Structural analysis of chordae tendineae in degenerative disease of the mitral valve.

BACKGROUND: Degenerative disease of the mitral valve (DDMV) is always accompanied by lengthening and/or rupture of chordae tendineae. However, the mechanisms and the mode of chordal rupture remain controversial, and the pathologic anatomy of the apparently healthy chordae has mostly been overlooked. We analyze the structural aspects of both ruptured and intact chordae tendineae in DDMV. METHODS AND RESULTS: Structural and ultrastructural microscopic analyses indicate that both the extracellular matrix and the interstitial cells are severely affected. Degenerative chordae show alterations in the synthesis and deposition of collagen and elastin, disorganization of collagen bundles and rupture of collagen fibres, accumulation of proteoglycans and of cellular and vesicular remnants, and cell transformation into a myofibroblast phenotype. Structural disruption makes the spongiosa and the dense collagenous core separate and break. Degeneration of the chordae is segmental, affecting both chordae that are clearly abnormal, and chordae that appear healthy on visual inspection. CONCLUSIONS: Changes in both matrix synthesis and degradation disturb the ordered collagen arrangement and modify the structural and physical properties of the chordae. Progressive structural disruption of the diseased chordae is the cause of chordal rupture. Mitral surgery corrects the damage, but the underlying causes of DDMV are not corrected. Thus, progression of the disease and affectation of additional chordae may be at the basis of the late complications and the recurrent mitral regurgitation which occurs several years after surgery. Our results indicate that a more aggressive approach to surgery may be needed.

Ultrastructure of porcine mitral valve chordae tendineae.

BACKGROUND AND AIM OF THE STUDY: The chordae tendineae, which form an important component of the mitral valve apparatus, experience continuous cyclic loading and are thus well-adapted for effectively storing and dissipating energy. An understanding of their microstructure would be expected to shed light on the mechanism of their remarkable durability. METHODS: In these studies, porcine mitral valve chordae from freshly slaughtered pigs were used. Histological samples of Picrosirius Red-stained and Movat's pentachrome-stained chordae were examined with optical microscopy and laser scanning confocal microscopy. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to study the ultrastructure at high magnification. RESULTS: Both, optical microscopy and SEM revealed that the waviness of collagen fibers was uniform across the thickness of the chordae, with no straight fibers in the core. Wavy fibers and fiber bundles were found to be in skewed-register, rather than transverse. Collagen fiber bundles were found to undulate in a three-dimensional path, rather than the planar waveform, as reported previously. TEM showed that different types of chordae had different fibril configurations. Marginal chordae had smaller diameters but a higher fibril density than did basal and strut chordae. CONCLUSION: The configuration of collagen fibrils in the mitral valve chordae is more complex than initially thought, and different chordae have morphologies that are likely specific to their mechanical role in the mitral apparatus. These findings provide insight into possible improvements for chordal repair surgery, and form a structural basis for accurate computational modeling.

Survival advantage and improved durability of mitral repair for leaflet prolapse subsets in the current era.

BACKGROUND: Factors predicting long-term survival and reoperative risk after mitral valve repair for subsets with prolapse involving the anterior leaflet in the current era are unclear. METHODS: Between January 1, 1980 and December 31, 1999, surgical correction of mitral regurgitation was performed in 2,219 patients. We analyzed a subset of 1,411 patients with isolated mitral regurgitation due to leaflet prolapse undergoing mitral repair or replacement (+/- coronary bypass). RESULTS: Mean age was 64 years, and 1,003 (71%) were men. Mitral repair was performed in 1,173 (83%) patients. Factors independently predicting overall long-term survival included valve repair, younger age, better functional class, and the absence of significant coronary artery disease. After adjusting for these, smaller preoperative left ventricular end-systolic dimension and greater preoperative ejection fraction were associated with superior survival. Mitral reoperation occurred in 97 patients (75 repairs, 22 replacements), at a mean of 4.8 years after initial procedure. Cumulative risk of reoperation was similar for patients having valve repair or replacement. Factors predictive of need for reoperation after initial repair were younger age, anterior leaflet prolapse, chordal shortening, no leaflet resection, no prosthetic annuloplasty, greater than mild residual mitral regurgitation, and coronary artery disease. After valve replacement, the sole determinant of reoperation was use of a biological prosthesis. The durability of repair for prolapse of the anterior leaflet improved significantly during the second decade of the study. CONCLUSIONS: Mitral repair affords superior long-term survival, with permanence comparable with mechanical valve replacement. In all categories of mitral leaflet prolapse, durability of valve repair has improved over the past decade.

Choice of artificial chordae length according to echocardiographic criteria.

A simple way to identify artificial chordae length is reported. The distance A between the edge of the prolapsing anterior leaflet and the plane of the mitral annulus is measured during perioperative transesophageal echocardiography. When the mitral valve is exposed, the elongated chorda, corresponding to the scallop previously evaluated, is measured with a ruler and A is subtracted. This is the length of the new chorda that is measured with a ruler and tied at that level after being properly positioned.

The chordae tendineae of the heart in chicken.

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.

A structural basis for the size-related mechanical properties of mitral valve chordae tendineae.

It has been reported previously that the mechanical properties of mitral valve chordae tendineae vary with chordal size and type. The popularity of mitral valve repair and chordal transposition warrant a better understanding of this phenomenon. The objectives of this study were to characterize the size- and type-related variations in chordal mechanics and explain them from the ultra-structural viewpoint. A total of 52 porcine mitral valve chordae from eight hearts were mechanically tested. We found that thicker chordae were more extensible than thinner chordae (4.2+/-1.5%, 8.1+/-2.5%, 15.7+/-3.9% and 18.4+/-2.8% strain corresponding to chordae with cross-sectional areas of 0.1-0.5, 0.5-1.0, 1.0-2.0, and 2.0-3.0mm(2), respectively), and had lower moduli (90.1+/-22.3, 83.7+/-18.5, 66.3+/-13.5 and 61.7+/-13.3 MPa corresponding to the same chordae groups). Polarized light microscopy was used to measure collagen fibril crimp. Thicker chordae had smaller crimp period than thinner chordae (11.3+/-1.4 microm vs. 14.8+/-3.0 microm), and were thus more highly crimped. Thicker chordae could therefore extend to greater strain before lock-up. Transmission electron microscopy (TEM) was used to measure choral fibril ultra-structure. Thinner chordae had lower average fibril diameter than thicker chordae but greater average fibril density. The cross-sectional area occupied by fibrils, however, was found to be constant at 49+/-2% regardless of chordal size or type. The difference in moduli between thick and thin chordae can therefore be explained by differences in fibril packaging and hence fibril-to-fibril interactions. According to a simple fibril interaction model, chordae with smaller diameter fibrils will have a greater number of fibril-to-fibril interactions, and hence a greater modulus.

Coil-like structure of the inner core of chordae tendineae.

Scanning electron microscopy was used to examine the chordae tendineae in young (approximately 20 years old) and old (approximately 85 years old) cadavers. A network of collagen fibrils was observed in both the outer and intersurface layers of the chordae tendineae. In young subjects, a regularly arranged series of disconnected collagenous ring-like structures surrounded the longitudinal collagen bundles forming the inner core of the chordae tendineae. In old subjects, the ring-like structures of the chordae tendineae were few or absent. The ring-like structures may be related to reducing mechanical stress during the tightening, twisting, and slackening of the chordae tendineae.

Ultrastructure abnormalities in proteoglycans, collagen fibrils, and elastic fibers in normal and myxomatous mitral valve chordae tendineae.

Normal and myxomatous chordae tendineae were studied using light and electron microscopy, to assess the alterations in the appearance and mutual arrangement of proteoglycans, collagen fibrils, and elastic fibers. Specific staining with ruthenium red and cuprolinic blue in a critical electrolyte concentration mode were used to localize proteoglycans. Fresh tissues were fixed in glutaraldehyde containing the cationic dyes and embedded into Spurr resin. Semithin sections of LR White (London Resin Co., Basingstoke, U.K.)-embedded tissue were used for histochemistry. In normal chordae tendineae, the fibrosa comprised close-packed collagen fibrils intermixed with elastic fibers. These were surrounded by a thin layer of elastic fibers and collagen fibrils, both of which were closely associated with proteoglycans. In myxomatous chordae tendineae, alterations were observed in the connective tissue. Proteoglycans were more abundant and were distributed throughout the tissue. The outermost layer was transformed into an undifferentiated electron-dense mass surrounding the central fibrosa, which contained degraded elastic fibers and collagen fibrils. Collagen fibrils had faint banding or lacked a banding pattern altogether. Spaces between collagen fibrils were occupied by abnormal proteoglycans or proteoglycan aggregates. Elastic fibers showed varying degrees of degeneration and were occasionally replaced by electron-lucent spaces containing microfibrils. Accumulation of abnormal proteoglycan was also observed around degenerated elastic fibres and collagen fibrils.

Structure of chordae tendineae in the left ventricle of the human heart.

The bicuspid (mitral) valve complex of the human heart consists of functional units which include the valve leaflets, chordae tendineae and the papillary muscles. The mechanical properties of these functional units depend to a large extent on the link between the muscle and the valve. This link is usually arranged in a branching network of avascular tendinous chordae composed of collagen and elastic fibres, which transmit contractions of the papillary muscle to the valve leaflets. In order to perform their function efficiently, the chordae have to possess a high degree of elasticity, as well as considerable strength and endurance. Human chordae tendineae originating from the left ventricles were obtained from 7 embalmed cadavers and 6 postmortem subjects of various ages. Samples washed in saline were fixed or postfixed in 9 % formol saline. Observations were made by illuminating the chordae along their axes. The reflected images originating from the superficial collagenous layers of the relaxed chordae showed a striped pattern 11 microm in width. Scanning electron and light microscopy of the chordae confirmed an undulating pattern of collagen fibrils arranged in bundles of planar waves in register and around the entire circumference of the chorda. The dimensions of the waves correlated with those of the striped reflected pattern. The observed undulating arrangement of the collagen fibrils appears to produce an inherent built-in elasticity which is likely to be of considerable advantage for a tissue which is under continuous repetitive stress. The chordae were covered by endocardium composed of a superficial layer of smooth squamous endothelial cells and an underlying dense layer of elastic fibres. It is suggested that the relaxed striped chordae, consisting of undulating collagen fibrils, straighten when the chordae become stretched by papillary muscle contraction, thereby mitigating the peak stress developed during muscle contraction. On relaxation the elastic tissue tends to return the collagen to its wavy configuration. It is also suggested that the regular wavy pattern of collagen seen in young individuals gradually changes with age by elongation of the wave pattern which eventually becomes randomised. In addition, with increasing age, substantial cushions of connective tissue appear below endocardium while the dense collagenous core has a reduced cross-sectional area which may lead to stretching and eventual rupture of the chordae.

Elastic fiber abnormalities associated with a leaflet perforation in floppy mitral valve.

The alterations observed in the elastic fibers of the perforated floppy mitral valve of a 68-year-old man are described. The patient had not history of infective endocarditis and no stigmata of Marfan syndrome or Ehlers-Danlos syndrome. Ultrastructurally, the elastic fibers in the area of the perforation showed unique, round-shaped expansion of the amorphous components, which lacked associated microfibrils. These features resembled those of the elastic fibers in animals treated with beta-aminopropionitrile, an inhibitor of lysyl oxidase. Aggregations of microfibrils without amorphous components were also observed. These abnormalities are considered to be related to the pathogenesis of the perforation in this valve.

Development of the papillary muscles of the mitral valve: morphogenetic background of parachute-like asymmetric mitral valves and other mitral valve anomalies.

OBJECTIVES: To understand papillary muscle malformations, such as in parachute mitral valves or parachute-like asymmetric mitral valves, we studied the development of papillary muscles. METHODS: Normal human hearts at between 5 and 19 weeks of development were studied with immunohistochemistry, three-dimensional reconstructions, and gross inspection. Scanning electron microscopy was used to study human and rat hearts. RESULTS: In embryonic hearts a prominent horseshoe-shaped myocardial ridge runs from the anterior wall through the apex to the posterior wall of the left ventricle. In the atrioventricular region this ridge is continuous with atrial myocardium and covered with cushion tissue. The anterior and posterior parts of the trabecular ridge enlarge and loosen their connections with the atrial myocardium. Their lateral sides gradually delaminate from the left ventricular wall, and the continuity between the two parts is incorporated in the apical trabecular network. In this way the anterior and posterior parts of the ridge transform into the anterolateral and the posteromedial papillary muscles, respectively. Simultaneously, the cushions remodel into valve leaflets and chordae. Only the chordal part of the cushions remains attached to the developing papillary muscles. CONCLUSIONS: Disturbed delamination of the anterior or posterior part of the trabecular ridge from the ventricular wall, combined with underdevelopment of chordae, seems to be the cause of asymmetric mitral valves. Parachute valves, however, develop when the connection between the posterior and anterior part of the ridge condenses to form one single papillary muscle. Thus parachute valves and parachute-like asymmetric mitral valves originate in different ways.

Atrioventricular valves of the mouse: III. Collagenous skeleton and myotendinous junction.

BACKGROUND: The leaflet tissue of the mouse atrioventricular (AV) valves contains a system of wavy collagen bundles that organize like tendons, orientate along lines of tension, and constitute an essential component of the valve tissue. The organization of these bundles is different in the two AV valves, reflecting differences in the anatomy of the entire valvular complex. Further insights into this kind of organization are needed to gain a complete understanding of the functional anatomy of the mouse AV valves. METHODS: The endocardial covering of the mouse AV valves (from 21 days to 1 year of age) was eliminated by the sonication or the maceration method. This allowed us to study in situ the organization of the collagenous valve skeleton, as well as the structure of the myotendinous junction. RESULTS: The leaflets of the two AV valves are formed by a fibrous layer (on the ventricular side) and a spongy layer (on the atrial side). The fibrosa is formed by undulating collagen bundles that organize and orientate differently on the right and left sides. The spongiosa is formed, on both sides, by a loose network of thin collagen fibers with no apparent orientation. Myocardial cells in the papillary muscles of the tricuspid valve are elongated and show cone-shaped tips. Collagen fibers attach to the myocyte surface. Collagen struts and thin septa can also be recognized. On the other hand, the collagenous components of the mitral leaflets attach tangentially to the mitral papillary muscles. On the two sides, the myocytes appear to be ensheathed in a layer of collagenous tissue. The sheaths are formed by circularly arranged fibers and appear to be tightly interconnected. CONCLUSIONS: The differences in the collagenous organization between the two AV valves reflect differences in the gross anatomy of the valves. The attachment of collagen to the papillary myocytes in the tricuspid valve resembles that of a typical myotendinous junction. However, the collagen-muscle junction in the mitral valve is more similar to the structure of a pennate muscle. The collagen matrix of the heart has been divided into endomysial, perimysial, and epimysial components. The presence of sheaths housing individual myocytes and capillaries, struts, and thin septa, corresponds to the endomysium. The absence of perimysial septa, which aggregate myocytes into groups, is striking, but this may just be a species difference. The appropriateness of the term epimysium, as applied to the heart, is discussed.

Abnormalities in elastic fibers and other connective-tissue components of floppy mitral valve.

Histologic, immunohistochemical, and ultrastructural studies were performed on 12 floppy mitral valves, 4 mitral valves showing focal myxomatous changes without prolapse, and 3 normal mitral valves. All floppy mitral valves were thickened by deposits of proteoglycans and also showed diverse structural abnormalities in collagen and elastic fibers. From these observations we conclude that (1) the structure of all major components of connective tissue in floppy mitral valves is abnormal; (2) alterations in collagen and accumulations of proteoglycans are nonspecific changes that may be caused by the abnormal mechanical forces to which floppy mitral valves are subjected because of their excessively large surface area; (3) the presence of excessive amounts of proteoglycans may interfere with the normal assembly of collagen and elastic fibers; (4) abnormalities of elastic fibers resemble those in other conditions characterized by structural dilatation or tissue expansion; and (5) alterations in elastin could result from defective formation, increased degradation, or both.

Ultrastructure of the rat papillary muscle-chorda tendineae junction.

The papillary muscle and chordae tendineae of the rat tricuspid valve were treated with tannic acid-glutaraldehyde fixative and examined with an electron microscope. In the junctional region, the papillary muscle cell tapered abruptly and separated into many processes. One end of bundles of elastic fibers approached these processes or lateral sides of the muscle cell and the other end extended in a longitudinal direction toward the chordae tendineae. Fine networks of elastic fibers were observed in the subendothelial layer of the junctional region.

Estudo morfológico e histoquímico em nível ultra-estrutural da corda tendínea de coraçöes de rato albino / Morphological and histochemical study in structural pattern of chordae tendinae of hearts from albino rat

Fragmentos de cordas tendíneas dos complexos valores mitral e tricúspide de ratos albinos foram observados ao microscópio eletrônico de transmissäo com o objetivo de estudar os componentes da matriz extracelulair. Foram utilizados dois tipos de fixador, um contendo ácido tânico para demonstrar a presença de fibras dos sistemas colágeno e elástico, e outro contendo vermelho de rutênio para a visualizaçäo de proteuglicans. Alguns fragmentos foram tratados previamente pela colagenase ou pela tripisina antes de serem fixados pelo glutaraldeído com vermelho de rutênio. Foi observado que as cordas tendíneas de rato säo revestidas por um endotélio contínuo que repousa sobre uma camada de conjuntivo contendo fibroblastos e esparsas fibras de colágeno, compondo a zona esponjosa. Tal camada circunda uma zona central (zaza fibrosa) constituída de grossos feixes de colágeno onde se encontram vários fibroblastos. Tanto na zona esponjosa como na fibrosa foram detectadas inúmeras fibras com padräo ultra-estrutural de fibras elaunínicas, os quais, juntamente com o colágeno, desempenham funçöes de resistência mecânica ao transmitirem as forças de traçäo exercidas pelo músculo papilar às bordas das válvulas. Adicionalmente, foram observadas as relaçöes morfológicas entre proteoglicans, fibrilas de colágeno e microfibrilas elaunínicas, tendo sido enfatizada a importância do equilíbrio de funçöes entre os diversos componentes da matriz extracelular concorrendo para o perfeito funcionamento deste complexo morfofuncional na fisiologia da corda tendínea.

Ultrastructural quantification of collagen in human chordae tendineae.

OBJECTIVE: To determine collagen fibril diameter distributions in the chordae tendineae and to see whether there are any differences between right and left sides of the human heart. DESIGN: Collagen fibril diameters and the percentage volume occupied by collagen fibrils (as opposed to ground substance) were determined by means of a planimeter with a digitising tablet from electron micrographs printed at a magnification of 136; 000. MATERIAL: Human chordae tendineae were obtained at postmortem examination from seven subjects aged 50-75 years. MEASUREMENTS AND MAIN RESULTS: Histograms of collagen fibril diameter distributions showed a sharp, unimodal distribution. The mean collagen fibril diameters associated with the tricuspid and mitral valves were 41.1 nm and 40.5 nm respectively. The percentage volume occupied by collagen was about 39% for each valve. There were no significant differences for any of these values between the right and left sides of the heart. CONCLUSIONS: The greater pressures present on the left side of the heart are not reflected in any difference in collagen fibril diameters within the chordae tendineae compared with the right side.

Structure and protein composition of sites of papillary muscle attachment to chordae tendineae in avian hearts.

Most cardiac myocytes transmit force across fasciae adherentes, specialized sites of cell-cell adhesion. However, some cardiac myocytes in papillary muscle terminate on collagenous connective tissue in the chordae tendineae. These papillary myotendinous junctions (MTJs) are specialized for force transmission from myocytes to extracellular matrix. In the present study, we compared structural molecules at papillary MTJs to those at fasciae adherentes and skeletal MTJs. By using indirect immunofluorescence, we found that papillary MTJs more closely resemble skeletal MTJs in their molecular composition in that they are enriched in talin, vinculin, integrin, and fibronectin. Zeugmatin and alpha-actinin, both components of fasciae adherentes, are absent from papillary MTJs. Although papillary MTJs and skeletal MTJs display strong similarities in structural protein composition, ultrastructural organization of the two junctions is different. Papillary MTJs display little folding of the junctional membrane and, according to morphological criteria, more closely resemble sites of thin filament-membrane association in smooth muscle than skeletal MTJs. Thus, papillary MTJs display a combination of structural characteristics described previously in skeletal and smooth muscles but exhibit few structural features observed previously in cardiac fasciae adherentes.

Ultrastructural quantification of collagen fibrils in chordae tendineae of the sheep and rabbit.

Collagen fibril diameters and the volume occupied by collagen were quantified at the ultrastructural level in the chordae tendineae of the rabbit and the sheep. Collagen fibril diameter distribution was unimodal and significant differences were found between values on the left and right sides, those on the left being greater than those on the right. The differences are discussed in terms of mechanical loading and compared with results obtained from other tendinous structures subjected to continuous loading.