Osteopontin, also called cytokine Eta-1, is a multifunctional protein containing Arg-Gly-Asp-Ser (RODS) cell-binding sequence. It interacts with αvβ1, αvβ3 and αvβ5 integrins and CD44 receptors. OPN is suggested to play a role during inflammation via the recruitment and retention of macrophages and T-cells to inflamed sites. OPN regulates the production of inflammatory cytokines and nitric oxide in macrophages. In this review, we will discuss diverse roles of OPN related to cardiovascular diseases, including atherosclerosis, valvular stenosis, hypertrophy, myocardial infarction and heart failure.

Klaffvitier är några av de vanligaste hjärtsjukdomarna och studier visar att fysisk aktivitet är en viktig del av den kliniska diagnostiken speciellt för individer med symtomfri problematik. Fysisk aktivitet leder hos en del individer till typiska symtom för klaffvitium och ger således möjlighet till förbättrad gradering av klaffvitier jämfört med i vila. Syftet med studien är att ekokardiografiskt studera eventuell förändring av trikuspidalisklaffunktion i vila och efter lättare fysisk ansträngning, samt undersöka hypotesen om trikuspidalisinsufficiens samt tryckgradienten över trikuspidalisklaffen förändras i samband med denna typ av diagnostik. Sexton deltagare inkluderas vid anamnes på andfåddhet eller ansträngningsutlösta hjärtbesvär samt även fynd av trikuspidalisinsufficiens i samband med ordinarie undersökningstillfälle. Även de med känd trikuspidalis-insufficiens sedan tidigare inkluderades. Efter ordinarie ekokardiografisk undersökning som individerna var remitterade till fick inkluderade deltagare utföra ett cykeltest på ergometercykel under sex minuter med en lättare belastning. Ultraljudsbilder på hjärtat samlades in direkt efter avslutad ansträngning. Två variabler, tryckgradient före respektive efter ansträngning över trikuspidalisklaffen, analyserades enligt dess differens och därefter analyserades differenserna i förhållande till nollhypotesen. Medianvärden av variablerna jämfördes i Wilcoxons teckenrangtest och med Spearmans rangkorrelation studerades förhållandet mellan stigande hjärtfrekvens samt tryckgradient vid fysisk ansträngning. Studien visade att tryckgradienten hos trikuspidalis-insufficiensen förändrades vid utförande av lättare fysisk ansträngning hos individer med ansträngningsutlösta hjärtbesvär samt att denna form av undersökning i anslutning till ordinarie undersökningstillfälle kan vara av värde bland individer med anamnes på ansträngningsutlösta hjärtbesvär. / Valvular heart disease are one of the most common heart diseases and previous studies have shown that exercise is an important part of the clinical diagnostics, especially in asymphtomatic individuals. In some cases, exercise lead to typical symptoms of valvular heart disease and improved grading compared to rest. The aim of the present study was to analyze tricuspid valvular function in rest compared to exercise and examine whether or not tricuspid regurgitation and pressure gradient over the tricuspid valve will alter after exercise. Sixteen participants was included with anamnesis of dyspnea or cardiac symptoms related to exercise as well as findings of tricuspid regurgitation during the echocardio-graphic examination. Individuals with known tricuspid regurgitation were also included. After the transthoracic echocardiographic examination, included individuals performed a bicycle test for six minutes with light workload. Additional ultrasound images of the heart was collected immediately after finished bicycle test. Two variables, pressure gradient over the tricuspid valve before and after right exercise, were analyzed according to its difference and then the differences were analyzed relative to the zero hypothesis. Median values of the variables were compared in Wilcoxon's signed-rank test and Spearman's rank correlation analyzed the relationship between increasing heart rate and pressure gradient under the influence of exercise. This study has shown that the pressure gradient of the tricuspid regurgitation changes in the performance of light exercise in individuals with history of dyspnea or cardiac symptoms related to exercise. It also showed the value of an exercise test in adherence to the echocardiographic examination in this group of individuals.

Tesla valve applications for passive flow enhancement in micro fluidic applications are promising, because of its design of no-moving-parts. The effectiveness of the valve (measured via its pressure and thermal diodicity) can be increased by creating a multi-staged Tesla valve. Present study investigates the effect of varying Reynolds number (25-200) on flow rectification and thermal enhancement capability of a Tesla valve. Gamboa Morris Forster (GMF) design with a cross-section of 1mm2 and constant valve-to-valve distance (1mm) was utilized for this research. An arbitrary fluid with constant properties at a reference temperature was used as the working fluid. Periodicity in flow and thermal distribution are noticed in the latter part of MSTV. Average friction factor and pressure diodicity decreased with increasing Reynolds number whereas average Nusselt number and thermal diodicity increased. Correlations for friction factor, pressure diodicity, Nusselt number, and thermal diodicity were derived by fitting a non-linear curve fit model.

This thesis is focused on the nursing care for patient after valvular defects surgery. The aim of this final paper is to ascertain the principles of specialized nursing care for patient after valvular defects surgery, analyse the condition of written standards for providing aftercare to patients who underwent valvular defects surgery, or the state of the nursing protocols in specialized nursing care. The purpose of qualitative - observational research in providing specialized nursing care is to find an answer to the question of whether the specifics of nursing care in Prague cardiac centres are significantly different. The theoretical section contains chapters describing cardiac centres, the history of surgical treatment of heart valves, and the most common valvular heart defects in adulthood. In the theoretical section of this study, I focus in detail on the nursing care for patients following cardiac procedure, ensuring not to forget the monitoring of physiological functions, artificial pulmonary ventilation, and immediate position after elective cardiac surgery. The empirical section is divided into quantitative and qualitative research. The quantitative empirical investigation is focused on an anonymous questionary survey that has been applied in three Prague cardiac centres. Approximately 150...

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Un lien entre certaines dysfonctions du système sérotoninergique et la survenue de valvulopathies a été suggéré par les lésions valvulaires observées au cours de l’utilisation chronique de certains agonistes des récepteurs 5-HT2 (dérivés de l’ergot de seigle, fenfluramine) et les atteintes tumorales carcinoïdes (qui entrainent une augmentation des taux de 5-HT circulante). Les lésions dégénératives associent une fibrose, une sténose et/ou une régurgitation des valves pouvant conduire à de nombreuses complications cardiovasculaires. À l’heure actuelle, il n’existe aucune thérapeutique pouvant freiner ou faire régresser les lésions. Nos travaux démontrent à partir de modèles animaux et cellulaires, l’implication effective des récepteurs 5-HT2B et 5-HT2A dans l’initiation des lésions. L’analyse histologique des valves à partir de nos modèles animaux a révélé la contribution des cellules endothéliales au cours des stades précoces. Ces cellules sont des progéniteurs endothéliaux (CD34+) recrutés à partir de la moelle au sein de la valve sous la stimulation des récepteurs 5-HT2 et par un mécanisme intracellulaire impliquant la eNOS. Des travaux ultérieurs permettront de mieux caractériser les différents types cellulaires et les biomarqueurs d’initiation du processus afin de déterminer de nouvelles pistes thérapeutiques. / Several studies have reported a strong correlation between the development of cardiac valve injury and some dysfunctions of the serotonergic system. Valve lesions are observed during the chronic use of some 5-HT2 receptors agonists (ergot derivates or fenfluramine derivatives) or are secondary to metastatic carcinoid tumours (with increased circulating 5-HT amount). These lesions show fibrosis, with thickened leaflets, valves stenosis and/or regurgitation followed by several cardiovascular complications. There is no medical treatment to stop or alter the natural course of the lesions. Surgical replacement by prosthesis is the only effective therapy. Our study based on animal and cellular pharmacological models, demonstrates the serotonergic system contribution through 5-HT2B and 5-HT2A receptors in the pathogenesis of valve degeneration. Histological analysis of the lesions reveals the contribution of endothelial cells to the initiation process. These cells are probably endothelial progenitors (CD34+) recruited inside the valve implying a NO-dependent mechanism. Further studies will characterize the specific cells to find biomarkers of valve remodelling initiation and at term, will identify best therapeutic targets around the serotonergic system.

Heart valve disease (HVD) or a damaged valve can severely compromise the heart's ability to pump efficiently. Balloon valvuloplasty is preferred on neonates with aortic valve stenosis. Even though this procedure decreases the gradient pressure across the aortic valve, restenosis is observed soon after balloon intervention. Tissue engineering heart valves (TEHV), using bone marrow stem cells (BMSCs) and biodegradable scaffolds, have been investigated as an alternative to current non-viable prosthesis. By observing the changes in hemodynamics following balloon aortic valvuloplasty, we could uncover a potential cause for rapid restenosis after balloon intervention. Subsequently, a tissue engineering treatment strategy based on BMSC mechanobiology could be defined. Understanding and identifying the mechanisms by which cytoskeletal changes may lead to cellular differentiation of a valvular phenotype is a first critical step in enhancing the promotion of a robust valvular phenotype from BMSCs.

Introduction and Objectives Calcific aortic valve disease (CAVD) is the most common valvular disease, accounting for 50% of all valve disorders and is the third most common cardiovascular disease following coronary disease and hypertension.[1,2] Currently, there is no pharmacological agent capable of reversing or slowing down the progression of CAVD and treatment of severe cases consists of surgical repair or valve replacement[2]. Hence, there is a crucial need for earlier detection using predictive biomarkers that will allow for preventative intervention as opposed to post-symptomatic disease treatment or management. Namely, one target of particular interest is the expression of matrix metalloproteinases (MMPs) (specifically MMP-1, -2, and -9) which are upregulated in CAVD prior to calcification events and have been previously shown to serve as an attractive molecular imaging target.1–3 The primary objective of this study is to assess the feasibility of detecting biomarkers of CAVD by various in vivo imaging modalities, such as PET and echocardiography. In addition, this study assesses disease progression in various mouse strains to qualify an appropriate CAVD animal model. Methods In vivo and ex vivo imaging of C57Bl/6 and ApoE-/- (n = 8 per strain cohort) mouse models are used to link unique features of matrix remodelling with CAVD progression. At baseline and longitudinal follow-up (4, 8, and 12 months), in vivo hemodynamic impairment is assessed through echocardiography, and calcification and MMP activity are measured using PET with a series of radiotracers: [18F]NaF for calcification, [18F]BR351 for the molecular targets of MMP-2 and -9, and [18F]FMBP with molecular target specificity for MMP-13. Following imaging, aortic valve (AV) tissue is harvested, sectioned, and analyzed for calcification, inflammatory markers, collagen types, and MMP activity in AV leaflets. Tracer autoradiography, immunofluorescence, and in situ zymography are used to confirm in vivo imaging results with improved resolution and quantification in valves. Histological sample preparation, experimentation, and analyses are then repeated in human AV tissue samples for relative comparison of biomarker expression in animal models. Results Echocardiography suggests positive signs of disease progression in experimental animal models. In comparison to WT, ApoE-/- mice show: increased peak velocity (p<0.0001), decreased aortic valve area (p<0.001), and irregular valve dynamics. [18F]NaF PET imaging shows expected bone uptake and low calcium-burden in young and WT animals. [18F]FMBP shows increased uptake in the valve area of diseased models at later timepoints, 1.530 compared to <0.001 %ID/g (p<0.005), in disease vs control animals respectively. Furthermore, confirmation of sought-after biomarkers has also been assessed by analysis of various histological sample preparations including the presence of leaflet calcification, upregulation of MMP-2, -9, and -13, matrix remodelling, lipids, inflammatory markers, and activated MMP expression. Conclusion Findings from this study suggest that molecular imaging techniques using target-specific radiotracers, as well as echocardiography for assessment of hemodynamic impairment, are feasible solutions in predicting disease onset in CAVD specific animal models.

Résumé - Les données concernant la prise en charge chirurgicale de la maladie tricuspidienne reposent sur des études de cohortes à petite échelle et peu d’entre elles se sont intéressées aux résultats échocardiographiques et aux facteurs de risque de mortalité et de morbidité. Une étude de cohorte rétrospective descriptive et analytique fut effectuée pour analyser l’expérience de l’Institut de Cardiologie de Montréal concernant la chirurgie de la VT. Les données ont été récoltées à l’aide des dossiers médicaux. Durant la période 1977-2008, 792 PVT et 134 RVT furent effectués (âge médian : 62 ans). La mortalité opératoire était de 13,8%. Les taux de survie actuarielle à 5, à 10 et à 15 ans étaient respectivement de 67±2%, de 47±2% et de 29±2%. Au dernier suivi, de l’IT ≥3/4 était présente chez 31% des patients du groupe PVT et chez 12% des patients du groupe RVT (p<0,001). La classe fonctionnelle NYHA s’est améliorée significativement au dernier suivi par rapport à la période pré-opératoire (p<0,001). L’analyse de propension montre que par rapport à une PVT, un RVT est associé significativement à des taux de mortalité opératoire et tardive accrus, mais à moins d’IT ≥2/4 ou ≥3/4 lors du suivi. Cette étude montre que malgré le risque chirurgical substantiel associé à la chirurgie de la VT, les patients bénéficient d’une amélioration fonctionnelle significative. Les facteurs de risque de mortalité et de morbidité sont décrits et des études de sous-groupes sur la chirurgie tri-valvulaire et la chirurgie isolée de la VT sont exposées. / Abstract - Data regarding surgical management of tricuspid valve disease are based on small cohort studies, and only few of them report echocardiographic results or risk factors for mortality and morbidity. A retrospective descriptive and analytic cohort study was performed in order to analyze the Montreal Heart Institute experience regarding tricuspid valve surgery. Data was extracted from the medical files of patients. During the 1977-2008 period, 792 tricuspid valve repairs and 134 tricuspid valve replacements were performed (median age of patients: 62 years). Operative mortality was 13.8%. Actuarial survival rates at 5, 10, and 15 years were 67±2%, 47±2%, and 29±2%, respectively. At last follow-up, 31% of patients who underwent repair and 12% of patients who underwent replacement had tricuspid regurgitation ≥3/4 (p<0,001). NYHA functional class improved significantly at last follow-up compared to baseline (p<0,001). Propensity score analysis showed that a replacement was associated with increased operative and late mortality rates compared to repair, but with less tricuspid regurgitation ≥2/4 or ≥3/4 at follow-up. The study shows that despite substantial mortality rates, patients experience a significant functional improvement following tricuspid valve surgery. Risk factors for mortality and morbidity are described, and sub-group analyses for triple valve surgery and for isolated tricuspid valve surgery are exposed.

Résumé - Les données concernant la prise en charge chirurgicale de la maladie tricuspidienne reposent sur des études de cohortes à petite échelle et peu d’entre elles se sont intéressées aux résultats échocardiographiques et aux facteurs de risque de mortalité et de morbidité. Une étude de cohorte rétrospective descriptive et analytique fut effectuée pour analyser l’expérience de l’Institut de Cardiologie de Montréal concernant la chirurgie de la VT. Les données ont été récoltées à l’aide des dossiers médicaux. Durant la période 1977-2008, 792 PVT et 134 RVT furent effectués (âge médian : 62 ans). La mortalité opératoire était de 13,8%. Les taux de survie actuarielle à 5, à 10 et à 15 ans étaient respectivement de 67±2%, de 47±2% et de 29±2%. Au dernier suivi, de l’IT ≥3/4 était présente chez 31% des patients du groupe PVT et chez 12% des patients du groupe RVT (p<0,001). La classe fonctionnelle NYHA s’est améliorée significativement au dernier suivi par rapport à la période pré-opératoire (p<0,001). L’analyse de propension montre que par rapport à une PVT, un RVT est associé significativement à des taux de mortalité opératoire et tardive accrus, mais à moins d’IT ≥2/4 ou ≥3/4 lors du suivi. Cette étude montre que malgré le risque chirurgical substantiel associé à la chirurgie de la VT, les patients bénéficient d’une amélioration fonctionnelle significative. Les facteurs de risque de mortalité et de morbidité sont décrits et des études de sous-groupes sur la chirurgie tri-valvulaire et la chirurgie isolée de la VT sont exposées. / Abstract - Data regarding surgical management of tricuspid valve disease are based on small cohort studies, and only few of them report echocardiographic results or risk factors for mortality and morbidity. A retrospective descriptive and analytic cohort study was performed in order to analyze the Montreal Heart Institute experience regarding tricuspid valve surgery. Data was extracted from the medical files of patients. During the 1977-2008 period, 792 tricuspid valve repairs and 134 tricuspid valve replacements were performed (median age of patients: 62 years). Operative mortality was 13.8%. Actuarial survival rates at 5, 10, and 15 years were 67±2%, 47±2%, and 29±2%, respectively. At last follow-up, 31% of patients who underwent repair and 12% of patients who underwent replacement had tricuspid regurgitation ≥3/4 (p<0,001). NYHA functional class improved significantly at last follow-up compared to baseline (p<0,001). Propensity score analysis showed that a replacement was associated with increased operative and late mortality rates compared to repair, but with less tricuspid regurgitation ≥2/4 or ≥3/4 at follow-up. The study shows that despite substantial mortality rates, patients experience a significant functional improvement following tricuspid valve surgery. Risk factors for mortality and morbidity are described, and sub-group analyses for triple valve surgery and for isolated tricuspid valve surgery are exposed.