Assessing the impact of including leaflets in the simulation of TAVI deployment into a patient-specific aortic root

Computational simulation of transcatheter aortic valve implantation (TAVI) device deployment presents a significant challenge over and above similar simulations for percutaneous coronary intervention due to the presence of prosthetic leaflets. In light of the complexity of these leaflets, simulations have been performed to assess the effect of including the leaflets in a complete model of a balloon-expandable TAVI device when deployed in a patient-specific aortic root. Using an average model discrepancy metric, the average frame positions (with and without the leaflets) are shown to vary by 0.236% of the expanded frame diameter (26 mm). This relatively small discrepancy leads to the conclusion that for a broad range of replacement valve studies, including new frame configurations and designs, patient-specific assessment of apposition, paravalvular leakage and tissue stress, modelling of the prosthetic leaflets is likely to have a marginal effect on the results     

Patient-specific modeling of biomechanical interaction in transcatheter aortic valve deployment

The objective of this study was to develop a patient-specific computational model to quantify the biomechanical interaction between the transcatheter aortic valve (TAV) stent and the stenotic aortic valve during TAV intervention. Finite element models of a patient-specific stenotic aortic valve were reconstructed from multi-slice computed tomography (MSCT) scans, and TAV stent deployment into the aortic root was simulated. Three initial aortic root geometries of this patient were analyzed: (a) aortic root geometry directly reconstructed from MSCT scans, (b) aortic root geometry at the rapid right ventricle pacing phase, and (c) aortic root geometry with surrounding myocardial tissue. The simulation results demonstrated that stress, strain, and contact forces of the aortic root model directly reconstructed from MSCT scans were significantly lower than those of the model at the rapid ventricular pacing phase. Moreover, the presence of surrounding myocardium slightly increased the mechanical responses. Peak stresses and strains were observed around the calcified regions in the leaflets, suggesting the calcified leaflets helped secure the stent in position. In addition, these elevated stresses induced during TAV stent deployment indicated a possibility of tissue tearing and breakdown of calcium deposits, which might lead to an increased risk of stroke. The potential of paravalvular leak and occlusion of coronary ostia can be evaluated from simulated post-deployment aortic root geometries. The developed computational models could be a valuable tool for pre-operative planning of TAV intervention and facilitate next generation TAV device design.     

Modeling leaflet correction techniques in aortic valve repair: A finite element study

In aortic valve sparing surgery, cusp prolapse is a common cause of residual aortic insufficiency. To correct cusp pathology, native leaflets of the valve frequently require adjustment which can be performed using a variety of described correction techniques, such as central or commissural plication, or resuspension of the leaflet free margin. The practical question then arises of determining which surgical technique provides the best valve performance with the most physiologic coaptation. To answer this question, we created a new finite element model with the ability to simulate physiologic function in normal valves, and aortic insufficiency due to leaflet prolapse in asymmetric, diseased or sub-optimally repaired valves. The existing leaflet correction techniques were simulated in a controlled situation, and the performance of the repaired valve was quantified in terms of maximum leaflets stress, valve orifice area, valve opening and closing characteristics as well as total coaptation area in diastole. On the one hand, the existing leaflet correction techniques were shown not to adversely affect the dynamic properties of the repaired valves. On the other hand, leaflet resuspension appeared as the best technique compared to central or commissural leaflet plication. It was the only method able to achieve symmetric competence and fix an individual leaflet prolapse while simultaneously restoring normal values for mechanical stress, valve orifice area and coaptation area.     

A calcified polymeric valve for valve-in-valve applications

The prevalence of aortic valve stenosis (AS) is increasing in the aging society. More recently, novel treatments and devices for AS, especially transcatheter aortic valve replacement (TAVR) have significantly changed the therapeutic approach to this disease. Research and development related to TAVR require testing these devices in the calcified heart valves that closely mimic a native calcific valve. However, no animal model of AS has yet been available. Alternatively, animals with normal aortic valve that are currently used for TAVR experiments do not closely replicate the aortic valve pathology required for proper testing of these devices. To solve this limitation, for the first time, we developed a novel polymeric valve whose leaflets possess calcium hydroxyapatite inclusions immersed in them. This study reports the characteristics and feasibility of these valves. Two types of the polymeric valve, i.e., moderate and severe calcified AS models were developed and tested by deploying a transcatheter valve in those and measuring the related hemodynamics. The valves were tested in a heart flow simulator, and were studied using echocardiography. Our results showed high echogenicity of the polymeric valve, that was correlated to the severity of the calcification. Aortic valve area of the polymeric valves was measured, and the severity of stenosis was defined according to the clinical guidelines. Accordingly, we showed that these novel polymeric valves closely mimic AS, and can be a desired cost-saving solution for testing the performance of the transcatheter aortic valve systems in vitro.     

The influence of the leaflets' curvature on the flow field in two bileaflet prosthetic heart valves

A successful mechanical prosthetic heart valve design is the bileaflet valve, which has been implanted for the first time more than 20 years ago. A key feature of bileaflet valves is the geometry of the two leaflets, which can be very important in determining the flow field. Laser Doppler anemometry (LDA) was used to perform an accurate study of the velocity and turbulence shear stress peak values (TSS(max)) fields at four distances from the valve plane. TSS(max) is a relevant parameter to assess the risk of hemolysis and platelet activation associated to the implantation of a prosthetic device, continuously interacting with blood. Two bileaflet valves were tested: the St. Jude HP and the Sorin Bicarbon, of the same nominal size (19mm). The former has flat leaflets, whereas the latter's leaflets have a cylindrical surface. A high regime (CO: 6l/min) was imposed, in order to test the two valves at maximum Reynolds number and consequent turbulence generation. The flat-leaflet design of the St. Jude generates a TSS field constant with distance; on the contrary, the Bicarbon's shear stress field undergoes an evident development, with an unexpected central peak at a distance comparable to the valve's dimensions (21mm). The two bileaflet valves tested, although very similar in design, behave very differently as for their turbulence properties. In particular, the concept of curved wake leads to conclude that the curvature of the leaflets' surface must be identified as an important parameter, which deserves careful attention in PHV design and development.     

Simulation of transcatheter aortic valve implantation through patient-specific finite element analysis: Two clinical cases

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure introduced to treat aortic valve stenosis in elder patients. Its clinical outcomes are strictly related to patient selection, operator skills, and dedicated pre-procedural planning based on accurate medical imaging analysis. The goal of this work is to define a finite element framework to realistically reproduce TAVI and evaluate the impact of aortic root anatomy on procedure outcomes starting from two real patient datasets. Patient-specific aortic root models including native leaflets, calcific plaques extracted from medical images, and an accurate stent geometry based on micro-tomography reconstruction are key aspects included in the present study. Through the proposed simulation strategy we observe that, in both patients, stent apposition significantly induces anatomical configuration changes, while it leads to different stress distributions on the aortic wall. Moreover, for one patient, a possible risk of paravalvular leakage has been found while an asymmetric coaptation occurs in both investigated cases. Post-operative clinical data, that have been analyzed to prove reliability of the performed simulations, show a good agreement with analysis results. The proposed work thus represents a further step towards the use of realistic computer-based simulations of TAVI procedures, aiming at improving the efficacy of the operation technique and supporting device optimization.     

A comparison between the inlet and outlet diameters of the normal aortic valve.

Two studies are described comparing the inlet and outlet diameters of the normal aortic valve. Both studies show the valve inlet to be smaller than the valve outlet. The first study is of measurements made on 12 casts of physiologically pressurised human aortic valves. The mean ratio between the diameter of the aortic ring and of the aorta just distal to the sinus ridge was 1.1, and the mean ratio between the diameter of the aortic ring and the maximum diameter of the valve leaflets was 1.18. The second study presents echocardiographic data from normal volunteers. The mean ratio between the diameter of the aortic ring and of the aorta just distal to the sinus ridge was 1.17. It is suggested that stents made to support the leaflets of prosthetic valves are made in conical or hyperbolic form, with the outlet being approximately 20% larger than the inlet.     

Turbulence downstream of subcoronary stentless and stented aortic valves

Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel wall as well as to aortic valve leaflets. Stentless aortic heart valves are known to posses several hemodynamic benefits such as larger effective orifice areas, lower aortic transvalvular pressure difference and faster left ventricular mass regression compared with their stented counterpart. Whether this is reflected by diminished turbulence formation, remains to be shown. We implanted either stented pericardial valve prostheses (Mitroflow), stentless valve prostheses (Solo or Toronto SPV) in pigs or they preserved their native valves. Following surgery, blood velocity was measured in the cross sectional area downstream of the valves using 10MHz ultrasonic probes connected to a dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at two different blood pressures (baseline and 50% increase). We found no difference in maximum RNS measurements between any of the investigated valve groups. The native valve had significantly lower mean RNS values than the Mitroflow (p=0.004), Toronto SPV (p=0.008) and Solo valve (p=0.02). There were no statistically significant differences between the artificial valve groups (p=0.3). The mean RNS was significantly larger when increasing blood pressure (p=0.0006). We, thus, found no advantages for the stentless aortic valves compared with stented prosthesis in terms of lower maximum or mean RNS values. Native valves have a significantly lower mean RNS value than all investigated bioprostheses.     

Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow – 23 years experience in the treatment of aortic valve or aortic root diseases.

Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries.Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.     

An in vitro model quantifying the effect of calcification on the tissue–stent interaction in a stenosed aortic root

Transcatheter Aortic Valves rely on the tissue-stent interaction to ensure that the valve is secured within the aortic root. Aortic stenosis presents with heavily calcified leaflets and it has been proposed that this calcification also acts to secure the valve, but this has never been quantified. In this study, we developed an in vitro calcified aortic root model to quantify the role of calcification on the tissue-stent interaction. The in vitro model incorporated artificial calcifications affixed to the leaflets of porcine aortic heart valves. A self-expanding nitinol braided stent was deployed into non-calcified and artificially calcified porcine aortic roots and imaged by micro computed tomography. Mechanical tests were then conducted to dislodge the stent from the aortic root and it was found that, in the presence of calcification, there was a significant increase in pullout force (8.59 ± 3.68 N vs. 2.84 ± 1.55 N p = 0.045), stent eccentricity (0.05 ± 0.01 vs. 0.02 ± 0.01, p = 0.049), and coefficient of friction between the stent and aortic root (0.36 ± 0.12 vs. 0.09 ± 0.05, p = 0.018), when compared to non-calcified roots. This study quantifies for the first time the impact of calcification on the friction between the aortic tissue and transcatheter aortic valve stent, showing the role of calcification in anchoring the valve stent in the aortic root.     

Angiogenic activation of valvular endothelial cells in aortic valve stenosis

Here, we demonstrate the angiogenic response of valvular endothelial cells to aortic valve (AV) stenosis using a new ex vivo model of aortic leaflets. Histological analysis revealed neovascularization within the cusps of stenotic but not of non-stenotic aortic valves. Correspondingly, the number of capillary-like outgrowth in 3D collagen gel was significantly higher in stenotic than in non-stenotic valves. Capillary-like sprouting was developed significantly faster in stenotic than in non-stenotic valves. New capillary sprouts from stenotic aortic valves exhibited the endothelial cell markers CD31, CD34 and von-Willebrand factor (vWF) as well as carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), Tie-2 and angiogenesis inhibitor endostatin. Western blot analyses revealed a significant increase of CEACAM1 and endostatin in stenotic aortic valve tissue. Electron microscopic examinations demonstrate that these capillary-like tubes are formed by endothelial cells containing Weibel-Palade bodies. Remarkably, inter-endothelial junctions are established and basement membrane material is partially deposited on the basal side of the endothelial tubes. Our data demonstrate the capillary-like sprout formation from aortic valves and suggest a role of angiogenesis in the pathogenesis of aortic valve stenosis. These data provide new insights into the mechanisms of valvular disorders and open new perspectives for prevention and early treatment of calcified aortic stenosis.     

Aortic valve leaflet mechanical properties facilitate diastolic valve function

This work was concerned with the numerical simulation of the behaviour of aortic valves whose material can be modelled as non-linear elastic anisotropic. Linear elastic models for the valve leaflets with parameters used in previous studies were compared with hyperelastic models, incorporating leaflet anisotropy with pronounced stiffness in the circumferential direction through a transverse isotropic model. The parameters for the hyperelastic models were obtained from fits to results of orthogonal uniaxial tensile tests on porcine aortic valve leaflets. The computational results indicated the significant impact of transverse isotropy and hyperelastic effects on leaflet mechanics; in particular, increased coaptation with peak values of stress and strain in the elastic limit. The alignment of maximum principal stresses in all models follows approximately the coarse collagen fibre distribution found in aortic valve leaflets. The non-linear elastic leaflets also demonstrated more evenly distributed stress and strain which appears relevant to long-term scaffold stability and mechanotransduction.     

Stress related collagen ultrastructure in human aortic valves--implications for tissue engineering

Understanding the response of tissue structures to mechanical stress is crucial for optimization of mechanical conditioning protocols in the field of heart valve tissue engineering. In heart valve tissue, it is unclear to what extent mechanical loading affects the collagen fibril morphology. To determine if local stress affects the collagen fibril morphology, in terms of fibril diameter, its distribution, and the fibril density, this was investigated in adult native human aortic valve leaflets. Transmission electron microscopy images of collagen fibrils were analyzed at three locations: the commissures, the belly, and the fixed edge of the leaflets. Subsequently, the mechanical behavior of human aortic valves was used in a computational model to predict the stress distribution in the valve leaflet during the diastolic phase of the cardiac cycle. The local stresses at the three locations were related to the collagen fibril morphology. The fibril diameter and density varied significantly between the measured locations, and appeared inversely related. The average fibril diameter increased from the fixed edge, to the belly, and to the commissures of the leaflets, while fibril density decreased. Interestingly, these differences corresponded well with the level of stress at the locations. The presented data showed that large tissue stress is associated with greater average fibril diameter, lower fibril density, and wider fibril size distribution compared with low stress locations in the leaflets. The findings here provide insight in the effect of mechanical loading on the collagen ultrastructure, and are valuable to improve conditioning protocols for tissue engineering.     

Two-component laser velocimeter measurements downstream of heart valve prostheses in pulsatile flow

Elevated turbulent shear stresses resulting from disturbed blood flow through prosthetic heart valves can cause damage to red blood cells and platelets. The purpose of this study was to measure the turbulent shear stresses occurring downstream of aortic prosthetic valves during in-vitro pulsatile flow. By matching the indices of refraction of the blood analog fluid and model aorta, correlated, simultaneous two-component laser velocimeter measurements of the axial and radial velocity components were made immediately downstream of two aortic prosthetic valves. Velocity data were ensemble averaged over 200 or more cycles for a 15-ms window opened at peak systolic flow. The systolic duration for cardiac flows of 8.4 L/min was 200 ms. Ensemble-averaged total shear stress levels of 2820 dynes/cm2 and 2070 dynes/cm2 were found downstream of a trileaflet valve and a tilting disk valve, respectively. These shear stress levels decreased with axial distance downstream much faster for the tilting disk valve than for the trileaflet valve.     

Evaluation of an aortic valve prosthesis: Fluid-structure interaction or structural simulation?

Bio-inspired polymeric heart valves (PHVs) are excellent candidates to mimic the structural and the fluid dynamic features of the native valve. PHVs can be implanted as prosthetic alternative to currently clinically used mechanical and biological valves or as potential candidate for a minimally invasive treatment, like the transcatheter aortic valve implantation. Nevertheless, PHVs are not currently used for clinical applications due to their lack of reliability. In order to investigate the main features of this new class of prostheses, pulsatile tests in an in-house pulse duplicator were carried out and reproduced in silico with both structural Finite-Element (FE) and Fluid-Structure interaction (FSI) analyses. Valve kinematics and geometric orifice area (GOA) were evaluated to compare the in vitro and the in silico tests. Numerical results showed better similarity with experiments for the FSI than for the FE simulations. The maximum difference between experimental and FSI GOA at maximum opening time was only 5%, as compared to the 46.5% between experimental and structural FE GOA. The stress distribution on the valve leaflets clearly reflected the difference in valve kinematics. Higher stress values were found in the FSI simulations with respect to those obtained in the FE simulation. This study demonstrates that FSI simulations are more appropriate than FE simulations to describe the actual behaviour of PHVs as they can replicate the valve-fluid interaction while providing realistic fluid dynamic results.     

Functional analysis of bioprosthetic heart valves

Glutaraldehyde-treated bovine pericardium is used successfully as bioprosthetic material in the manufacturing of heart valves leaflets. The mechanical properties of bovine pericardial aortic valve leaflets seem to influence its mechanical behaviour and the failure mechanisms. In this study the effect of orthotropy on tricuspid bioprosthetic aortic valve was analysed, using a three-dimensional finite element model, during the entire cardiac cycle. Multiaxial tensile tests were also performed to determine the anisotropy of pericardium. Seven different models of the same valve were analysed using different values of mechanical characteristics from one leaflet to another, considering pericardium as an orthotropic material. The results showed that even a small difference between values along the two axes of orthotropy can negatively influence leaflets performance as regard both displacement and stress distribution. Leaflets of bovine pericardium bioprostheses could be manufactured to be similar to natural human heart valves reproducing their well-known anisotropy. In this way it could be possible to improve the manufacturing process, durability and function of pericardial bioprosthetic valves.     

Dynamic simulation pericardial bioprosthetic heart valve function

While providing nearly trouble-free function for 10-12 years, current bioprosthetic heart valves (BHV) continue to suffer from limited long-term durability. This is usually a result of leaflet calcification and/or structural degeneration, which may be related to regions of stress concentration associated with complex leaflet deformations. In the current work, a dynamic three-dimensional finite element analysis of a pericardial BHV was performed with a recently developed FE implementation of the generalized nonlinear anisotropic Fung-type elastic constitutive model for pericardial BHV tissues (W. Sun and M.S. Sacks, 2005, [Biomech. Model. Mechanobiol., 4(2-3), pp. 190-199]). The pericardial BHV was subjected to time-varying physiological pressure loading to compute the deformation and stress distribution during the opening phase of the valve function. A dynamic sequence of the displacements revealed that the free edge of the leaflet reached the fully open position earlier and the belly region followed. Asymmetry was observed in the resulting displacement and stress distribution due to the fiber direction and the anisotropic characteristics of the Fung-type elastic constitutive material model. The computed stress distribution indicated relatively high magnitudes near the free edge of the leaflet with local bending deformation and subsequently at the leaflet attachment boundary. The maximum computed von Mises stress during the opening phase was 33.8 kPa. The dynamic analysis indicated that the free edge regions of the leaflets were subjected to significant flexural deformation that may potentially lead to structural degeneration after millions of cycles of valve function. The regions subjected to time varying flexural deformation and high stresses of the present study also correspond to regions of tissue valve calcification and structural failure reported from explanted valves. In addition, the present simulation also demonstrated the importance of including the bending component together with the in-plane material behavior of the leaflets towards physiologically realistic deformation of the leaflets. Dynamic simulations with experimentally determined leaflet material specification can be potentially used to modify the valve towards an optimal design to minimize regions of stress concentration and structural failure.     

Comparative study of cellular and extracellular matrix composition of native and tissue engineered heart valves.

Tissue engineering of heart valves utilizes biodegradable or metabolizable scaffolds for remodeling by seeded autologous cells. The aim of this study was to determine and compare extracellular matrix (ECM) formations, cellular phenotypes and cell location of native and tissue engineered (TE) valve leaflets. Ovine carotid arteries, ovine and porcine hearts were obtained from slaughterhouses. Cells were isolated from carotid arteries and dissected ovine, porcine and TE leaflets. TE constructs were fabricated from decellularized porcine pulmonary valves, seeded ovine arterial cells and subsequent 16 days dynamic in vitro culture using a pulsatile bioreactor. Native and TE valves were studied by histology (hematoxylin-eosin, resorcin-fuchsin, Movat pentachrome), NIR femtosecond multiphoton laser scanning microscopy and scanning electron microscopy (SEM). Cells of native and TE tissues were identified and localized by immunohistochemistry. Arterial, valvular and re-isolated TE-construct cells were processed for immunocytochemistry and Western blotting. ECM analysis and SEM revealed characteristical and comparable structures in native and TE leaflets. Most cells in native leaflets stained strongly positive for vimentin. Cells positive to alpha-smooth muscle actin (alpha-SMA), myosin and calponin were only found at the ventricular (inflow) side of ovine aortic and porcine pulmonary valve leaflets. Cells from TE constructs had a strong expression of vimentin, alpha-SMA, myosin, calponin and h-caldesmon throughout the entire leaflet. Comparable ECM formation and endothelial cell lining of native and TE leaflets could be demonstrated. However, immunostaining revealed significant differences between valvular cell phenotypes of native and TE leaflets. These results may be essential for further cardiovascular tissue engineering efforts.