.

Posterior spinal fixation systems are the gold standard to treat different column disorders using rods and screws. The proper connection between them is guaranteed by the Interconnection Mechanism (IM), consisting of different metallic subcomponents held together through the application of tightening torque. The response of the fixation system is defined by its overall stiffness, which in turn is governed by the local residual stress field arising during tightening. Although literature computational models for studying spinal fixation are becoming increasingly anatomically complex, most studies disregard completely the realistic modeling of the IM, namely choosing elastic-plastic material models and proper contact interactions. In this frame, the present study aims at increasing awareness in the field of spinal fixation modeling by investigating the mechanical response of the IM in terms of overall stiffness and local residual stresses. Once validated through dedicated experiments, the results of the proposed model have been compared with the current literature, highlighting the key role of the IM in the reliable modeling of spinal fixation.

Beliefs and Use of Palpatory Findings in Osteopathic Clinical Practice: A Qualitative Descriptive Study among Italian Osteopaths.

The Italian government has started the regulatory process of osteopathy to include it among the healthcare professions mentioning terms, such as "perceptual palpation" and "somatic dysfunction" within the professional profile. 'Palpatory findings' are one of the multidimensional aspects that can inform osteopathic clinical reasoning. The non-regulated educational system has led to heterogenic professionals working in Italy, thus, the aim of this study was to investigate how Italian experts use palpatory findings in their clinical practice. A total of 12 experts were selected to participate in four virtual focus groups. A qualitative inductive approach with a constructivist paradigm was chosen to describe the results. The themes that emerged were: osteopathic identity; evaluation; osteopathic diagnosis; and sharing with different recipients. Participants agreed on the peculiarity and distinctiveness of osteopathic palpation, but there was some disagreement on the clinical significance of the findings, highlighting a complex multidimensional approach to diagnosis and treatment. The results seem to reflect the history of the profession in Italy, which has evolved quickly, leading professionals to seek new paradigms blending tradition and scientific evidence. The authors suggest further investigation to verify the state of art among osteopaths not involved in research or a broader consensus of the results.

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.

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.

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.

Applicability assessment of a stent-retriever thrombectomy finite-element model.

An acute ischaemic stroke appears when a blood clot blocks the blood flow in a cerebral artery. Intra-arterial thrombectomy, a mini-invasive procedure based on stent technology, is a mechanical available treatment to extract the clot and restore the blood circulation. After stent deployment, the clot, trapped in the stent struts, is pulled along with the stent towards a receiving catheter. Recent clinical trials have confirmed the effectiveness and safety of mechanical thrombectomy. However, the procedure requires further investigation. The aim of this study is the development of a numerical finite-element-based model of the thrombectomy procedure. In vitro thrombectomy tests are performed in different vessel geometries and one simulation for each test is carried out to verify the accuracy and reliability of the proposed numerical model. The results of the simulations confirm the efficacy of the model to replicate all the experimental setups. Clot stress and strain fields from the numerical analysis, which vary depending on the geometric features of the vessel, could be used to evaluate the possible fragmentation of the clot during the procedure. The proposed in vitro/in silico comparison aims at assessing the applicability of the numerical model and at providing validation evidence for the specific in vivo thrombectomy outcomes prediction.

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.

Biomechanical interpretation of observed fatigue fractures of peripheral Nitinol stents in the superficial femoral arteries through in silico modelling.

PURPOSE: To suggest an in silico modelling approach to estimate the fatigue failure on peripheral Nitinol stents implanted in the superficial femoral artery (SFA) and interpret the clinically observed stent fractures of a retrospective series of patients. MATERIALS AND METHODS: Preoperative data of 27 patients who underwent SFA Nitinol stenting were retrospectively analyzed. Data about preoperative features of the SFA and the lesion were collected. Follow-up data were also collected about the occurrence of restenosis/occlusion and stent fracture. RESULTS: After a lengthening of the entire vessel, the occluded region was slightly stretched due to its high stiffness, whereas the healthy regions accommodated the artery length variation. The stent fatigue was predicted to be higher in the regions of low stiffness and higher shortening. In 7 out of 27 patients a stent fracture was clinically recorded. The model resulted to be accurate in 90% of the cases. CONCLUSIONS: The clinical outcomes in terms of biomechanical fatigue behavior of peripheral Nitinol stents of the SFA could be interpreted by our new approach.

Computational and Experimental Fatigue Analysis of Contoured Spinal Rods.

Posterior fixation with contoured rods is an established methodology for the treatment of spinal deformities. Both uniform industrial preforming and intraoperative contouring introduce tensile and compressive plastic deformations, respectively, at the concave and at the convex sides of the rod. The purpose of this study is to develop a validated numerical framework capable of predicting how the fatigue behavior of contoured spinal rods is affected by residual stresses when loaded in lordotic and kyphotic configurations. Established finite element models (FEM) describing static contouring were implemented as a preliminary simulation step and were followed by subsequent cyclical loading steps. The equivalent Sines stress distribution predicted in each configuration was compared to that in straight rods (SR) and related to the corresponding experimental number of cycles to failure. In the straight configuration, the maximum equivalent stress (441 MPa) exceeds the limit curve, as confirmed by experimental rod breakage after around 1.9 × 105 loading cycles. The stresses further increased in the lordotic configuration, where failure was reached within 2.4 × 104 cycles. The maximum equivalent stress was below the limit curve for the kyphotic configuration (640 MPa), for which a run-out of 106 cycles was reached. Microscopy inspection confirmed agreement between numerical predictions and experimental fatigue crack location. The contouring technique (uniform contouring (UC) or French bender (FB)) was not related to any statistically significant difference. Our study demonstrates the key role of residual stresses in altering the mean stress component, superposing to the tensile cyclic load, potentially explaining the higher failure rate of lordotic rods compared to kyphotic ones.

Effect of working environment and procedural strategies on mechanical performance of bioresorbable vascular scaffolds.

Polymeric bioresorbable scaffolds (BRS), at their early stages of invention, were considered as a promising revolution in interventional cardiology. However, they failed dramatically compared to metal stents showing substantially higher incidence of device failure and clinical events, especially thrombosis. One problem is that use of paradigms inherited from metal stents ignores dependency of polymer material properties on working environment and manufacturing/deployment steps. Unlike metals, polymeric material characterization experiments cannot be considered identical under dry and submerged conditions at varying rates of operation. We demonstrated different material behaviors associated with variable testing environment and parameters. We, then, have employed extracted material models, which are verified by computational methods, to assess the performance of a full-scale BRS in different working condition and under varying procedural strategies. Our results confirm the accepted notion that slower rate of crimping and inflation can potentially reduce stress concentrations and thus reduce localized damages. However, we reveal that using a universal set of material properties derived from a benchtop experiment conducted regardless of working environment and procedural variability may lead to a significant error in estimation of stress-induced damages and overestimation of benefits procedural updates might offer. We conclude that, for polymeric devices, microstructural damages and localized loss of structural integrity should complement former macroscopic performance-assessment measures (fracture and recoil). Though, to precisely capture localized stress concentration and microstructural damages, context-related testing environment and clinically-relevant procedural scenarios should be devised in preliminary experiments of polymeric resorbable devices to enhance their efficacy and avoid unpredicted clinical events. STATEMENT OF SIGNIFICANCE: Bioresorbable scaffolds (BRS) with the hope to become the next cardiovascular interventional revolution failed in comparison to metal stents. When BRS were characterized using methods for metal stents, designers were misled to seek problem sources at erroneous timeframe and use inefficient indicators, and thus no signal of concern emerged. We demonstrated fundamental flaws associated with applying a universal set of material properties to study device performances in different phases of manufacturing/implantation, and these may be responsible for failure in predicting performance in first-generation BRS. We introduced new criterion for the assessment of structural integrity and device efficacy in next-generation BRS, and indeed all devices using polymeric materials which evolve with the environment they reside in.

Residual Stresses in Titanium Spinal Rods: Effects of Two Contouring Methods and Material Plastic Properties.

Posterior spinal fixation based on long spinal rods is the clinical gold standard for the treatment of severe deformities. Rods need to be contoured prior to implantation to fit the natural curvature of the spine. The contouring processes is known to introduce residual stresses and strains which affect the static and fatigue mechanical response of the implant, as determined through time- and cost-consuming experimental tests. Finite element (FE) models promise to provide an immediate understanding on residual stresses and strains within a contoured spinal rods and a further insight on their complex distribution. This study aims at investigating two rod contouring strategies, French bender (FB) contouring (clinical gold standard), and uniform contouring, through validated FE models. A careful characterization of the elastoplastic material response of commercial implants is led. Compared to uniform contouring, FB induces highly localized plasticizations in compression under the contouring pin with extensive lateral sections undergoing tensile residual stresses. The sensitivity analysis highlighted that the assumed postyielding properties significantly affect the numerical predictions; therefore, an accurate material characterization is recommended.

The role of inelastic deformations in the mechanical response of endovascular shape memory alloy devices.

Nickel-titanium alloys are commonly adopted for producing cardiovascular minimally invasive devices such as self-expandable stents, aortic valves and stent-grafts. These devices are subjected to cyclic loads (due to blood pulsatility, leg or heart movements), that can induce fatigue fracture, and may also be subjected to very large deformations (due to crimping procedure, a tortuous physiological path or overloads), that can induce material yield. Recently, the authors developed a new constitutive model that considers inelastic strains due to not-completed reverse phase transformation (not all the stress-induced martensite turns back to austenite) or/and plasticity and their accumulation during cyclic loads. In this article, the model is implemented in the finite element code ABAQUS/Standard and it is used to investigate the effects of inelastic strain accumulation on endovascular nickel-titanium devices. In particular, the behavior of a transcatheter aortic valve is studied considering the following steps: (1) crimping, (2) expansion in a tube resembling a durability test chamber and (3) cyclic loads due to pressure variation applied on the inner surface of the tube. The analyses are performed twice, activating and not activating that part of the new model which describes the development of irreversible strain. From the results, it is interesting to note that plasticity has a very significant effect on the local material response, inducing stress modification from compression to tension. However, permanent deformations are concentrated in few zones of the stent frame and their presence does not affect the global behavior of the device that maintains its capability of recovering the original shape. In conclusion, this work suggests that at least for cardiovascular devices where the crimping is high (local strain may reach values of 8%-9%), taking into account inelastic effects due to plasticity and not-completed reverse phase transformation can be important, and hence using a suitable constitutive model is recommended.