Mitral Leaflet Tissue Research Articles

Biomechanical comparison of porcine mitral leaflets with porcine small intestinal submucosa extracellular matrix.

Porcine small intestinal submucosa extracellular matrix (SIS-ECM) used for cardiac valve repair has shown conflicting clinical outcomes with respect to calcification and failure. This may be related to differences in biomechanical properties of the material compared with the host site. The aim of this study was to compare the biomechanical properties of porcine mitral valve leaflets with SIS-ECM. Fresh porcine anterior and posterior mitral leaflet samples were cut radially and circumferentially. Similarly, 2- and 4-layered SIS-ECM were cut in orthogonal directions: length and width. Samples were subjected to a uniaxial tensile test or a dynamic mechanical analysis. Results show that the load of the porcine anterior circumferential leaflet was 39.5 N (2.4-48.5 N), which was significantly higher compared with the 2-layered length SIS-ECM which was 7.5 N (7-7.9 N), and the 4- layered length SIS-ECM which was 7.5 N (7.1-8.1 N) (p < 0.001). The load of the posterior circumferential leaflet was 9.7 N (8.3-10.7 N), which is still significantly higher when compared with the two versions of SIS-ECM. The degree of anisotropy (i.e. the ratio between circumferential-radial and width-length properties) was higher for the anterior- (ratio: 19) and posterior leaflet (ratio: 6) than the 2-layered (ratio: 5.1) and 4-layered SIS-ECM (ratio: 1.9). Especially 2-layered SIS-ECM more closely resembles the posterior mitral leaflet than the anterior mitral leaflet tissue and would be more suitable as a repair material in this position. Additionally, the anisotropic properties of mitral leaflets and SIS-ECM underscore the importance of correct orientation of the implant to ensure optimal reconstruction.

Mitral valve prolapse in patients with atrial septal defect: A quantitative three-dimensional echocardiographic analysis.

Mitral valve (MV) prolapse is highly prevalent in patients with atrial septal defect (ASD). Abnormal left ventricular geometry has been proposed as the main mechanism of MV prolapse in ASD, however, the changes in the morphology of the MV apparatus remain to be clarified. Our aim was to assess the MV geometry in patients with ASD and MV prolapse. We evaluated 99 patients (73% female, median age 40 years) with ASD who underwent a three-dimensional transesophageal echocardiogram. Three-dimensional analysis of the MV was done using dedicated automated software. Transthoracic echocardiographic parameters were assessed post ASD closure in 28 patients. MV prolapse was found in 39% of patients. Although smaller left ventricular dimensions and greater interatrial shunt were found in patients with MV prolapse compared with those without prolapse, there was no difference in the subvalvular parameters. MV prolapse was associated with larger mitral anterior-posterior diameter, anterolateral-posteromedial diameter, anterior perimeter, posterior perimeter, total perimeter, and anterior leaflet area (all p<0.05). Mitral regurgitation was more frequent in patients with MV prolapse (80vs. 48%, p=0.002). In patients with ASD, the main mechanism of MV prolapse is the presence of an organic primary process of the MV apparatus (excessive anterior mitral leaflet tissue and mitral annular enlargement).

Aborted sudden cardiac death due to ventricular fibrillation in a female patient with mitral valve prolapse

BackgroundMitral valve prolapse is the most frequent valvular defect associated with a wide range of electro-hemodynamic abnormalities, leading to heart failure, arrhythmias and sudden cardiac death. Mitral valve prolapse, first described from Barlow in the 1960s, is defined as displacement of mitral leaflet tissue into the left atrium past the mitral annular plane during systole. The correlation between mitral valve prolapse and sudden cardiac death has been investigated and clarified by various studies in recent years. However, identifying patients at risk and applying measures to prevent those from sudden cardiac death is challenging.Case presentationWe report on a 61-year-old female patient who had undergone an aborted sudden cardiac death. An arrythmogenic mitral valve prolapse was diagnosed. In addition, electrocardiographically and morphologically risk markers for sudden cardiac death were found in this case. We performed an ICD implantation as secondary prophylaxis and intended to reconstruct the mitral valve.ConclusionThis article examines the association of mitral valve prolapse with sudden cardiac death, the underlying pathophysiological mechanisms and the strategies leading to identify the risk group.

A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is one of the most common valvular disorders. However, the molecular and cellular mechanisms involved in fibromyxomatous changes in the mitral leaflet tissue have not been elucidated. Aldosterone (Aldo) promotes fibrosis in myocardium, and MR (mineralocorticoid receptor) antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis. We investigated the role of the Aldo/MR in the fibromyxomatous modifications associated with MVP. Aldo enhanced valvular interstitial cell activation markers and induced endothelial-mesenchymal transition in valvular endothelial cells, resulting in increased proteoglycan secretion. MRA blocked all the above effects. Cytokine arrays showed CT-1 (cardiotrophin-1) to be a mediator of Aldo-induced valvular interstitial cell activation and proteoglycan secretion and CD (cluster of differentiation) 14 to be a mediator of Aldo-induced endothelial-mesenchymal transition and proteoglycan secretion in valvular endothelial cells. In an experimental mouse model of MVP generated by nordexfenfluramine administration, MRA treatment reduced mitral valve thickness and proteoglycan content. Endothelial-specific MR deletion prevented fibromyxomatous changes induced by nordexfenfluramine administration. Moreover, proteoglycan expression was slightly lower in the mitral valves of MVP patients treated with MRA. These findings demonstrate, for the first time, that the Aldo/MR pathway regulates the phenotypic, molecular, and histological changes of valvular interstitial cells and valvular endothelial cells associated with MVP development. MRA treatment appears to be a promising option to reduce fibromyxomatous alterations in MVP.

A New Role For Aldosterone Mineralocorticoid Receptor Pathway In Mitral Valve Prolapse

Introduction and objectives: Mitral valve prolapse (MVP) is the most common cardiac valvular abnormality characterized by fibromyxomatous changes in the mitral leaflet tissue. There are currently n...

3D PRINTED PATIENT-SPECIFIC MULTI-MATERIAL MODELING OF MITRAL VALVE APPARATUS

Background: We have reported that the approximate mechanical properties of mitral leaflet tissue can be replicated using multi-material 3D printing. We sought to create multi-material patient-specific replicas of the entire mitral valve (MV) apparatus. Methods: CT images (systolic and diastolic) of

Epidemiology and Pathophysiology of Mitral Valve Prolapse

Mitral valve (MV) prolapse (MVP) is a common disorder, afflicting 2% to 3% of the general population.1,2 It is characterized by typical fibromyxomatous changes in the mitral leaflet tissue with superior displacement of 1 or both leaflets into the left atrium.3,4 With a prevalence of 2% to 3%, MVP is expected to affect ≈7.8 million individuals in the United States and >176 million people worldwide. MVP can be associated with significant mitral regurgitation (MR), bacterial endocarditis, congestive heart failure, and even sudden death.5–7 MVP is a clinical entity that is not fully understood, despite being known for more than a century. A “midsystolic click” was first described in 1887 by Cuffer and Barbillon.8 In 1963, Barlow and Pocock9 demonstrated the presence of MR by angiography in patients with the “click-murmur” syndrome. Criley et al10 subsequently coined the term MVP. MVP may be familial or sporadic. Despite being the most common cause of isolated MR requiring surgical repair,11 little is known about the genetic mechanisms underlying the pathogenesis and progression of MVP. Studies on the heritable features of MVP have been limited by the analysis of relatively small pedigrees and by self-referral and selection biases, including a preponderance of data from hospital-based cohorts.12,13 Nonetheless, the majority of data favor an autosomal-dominant pattern of inheritance in a large proportion of individuals with MVP.12,13 Despite the variability in clinical features, familial MVP might be considered a prevalent mendelian cardiac abnormality in humans. Although filamin-A has been identified as causing an X-linked form of MVP,14 the causative genes for the more common form of autosomal-dominant MVP have yet to be defined. In this review, we summarize our current knowledge of the diagnosis, epidemiology, prognosis, …

CONSTITUTIVE MODELING AND FINITE ELEMENT ANALYSIS OF MYXOMATOUS MITRAL LEAFLET TISSUE

Although rarely discussed, material modeling of the myxomatous leaflet is considered as the cornerstone of mitral valve finite element analysis. The present study presents an incompressible, hyperelastic constitutive model to characterize myxoid mitral leaflet tissue mechanics. The model incorporates the transversely isotropic response and the layered structure of the tissue. First, an analytical constitutive model for the tissue is developed based on continuum mechanics and layered composites theory. Second, the material constants of the constitutive equation are determined by fitting the model to the experimental data. The analytical material model is then implemented using solid finite element methods by simulating a biaxial tensile test. A numerical simulation of the out-of-plane pressure loading is also conducted. Both the analytical outcomes and the simulated results agree well with experimental data and show good mutual agreement. The calculated strain distribution of the out-of-plane pressure loading simulation indicates myxoid leaflets exhibit enhanced extensibility and decreased stiffness compared to normal valves; the radial direction is more extensible than the circumferential direction. The presented material approximation is able to capture the myxomatous mitral leaflet mechanics. The results of the numerical simulation conform to those of the experimental tests.

CLINICAL STUDY OF THE MECHANISM OF MITRAL REGURGITATION IN THE PAPILLARY MUSCLE DYSFUNCTION

Objectives目的: This investigation and report was a clinical study of the mechanism of mitral regurgitation in the papillary muscle dysfunction caused by coronary artery disease. We have studied correlation of...

Finite element modeling of mitral leaflet tissue using a layered shell approximation.

The current study presents a finite element model of mitral leaflet tissue, which incorporates the anisotropic material response and approximates the layered structure. First, continuum mechanics and the theory of layered composites are used to develop an analytical representation of membrane stress in the leaflet material. This is done with an existing anisotropic constitutive law from literature. Then, the concept is implemented in a finite element (FE) model by overlapping and merging two layers of transversely isotropic membrane elements in LS-DYNA, which homogenizes the response. The FE model is then used to simulate various biaxial extension tests and out-of-plane pressure loading. Both the analytical and FE model show good agreement with experimental biaxial extension data, and show good mutual agreement. This confirms that the layered composite approximation presented in the current study is able to capture the exponential stiffening seen in both the circumferential and radial directions of mitral leaflets.

The Mitral Valve in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) has evoked both fascination and controversy since its first modern description >50 years ago.1 Originally described as “functional aortic subvalvar stenosis” by Brock, the majority of articles about HCM in the ensuing first decade emanated from observations made in the operating room or in the cardiac catheterization laboratory.1 The actual cause of left ventricular outflow tract (LVOT) obstruction in patients with this condition had not yet been clarified. Ironically, the mechanisms of LVOT obstruction in HCM were only elucidated several years after surgery was first performed in these patients. In fact, an early report by Morrow described the septal myotomy procedure as surgical treatment for HCM and proposed that the myotomy interfered with the sphincter-like muscular contraction ring in the LVOT.1 Article see p 40 Noninvasive cardiovascular imaging studies have greatly advanced our knowledge about HCM.2 Hypertrophic cardiomyopathy is now felt to have tremendous genetic,3 clinical, morphological, and hemodynamic heterogeneity.1 Nevertheless, the presence of LVOT obstruction in patients with HCM has continued to inspire interest. The often contentious debates surrounding LVOT obstruction have centered on its very existence, its causes, its clinical impact and prognosis, and its optimal management.1 These issues have inextricably included the mitral valve, which has long been felt to play a pivotal role in the pathophysiology of LVOT obstruction in patients with HCM. In the present issue of Circulation , Maron et al use cardiovascular magnetic resonance (CMR) imaging to characterize mitral valve leaflets in patients with HCM.4 This study assessed the lengths of the anterior mitral leaflet (AML) and posterior mitral leaflet in 172 consecutive patients with HCM. Their findings were compared with 172 normal control subjects matched for age, sex, and body surface area. In addition, the study included a small cohort of …

Partial Resection of Mitral Leaflets during Mitral Valve Replacement

Usually, after mitral leaflet tissue is resected, artificial chordae are used to obtain papillary muscle-to-mitral annulus continuity so as to preserve left ventricular performance. A modified technique that does not require resection of the posterior mitral leaflet and permits implantation of an adequate size of prosthesis is described.

191 Investigation of the myxomatous mitral valve prolapse locus on chromosome 16

Myxomatous mitral valve prolapse (MMVP), also called Barlow disease, is a common cardiac disorder characterized by fibromyxomatous changes in the mitral leaflet tissue causing prolapse. Familial studies suggest a genetic heterogeneity and four loci have been identified to date. The MMVP1 locus that we identified in the past in two French families (Disse, Am J Hum Genet 1999) maps on chromosome 16p11-12. The locus interval is relatively large (15 cM). It comprised 185 genes but none has been implicated in the disease, yet. The objective of this work was to test relevant positional candidate genes. Six genes were tested by direct sequencing of all the coding sequences and of the intron-exon boundaries. For each gene, two affected and two unaffected patients of the two families linked to MMVP1 were tested, as well as 46 probands of smaller MVP families. We chose 3 genes belonging to the nodal modulators family that interact with proteins of the TGFβ protein superfamily and known to play a role in heart valve formation and in regulation of collagen and extracellular matrix gene expression. The Nomo1, Nomo2 and Nomo3 genes (located on 16p13.11, 16p12.3 and 16p13.11 respectively) extend on approximately 63 Kb and contain each 30 exons. No pathogenic mutation was identified in the coding region of these genes in these families but only known polymorphisms or rare non-coding variants. We also analysed 3 members of the heparan sulfate sulfotransferase enzymes (HS3ST1, HS3ST2 and HS3ST4) that regulate the heparan sulfate proteoglycan biosynthesis process. The HS3ST2 and HS3ST4 genes are located on 16p12, are extended on approximately123 Kb, but contain each only two exons separated by a large intron. Similarly, the genetic analysis was negative and no pathogenic mutation was identified. This study illustrates the difficulty to identify the causal gene when the linkage interval and the number of genes are large. Priority should be give to fine mapping of the MMVP1 locus.

Massive mitral annular calcification: A stone in the heart

An 82-year-old woman presented with hypertension (on treatment) and a three-month history of progressive shortness of breath. A transesophageal echocardiography showed severe mitral regurgitation with a centrally directed regurgitant jet, associated with severe mitral annular calcification (MAC). At surgery, the massive calcific deposits at the posterior annulus were removed (Figure 1), the annulus was reconstructed with bovine pericardium and the valve was replaced with a 27 mm Hancock II porcine valve (Medtronic Inc, USA). A left internal mammary artery was anastomosed to the left anterior descending artery. The postoperative course was uneventful, except for atrial fibrillation. Figure 1) Massive calcific deposits at the posterior annulus are seen. Some chordae tendinae appear to have ruptured and residual stumps are seen The excised mitral valve annulus and valve leaflet tissue weighed more than 22 g. The leaflets showed myxomatous change, and the calcific masses measured 0.2 cm × 0.9 cm × 0.2 cm to 3.1 cm × 1.7 cm × 1.6 cm (Figure 2). Some had adherent mitral leaflet tissue (mostly chordae tendineae). The large calcific fragment showed cardiac muscle, separated focally by a layer of fibrovascular tissue. Figure 2) A and B show the largest of the surgically excised calcific masses. Both show the deep surfaces and, clearly, there would be residual calcification (arrow). C The entire 22 g mass of surgically excised calcific tissue, some with a smooth endocardial surface ... MAC is a ‘degenerative’ change that is usually inconsequential and is seen in approximately 10% of patients older than 50 years of age. MAC is believed to be accelerated by hypertension, diabetes mellitus or hyperlipidemia (1), and involves the annulus to varying degrees, extending into the adjoining myocardium or even into the papillary muscle (2). The annular lesion can lead to significant manifestations such as mitral regurgitation (as in the present patient), mitral stenosis or a combination of the two. Massive annular calcification, as seen in the present case, has been reported to simulate an intracardiac tumour (3). Ulceration of the calcific masses through leaflet tissues can lead to thrombosis and infective endocarditis. The treatment is surgical excision with valve replacement (or repair, if possible) (4).

Distribution of the microelastic properties within the human anterior mitral leaflet

Knowledge of the biomechanical properties of the mitral valve leaflets and their relation to histologic structure is of importance for understanding the leaflet movement characteristics under normal and pathologic conditions, but such knowledge is not yet available. The aim of this study was to determine biomechanical properties of the human anterior mitral leaflet on a microscopic scale. We used scanning acoustic microscopy (SAM) to examine the human anterior mitral leaflet. Sections of fixed human anterior mitral leaflet tissue were obtained from postmortem human anterior mitral leaflets ( n = 5). We measured the speed of sound (ν L ) in each histologic layer in three regions-of-interest (ROIs): these were at the annular edge, at the valve midpoint and close to the free edge. ν L varied in the three histologic layers ( p < 0.01). It was higher in the fibrous layer (1.76 km/s) compared with the atrial layer (1.75 km/s) and ventricular layer (1.73 km/s). Also, ν L differed between positions along the length of the annulus-free edge line ( p < 0.01), showing a decline from the annular edge (1.76 km/s) to the free edge (1.73 km/s), both as a whole and also within the atrial and the fibrous layer. These results demonstrate that the fibrous layer is stiffer than the atrial and ventricular layer and that the leaflet as a whole and within the atrial and the fibrous layer is stiffer at the annulus part in comparison with those near the free edge. (E-mail: asj@ki.au.dk)

Double-orifice mitral valve: A study of 27 postmortem cases with developmental, diagnostic and surgical considerations

What is double-orifice mitral valve anatomically and embryologically? In 27 postmortem cases, an anomaly of the tensor apparatus was always found. These malformations may be summarized as: (1) chordal ring; (2) accessory papillary muscle or muscles; (3) subdividing muscular ridge; (4) fused papillary muscles (parachute mitral valve); (5) crossing chordae tendineae; and (6) central fibrous subdivision. More than 1 of these anomalies often coexisted per case. Double-orifice mitral valve almost always consisted of abnormal holes in essentially normal leaflets, rather than of abnormal fibrous bridges or adhesions between normal leaflets. Since these fibrous “bridges” between the smaller accessory orifice and the larger main orifice are composed of mitral leaflet tissue and chordae, not fibrous adhesions, these bridges should not be transected surgically, to avoid iatrogenic mitral regurgitation. The accessory (smaller) orifice was at the anterolateral commissure in 11 cases (41%), at the posteromedial commissure in 12 (44%) and there was a central fibrous subdivision with approximately equal-sized orifices in 4 (15%). The atrioventricular (AV) canal was normally divided in 12 cases (44%) and a common AV canal was present in 15 (56%). When the accessory orifice was at the anterolateral commissure, the AV canal usually was normally divided (8 of 11, 73%). But when the accessory orifice was at the posteromedial commissure, a common AV canal almost always was present (11 of 12, 92%). Functionally, the mitral valve was normal in 13 (48%), regurgitant in 7 (26%) and stenotic in 7 cases (26%). The key to the diagnostic and surgical understanding of the double-orifice mitral valve is the underlying tensor apparatus.

Two dimensional echocardiography in mitral, aortic and tricuspid valve prolapse: The clinical problem, cardiac nuclear imaging considerations and a proposed standard for diagnosis

The mitral valve prolapse syndrome may present with a variety of clinical manifestations and has proved to be a common cause of nonspecific cardiac symptoms in clinical practice. Primary and secondary forms must be distinguished. Myxomatous degeneration appears to be the common denominator of the primary form. The diagnostic standard of this form has not previously been defined because the detection of mitral leaflet tissue in the left atrium (prolapse) on physical examination or angiography is nonspecific. M mode echocardiography has greatly enhanced the recognition of this syndrome but has not proved to be the best diagnostic standard because of its limited view of mitral valve motion. The advent of two dimensional echocardiography has provided the potential means for specific identification of the mitral leaflet motion in systole and can be considered the diagnostic standard for this syndrome. Primary myxomatous degeneration with leaflet prolapse is not localized to the mitral valve. Two dimensional echocardiography has detected in preliminary studies tricuspid valve prolapse in up to 50 percent and aortic valve prolapse in about 20 percent of patients with idiopathic mitral valve prolapse.

Angiographic-echocardiographic correlation in mitral valve prolapse

Although mitral valve prolapse is easily identified with echocardiography, the angiographic diagnosis has been poorly understood. To determine relative specificity and sensitivity of recently established radiologic diagnostic criteria, prospective comparison of left ventriculograms with echocardiograms and clinical observations in patients undergoing routine cardiac catheterization from 1975 to 1977 and retrospective review of earlier catheterization data have been performed. Four types of normal mitral valve configurations were determined during protodiastole in the right anterior oblique (RAO) projection of left ventriculograms by identifying the fulcrum, the point of attachment of the mitral leaflets to the annulus fibrosus, and the fornix, that part of the left ventricular wall between the fulcrum and papillary muscles. Prolapse was present when mitral leaflet tissue extended inferiorly and posteriorly to the fulcrum during systole. Angiographic prolapse of the posteromedial commissural scallop of the posterior leaflet was diagnosed in RAO ventriculograms in 21 patients, approximately 1.9 per cent of the adult catheterization population. All of these patients also had positive echocardiograms. Three other patients had positive echocardiograms despite normal ventriculograms. In one of these three, isolated prolapse of the middle commissural scallop of the posterior leaflet was present. No patient with a normal mitral valve echocardiogram had an abnormal ventriculogram. The proposed angiographic criteria for mitral valve prolapse have eliminated false-positive diagnoses, and permitted accurate identification in approximately 88 per cent of cases. Improved imaging and additional left ventriculographic projections will probably improve sensitivity. The frequencies of angiographic, echocardiogrphic, and clinical diagnoses of mitral valve prolapse are not significantly different.

Fatigue-induced damage in glutaraldehyde-preserved heart valve tissue

Glutaraldehyde-preserved porcine mitral leaflet tissue has been subjected to extended accelerated fatigue loading in Ringer's solution containing 0.15% glutaraldehyde. Five tissue test pieces were subjected to cyclic tensile stresses of 50 and 200 Gm. per square millimeter and to 300 million to 800 million accumulated fatigue cycles. Tissue disruption occurred in each of the fatigued test pieces. Tensile loading, apart from reducing the acuteness of the collagen waveform and thereby decreasing tissue compliance, does not contribute significantly to the disruption process nor its rate of occurrence. Compressive flexure occurring during the unloading half of the fatigue cycle, however, does induce damage in the tissue. Mechanisms involved in the disruptive processes have been identified by conducting simultaneous morphologic and stress/strain observations on both the fatigued and unfatigued tissues in their wet functional condition. This vulnerability of the preserved tissue to compressive flexure could well affect the long-term durability of the glutaraldehyde-preserved heterograft valve, and this possibility is discussed in relation to the clinical use of these valves.