Euclidean and Shape-Based Analysis of the Dynamic Mitral Annulus in Children using a Novel Open-Source Framework.

BACKGROUND: The dynamic shape of the normal adult mitral annulus has been shown to be important to mitral valve function. However, annular dynamics of the healthy mitral valve in children have yet to be explored. The aim of this study was to model and quantify the shape and major modes of variation of pediatric mitral valve annuli in four phases of the cardiac cycle using transthoracic echocardiography. METHODS: The mitral valve annuli of 100 children and young adults with normal findings on three-dimensional echocardiography were modeled in four different cardiac phases using the SlicerHeart extension for 3D Slicer. Annular metrics were quantified using SlicerHeart, and optimal normalization to body surface area was explored. Mean annular shapes and the principal components of variation were computed using custom code implemented in a new SlicerHeart module (Annulus Shape Analyzer). Shape was regressed over metrics of age and body surface area, and mean shapes for five age-stratified groups were generated. RESULTS: The ratio of annular height to commissural width of the mitral valve ("saddle shape") changed significantly throughout age for systolic phases (P < .001) but within a narrow range (median range, 0.20-0.25). Annular metrics changed statistically significantly between the diastolic and systolic phases of the cardiac cycle. Visually, the annular shape was maintained with respect to age and body surface area. Principal-component analysis revealed that the pediatric mitral annulus varies primarily in size (mode 1), ratio of annular height to commissural width (mode 2), and sphericity (mode 3). CONCLUSIONS: The saddle-shaped mitral annulus is maintained throughout childhood but varies significantly throughout the cardiac cycle. The major modes of variation in the pediatric mitral annulus are due to size, ratio of annular height to commissural width, and sphericity. The generation of age- and size-specific mitral annular shapes may inform the development of appropriately scaled absorbable or expandable mitral annuloplasty rings for children.

Introduction of transcatheter edge-to-edge repair in patients with congenital heart disease at a children's hospital.

BACKGROUND: Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle physiology. Transcatheter edge-to-edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR in adults that avoids the morbidity and mortality associated with open heart surgery. However, application of TEER in in CHD and in children is quite novel. We describe the development of a peri-procedural protocol including image-derived pre-intervention simulation, with successful application to four patients. AIMS: To describe the initial experience using the MitraClip system for TEER of dysfunctional systemic atrioventricular valves in patients with congential heart disease within a pediatric hospital. METHODS: A standardized screening and planning process was developed using cardiac magnetic resonance imaging, three dimensional echocardiography and both virtual and physical simulation. Procedures were performed using the MitraClip G4 system and patients were clinically followed post-intervention. RESULTS: A series of four CHD patients with at least severe AVVR were screened for suitability for TEER with the MitraClip system: three patients had single ventricle physiology and Fontan palliation, and one had repair of a common atrioventricular canal defect. Each patient had at least severe systemic AVVR and was considered at prohibitively high risk for surgical repair. Each patient underwent a standardized preprocedural screening protocol and image-derived modeling followed by the TEER procedure with successful clip placement at the intended location in all cases. CONCLUSIONS: The early results of our protocolized efforts to introduce TEER repair of severe AV valve regurgitation with MitraClip into the CHD population within our institution are encouraging. Further investigations of the use of TEER in this challenging population are warranted.

3-Dimensional Modeling Guided Transcatheter Repair of Dehisced Pulmonary Venous Baffle With Gore ASD Device.

A 38-year-old woman with sinus venosus atrial septal defect and partial anomalous return of the right upper pulmonary vein underwent a Warden procedure but experienced a large residual defect after patch dehiscence. Image-derived 3D modeling informed novel device closure with a Gore Cardioform atrial septal occluder. (Level of Difficulty: Advanced.).

Hierarchical Geodesic Polynomial Model for Multilevel Analysis of Longitudinal Shape.

Longitudinal analysis is a core aspect of many medical applications for understanding the relationship between an anatomical subject's function and its trajectory of shape change over time. Whereas mixed-effects (or hierarchical) modeling is the statistical method of choice for analysis of longitudinal data, we here propose its extension as hierarchical geodesic polynomial model (HGPM) for multilevel analyses of longitudinal shape data. 3D shapes are transformed to a non-Euclidean shape space for regression analysis using geodesics on a high dimensional Riemannian manifold. At the subject-wise level, each individual trajectory of shape change is represented by a univariate geodesic polynomial model on timestamps. At the population level, multivariate polynomial expansion is applied to uni/multivariate geodesic polynomial models for both anchor points and tangent vectors. As such, the trajectory of an individual subject's shape changes over time can be modeled accurately with a reduced number of parameters, and population-level effects from multiple covariates on trajectories can be well captured. The implemented HGPM is validated on synthetic examples of points on a unit 3D sphere. Further tests on clinical 4D right ventricular data show that HGPM is capable of capturing observable effects on shapes attributed to changes in covariates, which are consistent with qualitative clinical evaluations. HGPM demonstrates its effectiveness in modeling shape changes at both subject-wise and population levels, which is promising for future studies of the relationship between shape changes over time and the level of dysfunction severity on anatomical objects associated with disease.

The effects of leaflet material properties on the simulated function of regurgitant mitral valves.

Advances in three-dimensional imaging provide the ability to construct and analyze finite element (FE) models to evaluate the biomechanical behavior and function of atrioventricular valves. However, while obtaining patient-specific valve geometry is now possible, non-invasive measurement of patient-specific leaflet material properties remains nearly impossible. Both valve geometry and tissue properties play a significant role in governing valve dynamics, leading to the central question of whether clinically relevant insights can be attained from FE analysis of atrioventricular valves without precise knowledge of tissue properties. As such we investigated (1) the influence of tissue extensibility and (2) the effects of constitutive model parameters and leaflet thickness on simulated valve function and mechanics. We compared metrics of valve function (e.g., leaflet coaptation and regurgitant orifice area) and mechanics (e.g., stress and strain) across one normal and three regurgitant mitral valve (MV) models with common mechanisms of regurgitation (annular dilation, leaflet prolapse, leaflet tethering) of both moderate and severe degree. We developed a novel fully-automated approach to accurately quantify regurgitant orifice areas of complex valve geometries. We found that the relative ordering of the mechanical and functional metrics was maintained across a group of valves using material properties up to 15% softer than the representative adult mitral constitutive model. Our findings suggest that FE simulations can be used to qualitatively compare how differences and alterations in valve structure affect relative atrioventricular valve function even in populations where material properties are not precisely known.

Physical Simulation of Transcatheter Edge-to-Edge Repair using Image-Derived 3D Printed Heart Models.

Background: Transcatheter edge-to-edge valve repair (TEER) is a complex procedure requiring delivery and alignment of the device to the target valve, which can be challenging in atypical or surgically palliated anatomy. We demonstrate application of virtual and physical simulation to plan optimal TEER access and catheter path in normal and congenitally abnormal cardiac anatomy. Methods: Three heart models were created from three-dimensional (3D) images and 3D printed, including two with congenital heart disease. TEER catheter course was simulated both virtually and physically using a commercial TEER system. Results: We demonstrate application of modeling in three patients, including two with congenital heart disease and a Fontan circulation. Access site and pathway to device delivery was simulated by members of a multidisciplinary valve team. Virtual and physical simulation were compared. Conclusions: Virtual and physical simulation of TEER using 3D printed heart models is feasible and may be beneficial for planning and simulation, particularly in patients with complex anatomy. Future work is required to demonstrate application in the clinical setting.

Modeling of the Tricuspid Valve and Right Ventricle in Hypoplastic Left Heart Syndrome With a Fontan Circulation.

BACKGROUND: In hypoplastic left heart syndrome, tricuspid regurgitation (TR) is associated with circulatory failure and death. We hypothesized that the tricuspid valve (TV) structure of patients with hypoplastic left heart syndrome with a Fontan circulation and moderate or greater TR differs from those with mild or less TR, and that right ventricle volume is associated with TV structure and dysfunction. METHODS: TV of 100 patients with hypoplastic left heart syndrome and a Fontan circulation were modeled using transthoracic 3-dimensional echocardiograms and custom software in SlicerHeart. Associations of TV structure to TR grade and right ventricle function and volume were investigated. Shape parameterization and analysis was used to calculate the mean shape of the TV leaflets, their principal modes of variation, and to characterize associations of TV leaflet shape to TR. RESULTS: In univariate modeling, patients with moderate or greater TR had larger TV annular diameters and area, greater annular distance between the anteroseptal commissure and anteroposterior commissure, greater leaflet billow volume, and more laterally directed anterior papillary muscle angles compared to valves with mild or less TR (all P<0.001). In multivariate modeling greater total billow volume, lower anterior papillary muscle angle, and greater distance between the anteroposterior commissure and anteroseptal commissure were associated with moderate or greater TR (P<0.001, C statistic=0.85). Larger right ventricle volumes were associated with moderate or greater TR (P<0.001). TV shape analysis revealed structural features associated with TR, but also highly heterogeneous TV leaflet structure. CONCLUSIONS: Moderate or greater TR in patients with hypoplastic left heart syndrome with a Fontan circulation is associated with greater leaflet billow volume, a more laterally directed anterior papillary muscle angle, and greater annular distance between the anteroseptal commissure and anteroposterior commissure. However, there is significant heterogeneity of structure in the TV leaflets in regurgitant valves. Given this variability, an image-informed patient-specific approach to surgical planning may be needed to achieve optimal outcomes in this vulnerable and challenging population.

The Effects of leaflet material properties on the simulated function of regurgitant mitral valves.

Advances in three-dimensional imaging provide the ability to construct and analyze finite element (FE) models to evaluate the biomechanical behavior and function of atrioventricular valves. However, while obtaining patient-specific valve geometry is now possible, non-invasive measurement of patient-specific leaflet material properties remains nearly impossible. Both valve geometry and tissue properties play a significant role in governing valve dynamics, leading to the central question of whether clinically relevant insights can be attained from FE analysis of atrioventricular valves without precise knowledge of tissue properties. As such we investigated 1) the influence of tissue extensibility and 2) the effects of constitutive model parameters and leaflet thickness on simulated valve function and mechanics. We compared metrics of valve function (e.g., leaflet coaptation and regurgitant orifice area) and mechanics (e.g., stress and strain) across one normal and three regurgitant mitral valve (MV) models with common mechanisms of regurgitation (annular dilation, leaflet prolapse, leaflet tethering) of both moderate and severe degree. We developed a novel fully-automated approach to accurately quantify regurgitant orifice areas of complex valve geometries. We found that the relative ordering of the mechanical and functional metrics was maintained across a group of valves using material properties up to 15% softer than the representative adult mitral constitutive model. Our findings suggest that FE simulations can be used to qualitatively compare how differences and alterations in valve structure affect relative atrioventricular valve function even in populations where material properties are not precisely known.

A Computational Framework for Atrioventricular Valve Modeling Using Open-Source Software.

Atrioventricular valve regurgitation is a significant cause of morbidity and mortality in patients with acquired and congenital cardiac valve disease. Image-derived computational modeling of atrioventricular valves has advanced substantially over the last decade and holds particular promise to inform valve repair in small and heterogeneous populations, which are less likely to be optimized through empiric clinical application. While an abundance of computational biomechanics studies has investigated mitral and tricuspid valve disease in adults, few studies have investigated its application to vulnerable pediatric and congenital heart populations. Further, to date, investigators have primarily relied upon a series of commercial applications that are neither designed for image-derived modeling of cardiac valves nor freely available to facilitate transparent and reproducible valve science. To address this deficiency, we aimed to build an open-source computational framework for the image-derived biomechanical analysis of atrioventricular valves. In the present work, we integrated an open-source valve modeling platform, SlicerHeart, and an open-source biomechanics finite element modeling software, FEBio, to facilitate image-derived atrioventricular valve model creation and finite element analysis. We present a detailed verification and sensitivity analysis to demonstrate the fidelity of this modeling in application to three-dimensional echocardiography-derived pediatric mitral and tricuspid valve models. Our analyses achieved an excellent agreement with those reported in the literature. As such, this evolving computational framework offers a promising initial foundation for future development and investigation of valve mechanics, in particular collaborative efforts targeting the development of improved repairs for children with congenital heart disease.

Skeletal model-based analysis of the tricuspid valve in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease characterized by incomplete development of the left heart. Children with HLHS undergo a series of operations which result in the tricuspid valve (TV) becoming the only functional atrioventricular valve. Many HLHS patients develop tricuspid regurgitation and right ventricle enlargement which is associated with heart failure and death without surgical intervention on the valve. Understanding the connections between the geometry of the TV and its function remains extremely challenging and hinders TV repair planning. Traditional analysis methods rely on simple anatomical measures which do not capture information about valve geometry in detail. Recently, surface-based shape representations such as SPHARM-PDM have been shown to be useful for tasks such as discriminating between valves with normal or poor function. In this work we propose to use skeletal representations (s-reps), a more feature-rich geometric representation, for modeling the leaflets of the tricuspid valve. We propose an extension to previous s-rep fitting approaches to incorporate application-specific anatomical landmarks and population information to improve correspondence. We use several traditional statistical shape analysis techniques to evaluate the efficiency of this representation: using principal component analysis (PCA) we observe that it takes fewer modes of variation compared to boundary-based approaches to represent 90% of the population variation, while distance-weighted discrimination (DWD) shows that s-reps provide for more significant classification between valves with less regurgitation and those with more. These results show the power of using s-reps for modeling the relationship between structure and function of the tricuspid valve.