Search Results (19)

Understanding the nonlinear mechanical behaviour of mitral valve chordae tendineae is critical for accurate biomechanical modelling in cardiac simulations. This study integrates high-resolution 3D finite element analysis with experimentally derived Cauchy stress–Green–Lagrange strain data to capture both material and geometric nonlinearities. A one-dimensional formulation incorporating strain-dependent elasticity and large deformation kinematics was developed and validated against 3D simulations in COMSOL Multiphysics. Calibrated using experimental stress–strain data and validated against high-fidelity 3D finite element simulations in COMSOL, it reveals that neglecting transverse deformation overestimates axial force by 7%. Cross-sectional area reduction during stretch remained consistently around 12%, underscoring the importance of Poisson effects. A polynomial fit to the strain-dependent modulus of elasticity enables efficient force prediction with excellent agreement to experimental data. These results advance the mathematical modelling of biological tissues with nonlinear hyperelastic behaviour, providing a foundation for patient-specific simulations and real-time predictive tools in cardiovascular engineering. Full article

We discuss a case of a patient who was referred to our department for an in-depth evaluation of aortic regurgitation severity and its underlying causes. By employing a multimodal imaging strategy that combined transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and cardiac magnetic resonance imaging (cMRI), we successfully identified a particularly rare cause of aortic regurgitation: chordae tendineae that lead to asymmetric retraction of the aortic cusps. Furthermore, this approach provided a clearer understanding of the aortic root anatomy and the hemodynamic effects of the regurgitant flow on the ventricle. This case demonstrates the diagnostic effectiveness of various imaging techniques and emphasizes the crucial importance of multimodal imaging for a thorough assessment of aortic valvular issues. Full article

There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model; in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus was accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed the measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich “transition zone” at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with “perforations” lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial cells within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations created by localized MMP activity serve as a site for the initiation of a “split” of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and its signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements. Full article

Due to the growing interest among veterinarians and the increasing market demands, the development of equine cardiology is necessary. Currently, veterinary medicine for companion animals needs to catch up to human medicine—equine medicine included. A common condition in older horses is aortic valve regurgitation resulting from fibrosis, while its more severe form occurs in younger horses or develops due to a bacterial infection. Mitral valve regurgitation, especially dangerous due to the possibility of sudden death, has a better prognosis if the horse has valve prolapse. Tricuspid valve regurgitation usually does not pose a clinical problem, although its severe cases may lead to heart failure. Some pathologies can be treated surgically, which requires excellent knowledge of anatomy. The object of this study consisted of twenty domestic horse hearts. The focus was on the normal and comparative anatomy of the left and right subvalvular apparatus. The number of muscular bellies of the papillary muscles and the type of connection of the muscles were analysed. Moreover, the height of muscle originating from the ventricle wall was determined, the morphological regularity of the papillary muscle was assessed, and the chordae tendineae originating from the papillary muscles were examined. The conducted research allowed for comparing domestic horses with different species through other studies, the authors of which described this particular aspect. Interspecies similarities which may be correlated with the evolutionary relatedness, as well as differences that could reflect adaptation to different lifestyles, environmental conditions, or metabolic requirements of the animals, have been found. This study expands the knowledge of animals’ normal and comparative anatomy, and contributes to the development of veterinary surgery, internal medicine, and biology. Full article

There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish, chicks, and small mammalian models, longitudinal studies in large mammals with a similar gestational period to humans are lacking. Further, the mechanism of chordae tendineae formation and multiplication remains unclear. The current study presents a comprehensive examination of mitral anterior leaflet and chordae tendineae development in a bovine model (a large mammal with the same gestational period as humans). Remarkably distinct from small mammals, bovine development displayed early branched chordae, with increasing attachments only until birth, while the anterior leaflet grew both during gestation and postnatally. Chordae also exhibited accelerated collagen deposition, maturation, and crimp development during gestation. These findings suggest that the bovine anterior leaflet and chordae tendineae possess unique processes of development despite being a continuous collagenous structure and could provide greater insight into human valve development. Full article

Background: Detailed surgical techniques for treating canine mitral regurgitation have not been previously reported. Method: This case series included six consecutive client-owned dogs with mitral regurgitation. All dogs underwent a combined protocol, including the modified loop technique and De Vega annuloplasty (MODEL surgery), in 2021. Artificial loops covering 80% of the length of the strut chordae tendineae were used for chordal replacement. Mitral annuloplasty was subjectively performed, targeting the circumference of the septal leaflet. Results: The breeds were Chihuahua-mixed breed, Spitz, Pomeranian, Cavalier King Charles Spaniel, and Chihuahua, with average ages and weights of 11.4 ± 2.3 years and 5.49 ± 2.98 kg, respectively. The aortic cross-clamp, pumping, and surgery times were 64.0 ± 7.5 min, 168.5 ± 39.1 min, and 321.0 ± 53.1 min, respectively. After MODEL surgery, left atrial-to-aortic ratios significantly decreased from 2.20 ± 0.18 to 1.26 ± 0.22 (p < 0.01), and left ventricular end-diastolic internal diameter normalized to body weight significantly decreased from 2.03 ± 0.26 to 1.48 ± 0.20 (p < 0.01). In all cases, the clinical signs disappeared or improved significantly. Conclusions: MODEL surgery increased mitral valve coaptation, normalized heart sizes, and significantly improved clinical signs in dogs with mitral regurgitation. Full article

Mitral regurgitation is a common valvular disorder. Transcatheter edge-to-edge repair (TEER) is a minimally invasive technique which involves holding together the middle segments of the mitral valve leaflets, thereby reducing regurgitation. To date, MitraClip™ is the only Food and Drug Administration (FDA)-approved device for TEER. The MitraClip procedure is technically challenging, characterised by a steep learning curve. Training is generally performed on simplified models, which do not emphasise anatomical features, realistic materials, or procedural scenarios. The aim of this study is to propose a novel, 3D printed simulator, with a major focus on reproducing the anatomy and plasticity of all areas of the heart involved and specifically the ones of the mitral valve apparatus. A three-dimensional digital model of a heart was generated by segmenting computed tomography (CT). The model was subsequently modified for: (i) adding anatomical features not fully visible with CT; (ii) adapting the model to interact with the MitraClip procedural equipment; and (iii) ensuring modularity of the system. The model was manufactured with a Polyjet technology printer, with a differentiated material assignment among its portions. Polypropylene threads were stitched to replicate chordae tendineae. The proposed system was successfully tested with MitraClip equipment. The simulator was assessed to be feasible to practice in a realistic fashion, different procedural aspects including access, navigation, catheter steering, and leaflets grasping. In addition, the model was found to be compatible with clinical procedural imaging fluoroscopy equipment. Future studies will assess the effect of the proposed training system on improving TEER training. Full article

Three-dimensional ultrasound mosaicing can increase image quality and expand the field of view. However, limited work has been done applying these compounded approaches for cardiac procedures focused on the mitral valve. For procedures targeting the mitral valve, transesophageal echocardiography (TEE) is the primary imaging modality used as it provides clear 3D images of the valve and surrounding tissues. However, TEE suffers from image artefacts and signal dropout, particularly for structures lying below the valve, including chordae tendineae, making it necessary to acquire alternative echo views to visualize these structures. Due to the limited field of view obtainable, the entire ventricle cannot be directly visualized in sufficient detail from a single image acquisition in 3D. We propose applying an image compounding technique to TEE volumes acquired from a mid-esophageal position and several transgastric positions in order to reconstruct a high-detail volume of the mitral valve and sub-valvular structures. This compounding technique utilizes both fully and semi-simultaneous group-wise registration to align the multiple 3D volumes, followed by a weighted intensity compounding step based on the monogenic signal. This compounding technique is validated using images acquired from two excised porcine mitral valve units and three patient data sets. We demonstrate that this compounding technique accurately captures the physical structures present, including the mitral valve, chordae tendineae and papillary muscles. The chordae length measurement error between the compounded ultrasound and ground-truth CT for two porcine valves is reported as 0.7 ± 0.6 mm and 0.6 ± 0.6 mm. Full article

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions. Full article

Collagen fibers are essential structural components of mitral valve leaflets, their tension apparatus (chordae tendineae), and the associated papillary muscles. Excess or lack of collagen fibers in the extracellular matrix (ECM) in any of these structures can adversely affect mitral valve function. The organization of collagen fibers provides a sophisticated framework that allows for unidirectional blood flow during the precise opening and closing of this vital heart valve. Although numerous ECM molecules are essential for the differentiation, growth, and homeostasis of the mitral valve (e.g., elastic fibers, glycoproteins, and glycans), collagen fibers are key to mitral valve integrity. Besides the inert structural components of the tissues, collagen fibers are dynamic structures that drive outside-to-inside cell signaling, which informs valvular interstitial cells (VICs) present within the tissue environment. Diversity of collagen family members and the closely related collagen-like triple helix-containing proteins found in the mitral valve, will be discussed in addition to how defects in these proteins may lead to valve disease. Full article

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve’s annulus region (p < 0.05) at 3 months compared to the 11- and 20-month explants, there were no other significant differences (p > 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur. Full article

Imaging subject-specific heart valve, a crucial step to its design, has experimental variables that if unaccounted for, may lead to erroneous computational analysis and geometric errors of the resulting model. Preparation methods are developed to mitigate some sources of the geometric error. However, the resulting 3D geometry often does not retain the original dimensions before excision. Inverse fluid–structure interaction analysis is used to analyze the resulting geometry and to assess the valve’s closure. Based on the resulting closure, it is determined if the geometry used can yield realistic results. If full closure is not reached, the geometry is adjusted adequately until closure is observed. Full article

The mitral valve apparatus is a complex structure consisting of the mitral ring, valve leaflets, papillary muscles and Chordae tendineae (CT). The latter are mainly responsible for the mechanical functions of the valve. Our study included investigations of the biomechanical and structural properties of CT collected from canine and porcine hearts, as there are no studies about these properties of canine CT. We performed a static uniaxial tensile test on CT samples and a histopathological analysis in order to examine their microstructure. The results were analyzed to clarify whether the changes in mechanical persistence of Chordae tendineae are combined with the alterations in their structure. This study offers clinical insight for future research, allowing for an understanding of the process of Chordae tendineae rupture that happens during degenerative mitral valve disease—the most common heart disease in dogs. Full article

Chordae tendineae rupture (CTR) is a potentially life-threatening cardiac event often resulting in Acute mitral regurgitation (AMR). We assessed Post-traumatic stress disorder (PTSD), depression, and anxiety symptoms in $n=21$ CTR patients with AMR (age 82.3 ± 4.2 years; 66.7% men) and compared them to $n=23$ CTR patients with Chronic mitral regurgitation (CMR) and $n=35$ Myocardial infraction (MI) patients. Regression analyses revealed that PTSD scores were significantly higher in CTR patients with AMR than in CTR patients with CMR or MI patients. CTR patients with CMR had the lowest levels of PTSD-symptoms. Depression and anxiety scores were elevated across all three groups. Our results suggest that psychosocial factors need to be considered in CTR patients’ care. Full article

Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair. Full article