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Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections. However, the sections are cut transmurally and provide a lateral view of the microstructure of the leaflet, while the mechanics and function are determined by the planar arrangement of the collagen fibers. This study, for the first time, quantitatively examined planar collagen distribution quantitatively in health and disease using second harmonic generation microscopy throughout the thickness of the mitral valve leaflets. Twenty diseased samples from eighteen patients and six control samples were included in this study. Healthy tissue had highly aligned collagen fibers. In fibroelastic deficiency they are less aligned and in Barlow's disease they are completely dispersed. In both diseases, collagen fibers have two preferred orientations, which, in contrast to the almost constant one orientation in healthy tissues, also vary across the thickness. The results indicate altered in vivo mechanical stresses and strains on the mitral valve leaflets as a result of disease-related collagen remodeling, which in turn triggers further remodeling., (© 2024. The Author(s).)

Collagen fibers are the main load carrier in the mitral valve (MV) leaflets. Their orientation and dispersion are an important factor for the mechanical behavior. Most recent studies of collagen fibers in MVs lack either entire thickness study or high transmural resolution. The present study uses second harmonic generation (SHG) microscopy in combination with planar biaxial mechanical tests to better model and examine collagen fibers and mechanical properties of MV leaflets. SHG in combination with tissue clearing enables the collagen fibers to be examined through the entire thickness of the MV leaflets. Planar biaxial mechanical tests, on the other hand, enable the characterization of the mechanical tissue behavior, which is represented by a structural tissue model. Twelve porcine MV leaflets are examined. The SHG recording shows that the mean fiber angle for all samples varies on average by ±12° over the entire thickness and the collagen fiber dispersion changes strongly over the thickness. A constitutive model based on the generalized structure tensor approach is used for the associated tissue characterization. The model represents the tissue with three mechanical parameters plus the mean fiber direction and the dispersion, and predicts the biomechanical response of the leaflets with a good agreement (average r 2 =0.94). It is found that the collagen structure can be represented by a mean direction and a dispersion with a single family of fibers despite the variation in the collagen fiber direction and the dispersion over the entire thickness of MV leaflets. STATEMENT OF SIGNIFICANCE: Despite its prominent role in the mechanical behavior of mitral valve (MV) leaflets, the collagen structure has not yet been investigated over the entire thickness with high transmural resolution. The present study quantifies the detailed through thickness collagen fiber structure and examines the effects of its variation on MV tissue modeling. This is important because the study evaluates the assumption that the collagen fibers can be modeled with a representative single fiber family despite the variation across the thickness. In addition, the current comprehensive data set paves the way for quantifying the disruption of collagen fibers in myxomatous MV leaflets associated with disrupted collagen fibers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The present study addresses the contributions of prestrains and muscle fiber activation to the global response of the mitral valve during systole. A finite element model of a porcine mitral valve is created using anatomical measurements and 3D echocardiographic recordings. The passive behavior of the leaflets is modeled using a transversely isotropic hyperelastic constitutive model, and we assume orthotropic muscle activations in the anterior leaflet. A simple approach to incorporate prestrains in the mitral valve apparatus is used by expanding the mitral annulus before applying the ventricular pressure to the mitral leaflets. Several finite element analyses are run with or without muscle activation and with or without prestrains. The analysis results are compared at peak systole with the echocardiograpic recordings. The case where prestrains and activation are accounted for simultaneously is the most efficient to approach the physiological flat shape of the closed valve observed in the echocardiograpic measurements. These results suggest that the active components present in the mitral leaflets and the presence of prestrains contribute to the physiological deformations of the mitral valve at peak systole and that material models based on in vitro mechanical testing are not sufficient for numerical studies of the mitral apparatus. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

The mitral valve is increasingly been regarded as having dynamic and contractile capabilities, but the presence of muscle in the valve has been investigated to a limited extent. The aim of this study was to investigate the presence, architecture and phenotype of muscle in the human mitral valve. Twelve mitral valves were cut into strips, sectioned for histology, and the cut edges examined by microscope after staining included immunophenotyping. Smooth muscle bundles were present at the atrial side of the leaflets, and distinctly more in the anterior leaflet than in the posterior leaflet. The smooth muscle bundles extended up to two-thirds the distance from the annulus to the rim of the leaflets, and they ran in various directions, but seemingly mainly perpendicular to the annulus. The thickness and density of the bundles seemed to decrease with the distance from the annulus, and also in a radial direction from the centre portion of each leaflets attachment at the annulus towards the rim. Cross striation was not detected. Cardiac muscle in the left atrial wall extended into the annular base of the leaflets in close proximity to the annular border of the smooth muscle bundles in the leaflets. In conclusion, especially the anterior leaflet of the mitral valve seems to have a separate smooth muscle formed as a meshwork of bundles close to the atrial surface., (© 2012 The Authors. APMIS © 2012 APMIS.)

In this article, we present a fluid-structure interaction algorithm accounting for the mutual interaction between two rigid bodies. The algorithm was used to perform a numerical simulation of mitral valve (MV) dynamics during diastolic filling. In numerical simulations of intraventricular flow and MV motion, the asymmetry of the leaflets is often neglected. In this study the MV was rendered as two rigid, asymmetric leaflets. The 2D simulations incorporated the dynamic interaction of blood flow and leaflet motion and an imposed subject-specific, transient left ventricular wall movement obtained from ultrasound recordings. By including the full Jacobian matrix in the algorithm, the speed of the simulation was enhanced by more than 20% compared to using a diagonal Jacobian matrix. Furthermore, our results indicate that important features of the flow field may not be predicted by the use of symmetric leaflets or in the absence of an adequate model for the left atrium.

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.

Biomechanical data and related constitutive modelling of the mitral apparatus served as a basis for finite element analyses to better understand the physiology of mitral valves in health and disease. Human anterior and posterior leaflets and chordae tendinae from an elderly heart showing no disease and a hypertrophic obstructive cardiomyopathic heart (HOCM) were mechanically tested by means of uniaxial cyclic extension tests under quasi-static conditions. Experimental data for the leaflets and the chordae tendinae showed highly nonlinear mechanical behaviours and the leaflets were anisotropic. The mitral valve from the HOCM heart exhibited a significantly softer behaviour than the valve from the healthy one. A comparison with porcine data was included because many previous mitral modelling studies have been based on porcine data. Some differences in mechanical response were observed. Material parameters for hyperelastic, transversely isotropic constitutive laws were determined. The experimental data and the related model parameters were used in two finite element studies to investigate the effects of the material properties on the mitral valve response during systole. The analyses showed that during systole the mitral valve from the HOCM heart bulged into the left atrium by taking on the shape of a balloon, whereas the anterior leaflet of the healthy valve remained in the left ventricle., (Copyright 2009 Elsevier Ltd. All rights reserved.)

This study presents a three-dimensional finite element model of the mitral apparatus using a hyperelastic transversely isotropic material model for the leaflets. The objectives of this study are to illustrate the effects of the annulus shape on the chordal force distribution and on the mitral valve response during systole, to investigate the role of the anterior secondary (strut) chordae and to study the influence of thickness of the leaflets on the leaflets stresses. Hence, analyses are conducted with a moving and fixed saddle shaped annulus and with and without anterior secondary chordae. We found that the tension in the secondary chordae represents 31% of the load carried by the papillary muscles. When removing the anterior secondary chordae, the tension in the primary anterior chordae is almost doubled, the displacement of the anterior leaflet toward the left atrium is also increased. The moving annulus configuration with an increasing annulus saddle height does not give significant changes in the chordal force distribution and in the leaflet stress compared to the fixed annulus. The results also show that the maximum principle stresses in the anterior leaflet are carried by the collagen fibers. The stresses calculated in the leaflets are very sensitive to the thickness employed.