Geometric data of commercially available tricuspid valve annuloplasty devices.

Tricuspid valve annuloplasty is the gold standard surgical treatment for functional tricuspid valve regurgitation. During this procedure, ring-like devices are implanted to reshape the diseased tricuspid valve annulus and to restore function. For the procedure, surgeons can choose from multiple available device options varying in shape and size. In this article, we provide the three-dimensional (3D) scanned geometry (*.stl) and reduced midline (*.vtk) of five different annuloplasty devices of all commercially available sizes. Three-dimensional images were captured using a 3D scanner. After extracting the surface geometry from these images, the images were converted to 3D point clouds and skeletonized to generate a 3D midline of each device. In total, we provide 30 data sets comprising the Edwards Classic, Edwards MC3, Edwards Physio, Medtronic TriAd, and Medtronic Contour 3D of sizes 26-36. This dataset can be used in computational models of tricuspid valve annuloplasty repair to inform accurate repair geometry and boundary conditions. Additionally, others can use these data to compare and inspire new device shapes and sizes.

Impact of tricuspid annuloplasty device shape and size on valve mechanics-a computational study.

Background: Tricuspid valve disease significantly affects 1.6 million Americans. The gold standard treatment for tricuspid disease is the implantation of annuloplasty devices. These ring-like devices come in various shapes and sizes. Choices for both shape and size are most often made by surgical intuition rather than scientific rationale. Methods: To understand the impact of shape and size on valve mechanics and to provide a rational basis for their selection, we used a subject-specific finite element model to conduct a virtual case study. That is, we implanted 4 different annuloplasty devices of 6 different sizes in our virtual patient. After each virtual surgery, we computed the coaptation area, leaflet end-systolic angles, leaflet stress, and chordal forces. Results: We found that contoured devices are better at normalizing end-systolic angles, whereas the one flat device, the Edwards Classic, maximized the coaptation area and minimized leaflet stress and chordal forces. We further found that reducing device size led to increased coaptation area but also negatively impacted end-systolic angles, stress, and chordal forces. Conclusions: Based on our analyses of the coaptation area, leaflet motion, leaflet stress, and chordal forces, we found that device shape and size have a significant impact on valve mechanics. Thereby, our study also demonstrates the value of simulation tools and device tests in "virtual patients." Expanding our study to many more valves may, in the future, allow for universal recommendations.

Leaflet remodeling reduces tricuspid valve function in a computational model.

Tricuspid valve leaflets have historically been considered "passive flaps". However, we have recently shown that tricuspid leaflets actively remodel in sheep with functional tricuspid regurgitation. We hypothesize that these remodeling-induced changes reduce leaflet coaptation and, therefore, contribute to valvular dysfunction. To test this, we simulated the impact of remodeling-induced changes on valve mechanics in a reverse-engineered computer model of the human tricuspid valve. To this end, we combined right-heart pressures and tricuspid annular dynamics recorded in an ex vivo beating heart, with subject-matched in vitro measurements of valve geometry and material properties, to build a subject-specific finite element model. Next, we modified the annular geometry and boundary conditions to mimic changes seen in patients with pulmonary hypertension. In this model, we then increased leaflet thickness and stiffness and reduced the stretch at which leaflets stiffen, which we call "transition-λ." Subsequently, we quantified mean leaflet stresses, leaflet systolic angles, and coaptation area as measures of valve function. We found that leaflet stresses, leaflet systolic angle, and coaptation area are sensitive to independent changes in stiffness, thickness, and transition-λ. When combining thickening, stiffening, and changes in transition-λ, we found that anterior and posterior leaflet stresses decreased by 26% and 28%, respectively. Furthermore, systolic angles increased by 43%, and coaptation area decreased by 66%; thereby impeding valve function. While only a computational study, we provide the first evidence that remodeling-induced leaflet thickening and stiffening may contribute to valvular dysfunction. Targeted suppression of such changes in diseased valves could restore normal valve mechanics and promote leaflet coaptation.

Untangling the mechanisms of pulmonary arterial hypertension-induced right ventricular stiffening in a large animal model.

Pulmonary hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) stiffening; thus, impeding diastolic filling. Multiple mechanisms may contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model to untangle these mechanisms. Thus, we induced pulmonary arterial hypertension (PAH) in sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. Finally, we used finite element modeling to disentangle the relative importance of each stiffening mechanism. We found that the RVs of PAH animals thickened most at the base and the free wall and that PAH induced excessive collagen synthesis, increased cardiomyocyte cross-sectional area, and led to microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with collagen synthesis. Finally, our computational models predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Thus, myocardial stiffening may be the most important predictor for PAH progression. Given the correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for estimating myocardial stiffness and predicting PAH outcomes. STATEMENT OF SIGNIFICANCE: Ventricular stiffening is a significant contributor to pulmonary hypertension-induced right heart failure. However, the mechanisms that lead to ventricular stiffening are not fully understood. The novelty of our work lies in answering this question through the use of a large animal model in combination with spatially- and directionally sensitive experimental techniques. We find that myocardial stiffness is the primary mechanism that leads to ventricular stiffening. Clinically, this knowledge may be used to improve diagnostic, prognostic, and therapeutic strategies for patients with pulmonary hypertension.

A Brief Note on Building Augmented Reality Models for Scientific Visualization.

Augmented reality (AR) has revolutionized the video game industry by providing interactive, three-dimensional visualization. Interestingly, AR technology has only been sparsely used in scientific visualization. This is, at least in part, due to the significant technical challenges previously associated with creating and accessing such models. To ease access to AR for the scientific community, we introduce a novel visualization pipeline with which they can create and render AR models. We demonstrate our pipeline by means of finite element results, but note that our pipeline is generally applicable to data that may be represented through meshed surfaces. Specifically, we use two open-source software packages, ParaView and Blender. The models are then rendered through the platform, which we access through Android and iOS smartphones. To demonstrate our pipeline, we build AR models from static and time-series results of finite element simulations discretized with continuum, shell, and beam elements. Moreover, we openly provide python scripts to automate this process. Thus, others may use our framework to create and render AR models for their own research and teaching activities.

Untangling the mechanisms of pulmonary hypertension-induced right ventricular stiffening in a large animal model.

Background: Pulmonary arterial hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) remodeling and stiffening; thus, impeding diastolic filling and ventricular function. Multiple mechanisms contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model as well as imaging, experimental, and computational approaches to untangle these mechanisms. Methods: We induced PHT in eight sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. All findings were compared to 12 control animals. Finally, we used computational modeling to disentangle the relative importance of each stiffening mechanism. Results: First, we found that the RVs of PHT animals thickened most at the base and the free wall. Additionally, we found that PHT induced excessive collagen synthesis and microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with excess collagen synthesis. Finally, our model of normalized RV pressure-volume relationships predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Conclusions: In summary, we found that PHT induces wall thickening, microstructural disorganization, and myocardial stiffening. These remodeling mechanisms were both spatially and directionally dependent. Using modeling, we show that myocardial stiffness is the primary contributor to RV stiffening. Thus, myocardial stiffening may be an important predictor for PHT progression. Given the significant correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for non-invasively estimating myocardial stiffness and predicting PHT outcomes.

Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation.

OBJECTIVES: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR. METHODS: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing. RESULTS: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer. CONCLUSIONS: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus.

The impact of thickness heterogeneity on soft tissue biomechanics: a novel measurement technique and a demonstration on heart valve tissue.

The mechanical properties of soft tissues are driven by their complex, heterogeneous composition and structure. Interestingly, studies of soft tissue biomechanics often ignore spatial heterogeneity. In our work, we are therefore interested in exploring the impact of tissue heterogeneity on the mechanical properties of soft tissues. Therein, we specifically focus on soft tissue heterogeneity arising from spatially varying thickness. To this end, our first goal is to develop a non-destructive measurement technique that has a high spatial resolution, provides continuous thickness maps, and is fast. Our secondary goal is to demonstrate that including spatial variation in thickness is important to the accuracy of biomechanical analyses. To this end, we use mitral valve leaflet tissue as our model system. To attain our first goal, we identify a soft tissue-specific contrast protocol that enables thickness measurements using a Keyence profilometer. We also show that this protocol does not affect our tissues' mechanical properties. To attain our second goal, we conduct virtual biaxial, bending, and buckling tests on our model tissue both ignoring and considering spatial variation in thickness. Thereby, we show that the assumption of average, homogeneous thickness distributions significantly alters the results of biomechanical analyses when compared to including true, spatially varying thickness distributions. In conclusion, our work provides a novel measurement technique that can capture continuous thickness maps non-invasively, at high resolution, and in a short time. Our work also demonstrates the importance of including heterogeneous thickness in biomechanical analyses of soft tissues.

Texas TriValve 1.0 : a reverse­engineered, open model of the human tricuspid valve.

Nearly 1.6 million Americans suffer from a leaking tricuspid heart valve. To make matters worse, current valve repair options are far from optimal leading to recurrence of leakage in up to 30% of patients. We submit that a critical step toward improving outcomes is to better understand the "forgotten" valve. High-fidelity computer models may help in this endeavour. However, the existing models are limited by averaged or idealized geometries, material properties, and boundary conditions. In our current work, we overcome the limitations of existing models by (reverse) engineering the tricuspid valve from a beating human heart in an organ preservation system. The resulting finite-element model faithfully captures the kinematics and kinetics of the native tricuspid valve as validated against echocardiographic data and others' previous work. To showcase the value of our model, we also use it to simulate disease-induced and repair-induced changes to valve geometry and mechanics. Specifically, we simulate and compare the effectiveness of tricuspid valve repair via surgical annuloplasty and via transcatheter edge-to-edge repair. Importantly, our model is openly available for others to use. Thus, our model will allow us and others to perform virtual experiments on the healthy, diseased, and repaired tricuspid valve to better understand the valve itself and to optimize tricuspid valve repair for better patient outcomes.

Right ventricular myocardial mechanics: Multi-modal deformation, microstructure, modeling, and comparison to the left ventricle.

The right ventricular myocardium, much like the rest of the right side of the heart, has been consistently understudied. Presently, little is known about its mechanics, its microstructure, and its constitutive behavior. In this work, we set out to provide the first data on the mechanics of the mature right ventricular myocardium in both simple shear and uniaxial loading and to compare these data to the mechanics of the left ventricular myocardium. To this end, we tested ovine tissue samples of the right and left ventricle under a comprehensive mechanical testing protocol that consisted of six simple shear modes and three tension/compression modes. After mechanical testing, we conducted a histology-based microstructural analysis on each right ventricular sample that yielded high resolution fiber distribution maps across the entire samples. Equipped with this detailed mechanical and histological data, we employed an inverse finite element framework to determine the optimal form and parameters for microstructure-based constitutive models. The results of our study show that right ventricular myocardium is less stiff then the left ventricular myocardium in the fiber direction, but similarly exhibits non-linear, anisotropic, and tension/compression asymmetric behavior with direction-dependent Poynting effect. In addition, we found that right ventricular myocardial fibers change angles transmurally and are dispersed within the sheet plane and normal to it. Through our inverse finite element analysis, we found that the Holzapfel model successfully fits these data, even when selectively informed by rudimentary microstructural information. And, we found that the inclusion of higher-fidelity microstructural data improved the Holzapfel model's predictive ability. Looking forward, this investigation is a critical step towards understanding the fundamental mechanical behavior of right ventricular myocardium and lays the groundwork for future whole-organ mechanical simulations.

Tricuspid Valve Anterior Leaflet Strains in Ovine Functional Tricuspid Regurgitation.

Functional tricuspid regurgitation (FTR) is thought to arise due to annular dilation and alteration of right ventricular (RV) geometry in the presence of normal leaflets, yet mitral leaflets have been shown to remodel significantly in functional mitral regurgitation. We set out to evaluate tricuspid valve anterior leaflet deformations in ovine FTR. Eleven animals (FTR group) underwent implantation of a pacemaker with high rate pacing to induce biventricular dysfunction and at least moderate TR. Subsequently, both FTR (n = 11) and Control (n = 12) animals underwent implantation of 6 sonomicrometry crystals around the tricuspid annulus, 4 on the anterior leaflet, and 14 on RV epicardium. Tricuspid valve geometry and anterior leaflet strains were calculated from crystal coordinates. Left ventricular ejection fraction and RV fractional area change were significantly lower in FTR animals versus Control. Tricuspid annular area, septo-lateral diameter, RV pressures were all significantly greater in the FTR group. Mean TR grade (+0-3) was 0.7 ± 0.5 in Control and 2.4 ± 0.5 in FTR (P = < 0.001). The anterior leaflet area and length increased significantly. Global radial leaflet strain was significantly lower in FTR mostly driven by decreased free edge leaflet strain. Global circumferential anterior leaflet strain was also significantly lower in FTR with more remarkable reduction in the belly region. Rapid ventricular pacing in sheep resulted in a clinically pertinent model of RV and annular dilation with FTR and leaflet enlargement. Both circumferential and radial anterior leaflet strains were significantly reduced with FTR. Functional TR may be associated with alteration of leaflet mechanical properties.

The tricuspid valve also maladapts as shown in sheep with biventricular heart failure.

Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve-extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, we induced biventricular heart failure in sheep that developed tricuspid valve leakage. In the anterior leaflets of those animals, we investigated maladaptation on multiple scales. We demonstrated alterations on the protein and cell-level, leading to tissue growth, thickening, and stiffening. These data provide a new perspective on a poorly understood, yet highly prevalent disease. Our findings may motivate novel therapy options for many currently untreated patients with leaky tricuspid valves.

Tricuspid Valve Annuloplasty Alters Leaflet Mechanics.

Tricuspid valve regurgitation is associated with significant morbidity and mortality. Its most common treatment option, tricuspid valve annuloplasty, is not optimally effective in the long-term. Toward identifying the causes for annuloplasty's ineffectiveness, we have previously investigated the technique's impact on the tricuspid annulus and the right ventricular epicardium. In our current work, we are extending our analysis to the anterior tricuspid valve leaflet. To this end, we adopted our previous strategy of performing DeVega suture annuloplasty as an experimental methodology that allows us to externally control the degree of cinching during annuloplasty. Thus, in ten sheep we successively cinched the annulus and quantified changes to leaflet motion, dynamics, and strain in the beating heart by combining sonomicrometry with our well-established mechanical framework. We found that successive cinching of the valve enforced earlier coaptation and thus reduced leaflet range of motion. Additionally, leaflet angular velocity during opening and closing decreased. Finally, we found that leaflet strains were also reduced. Specifically, radial and areal strains decreased as a function of annular cinching. Our findings are critical as they suggest that suture annuloplasty alters the mechanics of the tricuspid valve leaflets which may disrupt their resident cells' mechanobiological equilibrium. Long-term, such disruption may stimulate tissue maladaptation which could contribute to annuloplasty's sub-optimal effectiveness. Additionally, our data suggest that the extent to which annuloplasty alters leaflet mechanics can be controlled via degree of cinching. Hence, our data may provide direct surgical guidelines.

Tricuspid Annuloplasty Rings: A Quantitative Comparison of Size, Nonplanar Shape, and Stiffness.

BACKGROUND: Functional tricuspid regurgitation due to annular and ventricular dilatation is increasingly recognized as a significant source of morbidity and mortality. To repair the annulus, surgeons implant one of many annuloplasty devices that differ in size, 3-dimensional (3D) shape, and stiffness. However, there have been no quantitative comparisons between various available devices. METHODS: Three-dimensional scanning, micro-computed tomography imaging, analytical methods, and mechanical tests were used to compare 3 Edwards Lifesciences (Irvine, CA) and 3 Medtronic (Minneapolis, MN) annuloplasty devices of all available sizes. We measured in-plane metrics of maximum diameter, perimeter, area, height, as well as elevation and curvature profiles. Furthermore, we computed bending stiffness as well as the maximum and minimum axes of the bending stiffness. RESULTS: Most annular prostheses differed little in their in-plane geometries but varied significantly in height. In-plane properties deviated significantly from measurements of healthy human tricuspid annuli. Height of the Edwards' MC3 and Medtronic's Contour 3D resembled healthy human tricuspid valve annuli, whereas the Edwards' Physio and Classic, and Medtronic's TriAd, did not. Additionally, the elevation profiles of the MC3 and Contour 3D and curvature profiles between all devices were consistent and matched those of healthy human annuli. The tested devices also differed in their bending stiffness, both in terms of absolute values and their maximum and minimum axes. CONCLUSIONS: Contoured devices, such as Edwards' MC3 and Medtronic's Contour 3D, most accurately resembled the healthy human tricuspid annulus but differed significantly in bending stiffness. To what extent prosthesis properties and shape affect tricuspid valve function remains to be determined.

A detailed mechanical and microstructural analysis of ovine tricuspid valve leaflets.

The tricuspid valve ensures unidirectional blood flow from the right atrium to the right ventricle. The three tricuspid leaflets operate within a dynamic stress environment of shear, bending, tensile, and compressive forces, which is cyclically repeated nearly three billion times in a lifetime. Ostensibly, the microstructural and mechanical properties of the tricuspid leaflets have mechanobiologically evolved to optimally support their function under those forces. Yet, how the tricuspid leaflet microstructure determines its mechanical properties and whether this relationship differs between the three leaflets is unknown. Here we perform a microstructural and mechanical analysis in matched ovine tricuspid leaflet samples. We found that the microstructure and mechanical properties vary among the three tricuspid leaflets in sheep. Specifically, we found that tricuspid leaflet composition, collagen orientation, and valve cell nuclear morphology are spatially heterogeneous and vary across leaflet type. Furthermore, under biaxial tension, the leaflets' mechanical behaviors exhibited unequal degrees of mechanical anisotropy. Most importantly, we found that the septal leaflet was stiffer in the radial direction and not the circumferential direction as with the other two leaflets. The differences we observed in leaflet microstructure coincide with the varying biaxial mechanics among leaflets. Our results demonstrate the structure-function relationship for each leaflet in the tricuspid valve. We anticipate our results to be vital toward developing more accurate, leaflet-specific tricuspid valve computational models. Furthermore, our results may be clinically important, informing differential surgical treatments of the tricuspid valve leaflets. Finally, the identified structure-function relationships may provide insight into the homeostatic and remodeling potential of valvular cells in altered mechanical environments, such as in diseased or repaired tricuspid valves. STATEMENT OF SIGNIFICANCE: Our work is significant as we investigated the structure-function relationship of ovine tricuspid valve leaflets. This is important as tricuspid valves fail frequently and our current approach to repairing them is suboptimal. Specifically, we related the distribution of structural and cellular elements, such as collagen, glycosaminoglycans, and cell nuclei, to each leaflet's mechanical properties. We found that leaflets have different structures and that their mechanics differ. This may, in the future, inform leaflet-specific treatment strategies and help optimize surgical outcomes.

The Effect of Downsizing on the Normal Tricuspid Annulus.

Tricuspid annuloplasty is a surgical procedure that cinches the valve's annulus in order to reduce regurgitant blood flow. One of its critical parameters is the degree of downsizing. To provide insight into the effect of downsizing, we studied the annulus of healthy sheep during suture annuloplasty. To this end, we implanted fiduciary markers along the annulus of sheep and subsequently performed a DeVega suture annuloplasty. We performed five downsizing steps in each animal while recording hemodynamic and sonomicrometry data in beating hearts. Subsequently, we used splines to approximate the annulus at baseline and at each downsizing step. Based on these approximations we computed clinical metrics of annular shape and dynamics, and the continuous field metrics height, strain, and curvature. With these data, we demonstrated that annular area reduction during downsizing was primarily driven by compression of the anterior annulus. Similarly, reduction in annular dynamics was driven by reduced contractility in the anterior annulus. Finally, changes in global height and eccentricity of the annulus could be explained by focal changes in the continuous height profile and changes in annular curvature. Our findings are important as they provide insight into a regularly performed surgical procedure and may inform the design of transcatheter devices that mimic suture annuloplasty.

Biomechanics of the Tricuspid Annulus: A Review of the Annulus' In Vivo Dynamics With Emphasis on Ovine Data.

The tricuspid annulus forms the boundary between the tricuspid valve leaflets and their surrounding perivalvular tissue of the right atrioventricular junction. Its shape changes throughout the cardiac cycle in response to the forces from the contracting right heart myocardium and the blood-valve interaction. Alterations to annular shape and dynamics in disease lead to valvular dysfunctions such as tricuspid regurgitation from which millions of patients suffer. Successful treatment of such dysfunction requires an in-depth understanding of the normal shape and dynamics of the tricuspid annulus and of the changes following disease and subsequent repair. In this manuscript we review what we know about the shape and dynamics of the normal tricuspid annulus and about the effects of both disease and repair based on non-invasive imaging studies and invasive fiduciary marker-based studies. We further show, by means of ovine data, that detailed engineering analyses of the tricuspid annulus provide regionally-resolved insight into the kinematics of the annulus which would remain hidden if limiting analyses to simple geometric metrics.