Search

In cases of aortic stenosis, bioprosthetic heart valves (BHVs), with glutaraldehyde-fixed bovine pericardium leaflets (GLBP), are often implanted to replace the native diseased valve. Widespread use of BHVs, however, is restricted due to inadequate long-term durability, owing specifically to premature leaflet failure. Mechanical fatigue damage and calcification remain the primary leaflet failure modes, where glutaraldehyde treatment is known to accelerate calcification. The literature in this area is limited, with some studies suggesting mechanical damage increases calcification and others that they are independent degenerative mechanisms. In this study, specimens which were non-destructively pre-sorted according to collagen fibre architecture and uniaxially cyclically loaded until failure or 1 million cycles, were placed in an in vitro calcification solution. The weakest specimen group (those with fibres aligned perpendicular to the load) had statistically significantly higher volumes of calcification when compared to those with a high fatigue life. Moreover, SEM imaging revealed that ruptured and damaged fibres presented calcium binding sites; resulting in 4 times more calcification in fractured samples in comparison to those which did not fail by fatigue. To the authors’ knowledge, this study quantifies for the first time, that mechanical damage drives calcification in commercial-grade GLBP and that calcification varies spatially according to localised damage levels. These findings illustrate that not only is calcification of GLBP exacerbated by fatigue damage, but that both failure phenomena are underpinned by the collagen fibre organisation. Consequently, controlling for GLBP collagen fibre architecture in leaflets could minimise the progression of these primary failure modes in patient BHVs. Statement of significance Mechanical damage and calcification are the primary premature failure modes of glutaraldehyde-fixed bovine pericardial (GLBP) leaflets in bioprosthetic heart valves. In this study, commercial-grade GLBP specimens which were uniaxially cyclically loaded to failure or 1 million cycles, were placed in an in vitro calcification solution. MicroCT and SEM analysis showed that localised calcification levels varied spatially according to damage, where ruptured fibres offered additional calcium binding sites. Furthermore, specimens with a statistically significant lower fatigue life were associated with statistically significant higher calcification. This study revealed that mechanical damage drives calcification of GLBP. Non-destructive pre-screening of collagen fibres demonstrated that both the fatigue life and calcification potential of commercial-grade GLBP, are underpinned by the collagen fibre architecture.

Bioprosthetic heart valves (BHVs) are implanted in aortic valve stenosis patients to replace the native, dysfunctional valve. Yet, the long-term performance of the glutaraldehyde-fixed bovine pericardium (GLBP) leaflets is known to reduce device durability. The aim of this study was to investigate a type of commercial-grade GLBP which has been over-looked in the literature to date; that of high collagen fibre dispersion (HD). Under uniaxial cyclic loading conditions, it was observed that the fatigue behaviour of HD GLBP was substantially equivalent to GLBP in which the fibres are highly aligned along the loading direction. It was also found that HD GLBP had a statistically significant 9.5% higher collagen content when compared to GLBP with highly aligned collagen fibres. The variability in diseased BHV delivery sites results in unpredictable and complex loading patterns across leaflets in vivo. This study presents the possibility of a shift from the traditional choice of circumferentially aligned GLBP leaflets, to that of high fibre dispersion arrangements. Characterised by its high fatigue life and increased collagen content, in addition to multiple fibre orientations, GLBP of high fibre dispersion may provide better patient outcomes under the multi-directional loading to which BHV leaflets are subjected in vivo.

In cases of aortic stenosis, bioprosthetic heart valves (BHVs), with leaflets made from glutaraldehyde fixed bovine pericardium (GLBP), are often implanted to replace the native diseased valve. Widespread use of these devices, however, is restricted due to inadequate long-term durability owing specifically to premature leaflet failure. Mechanical fatigue damage and calcification remain the primary leaflet failure modes, where glutaraldehyde treatment is known to accelerate calcification. The literature in this area is limited, with some studies suggesting mechanical damage increases calcification and others that they are independent degenerative mechanisms. In this study, specimens which were non-destructively pre-sorted according to collagen fibre architecture and then uniaxially cyclically loaded until failure or 1 million cycles, were placed in anin-vitrocalcification solution. Measurements of percentage volume calcification demonstrated that the weakest specimen group (those with fibres aligned perpendicular to the load) had statistically significantly higher volumes of calcification when compared to those with a high fatigue life. Moreover, SEM imaging revealed that ruptured and damaged fibres presented binding sites for calcium to attach; resulting in more than 4 times the volume of calcification in fractured samples when compared to those which did not fail by fatigue. To the authors’ knowledge, this study quantifies for the first time, that mechanical damage drives calcification in commercial-grade GLBP and that this calcification varies spatially according to localised levels of damage. These findings illustrate that not only is calcification potential in GLBP exacerbated by fatigue damage, but that both failure phenomena are underpinned by the unloaded collagen fibre organisation. Consequently, controlling for GLBP collagen fibre architecture in leaflets could minimise the progression of these prevalent primary failure modes in patient BHVs.

It has been proposed that inappropriate positioning of transcatheter aortic valves (TAVs) is associated with procedural complications and decreased device durability. Second-generation TAVs allow for repositioning giving greater control over the final deployment position. However, the impact of positioning on the tissue surrounding these devices needs to be better understood, in particular for the interleaflet triangle in which the conductance system (bundle of His) resides. In this study, we investigate the impact of implantation depth on the frame-tissue interaction for a next-generation repositionable Lotus™ valve. For this purpose, a computational model simulating deployment of the Lotus valve frame into a calcified patient-specific aortic root geometry was generated to predict aortic root stress and frame eccentricity at three different deployment depths. The results of this study predicted that positioning of the Lotus valve had an influence on the stresses in the aortic sinus and frame eccentricity. An analysis of levels of stress arising in the vicinity of the bundle of His, as a function of implantation depth, was conducted, and it was found that, for the specific patient anatomy studied, although the sub-annular position showed reduced peak stress in the aortic sinus, this implantation position showed the highest stress in the area of greatest risks of conductance interference. In contrast, while a supra-annular position increased the peak arterial stress, this implantation position resulted in lower stress in the interleaflet triangle and thus might reduce the risk of conductance interference. These results provide pre-operative information that can inform clinical decision-making regarding TAVI positioning.

Bioprosthetic heart valves (BHVs) are implanted in aortic valve stenosis patients to replace the native, dysfunctional valve. Yet, the long-term performance of the glutaraldehyde-fixed bovine pericardium (GLBP) leaflets is known to reduce device durability. The aim of this study was to investigate a type of commercial-grade GLBP which has been over-looked in the literature to date; that of high collagen fibre dispersion (HD). Under uniaxial cyclic loading conditions, it was observed that the fatigue behaviour of HD GLBP was substantially equivalent to GLBP in which the fibres are highly aligned along the loading direction. It was also found that HD GLBP had a statistically significant 9.5% higher collagen content when compared to GLBP with highly aligned collagen fibres. The variability in diseased BHV delivery sites results in unpredictable and complex loading patterns across leaflets in vivo. This study presents the possibility of a shift from the traditional choice of circumferentially aligned GLBP leaflets, to that of high fibre dispersion arrangements. Characterised by its high fatigue life and increased collagen content, in addition to multiple fibre orientations, GLBP of high fibre dispersion may provide better patient outcomes under the multi-directional loading to which BHV leaflets are subjected in vivo.

The durability of bovine pericardium leaflets employed in bioprosthetic heart valves (BHVs) can significantly limit the longevity of heart valve prostheses. Collagen fibres are the dominant load bearing component of bovine pericardium, however fibre architecture within leaflet geometries is not explicitly controlled in the manufacture of commercial devices. Thus, the purpose of this study was to ascertain the influence of pre-determined collagen fibre orientation and dispersion on the mechanical performance of bovine pericardium. Three tissue groups were tested in uniaxial tension: cross-fibre tissue (XD); highly dispersed fibre-orientations (HD); or preferred-fibre tissue (PD). Both the XD and PD tissue were tested under cyclic loading at 1.5 Hz and a stress range of 2.7 MPa. The results of the static tensile experiments illustrated that collagen fibre orientation and degree of alignment significantly influenced the material's response, whereby, there was a statistically significant decrease in material properties between the XD groups and both the PD and HD groups for ultimate tensile strength and stiffness (p 0.01). Furthermore, HD tissue had a stiffness of approximately 58% of the PD group, and XD tissue had a stiffness of approximately 18% of the PD group. The dynamic behaviour of the XD and PD groups was extremely distinct; for example a Weibull analysis indicated that the 50% probability of failure in specimens with fibres orientated perpendicular (XD) to the loading direction occurred at 375 cycles. Due to this failure, XD specimens survived on average less than 20% of the cycles completed by those in which fibres were aligned along the loading direction (PD). The results from this study indicate that fibre architecture is a significant factor in determining static strength and fatigue life in bovine pericardium, and thus must be incorporated in the design process to improve future device durability.

Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro . Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo . It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a ‘peel-back’ leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 ± 2.04% versus circular = 11.77 ± 1.61%, p = 0.0014, hypertension: eccentric = 15.07 ± 1.13% versus circular = 13.56 ± 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve.

Self expanding Transcatheter Aortic Valve Replacements (TAVR) can conform to the geometry of the aortic annulus and the calcified leaflet complex, which may result in leaflet distortion and altered leaflet kinematics, but such changes have not yet been characterized. In this study we developed a computational model to investigate the deployment of a self expanding TAVR in a realistic aortic root model derived from multi-slice computed tomography (MSCT) images. We simulated TAVR crimping/deployment in realistic and idealized aortic root models, followed by diastolic loading of the TAVR leaflets in its final deployed configuration. The TAVR deployed in a realistic aortic root had increased peak loading in the commissural region of the leaflets compared to TAVRs under idealized circular deployment conditions (2.97 vs. 1.52 MPa). Furthermore, orientation of the TAVR in the asymmetric aortic annulus such that the commissures of the TAVR are aligned with the native valve commissures minimized the effect of TAVR stent distortion on peak stresses in the TAVR leaflets (2.97 vs. 2.35 MPa). We propose that preoperative planning of the orientation of the TAVR in the aortic root annulus might minimize the impact of potential stent distortion on leaflet function and may in turn increase long term leaflet durability.

Patients with aortic stenosis present with calcium deposits on the native aortic valve, which can result in non-concentric expansion of Transcatheter Aortic Valve Replacement (TAVR) stents. The objective of this study is to evaluate whether eccentric deployment of TAVRs lead to turbulent blood flow and blood cell damage. Particle Image Velocimetry was used to quantitatively characterize fluid velocity fields, shear stress and turbulent kinetic energy downstream of TAVRs deployed in circular and eccentric orifices representative of deployed TAVRs in vivo. Effective orifice area (EOA) and mean transvalvular pressure gradient (TVG) values did not differ substantially in circular and eccentric deployed valves, with only a minor decrease in EOA observed in the eccentric valve (2.0 cm(2) for circular, 1.9 cm(2) for eccentric). Eccentric deployed TAVR lead to asymmetric systolic jet formation, with increased shear stresses (circular = 97 N/m(2) vs. eccentric = 119 N/m(2)) and regions of turbulence intensity (circular = 180 N/m(2) vs. eccentric = 230 N/m(2)) downstream that was not present in the circular deployed TAVR. The results of this study indicate that eccentric deployment of TAVRs can lead to altered flow characteristics and may potentially increase the hemolytic potential of the valve, which were not captured through hemodynamic evaluation alone.

This paper describes three different versions of left heart simulators that have been developed at the Cardiovascular Fluid Mechanics Laboratory at Georgia Institute of Technology, specifically designed to provide high fidelity experimental datasets necessary for rigorous validation of computational tools. These systems are capable of simulating physiological and pathological flow, pressure and geometric conditions, and can be investigated using a variety of experimental tools to measure relevant biomechanical quantities. The development of such robust simulators is a critical step in ensuring applicability of patient specific computational tools.Copyright © 2013 by ASME

Aortic stenosis is an age related degenerative disease of the aortic valve that causes narrowing of the valve and aortic regurgitation [1]. Transcatheter Aortic Valve (TAV) implantation is a percutaneous alternative to open heart surgery, which allows for the treatment of a cohort of patients for whom conventional surgery is deemed excessively risky due to high postoperative mortality rates or pre-existing illness [2].Copyright © 2013 by ASME

Patient specific computational analyses can aid in preoperative planning and long term evaluation of asymmetric deployed Transcatheter Aortic Valves (TAV) in calcified aortic annuli. In this study we developed and validated a preclinical computational tool to predict the performance of TAVs in vivo

The aortic valve is responsible for controlling the unidirectional flow of blood within the heart during the cardiac cycle [1]. Aortic stenosis reduces the opening area of the valve, impeding blood flow and can lead to increased strain on the heart muscle, onset of early fatigue and heart failure. The disease is prevalent in the elderly population and is predicted to affect 88.5 million people by 2050 [2]. Open heart surgery to replace stenotic valves with either bioprosthetic or mechanical surgical valves is the current gold standard of care. However 30% of patients presenting with stenosis are refused this highly invasive surgery because of high postoperative mortality rates in elderly patients or those with pre-existing illnesses [2]. Transcatheter Aortic Valves (TAV) are an alternative to conventional heart valve surgery [2, 3–4], which use minimally invasive techniques to replace stenotic valves. TAV’s consist of tissue leaflets on a self or balloon expandable percutaneous valve stent which is deployed via a transfemoral or transapical based approach. Owing to the fact that the first CE certification of a TAV (Edwards SAPIEN) was only in 2010 and received FDA approval for clinical trials in 2011, the long term performance of implanted TAV’s is as of yet unknown.Copyright © 2012 by ASME

PEG based hyperbranched copolymers have been synthesised using a high concentration of ethylene glycol dimethacrylate (EGDMA) as the branching agent (up to 10% molar ratio of total feed monomers) via a new in situ deactivation enhanced atom transfer radical polymerisation (DE-ATRP). These hyperbranched copolymers exhibited a lower critical solution temperature (LCST) close to body temperature and photo-crosslinkable behavior.