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

Finite Element Analysis to Study Percutaneous Heart Valves

Communications engineering / telecommunication

A finite element analysis study from 3D CT to predict transcatheter heart valve thrombosis

Background: Transcatheter aortic valve replacement has proved its safety and effectiveness in intermediate- to high-risk and inoperable patients with severe aortic stenosis. However, despite current guideline recommendations, the use of transcatheter aortic valve replacement (TAVR) to treat severe aortic valve stenosis caused by degenerative leaflet thickening and calcification has not been widely adopted in low-risk patients. This reluctance among both cardiac surgeons and cardiologists could be due to concerns regarding clinical and subclinical valve thrombosis. Stent performance alongside increased aortic root and leaflet stresses in surgical bioprostheses has been correlated with complications such as thrombosis, migration and structural valve degeneration. Materials and Methods: Self-expandable catheter-based aortic valve replacement (Medtronic, Minneapolis, MN, USA), which was received by patients who developed transcatheter heart valve thrombosis, was investigated using high-resolution biomodelling from computed tomography scanning. Calcific blocks were extracted from a 250 CT multi-slice image for precise three-dimensional geometry image reconstruction of the root and leaflets. Results: Distortion of the stent was observed with incomplete cranial and caudal expansion of the device. The incomplete deployment of the stent was evident in the presence of uncrushed refractory bulky calcifications. This resulted in incomplete alignment of the device within the aortic root and potential dislodgment. Conclusion: A Finite Element Analysis (FEA) investigation can anticipate the presence of calcified refractory blocks, the deformation of the prosthetic stent and the development of paravalvular orifice, and it may prevent subclinical and clinical TAVR thrombosis. Here we clearly demonstrate that using exact geometry from high-resolution CT scans in association with FEA allows detection of persistent bulky calcifications that may contribute to thrombus formation after TAVR procedure

Development of a patient-specific finite element model of the transcatheter aortic valve implantation (TAVI) procedure

Transcatheter Aortic Valve Implantation (TAVI) is a procedure developed for replacing the defective aortic valve of a patient as an alternative to open heart Surgical Aortic Valve Replacement (SAVR). In the TAVI procedure a prosthetic valve, which is assembled on to a stent, is crimped and delivered to the patient's aortic root site through several available percutaneous means. The percutaneous nature of TAVI, which is its core advantage in comparison to other SAVR procedures, can however also be its main disadvantage. This is due to lack of direct access to the calcified leaflets, and hence reliance on the host tissue for the proper positioning and anchorage of the deployed prosthetic valve. Therefore, it is desired to have a preoperative quantitative understanding of patient-specific biomechanical interaction of the stent and the native valve to be able to maximise the chance of success of the procedure. The aim of this study was to develop a patient-specific Finite Element (FE) model of the Transcatheter Aortic Valve Implantation (TAVI) procedure for two patients, using a model of the 23 mm percutaneous prosthetic aortic valve developed by Strait Access Technologies (SAT), for the purpose of its post-operative performance. In this regard, the image processing software ScanIP was used to extract the 3D models of the patient-specific aortic roots and leaflets from the provided Multi-Slice Computer Tomography (MSCT) images of the patients. An anisotropic hyperelastic material model was implemented for the roots and leaflets, using two and one families of collagen fibres for their tissues respectively. The stent is made of a cobalt-chromium alloy and its mechanical response was modelled as an isotropic elastoplastic material, with a linear elastic initial response, followed by plastic behaviour with isotropic hardening. The prosthetic leaflets are made of polymer and were modelled as an isotropic hyperelastic material, using the provided experimental test data. The results for the first patient showed that the stent maintained its structural integrity after deployment, and successfully pushed the native leaflets back to keep the aortic root clear of all impediments. No obstruction of the coronary ostia was observed, and prosthetic leaflets were seen to function normally. The stent radial recoil was calculated to be between 2 to 4.28 % after deployments. Its foreshortening was calculated to be approximately 20%. The stent was observed to move back and forth by approximately 3 mm in the last simulation step in which cardiac cycle pressure were applied to the aortic root and prosthetic leaflets. Also, two openings were observed between the stent and aortic root wall during this simulation step, which indicates the possibility of paravalvular leakage. From the second patient simulation, it was observed that the 23 mm stent was not a good choice for this patient, and will cause severe damage or tissue tearing. The maximum principal stress in the aortic root and valve tissues were observed to follow approximately the defined collagen fibre directions

Biomaterials in Valvular Heart Diseases

Valvular heart disease (VHD) occurs as the result of valvular malfunction, which can greatly reduce patient\u27s quality of life and if left untreated may lead to death. Different treatment regiments are available for management of this defect, which can be helpful in reducing the symptoms. The global commitment to reduce VHD-related mortality rates has enhanced the need for new therapeutic approaches. During the past decade, development of innovative pharmacological and surgical approaches have dramatically improved the quality of life for VHD patients, yet the search for low cost, more effective, and less invasive approaches is ongoing. The gold standard approach for VHD management is to replace or repair the injured valvular tissue with natural or synthetic biomaterials. Application of these biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of this type of heart disease. The focus of the present review is the current use of different types of biomaterials in treatment of valvular heart diseases

On the modeling of patient-specific transcatheter aortic valve replacement: a fluid–structure interaction approach

This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular engineering and technology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s13239-019-00427-0Purpose Transcatheter aortic valve replacement (TAVR) is a minimally invasive treatment for high-risk patients with aortic diseases. Despite its increasing use, many influential factors are still to be understood and require continuous investigation. The best numerical approach capable of reproducing both the valves mechanics and the hemodynamics is the fluid–structure interaction (FSI) modeling. The aim of this work is the development of a patient-specific FSI methodology able to model the implantation phase as well as the valve working conditions during cardiac cycles. Methods The patient-specific domain, which included the aortic root, native valve and calcifications, was reconstructed from CT images, while the CAD model of the device, metallic frame and pericardium, was drawn from literature data. Ventricular and aortic pressure waveforms, derived from the patient’s data, were used as boundary conditions. The proposed method was applied to two real clinical cases, which presented different outcomes in terms of paravalvular leakage (PVL), the main complication after TAVR. Results The results confirmed the clinical prognosis of mild and moderate PVL with coherent values of regurgitant volume and effective regurgitant orifice area. Moreover, the final release configuration of the device and the velocity field were compared with postoperative CT scans and Doppler traces showing a good qualitative and quantitative matching. Conclusion In conclusion, the development of realistic and accurate FSI patient-specific models can be used as a support for clinical decisions before the implantation.Peer ReviewedPostprint (author's final draft

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

Stent’s Manufacturing Field: Past, Present, and Future Prospects

From the introduction of stents, nobody was able to predict the advances that will occur in stent technology over the upcoming decades. Since their appearances, it became evident that this device had significant limitations, such as vessel occlusion and/or restenosis. Despite that, this medical device is the best clinical solution for cardiovascular vessel occlusions. Stents require a deep analysis, in terms of thrombogenicity, manufacturing process, geometrical aspects, and mechanical performance, among many other characteristics. The surface quality obtained in their manufacture process is crucial to blood compatibility, prevents the activation process of thrombosis, and improves the healing efficiency. The forecast stent market makes necessary continuous studies on this field, which help to solve the medical and engineering problems of this device, which are in constant development. Stents have been the center of many research lines over the last decades. The present chapter aims to summarize the state of the art of this medical device in the last years in the fields of design, manufacturing, and materials

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

Understanding the mechanism & effects of stent fracture : a combined experimental & finite element analysis

Atherosclerosis is a common heart disease, categorised by a build-up of fatty substances (plaque) in the inner surface of the coronary arteries and causing obstruction to the blood flow to vital organs and other parts of body. Over time, the arteries become narrowed which can lead to serious complications such as angina, heart attack, and stroke. There are several treatments to slow down the progress and reduce the risk, including medication and medical procedures. Percutaneous coronary intervention (PCI) is a non-surgical procedure which reopens blocked arteries and restores the blood flow. In some cases the PCI involves a tiny mesh tube known as a stent, which is placed in the narrowed artery to widen the lumen, support the vessel wall and prevent restenosis. Whilst this is generally successful procedure, stents might cause further problems such as stent fracture, in-stent restenosis, and stent thrombosis. Stent fracture is known to be associated with a number of factors; stent length, stent overlap, vessel tortuosity, degree of calcification of lesions, stent design, and the conditions under which the stent operates.The first part of this thesis presents a design-independent finite element analysis evaluation of the relative stresses induced in a coronary stent when placed in an angulated vessel geometry. This was achieved by idealising the stent to a thin tube, with the structural modulus of the tube representing that of a stent-like structure (this could be adapted for different types of stent structure). The artery and stent were then subjected to a displacement representing a bending movement of 20˚. Furthermore, various artery angles were modelled from 30˚ to 90˚ and each time the angle was transformed in 10˚. This series of finite element analyses computed the stress distribution associated with the displacement, hence quantifying the relationship between the vessel angle and the stress when considering the “hinge-type” movement that the vessel will undergo with each heartbeat. This constant repetitive loading constitutes the most severe mechanical loading that the stent will undergo, which far exceeds the radial expansion/contraction systolic/diastolic of the vessel or any torsional effects. It was observed that changes in stresses within the stent model are directly proportional to the vessel angulation, which stresses increased when the vessel angles became more severe. Furthermore, the bending region where was associated with the hinge-type movement experienced higher amounts of stress in the idealised stent model, and severe vessel angle caused a larger area undergo higher stress. The values increase at a greater rate once an angle of 75 degree has been exceeded, which agrees with clinical observation. Also areas of high stress corresponded to areas where fractures are seen clinically.The second part involved the mechanical testing of 9 samples of four different stent designs; Muilti-Link Vision®, PRO-Kinetic Energy, BioMatrix NeoFlexTM and Promus PREMIER. Stents deployed at nominal pressure into physiological mock artery at initial angle of 90˚, were then subjected to a 20˚ continuous repetitive hinge-type movement, at a rate of approximately 1100rpm (cycles per minute). By 300 million cycles fractures were identified in 7 stents, and are limited to only the Biomatrix design (34.67±28.78 million cycles), exhibiting between one and four strut fractures. Fractures were first seen to occur at 13.5 million cycles, where fractures were observed in 2 stents. All fractures were seen to occur at the ring linker parts of the stent and in the areas which would undergo the most severe tensile and compressive loading.This study shows that artery angulation has a significant impact on the stent stress, and more tortuous vessel increases the risk of stent fracture. Also in vitro experimental work illustrates that stent material and structure play an important role in stent flexibility