Valves Leaflets Research Articles

Pathophysiological aspects of morphological changes in the structure of atrioventricular valves leafl ets in diabetes mellitus

The increasing number of patients with diabetes in the structure of comorbid cardiothoracic patients necessitates a more detailed study of the pathophysiological mechanisms of the modifying infl uence of diabetes, taking into account new scientific data. This allows for a more systematic view of processes that were previously the prerogative of specialists. Content. A modern perspective on the pathophysiological mechanisms of diabetes on cardiac structures is presented, with a description of the two most signifi cant pathological syndromes — diabetic cardiomyopathy and changes in the morphological structure of the atrioventricular valve leafl ets. The expansion of the endocrinologist’s role in the examination and treatment of cardiothoracic patients is justifi ed. Conclusion. A systemic approach to the problem of diabetes in cardiothoracic surgery, incorporating a multidisciplinary approach and active involvement of endocrinologists at all stages of the treatment process, will improve treatment outcomes for cardiothoracic patients and reduce their postoperative recovery times.

Dental Pulp Stem Cells for Tissue Engineered Heart Valve

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.

Paroxetine Alters Cardiac Stress Markers in Rats with Aortic Regurgitation

Background: Aortic regurgitation (AR) is a valvulopathy that causes volume overload to the heart leading to left ventricle dilation and eccentric hypertrophy. A common co-morbidity associated with cardiovascular disease is depression. We have previously shown that paroxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, improves cardiac contractility by preserving fractional shortening (FS) of AR rat hearts. In failing hearts, decrease of the ability of the myocardium to generate an effective shortness velocity is well correlated with the shift of myosin isoform distribution from α to β- MyHC expression. In order to understand the molecular mechanism involved in the improvement of FS after paroxetine treatment, we verified the expression of genes involved in heart contractility and hypertrophy. Methods and Findings: Male Wistar rats were submitted to AR surgery, by retrograde puncture of the aortic valves leaflets, or sham surgery. Morphofunctional variables of the hearts were analyzed by echocardiograms at weeks 4 and 8 after the induction of AR. At week 8 the animals were euthanized for tissue collection and posterior analysis of gene expression by RTq-PCR. Paroxetine treatment for 4 weeks in AR rats reduced the gene expression of β-MyHC and its myomiRs (miR-208 and miR-499). BNP, a molecular biomarker of hypertrophy, also showed their gene expression reduction after paroxetine treatment. Conclusion: These results suggest that paroxetine treatment improves FS in AR hearts through reductions in the expression of several genes involved with cardiac contractility and hypertrophy.

Possibilities of Echocardiography at the Stages of Surgical Treatment of the Patient with the Mitral Valve Posterior Leaflet Prolapse Resulted in Mitral Insufficiency and Atrial Fibrillation (A Case Report)

The mitral valve prolapse is characterized by the degeneration of the valve leaflets, accompanied by their thickening, increasing surface area and flexibility. The mitral valves leaflets bulge (prolapse) beyond the plane of the atrioventricular ring into the left atrium during ventricular systole and lose the ability to close tightly, leading to the mitral regurgitation. Acute chord rupture of the mitral valve posterior leaflet is a rare but important cause of severe mitral regurgitation and the development of acute or progressive chronic heart failure. Acute mitral insufficiency, accompanied by hemodynamic disorders, requires an urgent valve plastic surgery or valve prosthetics. The mitral valve plastic surgery gives a number of undeniable advantages over prosthetics, providing the best hemodynamic parameters, saving the patient from lifelong receiving of anticoagulant drugs. Detailed qualified echocardiographic evaluation of all structures of the mitral valve (fibrous ring, MV leaflets by segments, overlapping structures, structure of the chordal apparatus, papillary muscles) provides the necessary information for the mitral valve reconstructive plastic surgery with the choice of the method that is most optimal for a certain patient at the preoperative stage. We report herein a clinical observation of the patient with a diagnosis: acquired heart disease, the mitral valve posterior leaflet prolapse with mitral insufficiency Grade 3. Chronic heart failure IIA. II FC. Atrial fibrillation. The patient underwent multicomponent mitral valve reconstruction with the creation of a neochord and the fibrous ring plastic on the duplicate of a PTFE strip (soft support ring), pairwise isolation of the pulmonary vein entrance and right cavotricuspid isthmus.

Promotion of adhesion and proliferation of endothelial progenitor cells on decellularized valves by covalent incorporation of RGD peptide and VEGF.

Tissue engineered heart valve is a promising alternative to current heart valve surgery, for its capability of growth, repair, and remodeling. However, extensive development is needed to ensure tissue compatibility, durability and antithrombotic potential. This study aims to investigate the biological effects of multi-signal composite material of polyethyl glycol-cross-linked decellularized valve on adhesion and proliferation of endothelial progenitor cells. Group A to E was decellularized valve leaflets, composite material of polyethyl glycol-cross-linked decellularized valves leaflets, vascular endothelial growth factor-composite materials, Arg-Gly-Asp peptide-composite materials and multi-signal modified materials of polyethyl glycol-cross-linked decellularized valve leaflets, respectively. The endothelial progenitor cells were seeded for each group, cell adhesion and proliferation were detected and neo-endothelium antithrombotic function of the multi-signal composite materials was evaluated. At 2, 4, and 8 h after the seeding, the cell numbers and 3H-TdR incorporation in group D were the highest. At 2, 4, and 8 days after the seeding, the cell numbers and 3H-TdR incorporation were significantly higher in groups C, D, and E compared with groups A and B (P < 0.05) and cell numbers and the expression of t-PA and eons in the neo-endothelium were quite similar to those in the human umbilical vein endothelial cells at 2, 4, and 8 days after the seeding. The Arg-Gly-Asp- peptides(a sequential peptide composed of arginine (Arg), glycine (Gly) and aspartic acid (Asp)) and VEGF-conjugated onto the composite material of PEG-crosslinked decellularized valve leaflets synergistically promoted the adhesion and proliferation of endothelial progenitor cells on the composite material, which may help in tissue engineering of heart valves.

Aortic valve disease and gamma-glutamyltransferase: Accumulation in tissue and relationships with calcific degeneration

Objective Degenerative aortic valve disease is characterized by some of the histological features of atherosclerotic lesions. Gamma-glutamyltransferase (GGT) has been recently implicated in pathogenesis of atherosclerosis, as well as in modulation of cells involved in calcium metabolism. We aimed to evaluate the possible implication of this enzyme activity in aortic valve disease. Methods GGT immunohistochemistry was performed on valve leaflets of 64 patients with aortic valve stenosis undergoing valve replacement. Fractional GGT activity in plasma and tissue was analysed in a subgroup of cases by molecular exclusion chromatography. Results A close association was found between tissue extracellular GGT staining and lipid deposits ( p < 0.0001). GGT was expressed by CD68-positive cells around neovessels, as well as by MMP-9- and TRAP-positive multinucleated cells in the vicinity of bone metaplasia areas. Total plasma GGT levels were associated with low HDL-c ( p = 0.028) and high triglycerides ( p = 0.017). Total GGT activity in tissue was negatively correlated with the extent of valves calcification ( p = 0.03). Both serum and tissue GGT levels were negatively associated with severity of valve stenosis, as judged by peak transvalvular pressure gradients ( p < 0.0003 and p < 0.002, respectively). Conclusions Accumulation of GGT activity inside the lipid component of valves leaflets suggests a common mechanism of lesion shaping underlying both atherosclerosis and degenerative aortic valve disease. Moreover, the finding of GGT expression in cells with an osteoclast-like phenotype, and its negative correlation with both valves calcification and degree of valvular stenosis lend additional support to the recently envisaged involvement of GGT in the homeostasis of calcified tissues.

Tricuspid and pulmonary valve involvement in carcinoid heart disease

A 55-year-old woman with a history of proven carcinoid syndrome due to an enterochromaffin ileal tumour was evaluated with transthoracic echocardiography for dyspnoea on exertion. The patient had flushing and severe diarrhoea. Urinary excretion of 5-hydroxyindoleacetic acid was 250 mmol/L per 24 hours. Treatment with a somatostatin analogue had been initiated 5 months earlier. Physical examination revealed a 3/6 systolic ejection murmur at the left upper sternal border. No signs of right-sided heart failure were found. The electrocardiographic data were within normal limits. Transthoracic two-dimensional echocardiography revealed restricted motion of the septal and anterior tricuspid valve leaflets both during systole and diastole, leading to an eccentric jet and mild to moderate tricuspid regurgitation (Fig. 1 and Movie 1). Continuous wave (CW) Doppler documented an associated tricuspid stenosis with a mean diastolic gradient of 5 mmHg (Fig. 2). The pulmonary valve was also involved, defined by a limited excursion of the pulmonary valve leaflets without a complete coaptation. CW Doppler of the pulmonary valve demonstrated the presence of both pulmonary stenosis defined by a mean gradient of 40mmHg (Fig. 3) and pulmonary regurgitation (Movie 2). No patent foramen ovale was found at contrast echocardiography. Pulmonary and tricuspid valves were replaced with bioprosthetic valves. A surgical view of the tricuspid and pulmonary valve revealed immobile, thickened and retracted pulmonary and tricuspid valves leaflets (Figs. 4 and 5). Characteristic echocardiographic features of advanced carcinoid heart disease include thickening, retraction of immobile tricuspid valve leaflets with associated tricuspid regurgitation in 90% of cases and pulmonary involvement, mainly immobility of the pulmonary valve cusps, in at least 50% of cases [1]. Contrast transthoracic echocardiography should be performed systematically, searching for a right-to-left atrial shunt through a patent foramen ovate [2].

Abstract 5839: Living Tissue Engineered Heart Valves Based On A Composite Self-Expandable Sandwich-Structured Scaffold And Autolgous Adult Stem Cells: First In Vivo Experiences Towards A Complete Minimally Invasive Approach

Background : A clinically relevant heart valve tissue engineering concept requires minimally invasive techniques for both cell harvest and valve implantation. Here, we present first experiences with autologous tissue engineered heart valves fabricated from composite self-expandable biodegradable scaffolds and adult stem cells implanted by minimally invasive procedures in a sheep model. Methods : Sandwich-structured heart valve scaffolds (n= 12) were fabricated from non-woven PLDLA meshes coated with electrospun PLDLA nanofibers and integrated in self-expanding nitinol stents. Scaffolds were seeded with either autologous ovine bone marrow (BMC; n= 4) or jugular vein-derived cells (JVC; n= 8) and cultured in bioreactors. After 9d, heart valves were endothelialized with autologous peripheral blood-derived endothelial progenitor cells and jugular vein-derived endothelial cells, respectively. After additional 3d, heart valves (n= 6) were implanted trans-apically in pulmonary position. Controls were analysed (n= 6) as to tissue formation and composition (histology, biochemical assays). Mechanical properties were determined by tensile tests. In vivo performance was assessed by echocardiography up to 4 weeks. Results : Histology revealed cell attachment and ingrowth into the scaffold material resulting in layered tissues with endothelialized, eNOS positive surfaces. Amounts of GAG and cell number were similar in all heart valves, comparable to native tissues. Collagen production was higher in BMC based heart valves compared to JVC-derived tissues (Hydroyproline amount 34% vs. 20% of native tissues). Mechanical profiles demonstrated physiological tissue strength (max. tensile stress 0.41± 0.21 MPa) but less elasticity (E-Moduli 1.89± 0.79 MPa) independent of the cell source. Echocardiography displayed in vivo functionality (transvalvular mean pressure gradient 10.36± 3.17 mm/Hg) with more flexibility of BMC based heart valves leaflets. Conclusions : These results demonstrate that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve implantation is feasible. This clinically relevant approach is currently investigated in long-term animal studies.

Periostin Is Required for Maturation and Extracellular Matrix Stabilization of Noncardiomyocyte Lineages of the Heart

The secreted periostin protein, which marks mesenchymal cells in endocardial cushions following epithelial-mesenchymal transformation and in mature valves following remodeling, is a putative valvulogenesis target molecule. Indeed, periostin is expressed throughout cardiovascular morphogenesis and in all 4 adult mice valves (annulus and leaflets). Additionally, periostin is expressed throughout the fibrous cardiac skeleton and endocardial cushions in the developing heart but is absent from both normal and/or pathological mouse cardiomyocytes. Periostin (peri(lacZ)) knockout mice exhibit viable valve disease, with neonatal lethality in a minority and latent disease with leaflet abnormalities in the viable majority. Surviving peri(lacZ)-null leaflets are truncated, contain ectopic cardiomyocytes and smooth muscle, misexpress the cartilage proteoglycan aggrecan, demonstrate disorganized matrix stratification, and exhibit reduced transforming growth factor-beta signaling. Neonatal peri(lacZ) nulls that die (14%) display additional defects, including leaflet discontinuities, delamination defects, and deposition of acellular extracellular matrix. Assessment of collagen production, 3D lattice formation ability, and transforming growth factor-beta responsiveness indicate periostin-deficient fibroblasts are unable to support normal valvular remodeling and establishment of a mature cardiac skeleton. Furthermore, pediatric stenotic bicuspid aortic valves that have lost normal extracellular matrix trilaminar stratification have greatly reduced periostin. This suggests that loss of periostin results in inappropriate differentiation of mesenchymal cushion cells and valvular abnormalities via a transforming growth factor-beta-dependent pathway during establishment of the mature heart. Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease.

Functional analysis of bioprosthetic heart valves

Glutaraldehyde-treated bovine pericardium is used successfully as bioprosthetic material in the manufacturing of heart valves leaflets. The mechanical properties of bovine pericardial aortic valve leaflets seem to influence its mechanical behaviour and the failure mechanisms. In this study the effect of orthotropy on tricuspid bioprosthetic aortic valve was analysed, using a three-dimensional finite element model, during the entire cardiac cycle. Multiaxial tensile tests were also performed to determine the anisotropy of pericardium. Seven different models of the same valve were analysed using different values of mechanical characteristics from one leaflet to another, considering pericardium as an orthotropic material. The results showed that even a small difference between values along the two axes of orthotropy can negatively influence leaflets performance as regard both displacement and stress distribution. Leaflets of bovine pericardium bioprostheses could be manufactured to be similar to natural human heart valves reproducing their well-known anisotropy. In this way it could be possible to improve the manufacturing process, durability and function of pericardial bioprosthetic valves.