Structural analysis of the natural aortic valve in dynamics: From unpressurized to physiologically loaded

A novel finite element model of the natural aortic valve was developed implementing anisotropic hyperelastic material properties for the leaflets and aortic tissues, and starting from the unpressurized geometry. Static pressurization of the aortic root, silicone rubber moulds and published data helped to establish the model parameters, while high-speed video recording of the leaflet motion in a left-heart simulator allowed for comparisons with simulations. The model was discretized with brick elements and loaded with time-varying pressure using an explicit commercial solver. The aortic valve model produced a competent valve whose dynamic behavior (geometric orifice area vs. time) closely matched that observed in the experiment. In both cases, the aortic valve took approximately 30 ms to open to an 800 mm² orifice and remained completely or more than half open for almost 200 ms, after which it closed within 30–50 ms. The highest values of stress were along the leaflet attachment line and near the commissure during diastole. Von Mises stress in the leaflet belly reached 600–750 kPa from early to mid-diastole. While the model using the unpressurized geometry as initial configuration was specially designed to satisfy the requirements of continuum mechanics for large deformations of hyperelastic materials, it also clearly demonstrated that dry models can be adequate to analyze valve dynamics. Although improvements are still needed, the advanced modeling and validation techniques used herein contribute toward improved and quantified accuracy over earlier simplified models.     

Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease

The bicuspid aortic valve (BAV) is associated with a high prevalence of calcific aortic valve disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid aortic valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian–Eulerian approach. Valvular performance and regional leaflet wallshear stress were quantified in terms of valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV.     

Computational model of aortic valve surgical repair using grafted pericardium

Aortic valve reconstruction using leaflet grafts made from autologous pericardium is an effective surgical treatment for some forms of aortic regurgitation. Despite favorable outcomes in the hands of skilled surgeons, the procedure is underutilized because of the difficulty of sizing grafts to effectively seal with the native leaflets. Difficulty is largely due to the complex geometry and function of the valve and the lower distensibility of the graft material relative to native leaflet tissue. We used a structural finite element model to explore how a pericardial leaflet graft of various sizes interacts with two native leaflets when the valve is closed and loaded. Native leaflets and pericardium are described by anisotropic, hyperelastic constitutive laws, and we model all three leaflets explicitly and resolve leaflet contact in order to simulate repair strategies that are asymmetrical with respect to valve geometry and leaflet properties. We ran simulations with pericardial leaflet grafts of various widths (increase of 0%, 7%, 14%, 21% and 27%) and heights (increase of 0%, 13%, 27% and 40%) relative to the native leaflets. Effectiveness of valve closure was quantified based on the overlap between coapting leaflets. Results showed that graft width and height must both be increased to achieve proper valve closure, and that a graft 21% wider and 27% higher than the native leaflet creates a seal similar to a valve with three normal leaflets. Experimental validation in excised porcine aortas (n=9) corroborates the results of simulations.     

Direct numerical simulation of a 2D-stented aortic heart valve at physiological flow rates

We study the nonlinear interaction of an aortic heart valve, composed of hyperelastic corrugated leaflets of finite density attached to a stented vessel under physiological flow conditions. In our numerical simulations, we use a 2D idealised representation of this arrangement. Blood flow is caused by a time-varying pressure gradient that mimics that of the aortic valve and corresponds to a peak Reynolds number equal to 4050. Here, we fully account for the shear-thinning behaviour of the blood and large deformations and contact between the leaflets by solving the momentum and mass balances for blood and leaflets. The mixed finite element/Galerkin method along with linear discontinuous Lagrange multipliers for coupling the fluid and elastic domains is adopted. Moreover, a series of challenging numerical issues such as the finite length of the computational domain and the conditions that should be imposed on its inflow/outflow boundaries, the accurate time integration of the parabolic and hyperbolic momentum equations, the contact between the leaflets and the non-conforming mesh refinement in part of the domain are successfully resolved. Calculations for the velocity and the shear stress fields of the blood reveal that boundary layers appear on both sides of a leaflet. The one along the ventricular side transfers blood with high momentum from the core region of the vessel to the annulus or the sinusoidal expansion, causing the continuous development of flow instabilities. At peak systole, vortices are convected in the flow direction along the annulus of the vessel, whereas during the closure stage of the valve, an extremely large vortex develops in each half of the flow domain.     

Modeling active muscle contraction in mitral valve leaflets during systole: a first approach

The present study addresses the effect of muscle activation contributions to mitral valve leaflet response during systole. State-of-art passive hyperelastic material modeling is employed in combination with a simple active stress part. Fiber families are assumed in the leaflets: one defined by the collagen and one defined by muscle activation. The active part is either assumed to be orthogonal to the collagen fibers or both orthogonal to and parallel with the collagen fibers (i.e. an orthotropic muscle fiber model). Based on data published in the literature and information herein on morphology, the size of the leaflet parts that contain muscle fibers is estimated. These parts have both active and passive materials, the remaining parts consist of passive material only. Several solid finite element analyses with different maximum activation levels are run. The simulation results are compared to corresponding echocardiography at peak systole for a porcine model. The physiologically correct flat shape of the closed valve is approached as the activation levels increase. The non-physiological bulging of the leaflet into the left atrium when using passive material models is reduced significantly. These results contribute to improved understanding of the physiology of the native mitral valve, and add evidence to the hypothesis that the mitral valve leaflets not are just passive elements moving as a result of hemodynamic pressure gradients in the left part of the heart.     

Interlayer micromechanics of the aortic heart valve leaflet

While the mechanical behaviors of the fibrosa and ventricularis layers of the aortic valve (AV) leaflet are understood, little information exists on their mechanical interactions mediated by the GAG-rich central spongiosa layer. Parametric simulations of the interlayer interactions of the AV leaflets in flexure utilized a tri-layered finite element (FE) model of circumferentially oriented tissue sections to investigate inter-layer sliding hypothesized to occur. Simulation results indicated that the leaflet tissue functions as a tightly bonded structure when the spongiosa effective modulus was at least 25 % that of the fibrosa and ventricularis layers. Novel studies that directly measured transmural strain in flexure of AV leaflet tissue specimens validated these findings. Interestingly, a smooth transmural strain distribution indicated that the layers of the leaflet indeed act as a bonded unit, consistent with our previous observations (Stella and Sacks in J Biomech Eng 129:757–766, 2007) of a large number of transverse collagen fibers interconnecting the fibrosa and ventricularis layers. Additionally, when the tri-layered FE model was refined to match the transmural deformations, a layer-specific bimodular material model (resulting in four total moduli) accurately matched the transmural strain and moment-curvature relations simultaneously. Collectively, these results provide evidence, contrary to previous assumptions, that the valve layers function as a bonded structure in the low-strain flexure deformation mode. Most likely, this results directly from the transverse collagen fibers that bind the layers together to disable physical sliding and maintain layer residual stresses. Further, the spongiosa may function as a general dampening layer while the AV leaflets deforms as a homogenous structure despite its heterogeneous architecture.     

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.     

Subject-specific multiscale modeling of aortic valve biomechanics

A Finite Element workflow for the multiscale analysis of the aortic valve biomechanics was developed and applied to three physiological anatomies with the aim of describing the aortic valve interstitial cells biomechanical milieu in physiological conditions, capturing the effect of subject-specific and leaflet-specific anatomical features from the organ down to the cell scale. A mixed approach was used to transfer organ-scale information down to the cell-scale. Displacement data from the organ model were used to impose kinematic boundary conditions to the tissue model, while stress data from the latter were used to impose loading boundary conditions to the cell level. Peak of radial leaflet strains was correlated with leaflet extent variability at the organ scale, while circumferential leaflet strains varied over a narrow range of values regardless of leaflet extent. The dependency of leaflet biomechanics on the leaflet-specific anatomy observed at the organ length-scale is reflected, and to some extent emphasized, into the results obtained at the lower length-scales. At the tissue length-scale, the peak diastolic circumferential and radial stresses computed in the fibrosa correlated with the leaflet surface area. At the cell length-scale, the difference between the strains in two main directions, and between the respective relationships with the specific leaflet anatomy, was even more evident; cell strains in the radial direction varied over a relatively wide range (\(0.36-0.87\)) with a strong correlation with the organ length-scale radial strain (\(R^{2}= 0.95\)); conversely, circumferential cell strains spanned a very narrow range (\(0.75-0.88\)) showing no correlation with the circumferential strain at the organ level (\(R^{2}= 0.02\)). Within the proposed simulation framework, being able to account for the actual anatomical features of the aortic valve leaflets allowed to gain insight into their effect on the structural mechanics of the leaflets at all length-scales, down to the cell scale.

     

Simulated elliptical bioprosthetic valve deformation: Implications for asymmetric transcatheter valve deployment

The asymmetric, elliptical shape of a transcatheter aortic valve (TAV), after implantation into a calcified aortic root, has been clinically observed. However, the impact of elliptical TAV configuration on TAV leaflet stress and strain distribution and valve regurgitation is largely unknown. In this study, we developed computational models of elliptical TAVs based on a thin pericardial bioprosthetic valve model recently developed. Finite element and computational fluid dynamics simulations were performed to investigate TAV leaflet structural deformation and central backflow leakage, and compared with those of a nominal symmetric TAV. From the results, we found that for a distorted TAV with an elliptical eccentricity of 0.68, the peak stress increased significantly by 143% compared with the nominal circular TAV. When the eccentricity of an elliptical TAV was larger than 0.5, a central backflow leakage was likely to occur. Also, deployment of a TAV with a major calcified region perpendicular to leaflet coaptation line was likely to cause a larger valve leakage. In conclusion, the computational models of elliptical TAVs developed in this study could improve our understanding of the biomechanics involved in a TAV with an elliptical configuration and facilitate optimal design of next-generation TAV devices.     

Fundamental mechanics of aortic heart valve closure

Stresses in a prosthetic heart valve at closure are determined by its geometrical and structural characteristics, by the mechanical support environment, and by the momentum of the valve leaflets or occluder and of the blood at the instant of closure. The mass of blood to be arrested is significantly greater than that of the leaflets or occluder, and is therefore likely to dominate the closure impulse. The kinetic energy of the blood must be transduced into potential energy in the structural components (valve leaflets, aortic root and aorta). This paper presents a methodology for computation and parameterisation of the blood momentum associated with a valve in the aortic position. It is suggested that the influence of physiological parameters, such as systolic waveform and systemic impedance, on the closure characteristics can be investigated based on the fluid dynamic implications. Detailed results are presented for a single leaflet mechanical valve (Bjork-Shiley 60 degrees Convexo-Concave). It is demonstrated that a simple analytical method can yield results that might be adequate for the purposes of valve design.     

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.     

A mechanical analysis of the closed Hancock heart valve prosthesis

In order to obtain mechanical specifications for the design of an artificial leaflet valve prosthesis, a geometrically non-linear numerical model is developed of a closed Hancock leaflet valve prosthesis. In this model, the fibre reinforcement of the leaflet and the viscoelastic properties of frame and leaflets are incorporated. The calculations are primarily restricted to 1/6 part of the valve and a time varying pressure load is applied. The calculations are verified experimentally by measuring the commissure displacements and leaflet centre displacement of a Hancock valve. The numerically obtained commissure displacements are found to be linearly dependent on the pressure load, and the slope of the curves is hardly dependent on loading type and loading velocity. Experimentally a difference is found between the three commissure displacements, which is also predicted numerically using a simplified asymmetric total valve model. Besides, experimentally a clear dependency of commissure displacements on frame size is found. For the leaflet centre displacement, a qualitative agreement exists between numerical prediction and experimental result, although the numerical predicted values are systematically higher. The numerically obtained stress distributions revealed that the maximum von Mises intensity in the membranes occurs in the vicinity of the commissure in the free leaflet area (0.2 N mm-2). Wrinkling of the membranes may occur in the coaptation area near the leaflet suspension. The maximum fibre stress is found near the aortic ring in the fibres which form the boundaries of the coaptation area (0.64 N mm-2). These locations seem to correlate with some common regions of tissue valve failure.     

Biaxial mechanical properties of bovine jugular venous valve leaflet tissues

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress–strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress–strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson’s trichrome and Verhoeff–Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic; \(p<0.01\)); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors’ knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.     

Patient-specific simulation of a stentless aortic valve implant: the impact of fibres on leaflet performance

In some cases of aortic valve leaflet disease, the implant of a stentless biological prosthesis represents an excellent option for aortic valve replacement (AVR). In particular, if compared with the implant of mechanical valves, it provides a more physiological haemodynamic performance and a reduced thrombogeneticity, avoiding the use of anticoagulants. The clinical outcomes of AVR are strongly dependent on an appropriate choice of both prosthesis size and replacement technique, which is, at present, strictly related to surgeon's experience and skill. This represents the motivation for patient-specific finite element analysis able to virtually reproduce stentless valve implantation. With the aim of performing reliable patient-specific simulations, we remark that, on the one hand, it is not well established in the literature whether bioprosthetic leaflet tissue is isotropic or anisotropic; on the other hand, it is of fundamental importance to incorporate an accurate material model to realistically predict post-operative performance. Within this framework, using a novel computational methodology to simulate stentless valve implantation, we test the impact of using different material models on both the stress pattern and post-operative coaptation parameters (i.e. coaptation area, length and height). As expected, the simulation results suggest that the material properties of the valve leaflets affect significantly the post-operative prosthesis performance.     

Mapping the spatial variation of mitral valve elastic properties using air-pulse optical coherence elastography

The mitral valve is a highly heterogeneous tissue composed of two leaflets, anterior and posterior, whose unique composition and regional differences in material properties are essential to overall valve function. While mitral valve mechanics have been studied for many decades, traditional testing methods limit the spatial resolution of measurements and can be destructive. Optical coherence elastography (OCE) is an emerging method for measuring viscoelastic properties of tissues in a noninvasive, nondestructive manner. In this study, we employed air-pulse OCE to measure the spatial variation in mitral valve elastic properties with micro-scale resolution at 1 mm increments along the radial length of the leaflets. We analyzed differences between the leaflets, as well as between regions of the valve. We found that the anterior leaflet has a higher elastic wave velocity, which is reported as a surrogate for stiffness, than the posterior leaflet, most notably at the annular edge of the sample. In addition, we found a spatial elastic gradient in the anterior leaflet, where the annular edge was found to have a greater elastic wave velocity than the free edge. This gradient was less pronounced in the posterior leaflet. These patterns were confirmed using established uniaxial tensile testing methods. Overall, the anterior leaflet was stiffer and had greater heterogeneity in its mechanical properties than the posterior leaflet. This study measures differences between the two mitral leaflets with greater resolution than previously feasible and demonstrates a method that may be suitable for assessing valve mechanics following repair or during the engineering of synthetic valve replacements.     

Aortic valve leaflet wall shear stress characterization revisited: impact of coronary flow

Computational characterizations of aortic valve hemodynamics have typically discarded the effects of coronary flow. The objective of this study was to complement our previous fluid–structure interaction aortic valve model with a physiologic coronary circulation model to quantify the impact of coronary flow on aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow suppressed vortex development in the two coronary sinuses and altered WSS magnitude and directionality on the three leaflets, with the most substantial differences occurring in the belly and tip regions.     

Pericardial heterograft valves: An assessment of leaflet stresses and their implications for heart valve design

Bovine pericardium, stabilized with glutaraldehyde, is used widely in the construction of heart valve substitutes, but the design and construction of valve substitutes from this material are empirically based. Collagenous tissue can support tension, but experimental evidence indicates that flexure-induced compressive stresses can lead to fatigue failure. This study uses experimental results obtained from cyclic uniaxial load tests to predict the type and magnitude of operational stresses which occur in pericardial heterograft leaflets. Both Young's modulus and Poisson's ratio varied with uniaxial loading in pericardium, chemically modified free of tension. Leaflet stresses were analysed by using effective incremental representations of these parameters. In leaflets with unrestricted rotation at the point of attachment to the stent, the mid-plane tensions always exceeded the bending stresses, and no zones of leaflet compression were predicted. In contrast, with totally restricted leaflet rotation induced by clamping (possibly between a male and female frame) the bending stresses were greater than the mid-plane tensions at the hinge line and significant compressive stresses were predicted at this site. If elastic boundary conditions were introduced at the stent (possibly by wrapping the stent in pericardium) then the compressive stresses were reduced as the degree of elasticity was increased. Glutaraldehyde fixation of the pericardium under load produced a stiffer material; higher compressive stresses at the stent and significant increases in total stress were predicted for this tissue. The application of elevated pressure loading also increased the compressive and total stresses in the leaflet. Finally, it was shown that bicuspid leaflets were likely to experience higher stresses than tricuspid leaflets. This simple stress analysis should help valve designers of pericardial heterografts to identify those conditions which lead to tissue compression, high total stress, and ultimately material fatigue.     

A three-dimensional mechanical analysis of a stentless fibre-reinforced aortic valve prosthesis

Failure of bioprosthetic and synthetic three-leaflet valves has been shown to occur as a consequence of high tensile and bending stresses, acting on the leaflets during opening and closing. Moreover, in the stented prostheses, whether synthetic or biological, the absence of contraction of the aortic base, due to the rigid stent, causes the leaflets to be subjected to an unphysiological degree of flexure, which is related to calcification. It is shown that the absence of the stent, which gives a flexible aortic base and leaflet attachment, and leaflet fibre-reinforcement result in reduced stresses in the weaker parts of the leaflets in their closed configuration. It is postulated that this leads to a decrease of tears and perforations, which may result in a improved long-term behaviour. The effect of a flexible leaflet attachment and aortic base of a synthetic valve is investigated with a finite element model. Different fibre-reinforced structures are analysed with respect to the stresses that are likely to contribute to the failure of fibre-reinforced prostheses and compared with the results obtained for a stented prosthesis. Results show that for the stentless models a reduction of stresses up to 75% is obtained with respect to stented models with the same type of reinforcement.     

Stresses in the closed mitral valve: a model study

In the present model study on the closed mitral valve, tensile force in the chordae tendineae is related to transvalvular pressure using a mathematical model of mechanics of the closed mitral valve. Circumferential stress as well as bending stress in the valve leaflets were neglected. Without precisely knowing the mechanical properties of the leaflet material, geometry of the leaflets was estimated by applying Laplace's law, which relates leaflet stress to leaflet curvature. Independent of shape of the mitral valve orifice, under all circumstances tensile force in the chordae tendineae was calculated to be equal or greater than half the force exerted on the mitral valve orifice by the transvalvular pressure.     

A functionally graded material model for the transmural stress distribution of the aortic valve leaflet

Heterogeneities in structure and stress within heart valve leaflets are of significant concern to their functional physiology, as they affect how the tissue constituents remodel in response to pathological and non-pathological (e.g. exercise, pregnancy) alterations in cardiac function. Indeed, valve interstitial cells (VICs) are known to synthesize and degrade leaflet extracellular matrix (ECM) components in a manner specific to their local micromechanical environment. Quantifying local variations in ECM structure and stress is thus necessary to understand homeostatic valve maintenance as well as to develop predictive models of disease progression and post-surgical outcomes. In the aortic valve (AV), transmural variations in stress have previously been investigated by modeling the leaflet as a composite of contiguous but mechanically distinct layers. Based on previous findings about the bonded nature of these layers (Buchanan and Sacks, BMMB, 2014), we developed a more generalized structural constitutive model by treating the leaflet as a functionally graded material (FGM), whose properties vary continuously over the thickness. We informed the FGM model using high-resolution morphological measurements, which demonstrated that the composition and fiber structure change gradually over the thickness of the AV leaflet. For validation, we fit the model against an extensive database of whole-leaflet and individual-layer mechanical responses. The FGM model predicted large stress variations both between and within the leaflet layers at end-diastole, with low-collagen regions bearing significant radial stress. These novel results suggest that the continually varying structure of the AV leaflet has an important purpose with regard to valve function and tissue homeostasis.