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Chordae tendineae, referred to as heart tendinous cords, act as tendons connecting the papillary muscles to the valves in the heart. Their role is analogous to tendons in the musculoskeletal system. Despite being exposed to millions of cyclic tensile stretches over a human's lifetime, chordae tendineae rarely suffer from overuse injuries. On the other hand, musculoskeletal tendinopathy is very common and remains challenging in clinical treatment. The objective of this study was to investigate the mechanism behind the remarkable durability and resistance to overuse injuries of chordae tendineae, as well as to explore their effects on flexor tenocyte biology. The messenger RNA expression profiles of chordae tendineae were analyzed using RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction  and immunohistochemistry. Interestingly, we found that periostin (Postn) and fibroblast growth factor 7 (FGF7) were expressed at significantly higher levels in chordae tendineae, compared to flexor tendons. We further treated flexor tenocytes in vitro with periostin and FGF7 to examine their effects on the proliferation, migration, apoptosis, and tendon-related gene expression of flexor tenocytes. The results displayed enhanced cell proliferation ability at an early stage and an antiapoptotic effect on tenocytes, while treated with periostin and/or FGF7 proteins. Furthermore, there was a trend of promoted tenocyte migration capability. These findings indicated that Postn and FGF7 may represent novel cytokines to target flexor tendon healing. Clinical significance: The preliminary discovery leads to a novel idea for treating tendinopathy in the musculoskeletal system using specific molecules identified from chordae tendineae., (© 2023 Orthopaedic Research Society.)

This study aimed to provide comparative anatomical data on the mitral valve and to substantiate the choice between large species for pre-clinical testing of cardiac devices. Different anatomical parameters of the anterior and posterior leaflets, chordae and papillary muscles were measured to characterize the anatomy of the mitral valve in 10 individuals for each four species. Ratios were calculated and used to circumvent the interspecies variations of body and heart size and weight. The results underline many relevant anatomical similarities and differences between man and the three animal species. We confirm that the porcine species is a better model based on anatomical measurements. But many parameters should be considered depending on the shape, size and purpose of the device. The mitral and aortic valve are closer than in man leading to potential damage of the aortic valve by a mitral device. The ovine mitral annulus is more flattened and would sustain more mechanical forces on a round-shaped stent. The anterior and posterior leaflets have comparable height in the animal species leading to more space for implantation. The porcine valve has more chordae allowing less space around the valve for a transcatheter stent. Our observations introduce new comparative data in the perspective of the choice of a large animal model for pre-clinical testing of mitral devices. They are very helpful for all cardiologists, surgeons or engineers who need to understand the reasons for success or failure of a device and to have key elements of discussion., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Atrioventricular heart valves (AHVs) regulate the unidirectional flow of blood through the heart by opening and closing of the leaflets, which are supported in their functions by the chordae tendineae (CT). The leaflets and CT are primarily composed of collagen fibers that act as the load-bearing component of the tissue microstructures. At the CT-leaflet insertion, the collagen fiber architecture is complex, and has been of increasing focus in the previous literature. However, these previous studies have not been able to quantify the load-dependent changes in the tissue's collagen fiber orientations and alignments. In the present study, we address this gap in knowledge by quantifying the changes in the collagen fiber architecture of the mitral and tricuspid valve's strut CT-leaflet insertions in response to the applied loads by using a unique approach, which combines polarized spatial frequency domain imaging with uniaxial mechanical testing. Additionally, we characterized these microstructural changes across the same specimen without the need for tissue fixatives. We observed increases in the collagen fiber alignments in the CT-leaflet insertion with increased loading, as described through the degree of optical anisotropy. Furthermore, we used a leaflet-CT-papillary muscle entity method during uniaxial testing to quantify the chordae tendineae mechanics, including the derivation of the Ogden-type constitutive modeling parameters. The results from this study provide a valuable insight into the load-dependent behaviors of the strut CT-leaflet insertion, offering a research avenue to better understand the relationship between tissue mechanics and the microstructure, which will contribute to a deeper understanding of AHV biomechanics.

Surgical simulators and injury-prediction human models require a combination of representative tissue geometry and accurate tissue material properties to predict realistic tool-tissue interaction forces and injury mechanisms, respectively. While biological tissues have been individually characterized, the transition regions between tissues have received limited research attention, potentially resulting in inaccuracies within simulations. In this work, an approach to characterize the transition regions in transversely isotropic (TI) soft tissues using functionally graded material (FGM) modeling is presented. The effect of nonlinearities and multi-regime nature of the TI model on the functional grading process is discussed. The proposed approach has been implemented to characterize the transition regions in the leaflet (LL), chordae tendinae (CT) and the papillary muscle (PM) of porcine tricuspid valve (TV) and mitral valve (MV). The FGM model is informed using high resolution morphological measurements of the collagen fiber orientation and tissue composition in the transition regions, and deformation characteristics predicted by the FGM model are numerically validated to experimental data using X-ray diffraction imaging. The results indicate feasibility of using the FGM approach in modeling soft-tissue transitions and has implications in improving physical representation of tissue deformation throughout the body using a scalable version of the proposed approach.

Proper blood flow through the atrioventricular heart valves (AHVs) relies on the holistic function of the valve and subvalvular structures, and a failure of any component can lead to life-threatening heart disease. A comprehension of the mechanical characteristics of healthy valvular components is necessary for the refinement of heart valve computational models. In previous studies, the chordae tendineae have been mechanically characterized as individual structures, usually in a clamping-based approach, which may not accurately reflect the in vivo chordal interactions with the leaflet insertion and papillary muscles. In this study, we performed uniaxial mechanical testing of strut chordae tendineae of the AHVs under a unique tine-based leaflet-chordae-papillary muscle testing to observe the chordae mechanics while preserving the subvalvular component interactions. Results of this study provided insight to the disparity of chordae tissue stress-stretch responses between the mitral valve (MV) and the tricuspid valve (TV) under their respective emulated physiological loading. Specifically, strut chordae tendineae of the MV anterior leaflet had peak stretches of 1.09-1.16, while peak stretches of 1.08-1.11 were found for the TV anterior leaflet strut chordae. Constitutive parameters were also derived for the chordae tissue specimens using an Ogden model, which is useful for AHV computational model refinement. Results of this study are beneficial to the eventual improvement of treatment methods for valvular disease.

Few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker-based strain measurements can be performed, but chordal geometry and restricted optical access are limitations. Foil-based strain sensors have been described and work well, but the sensor footprint limits the number of chordae that can be measured. We instead utilized fiber Bragg grating (FBG) sensors-optical strain gauges made of 125 μm diameter silica fibers-to overcome some limitations of previous methods of measuring chordae tendineae forces. Using FBG sensors, we created a force-sensing neochord (FSN) that mimics the natural shape and movement of native chordae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings. When force is applied, the gratings move relative to one another, shifting the wavelength of reflected light. This shift is directly proportional to force applied. The FBG sensors were housed in a protective sheath fashioned from a 0.025 in. flat coil, and attached to the chordae using polytetrafluoroethylene suture. The function of the force-sensing neochordae was validated in a three-dimensional (3D)-printed left heart simulator, which demonstrated that FBG sensors provide highly sensitive force measurements of mitral valve chordae at a temporal resolution of 1000 Hz. As ventricular pressures increased, such as in hypertension, chordae forces also increased. Overall, FBG sensors are a viable, durable, and high-fidelity sensing technology that can be effectively used to measure mitral valve chordae forces and overcome some limitations of other such technologies.

Background: Neochordoplasty is an important repair technique, but optimal anchoring position is unknown. Although typically anchored at papillary muscles, new percutaneous devices anchor the neochordae at or near the ventricular apex, which may have an effect on chordal forces and the long-term durability of the repair., Methods: Porcine mitral valves (n = 6) were mounted in a left heart simulator that generates physiologic pressure and flow through the valves, and chordal forces were measured with Fiber Bragg Grating strain gauge sensors. Isolated mitral regurgitation was induced by cutting P2 primary chordae, and the regurgitant valve was repaired with polytetrafluoroethylene neochord with apical anchoring, followed by papillary muscle fixation for comparison. In both situations, the neochord was anchored to a customized force-sensing post positioned to mimic the relevant in vivo placement., Results: Echocardiographic and hemodynamic data confirmed that the repairs restored physiologic hemodynamics. Forces on the chordae and neochord were lower for papillary fixation than for the apical fixation (p = 0.003). In addition, the maximum rate of change of force on the chordae and neochordae was higher for apical fixation than for papillary fixation (p = 0.028)., Conclusions: Apical neochord anchoring results in effective repair of mitral regurgitation, albeit with somewhat higher forces on the chordae and neochord suture, as well as an increased rate of loading on the neochord compared with the papillary muscle fixation. These results may guide strategies to reduce stresses on neochordae as well as aid optimal patient selection., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Healthy function of tricuspid valve (TV) structures is essential to avoid tricuspid regurgitation (TR) and may significantly improve disease prognosis. Mitral valve (MV) structures have been extensively studied, but little is known about the TV and right-sided heart diseases. Therefore, clinical decisions and finite element (FE) simulations often rely heavily on MV data for TV applications, despite fundamentally different mechanical and physiological environments., Method/results: To bridge this gap, we performed a rigorous mechanical, morphological, and microstructural characterization of the MV and TV leaflets and chordae in a porcine model. Planar biaxial testing, uniaxial testing, second harmonic generation imaging and Verhoeff Van Gieson staining were performed. Morphological parameters, tissue moduli, extensibility, and anisotropy were quantified and compared. No major differences in leaflet mechanics or structure were found between TV and MV; chordal mechanics, morphology, and structure were found to compensate for anatomical and physiological loading differences between the valves. No differences in chordal mechanics were observed by insertion point within a leaflet; the septal tricuspid leaflet (STL) and posterior mitral leaflet (PML) did not have distinguishable strut chords, and the STL had the shortest chords. Within a valve, chords from septally-located leaflets were more extensible. MV chords were stiffer., Conclusions: This study presents the first rigorous comparative mechanical and structural dataset of MV and TV structures. Valve type and anatomical location may be stronger predictors of chordal mechanics. Chords from septally-located leaflets differ from each other and from their intravalvular counterparts; they merit special consideration in surgical and computational applications., Statement of Significance: A better understanding of the tricuspid valve (TV) and its associated structures is important for making advancements towards the repair of tricuspid regurgitation. Mitral valve structures have been extensively studied, but little is known about the TV and right-sided heart diseases. Clinical decisions and computational simulations often rely heavily on MV data for TV applications, despite fundamentally different environments. We therefore performed a rigorous mechanical, morphological, and microstructural characterization of atrioventricular leaflets and chordae tendineae in a porcine model. Finding that valve type and anatomical location may be strong predictors of chordal mechanics, chords from septally-located leaflets differ from each other and from their intravalvular counterparts; they merit special consideration in surgical and computational applications., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this paper a computational model for the ventricular flow with a mitral valve and modeled chordae tendineae is presented. The results are compared with an analogous case in which the chordae are not included and their presence is replaced by kinematic boundary conditions. The problem is studied using direct numerical simulation of the Navier-Stokes equations, two-way coupled with a structural solver for the ventricle and mitral valve dynamics. An experimental validation of the model is performed by a comparison of the results with a companion dedicated experiment. It is found that the inclusion of the chordae tendineae makes the model self-consistent thus avoiding the use of ad hoc kinematic constraints to mimic their effect. In this way it is possible to simulate the correct system dynamics without user-defined parameters. More in detail, the results have shown that the mitral valve dynamics can be described also without chordae with the help of ad hoc kinematic constrains, whereas the changes produced in the intra-ventricular flow need the explicit consideration of the chordae in the model. On the other hand, the computational load increases owing to the presence of additional structures that, being thin filaments, are also demanding for the spatial resolution requirements. Since the presence of the chordae tendineae produces only specific differences in the overall flow structure, we conclude that their explicit modeling should be limited to those cases in which their presence is unavoidable.

Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be 'invisible' to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid-structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid-structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

The mitral valve (MV) is a highly complex cardiac valve consisting of an annulus, anterior and posterior leaflets, chordae tendineae (chords) and two papillary muscles. The chordae tendineae mechanics play a pivotal role in proper MV function: the chords help maintain proper leaflet coaptation and rupture of the chordae tendineae due to disease or aging can lead to mitral valve insufficiency. Therefore, the aim of this study was to characterize the mechanical properties of aged human and ovine mitral chordae tendineae. The human and ovine chordal specimens were categorized by insertion location (i.e., marginal, basal and strut) and leaflet type (i.e., anterior and posterior). The results show that human and ovine chords of differing types vary largely in size but do not have significantly different elastic and failure properties. The excess fibrous tissue layers surrounding the central core of human chords added thickness to the chords but did not contribute to the overall strength of the chords. In general, the thinner marginal chords were stiffer than the thicker basal and strut chords, and the anterior chords were stiffer and weaker than the posterior chords. The human chords of all types were significantly stiffer than the corresponding ovine chords and exhibited much lower failure strains. These findings can be explained by the diminished crimp pattern of collagen fibers of the human mitral chords observed histologically. Moreover, the mechanical testing data was modeled with the nonlinear hyperelastic Ogden strain energy function to facilitate accurate computational modeling of the human MV., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate the regional and directional differences in the biomechanics and histoarchitecture of the porcine mitral valve (MV) apparatus, with a view to tailoring tissue-engineered constructs for MV repair. The anterior leaflet displayed the largest directional anisotropy with significantly higher strength in the circumferential direction compared to the posterior leaflet. The histological results indicated that this was due to the circumferential alignment of the collagen fibers. The posterior leaflet demonstrated no significant directional anisotropy in the mechanical properties, and there was no significant directionality of the collagen fibers in the main body of the leaflet. The thinner commissural chordae were found to be significantly stiffer and less extensible than the strut chordae. Histological staining demonstrated a tighter knit of the collagen fibers in the commissural chordae than the strut chordae. By elucidating the inhomogeneity of the histoarchitecture and biomechanics of the MV apparatus, the results from this study will aid the regional differentiation of MV repair strategies, with tailored mitral-component-specific biomaterials or tissue-engineered constructs., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

In cases of severely diseased mitral valves (MV), the required treatment is often valve replacement. Bioprosthetic and stentless replacement valves are usually either fully or partially composed of animal derived tissue treated with a decellularization process, a cross-linking process, or both. In this study, we analysed the effects of these treatments on the fatigue properties of porcine MV chordae tendineae (CT), as well as on the calcification of the CT using an in vitro technique. CT were tested in 4 groups; (1) native, (2) decellularized (DC), (3) decellularized and cross-linked with glutaraldehyde (DC-GTH), and (4) decellularized and cross-linked with 1-ehtyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)(DC-EDC). CT were tested in both uniaxial tension, and in fatigue at 10MPa peak stress (1Hz). The cycles to failure (mean±SD) for the four groups are as follows; Native- 53,397±55,798, DC- 28,013±30,634, DC-GTH- 97,665±133,556, DC-EDC- 318,601±322,358. DC-EDC CT were found to have a slightly longer fatigue life than the native and DC groups. The DC-EDC group also had a marginally lower dynamic creep rate, meaning those CT elongate more slowly. After in vitro calcification, X-ray microtomography was used to determine relative levels of calcification. The DC-EDC and DC-GTH groups had the lowest volume of calcific deposits. Under uniaxial testing, the ultimate tensile strength (UTS) of the DC-GTH CT was statistically significantly reduced after calcification, while the UTS was relatively unchanged for the DC-EDC group. Overall, these results indicate that a treatment of decellularization plus cross-linking with EDC may improve the fatigue life of porcine CT, reduce the rate of elongation, and help the CT resist the negative effects of calcification. This may be a preferable treatment in the preparation of porcine MVs for the replacement of diseased MVs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Numerical models of native heart valves are being used to study valve biomechanics to aid design and development of repair procedures and replacement devices. These models have evolved from simple two-dimensional approximations to complex three-dimensional, fully coupled fluid-structure interaction (FSI) systems. Such simulations are useful for predicting the mechanical and hemodynamic loading on implanted valve devices. A current challenge for improving the accuracy of these predictions is choosing and implementing modeling boundary conditions. In order to address this challenge, we are utilizing an advanced in vitro system to validate FSI conditions for the mitral valve system. Explanted ovine mitral valves were mounted in an in vitro setup, and structural data for the mitral valve was acquired with [Formula: see text]CT. Experimental data from the in vitro ovine mitral valve system were used to validate the computational model. As the valve closes, the hemodynamic data, high speed leaflet dynamics, and force vectors from the in vitro system were compared to the results of the FSI simulation computational model. The total force of 2.6 N per papillary muscle is matched by the computational model. In vitro and in vivo force measurements enable validating and adjusting material parameters to improve the accuracy of computational models. The simulations can then be used to answer questions that are otherwise not possible to investigate experimentally. This work is important to maximize the validity of computational models of not just the mitral valve, but any biomechanical aspect using computational simulation in designing medical devices.

A number of studies have investigated the morphological and mechanical properties of the chordae tendineae of the mitral valve, providing comparisons between basal, marginal, and strut chordae and between chordae at the anterior and posterior leaflets. This study contributes to the literature by comparing the failure load of the chordae tendineae attached to the three posterior leaflet scallops, the anterolateral scallop (P1), middle scallop (P2), and posteromedial scallop (P3) of the mitral valve. In all, 140 chordae isolated from 23 porcine hearts were tested. First, the cross-sectional diameters of all branches in each chorda were measured using a microscope. Next, after positioning the chorda in a tensile testing machine, a preload of 0.2 N was applied, and the chordal length was measured. Cyclic loading between 0 and 0.3 N, 10 times with a speed of 1.5 mm/s, was conducted, after which the machine travelled at 1.5 mm/s until the chorda broke. We found that P2 chordae were thicker than P1 and P3 chordae and longer than P1 chordae. P2 chordae failed at significantly higher loads than P1 and P3 chordae. For all three types of chordae, almost half of the failures occurred at the chordal branch that was closest to the leaflet., (© IMechE 2015.)

This study aimed to characterise viscoelastic properties of different categories of chordae tendineae over a range of frequencies. Dynamic Mechanical Analysis (DMA) was performed using a materials testing machine. Chordae (n=51) were dissected from seven porcine hearts and categorised as basal, marginal, strut or commissural. Chordae were loaded under a sinusoidally varying tensile load at a range of frequencies between 0.5 and 5Hz, both at a standardised load (i.e. same mean load of 4N for all chordae) and under chordal specific loading (i.e. based on in vivo loads for different chordae). Storage modulus and stiffness were frequency-dependent. Loss modulus and stiffness were frequency-independent. Storage and loss moduli, but not stiffness, decreased with chordal diameter. Therefore, strut chordae have the lowest moduli and marginal chordae the highest moduli. The hierarchy of dynamic storage and loss moduli is: marginal, commissural, basal and strut. In conclusion, viscoelastic properties of chordae are dependent on both frequency and chordal type. Future/novel replacement chordal materials should account for frequency and diameter dependent viscoelastic properties of chordae tendineae., (© 2013 Published by Elsevier Ltd.)

The objective of this study was to develop a patient-specific finite element (FE) model of a human mitral valve. The geometry of the mitral valve was reconstructed from multi-slice computed tomography (MSCT) scans at middle diastole with distinguishable mitral leaflet thickness, chordal origins, chordal insertion points, and papillary muscle locations. Mitral annulus and papillary muscle dynamic motions were also quantified from MSCT scans and prescribed as boundary conditions for the FE simulation. Material properties of the human mitral leaflet tissues were obtained from biaxial tests and characterized by an anisotropic hyperelastic material model. In vivo dynamic closing of the mitral valve was simulated. The closed shape of the mitral valve output from the simulation was similar to the mitral valve geometry reconstructed from MSCT images at middle systole. Forces from the anterolateral and posteromedial papillary muscle groups at middle systole were 4.51 N and 5.17 N, respectively. The average maximum principal stress of the midsection of the anterior mitral leaflet was approximately 160 kPa at the systolic peak. Results demonstrated that the developed FE model could closely replicate in vivo mitral valve dynamic motion during middle diastole and systole. This model may serve as a basis for utilizing computational simulations to obtain a better understanding of mitral valve mechanics, disease and surgical repair.

Background and Aim of the Study: Attention towards the optimization of mitral valve repair methods is increasing. Patch augmentation is one strategy used to treat functional ischemic mitral regurgitation (FIMR). The study aim was to investigate the force balance changes in specific chordae tendineae emanating from the posterior papillary muscle in a FIMR-simulated valve, following posterior leaflet patch augmentation., Methods: Mitral valves were obtained from 12 pigs (body weight 80 kg). An in vitro test set-up simulating the left ventricle was used to hold the valves. The left ventricular pressure was regulated with water to simulate different static pressures during valve closure. A standardized oval pericardial patch (17 x 29 mm) was introduced into the posterior leaflet from mid P2 to the end of the P3 scallop. Dedicated miniature transducers were used to record the forces exerted on the chordae tendineae. Data were acquired before and after 12 mm posterior and 5 mm apical posterior papillary muscle displacement to simulate the effect from one of the main contributors of FIMR, before and after patch augmentation., Results: The effect of displacing the posterior papillary muscle induced tethering on the intermediate chordae tendineae to the posterior leaflet, and resulted in a 39.8% force increase (p = 0.014). Posterior leaflet patch augmentation of the FIMR valve induced a 31.1% force decrease (p = 0.007). There was no difference in force between the healthy and the repaired valve simulations (p = 0.773)., Conclusion: Posterior leaflet patch augmentation significantly reduced the forces exerted on the intermediate chordae tendineae from the posterior papillary muscle following FIMR simulation. As changes in chordal tension lead to a redistribution of the total stress exerted on the valve, patch augmentation may have an adverse long-term influence on mitral valve function and remodeling.

The aim of the present research is to determine the influence of the calcification of human mitral valves on the mechanical properties of their marginal chordae tendineae. The study was performed on marginal chords obtained from thirteen human mitral valves, explanted at surgery, including six non-calcified, four moderately calcified and three strongly calcified valves. The mechanical response of the chords from the non-calcified and moderately calcified valves was determined by means of quasi-static tensile tests (the poor condition of the strongly calcified valves prevented them from being mechanically characterised). The material parameters that were obtained and analysed (the Young's modulus, the secant modulus, the proportional limit stress, the ultimate strength, the strain at fracture and the density of energy stored up to maximum load) revealed noticeable differences in mechanical behaviour between the two groups of mitral chordae tendineae. Large scatter was obtained in all cases, nevertheless, considering the mean values, it was observed that the normal chords are between three and seven times stiffer or more resistant than the moderately calcified ones. On the contrary, the results obtained for the strain at fracture showed a rather different picture as, in this case, no significant differences were observed between the two families of chords. A scanning electron microscopy study was conducted in order to find out the relevant features of the calcium deposits present in the calcified chordae tendineae. In addition, the general aspects appreciated in the stress vs. strain curves were correlated with the collagen morphological evidences determined microscopically. Finally, the calcium content present in the three groups of chords was quantitatively determined through atomic absorption spectroscopy; then, the relation between the mechanical properties of normal and moderately calcified chords as a function of its calcium content was obtained. This analysis confirmed the existence of a strong correlation between calcium content and stiffness or resistance whereas the influence on the ductility seems to be negligible., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Aim of the Study: Mitral valve chordae tendineae are an essential component for correct functioning of the human heart. The microstructural make-up of the chordae is responsible for their tensile properties, and is seen gradually to change with age. However, little is known of the maturation of chordae tendineae and their microstructure., Methods: To examine such maturation, structural changes in chordae tendineae were studied in rats at 1, 3, 7, 15 and 30 days of postnatal life, and in adult rats. Differences in the chordae microstructure of each age group were observed using light microscopy. The collagen fibril crimp period was determined using polarized light microscopy., Results: At day 1 after birth the chordae had yet to develop, and the lateral sides of the mitral valve leaflets were completely attached to the papillary muscles. Chordae developed through the formation of gaps in the leaflet tissue. From day 7 on, numerous chordae were seen. As the chordae matured, crimped collagen fibrils were formed and began to align in a longitudinally packed core with increasing density. The collagen fibril crimp period increased significantly with the age of the animal., Conclusion: Rat chordae tendineae have yet to develop at postnatal day 1. Morphological development and microstructural maturation of the chordae are not completed until adulthood (>30 days). A further understanding of the development of mitral valve chordae tendineae will provide insight for the use of tissue-engineered chordae in surgical repair.

Purpose: We developed a new pulsatile hydrodynamic simulator for the in vitro testing of mitral valve (MV) samples. The required specifications included a 3D positioning system for the papillary muscles (PMs) that is accurate and simple to manage; measurement of the force exerted by the chordae tendineae on the PMs; and the possibility to visually inspect the MV for kinematic analysis., Methods: An atrial/ventricular chamber system was developed. The ventricular chamber housed a tri-axial actuator system that was aligned to a morphometric Cartesian frame, allowing for PM positioning even while tests are running. Each PM holder had an embedded load cell for force measurement. The atrial chamber was designed so as to permit MV visual inspection, maintaining a non-disturbed flow at the sample inlet. The setup was subjected to trials with fresh porcine MVs. Flow and pressure difference across the MVs and PM forces were measured in different MV configurations, with different PM spatial dislocations. High speed video recordings were acquired., Results: The positioning accuracy was assessed. Tests with MVs showed good usability, even by the non-engineering personnel. The effects of PM displacement on valve function (valve competence and PM forces) was consistent with previously published data, thus confirming the general soundness of the design principles., Conclusions: The developed simulator is a promising instrument for performing MV in vitro tests in a precise, well-repeatable manner. The ability to completely adjust the PM position while a test is running boosts the simulator's potential for detailed investigations of the pathological and surgically treated MV.

This article reviews the right atrioventricular and pulmonary valves, along with their anatomic variations as well as the papillary muscles and chordae tendineae of the right ventricle of the human heart. A brief anatomical background is given for every structure, as well as a gross review of their embryological basis. Although the normal morphology of the right atrioventricular valve is tricuspid, this is not always the case; its anatomic variations involve, firstly, the number of cusps and accessory leaflets. Anatomic variations of the right atrioventricular valve may occur in association with other congenital anomalies and syndromes. Also the number, length and shape of the papillary muscles and chordae tendineae are variable. This can be of clinical significance since the papillary muscles play an important role in the contraction of the right ventricle and in the closure of the tricuspid valve so as to prevent ventricular blood from passing back into the right atrium. The pulmonary valve may present variations in the number of cusps, stenosis or atresia, either as isolated clinical findings or in association with congenital syndromes.

Modelling and simulation of heart valves is a challenging biomechanical problem due to anatomical variability, pulsatile physiological pressure loads and 3D anisotropic material behaviour. Current valvular models based on the finite element method can be divided into: those that do model the interaction between the blood and the valve (fluid-structure interaction or 'wet' models) and those that do not (structural models or 'dry' models). Here an anatomically sized model of the mitral valve has been used to compare the difference between structural and fluid-structure interaction techniques in two separately simulated scenarios: valve closure and a cardiac cycle. Using fluid-structure interaction, the valve has been modelled separately in a straight tubular volume and in a U-shaped ventricular volume, in order to analyse the difference in the coupled fluid and structural dynamics between the two geometries. The results of the structural and fluid-structure interaction models have shown that the stress distribution in the closure simulation is similar in all the models, but the magnitude and closed configuration differ. In the cardiac cycle simulation significant differences in the valvular dynamics were found between the structural and fluid-structure interaction models due to difference in applied pressure loads. Comparison of the fluid domains of the fluid-structure interaction models have shown that the ventricular geometry generates slower fluid velocity with increased vorticity compared to the tubular geometry. In conclusion, structural heart valve models are suitable for simulation of static configurations (opened or closed valves), but in order to simulate full dynamic behaviour fluid-structure interaction models are required., (Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.)

Interest in developing durable mitral valve repair methods is growing, underscoring the need to better understand the native mitral valve mechanics. In this study, the authors investigate the dynamic deformation of the mitral valve strut chordae-to-anterior leaflet transition zone using a novel stretch mapping method and report the complex mechanics of this region for the first time. Eight structurally normal porcine mitral valves were studied in a pulsatile left heart simulator under physiological hemodynamic conditions -120 mm peak transvalvular pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was marked with a structured array of 31 miniature markers, and their motions throughout the cardiac cycle were tracked using two high speed cameras. 3D marker coordinates were calculated using direct linear transformation, and a second order continuous surface was fit to the marker cloud at each time frame. Average areal stretch, principal stretch magnitudes and directions, and stretch rates were computed, and temporal changes in each parameter were mapped over the insertion region. Stretch distribution was heterogeneous over the entire strut chordae insertion region, with the highest magnitudes along the edges of the chordal insertion region and the least along the axis of the strut chordae. At early systole, radial stretch was predominant, but by mid systole, significant stretch was observed in both radial and circumferential directions. The compressive stretches measured during systole indicate a strong coupling between the two principal directions, explaining the small magnitude of the systolic areal stretch. This study for the first time provides the dynamic kinematics of the strut chordae insertion region in the functioning mitral valve. A heterogeneous stretch pattern was measured, with the mechanics of this region governed by the complex underlying collagen architecture. The insertion region seemed to be under stretch during both systole and diastole, indicating a transfer of forces from the leaflets to the chordae and vice versa throughout the cardiac cycle, and demonstrating its role in optimal valve function.

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.)

The mitral valve is a highly complex structure the normal functioning of which requires the coordinated interaction of the leaflets, annulus, chordae tendineae, and papillary muscles. Perturbations of any of these components can interfere with normal valve function. The integrity of the mitral valve is also essential to maintaining normal left ventricular geometry and function through closely coupled ventricular-valvular interactions. This review summarizes recent developments in our understanding of the anatomy and physiology of the mitral valve.

Objective: The aims of this work were to employ functional imaging capabilities of the Visible Heart laboratory and endoscopic visualization of mitral valves in perfusion-fixed specimens to better characterize variability in mitral valve leaflet anatomy and to provide a method to classify mitral leaflets that varies from the current nomenclature., Methods: We gathered functional endoscopic video footage (11 isolated reanimated human hearts) and static endoscopic anatomical images (38 perfusion-fixed specimens) of mitral leaflets. Commissure and cleft locations were charted using Carpentier's accepted description., Results: All hearts had 2 commissures separating anterior and posterior leaflets. "Standard" clefts separating P1/P2 were found in 66% of hearts (n = 25), and standard clefts separating P2/P3 were present in 71% of hearts (n = 27). "Deviant" clefts occurred in each region of the anterior leaflet (A1, A2, A3), and their relative occurrences were 5%, 8%, and 13% (n = 2, 3, 5), respectively. Deviant clefts were found in posterior leaflets: 13.2% in P1 (n = 5), 32% in P2 (n = 12), and 21% in P3 (n = 8)., Conclusions: Humans elicit complex and highly variable mitral valve anatomy. We suggest a complementary, yet simple nomenclature to address variation in mitral valve anatomy by describing clefts as either standard or deviant and locating regions in which they occur (A1 to A3 or P1 to P3).

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.

Proper leaflet coaptation of the mitral valve is vital for a healthy functioning heart. Chordal tension directly affects leaflet coaptation. The C-shaped transducer used previously to measure chordal tension was too big for tension measurement of multiple chordae and their branches. A new method is needed to measure chordal tension with minimum interference with chord and leaflet motion. The method was to extrapolate longitudinal chordal tension from transverse chordal fibril force measured by inserting a small elliptical AIFP4 sensor from MicroStrain Inc. (Williston, VT) through a chord. Sensitivity of the method has been tested with the sensor implanted in chordae, and error of the method has been estimated at various sensor deviation angles. Intact porcine and ovine hearts were used to measure mitral valve strut and marginal chordal tensions at static transmitral pressures of 120 mm Hg and 160 mm Hg under an in vitro condition. The results obtained from the AIFP4 sensor were similar to the results obtained previously by C-shaped transducers in the porcine mitral valves. The sensor output errors increased with the increase in sensor deviation angle in the chord at a peak systolic tension. Strut chordal tensions of four ovine mitral valves of Edwards ring size M 28 were 0.29+/-0.06 N at the transmitral pressure of 120 mm Hg. The tension of 18 porcine strut chordae of porcine mitral valves of Edwards ring size M 32 was 1.00+/-0.42 N at the transmitral pressures of 120 mm Hg. The tension of 22 anterior leaflet marginal chordae from porcine mitral valves of Edwards ring size M 32 was 0.10+/-0.04 N at the transmitral pressure of 120 mm Hg. A new method using an AIFP4 miniature force sensor to measure mitral valve chordal tension indirectly is successfully developed. This force sensor works well in measuring mitral valve chordal tension at an in vitro hydrostatic transmitral pressure. The size and simple fixation of the sensor make it favorable for chordal tension measurement of multiple chordae and their branches under in vitro or in vivo conditions with minimal interference with chordal geometry and dynamics.

Background and Aim of the Study: The technique of strut chordaesc (SC) cutting, which was proposed for the correction of ischemic mitral regurgitation, has been shown to be an effective short-term procedure. However, the effects of SC cutting on other chordal tensions are unknown. The study aim was to assess anterior leaflet marginal chord tensions after SC cutting., Methods: Tensions of anterior leaflet marginal chordae were measured before and after the cutting of each strut chord independently, or of both SC together, in an intact porcine mitral valve. The cutting positions were chosen between intermediate and marginal chord branching positions. Transmitral pressures were 120 and 160 mmHg. A total of 12 mitral valves was tested., Results: At a transmitral pressure of 120 mmHg, anterolateral SC cutting increased the tension of the marginal chord from the anterolateral papillary muscle (from 0.10 +/- 0.02 to 0.29 +/- 0.11 N; p = 0.02), but not from the posteromedial papillary muscle. At a transmitral pressure of 120 mmHg, posteromedial SC cutting significantly increased the tension of the marginal chord from the posteromedial papillary muscle (from 0.08 +/- 0.03 to 0.34 +/- 0.20 N; p = 0.029), but not from the anterolateral papillary muscle. Cutting both SC at a transmitral pressure of 120 mmHg increased the tension of the marginal chord from both the posteromedial papillary muscle (from 0.09 +/- 0.04 to 0.40 +/- 0.26 N; p = 0.001) and from the anterolateral papillary muscle (from 0.11 +/- 0.03 to 0.48 +/- 0.13 N; p <0.000001)., Conclusion: Cutting either of the SC significantly increases the tension of the anterior leaflet marginal chord from the same papillary muscle, but not from the other papillary muscle. Cutting both SCs significantly increases the anterior leaflet marginal chord tensions from both papillary muscles by approximately four-fold.

Background: Rupture of the chordae tendineae cordis (CTC) is a well-known cause of mitral regurgitation. Despite its importance, the mechanisms by which the CTC is protected and the cause of its rupture remain unknown. CTC is an avascular tissue. We investigated the molecular mechanisms underlying the avascularity of CTC and the correlation between avascularity and CTC rupture., Methods and Results: We found that tenomodulin, which is a recently isolated antiangiogenic factor, was expressed abundantly in the elastin-rich subendothelial outer layer of normal rodent, porcine, canine, and human CTC. Conditioned medium from cultured CTC interstitial cells strongly inhibited tube formation and mobilization of endothelial cells; these effects were partially inhibited by small-interfering RNA against tenomodulin. The immunohistochemical analysis was performed on 12 normal and 16 ruptured CTC obtained from the autopsy or surgical specimen. Interestingly, tenomodulin was locally absent in the ruptured areas of CTC, where abnormal vessel formation, strong expression of vascular endothelial growth factor-A and matrix metalloproteinases, and infiltration of inflammatory cells were observed, but not in the normal or nonruptured area. In anesthetized open-chest dogs, the tenomodulin layer of tricuspid CTC was surgically filed, and immunohistological analysis was performed after several months. This intervention gradually caused angiogenesis and expression of vascular endothelial growth factor-A and matrix metalloproteinases in the core collagen layer in a time-dependent manner., Conclusions: These findings provide evidence that tenomodulin is expressed universally in normal CTC in a concentric pattern and that local absence of tenomodulin, angiogenesis, and matrix metalloproteinase activation are associated with CTC rupture.

There are frequent citations in the literature stating that lesions of the tendinous cords cause functional disorders of the heart valves. This led us to conduct the present investigation on the anatomy of the tendinous cords. Our objective was to focus on the morphological characteristics of tendinous cords that are inserted directly into the interventricular septum, such as their frequency, number, dimensions and This study was conducted on 50 hearts from adults of both sexes that had been fixed in 10% formaldehyde. The right ventricle was opened by means of an incision parallel to the anterior interventricular groove, and the left ventricle was opened by means of a longitudinal incision in the middle of the pulmonary (left) surface. Our results showed that, in the right ventricle, these tendinous cords constantly appeared without the involvement of papillary muscles (98%). They ranged in number from one to ten, and between two and five was the most common (72%). They were short, mostly ranging from 0.3 to 1.9 cm in length (81.5%) and were preferentially located in the upper third of the interventricular septum (71.4%). They were usually attached to the septal cusp (76.7%) and sometimes to the anterior cusp (21.3%). The cusp insertion sites were the free edge (62%), ventricular surface (32%) and basal edge (6%). It was exceptional to find tendinous cords in the ventricular septum of the left ventricle. Tendinous cords directly inserted into the atrioventricular septum were constantly present in the right ventricle, with varying numbers. They were predominantly short because they were inserted into the upper third of the septum and most often headed towards the septal cusp. It was exception to find tendinous cords in the atrioventricular septum of the left ventricle.

In highly aligned connective tissues, such as tendon, collagen fibrils are linked together by proteoglycans (PGs). Recent mechanical and theoretical studies on tendon micromechanics have implied that PGs mediate mechanical interactions between adjacent collagen fibrils. We used transmission electron microscopy to observe the collagen fibril-PG interactions in porcine mitral valve chordae under variable loading conditions and found that PGs attached to collagen fibrils perpendicularly in the load-free situation, and became skewed when the chordae were loaded. The average skewness angle of PGs increased with the applied load, and hence the strain in the chordae. The observation of PG skewing with the application of load demonstrates that, in mitral valve chordae, interfibrillar slippage occurs and that PGs play a role in fibril-to-fibril interaction and likely transfer force. The results of this study provide new insights into the mechanical role of PGs and support some recent theoretical models.

Objective: To determinate the extension and the resistance of the primary mitral valve chordae tendineae when submitted to traction. The importance of keeping the integrity of papillary muscle, chordae tendineae, and mitral valve cuspid when the replacement of this valve occurs is clear, but the knowledge of the maximum resistance that a primary tendinea chorda can withstand is not known., Methods: Eight hearts were dissected, and one hundred and thirty two primary human chordae tendineae were measured (length and thickness) and submitted to traction under controlled conditions so that the absolute resistance, resistance relative to thickness (relative resistance), and elongation could be measured., Results: The correlation between the elongation at the moment of rupture and the thickness was equal to 1.54 + 17.02 x thickness (P = 0.026); and to absolute resistance was equal to 0.95 + 1.42 x resistance (P < 0.001); and to the resistance relative to thickness (relative resistance) was equal to 1.95 + 0.08 x relative resistance (P = 0.009). The correlation between the absolute resistance and the thickness was equal to 0.26 + 14.53 x thickness (P < 0.001)., Conclusion: The resistance of primary mitral valve chordae tendineae is associated with its thickness and elongation at the moment of rupture, but is not associated with the length. The elongation at the moment of rupture shows a relationship with the resistance relative to thickness (relative resistance) and with the thickness of the primary chordae tendineae, but not with the length of the chordae tendineae.

Background: Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load., Methods and Results: Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2+/-3.3 after cutting versus 48.4+/-4.6 mL before cutting, P=0.66), end-systolic volume (21.5+/-1.2 versus 22.3+/-2.8 mL, P=0.68), ejection fraction (54.2+/-1.8 versus 54.2+/-2.7%, P=0.96), systolic ventricular elastance (7.28+/-1.68 versus 7.66+/-2.11 mm Hg/mL, P=0.64), preload-recruitable stroke work (46.6+/-7.7 versus 50.2+/-10.7 mm Hg, P=0.76), and LVdP/dt (1480+/-238 versus 1392+/-250 mm Hg/s, P=0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed., Conclusions: We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.

Strut chordae transection (SCT) has been recommended as a surgical treatment for mitral regurgitation (MR) arising from ischemic heart disease. However, little is known about the contribution of anterior strut chordae to leaflet tissue mechanics. In this study, experimental measurements of mitral valve deformation under quasi-static pressure loading were performed on isolated pig hearts before and after transecting both strut chordae. Biplane video images of markers placed on the anterior leaflet surface were used to reconstruct the 3D position of the markers. The 2D nonhomogeneous deformations in the anterior leaflet were calculated by least squares fit to the 3D marker coordinates in successive pressure loading states. Results show that the anterior leaflet undergoes large, anisotropic and nonhomogeneous deformation, with a significant radial stretch gradient and smaller, uniform circumferential stretch. Following chordal transection, the radial deformation decreases. A gradient in the circumferential stretch is observed as an increase from the annulus toward the coaptation line. Without the support provided by the strut chordae, the center portion of the anterior leaflet experienced a substantial change in shape in response to the systolic pressure, altering the load-bearing mechanism in the valvular structure. The shift of the deformation distribution suggests that additional strain energy is absorbed by the circumferentially oriented collagen fibers following SCT and may result in long-term tissue remodeling. This study provides detailed biomechanical data for interpreting the results of previous investigations of SCT, as well as for exploring a greater understanding of how SCT affects MR through computational modeling.

The material properties of the mitral valve chordae tendineae are important for the understanding of leaflet coaptation configuration and chordal pathology. There is limited information about the mechanical properties of the chordae during physiologic loading. Dual camera stereo photogrammetry was used to measure strains of the chordae in vitro under physiologic loading conditions. Two high-speed, high-resolution cameras captured the movement of graphite markers attached to the central section of the chordae. A uniaxial test simulating the same loading conditions was conducted on the same chordae using the same markers. The maximum strain experienced during the cardiac cycle was 4.29% +/- 3.43%. The loading rate was higher at 75.3% +/- 48.6% strain per second than the unloading rate at -54.8% +/- -56.6% strain per second. The anterior lateral strut chordae had a higher maximum strain (5.7% +/- 3.8%) and loading rate (80.5% +/- 51.9% strain per second) than the posterior medial strut chordae (5.5% +/- 2.3% strain and 68.1% +/- 48.3% strain per second). The posterior medial strut chordae had a higher unloading rate (-68.5% +/- -59.1% strain per second) than the anterior lateral strut chordae (-44.9% +/- -57.2% strain per second). Although the anterior lateral and posterior medial strut chordae have a significantly different diameter and length, they experience a similar strain, strain rate, and tension. In conclusion, a non-destructive technique was developed to measure in vitro chordal strain in the mitral valve. This technique allows the investigation of the behavior of biological tissues under physiologic loading conditions.

Background and Aim of the Study: The study aim was to understand the role of different mitral valve chordae tendineae, and how damage to them affects valve competence., Methods: A test apparatus was used to apply pressure to porcine mitral heart valves that were intact and have had selected chords severed. Anterior leaflet strut and marginal chords were selectively severed, as were posterior leaflet basal and marginal chords. Commissural chords were also severed., Results: Severing anterior leaflet marginal chords (p = 0.018) and commissural chords (p = 0.018) significantly reduced mitral valve competence. Severing posterior leaflet marginal and basal chords, and anterior leaflet strut chords, had no significant effect in reducing the pressures that the valves could withstand. Severing a mixture of posterior leaflet basal and marginal chords significantly reduced the pressure withstood by the valves (p = 0.004)., Conclusion: The study results confirmed that anterior leaflet marginal chords, but not strut chords, are vital for valve competence. Commissural chords were also shown to be vital for mitral valve competence. Several posterior leaflet chords had to be severed to affect mitral valve competence.

A physiologic constitutive expression is presented in algorithmic format for the nonlinear elastic response of wavy collagen fibrils found in soft connective tissues. The model is based on the observation that crimped fibrils in a fascicle have a three-dimensional structure at the micron scale that we approximate as a helical spring. The symmetry of this wave form allows the force/displacement relationship derived from Castigliano's theorem to be solved in closed form: all integrals become analytic. Model predictions are in good agreement with experimental observations for mitral-valve chordae tendinece.

Background and Aim of the Study: Previous computational studies of the normal mitral valve have been limited because they assumed symmetrical modeling and artificial boundary conditions. The study aim was to model the mitral valve complex asymmetrically with three-dimensional (3-D) dynamic boundaries obtained from in-vivo experimental data., Methods: Distance tracings between ultrasound crystals placed in the sheep mitral valve were converted into 3-D coordinates to reconstruct an initial asymmetric mitral model and subsequent dynamic boundary conditions. The non-linear, real-time left ventricular and aortic pressure loads were acquired synchronously. A quasi-static solution was applied over one cardiac cycle., Results: The mitral valve leaflet stress was heterogeneous. The trigones experienced highest stresses, while the mid-anterior annulus between trigones experienced low stress. High leaflet stress was observed during peak pressure loading. During isovolumic relaxation, the leaflets were highly stretched between the anterolateral trigone and the posteromedial commissure, resulting in a prominent secondary leaflet stress re-increment. This has not been observed previously, as symmetric models with artificial boundary conditions were studied only in the ejection phase., Conclusion: Here, the first asymmetrical mitral valve model synchronized with 3-D dynamic boundaries and non-linear pressure loadings over the whole cardiac cycle based on in vivo experimental data is described. Despite its limitations, this model provides new insights into the distribution of leaflet stress in the mitral valve.

Background and Aim of the Study: Mitral insufficiency, a common and morbid pathology, has been related to topological changes in the left ventricle. These changes may affect mitral leaflet coaptation by displacing the tips of the papillary muscles (PMs), subsequently changing the tension distribution on the chordae tendineae. Therefore, further understanding of the effects of PM displacement on chordal force distribution is required., Methods: Six human and five porcine mitral valves were studied in a physiological left heart simulator. Cardiac output and transmitral pressure were recorded online and maintained within physiological ranges. Force transducers were placed on six chordae tendineae to measure chordal force distribution. Tension on individual chordae tendineae was recorded online during the cardiac cycle. The experiment was conducted for eight different PM positions, which were constructed from 5-mm vectorial displacements from the normal PM position., Results: The anterior strut chord showed significant (p <0.05) variations in peak systolic tension (PST) for those positions associated with apical motion of the PMs. The posterior intermediate chord also showed significant variations in PST for positions associated with apical displacement of the PMs, whereas posterior displacement of the PMs resulted in a reduction in tension. In contrast, both the anterior marginal and posterior marginal chords showed a relatively uniform PST for the eight different PM positions. The posterior basal and commissural chords were the most sensitive to tension variations due to PM displacement. These chords showed relatively large and significant (p <0.05) variations in PST for most of the different PM displacements., Conclusion: The effects of PM relocation on chordal tension depended on chordal type. Chords which insert closer to the annulus were more sensitive to PM displacement, whereas those further from the annulus, the marginal chords, were the least sensitive to PM displacement.

Background and Aim of the Study: The dynamics of the mitral valve result from the synergy of left heart geometry, local blood flow and tissue integrity. Herein is presented the first coupled fluid-structure computational model of the mitral valve in which valvular kinematics result from the interaction of local blood flow and a continuum representation of valvular microstructure., Methods: The diastolic geometry of the mitral valve was assembled from previously published experimental data. Anterior and posterior leaflets were modeled as networks of entangled collagen fibers, embedded in an isotropic matrix. The resulting non-linear continuum description of mitral tissue was implemented in a three-dimensional membrane formulation. Chordal tension-only behavior was defined from experimental tensile tests. The computational model considered the valve immersed in a domain of Newtonian blood, with an experimentally determined viscosity corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and atrial pressure curves were applied to ventricular and atrial surfaces of the blood domain., Results: Peak closing flow and volume were 51 ml/s and 1.17 ml, respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N. Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at 0.064 s from the onset of systole. Model predictions showed excellent agreement with available transmitral flow, papillary force and first heart sound (S1) acoustic data., Conclusion: The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent a significant advance in computational studies of the mitral valve. This model will be the foundation for future computational studies on the effect of pathophysiological tissue alterations on mitral valve competence.

Automatic acoustic classification and diagnosis of mitral valve disease remain outstanding biomedical problems. Although considerable attention has been given to the evolution of signal processing techniques, the mechanics of the first heart sound generation has been largely overlooked. In this study, the haemodynamic determinants of the first heart sound were examined in a computational model. Specifically, the relationship of the transvalvular pressure and its maximum derivative to the time-frequency content of the acoustic pressure was examined. To model the transient vibrations of the mitral valve apparatus bathed in a blood medium, a dynamic, non-linear, fluid-coupled finite element model of the mitral valve leaflets and chordae tendinae was constructed. It was found that the root mean squared (RMS) acoustic pressure varied linearly (r2= 0.99) from 0.010 to 0.259 mmHg, following an increase in maximum dP/dt from 415 to 12470 mm Hg s(-1). Over that same range, peak frequency varied non-linearly from 59.6 to 88.1 Hz. An increase in left-ventricular pressure at coaptation from 22.5 to 58.5mm Hg resulted in a linear (r2= 0.91) rise in RMS acoustic pressure from 0.017 to 1.41mm Hg. This rise in transmitral pressure was accompanied by a non-linear rise in peak frequency from 63.5 to 74.1 Hz. The relationship between the transvalvular pressure and its derivative and the time-frequency content of the first heart sound has been examined comprehensively in a computational model for the first time. Results suggest that classification schemes should embed both of these variables for more accurate classification.

Background: Mitral valvular-ventricular continuity is important for left ventricular (LV) systolic function, but the specific contributions of the anterior leaflet second-order "strut" chordae are unknown., Methods and Results: Eight sheep had radiopaque markers implanted to silhouette the LV, annulus, and papillary muscles (PMs); 3 transmural bead columns were inserted into the mid-lateral wall between the PMs. The strut chordae were encircled with exteriorized wire snares. Three-dimensional marker images and hemodynamic data were acquired before and after chordal cutting. Preload recruitable stroke work (PRSW) and end-systolic elastance (E(es)) were calculated to assess global LV systolic function (n=7). Transmural strains were measured from bead displacements (n=4). Chordal cutting caused global LV dysfunction: E(es) (1.48+/-1.12 versus 0.98+/-1.30 mm Hg/mL, P=0.04) and PRSW (69+/-16 versus 60+/-15 mm Hg, P=0.03) decreased. Although heart rate and time from ED to ES were unchanged, time of mid-ejection was delayed (125+/-18 versus 136+/-19 ms, P=0.01). Globally, the LV apex and posterior PM tip were displaced away from the fibrous annulus and LV base-apex length increased at end-diastole and end-systole (all +1 mm, P<0.05). Locally, subendocardial end-diastolic strains occurred: Longitudinal strain (E22) 0.030+/-0.013 and radial thickening (E33) 0.081+/-0.041 (both P<0.05 versus zero). Subendocardial systolic shear strains were also perturbed: Circumferential-longitudinal "micro-torsion" (E12) (0.099+/-0.035 versus 0.075+/-0.025) and circumferential radial shear (E13) (0.084+/-0.023 versus 0.039+/-0.008, both P<0.05)., Conclusions: Cutting second-order chords altered LV geometry, remodeled the myocardium between the PMs, perturbed local systolic strain patterns affecting micro-torsion and wall-thickening, and caused global systolic dysfunction, demonstrating the importance of these chordae for LV structure and function.

C-shaped strain gauge force transducers were designed to enable dynamic measurements of the tension of the individual mitral valve chordae tendineae during the cardiac cycle. The force transducers were constructed from a C-shaped brass ring with a diameter of 6 mm, width of 2 mm, thickness of 0.5 mm, and a mass of <80 mg. Miniature strain gauges elements were cemented onto the inner and outer side of the ring. The strain gauges were connected to thin Teflon wires and coupled in a Wheat-stone half-bridge circuit to a signal conditioner and amplifier. The transducer was coated with a resistive sealing ensuring electrical insulation as well as mechanical protection. Technical testings of sensitivity, linearity, noise level, and frequency response characteristics demonstrated that the transducers were suitable for dynamic chordal force measurements performed under in vitro and in vivo experimental conditions.

In this study, the chordae tendineae of 10 adult chickens have been investigated by means of scanning electron microscopy (SEM). It has been observed that the diameter of the collagen fibrils on the left side of the heart was greater than those on the right side. The present study has determined that only perichordal and interchordal ligaments are present in the chicken. It was also observed that axial tendons were surrounded by perichordal membrane. Although no difference was evident among the apex of the chordae, differences were observed between the base and apex of the same chordae.

The tensile properties of mitral valve chordae tendineae derive from their structural make-up. The objectives of this study were to compare the stress relaxation properties of different types of chordae and relate their variation to structural features. Fifty chordae from eight hearts were subjected to stress relaxation tests. The percent stress relaxation and the relaxation rates were found to increase in the order of marginal. basal, and strut chordae. The water content of the three types of chordae was the same (marginal 77.1+/-5.9%, basal 77.0+/-3.4%, strut 78.0+/-2.3% wet weight). The collagen, elastin, and glycosaminoglycan (GAG) content in chordae were quantified using hydroxyproline assay, fastin elastin assay, and fluorophore-assisted carbohydrate electrophoresis, respectively. Collagen content of marginal chordae was only slightly less than that of basal and strut chordae (marginal 56.6+/-8.2%, basal 61.4+/-5.6%, strut 63.8+/-3.9% dry weight). There was also no significant difference in elastin content between the chordae (marginal 5.3+/-3.2%, basal 5.4+/-2.7%, strut 4.6+/-1.7% dry weight). However, the concentrations of unsulfated chondroitin/dermatan sulfate, 6-sulfated chondroitin sulfate, and 4-sulfate chondroitin sulfate significantly decreased in the order of marginal, basal, and strut. The total GAG-content also decreased in the order of marginal, basal, and strut (p = 0.06). The greater amount of GAGs in marginal versus strut chordae is consistent with our previous observations that marginal chordae have a greater collagen fibril density and thus more GAG-mediated, fibril-to-fibril linkages. The greater number of proteoglycan linkages may prevent the slippage of fibrils with respect to each other, and thus reduce stress relaxation. The different viscoelastic properties of mitral valve chordae can thus be explained morphologically.

Biaxial testing, histological measurements and theoretical continuum mechanics modeling were employed to investigate the structure and mechanical properties of the mitral valve leaflet-strut chordae transition zone (LCT). The results showed that geometry changes and collagen fiber angle distribution contribute to variations in mechanical properties in the LCT zone. A simple three-coefficient exponential constitutive law was able to simulate the variation in stress-stretch behavior in the LCT zone by spatially varying a single coefficient and incorporating collagen fiber angle and degree of alignment. This quantitative information can greatly improve the predictions from biomechanical valve models by incorporating regional variations of structure and properties in the mitral leaflet-chordae tendineae system. These data provide the foundation for a computational model for studying stress distributions before and following chordal rupture, which may indicate the underlying reasons for the development of valve insufficiency in patients.