Thèse--Méd.--Reims, 1974. N°: N° 9. / Bibliogr. ff. I-XXX.

In calcific aortic valve disease, the early sclerotic valve lesion is similar to the atherosclerotic arterial plaque, but at the later stage calcification prevails. Our aim was to assess the association of several new potential risk factors, eg. systemic inflammation, neurohormonal activation and altered calcium metabolism with aortic stenosis (AS) in patients with significant coronary artery disease..

BACKGROUND: Treatment of left-sided Infective Endocarditis (IE) is challenging due to the presence of both surgical and medical interventions. The choice typically depends on the patient’s surgical risk and severity of infection. Our aim is to compare outcomes of IE patients who undergo valve replacement surgery with patients who are treated with solely antibiotics. METHODS: Patients undergoing valve surgery at our institution from 1995 to 2014 (n=196) and patients who were treated medically for IE from 2001 to 2014 (n=120) were included in this study. In total, 316 patients were included and clinical data was retrospectively collected from chart review. Society of Thoracic Surgeons (STS) Scores were calculated to assess for surgical risk and data for preoperative fever, angina, and abscess was collected to assess for severity of infection. The primary outcome of interest was mortality at 30 days and 1 year post-treatment and secondary outcomes included post-treatment development of septic shock, MI, embolic events, recurrence of infection, stroke, and renal dysfunction. Cox regression analyses were performed to assess the likelihood of mortality based on the patient’s pre-intervention comorbidities and characteristics. A Kaplan-Meier Analysis was also conducted to assess for survival at both 30 days and 1 year. RESULTS: Pre-operative fever (68.88% surgical vs 52.50% medical, p=0.002), angina (13.78% surgical vs 2.50% medical, p<0.05), and presence of abscess (33.37% surgical vs 6.67% medical, p<0.05) were significantly higher in the surgical population. Mortality at both 30-days (7.65% surgical vs 29.17% medical, p<0.05) and 1 year (17.35% surgical vs 46.67% medical, p<0.05) was significantly higher in the medical cohort. Mortality in patients presenting with valvular abscess was significantly higher in the surgical population at 30 days (4.5% surgical vs 62.5% medical, p<0.05) and 1 year (15.15% surgical vs. 75.00% medical, p<0.05). Surgical risk was significantly higher in medical patients overall (p<0.05), but not significantly higher in the pathogen specific subgroups. By individual pathogen, medical mortality was significantly higher at both 30 days and 1 year in the MRSA (p=0.0004 and p=0.0002) and Staphylococcus population (p=0.001 and p=0.0005) but only significantly higher in the Streptococcus population at 1 year (p=0.032). CONCLUSION: Valve Replacement Surgery in patients with left-sided MRSA and non-MRSA Staphylococcus IE leads to significantly better mortality outcomes at 30 days and 1 year than medical management. Specifically, we suggest that patients with preoperative valvular abscess undergo valve replacement surgery, regardless of pathogen, and that patients with MRSA and non-MRSA Staphylococcus IE be strongly considered for surgical intervention.

La bicuspidie aortique représente la malformation cardiaque congénitale la plus fréquente, affectant environ 2% de la population. Paradoxalement, le mécanisme de dégénérescence accélérée d’une valve bicuspide n’est pas encore élucidé. Ce travail s’appuie sur l’analyse de modèles animaux et sur l’analyse d’une cohorte prospective de 300 patients porteurs d’une valve aortique bicuspide.Notre cohorte de 300 patients nous a permis de chercher à identifier de nouveaux gènes impliqués dans la bicuspidie aortique par des approches de séquençage nouvelle génération, mais aussi par une approche de gène candidat. La comparaison des données cliniques et échographiques des patients porteurs de bicuspidie aortique avec et sans dysfonctionnement nous a permis d’établir une corrélation entre le phénotype de la bicuspidie et fonction valvulaire.Ce travail a eu pour objectif d’améliorer la compréhension de la physiopathologie de la bicuspidie aortique en identifiant de nouveaux gènes candidats et d’acquérir une meilleure connaissance du processus de dégénérescence valvulaire accélérée par le biais de modèles murins et d’études cliniques. / Bicuspid Aortic Valve (BAV) is the most common congenital heart defect, affecting about 2% of the population. BAV is a heritable trait, but the genetic basis underlying this defect remains unclear. BAV is associated with an excess of morbidity and mortality related to several complications such as accelerated valve degeneration that required earlier and more frequent referral for surgery. Despite its burden, the mechanism underlying BAV degeneration has not been elucidated. Aortic valve replacement constitutes a late response to a disease whose diagnosis is often carried out earlier, at the stage of non-severity. My thesis aims to identify the pathophysiology of BAV and to investigate the mechanisms involved in BAV degeneration. Thus, this study was based on the analysis of animal models and on the examination of a prospective cohort of 300 patients with BAV. Three hundred patients with BAV were prospectively included in our cohort to identify new genes involved in BAV by next generation sequencing and candidate-gene approach. The objective of this thesis was to improve our understanding of the pathophysiology of BAV and to assess the mechanisms underlying BAV degeneration by analyzing animal and clinical models.

Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated, and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically-inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Further, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects. This work suggests that Wnt/β-catenin maintains a subpopulation of valve mesenchyme in a less-differentiated, progenitor-like state that allows these cells to respond to mitogens and morphogens. The coordinated interplay of signals with distinct effects on a “progenitor cell” pool is a common logic mechanism for balanced tissue growth and differentiation in many biological contexts. Inspired by epithelial organ homeostasis processes, we identified specific and dynamic expression of the well-established quiescent stem cell marker Lrig1 in the developing valves. Endocardial Lrig1 likely moderates ErbB2 levels and thereby signaling output to prevent excessive EMT and resulting pathologically enlarged valves. Finally, we use Cre-mediated lineage labeling to show that the cusps of the semilunar valves have differential mesenchymal origins and that the localization of said distinct mesenchyme may account for the discretely patterned extracellular matrix of mature valves. This dissertation includes previously published and unpublished coauthored material. / 10000-01-01

The content of this master‘s thesis is a study of diaphragm pump with linear drive. Linear motor was used as the linear drive. Thesis is well – founded by theoretic calculation of pump and its design draft. Likewise, the thesis includes optimalization of suction, or pressure, valve for pump, created by using computer fluid dynamics software. Thesis is complemented by basic view of different types of pumps based on the classification by hydrodynamic and hydrostatic pumps. Subsequently, the preview of blood – flow pumps is presented.

No description available.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, for the degree of Doctor of Philosophy. Johannesburg, South Africa September 2017. / Although brachial blood pressure (BP) is a well-recognized risk factor for predicting cardiovascular events, aspects of aortic BP may enhance risk prediction. Pulse pressure (PP) is amplified from the aorta to peripheral arteries and variations in differences between brachial and aortic PP (PP amplification) are determined by factors that influence either the aortic forward (Pf) or backward (Pb)(reflected) pressure waves. Although aortic Pb may be more important than Pf in mediating cardiovascular risk, the best approach to assessing backward wave function (augmentation pressures [Pa] and index [AIx] or wave separation analysis); the relative impact of aortic Pb versus Pf on cardiovascular damage; and whether the ability of aortic-to-brachial PP amplification (PPamp) to add to risk prediction reflects backward or forward wave effects, is uncertain. In the present thesis I therefore first assessed in 808 community participants whether gender influences relations between Pa or AIx and left ventricular mass (LVM), a well-accepted end-organ measure. Aortic haemodynamics were determined using radial applanation tonometry and SphygmoCor software and LVM from echocardiography. In men, both AIx derived from Pa/central aortic PP (Pa/PPc) (p<0.01) and AIx derived from the second peak/first peak (P2/P1) of the aortic pulse wave (p<0.0005) were associated with LVM. In contrast, in women neither AIx derived from Pa/PPc (p=0.08) nor AIx derived from P2/P1 (p=0.17) were associated with LVM. Both the strength of the correlations (p<0.001 and p<0.0005) and the slope of the AIx-LVM relationships (p=0.001 and p<0.0005) were greater in men as compared to women. Therefore, in the present study I show that AIx is independently associated with LVMI in men, but not in women. I subsequently evaluated whether in women, measures of aortic systolic pressure augmentation (Pa or AIx) underestimate the effects of reflected waves on cardiovascular risk or whether Pb plays little role in cardiovascular risk prediction. In the same community sample I therefore evaluated sex-specific contributions of reflected (Pb and the reflection index [RI]) versus augmented (Pa and AIx) pressure wave indices to iii variations in PPc (n=1185, 65.0% women), and LVM (n=793, 64.9% women). Aortic Pb and Pf were determined using wave separation analysis. In both women and in men, independent of confounders, RI and Pb contributed more than Pf, whilst Pa and AIx contributed less than incident wave pressure (Pi) to variations in PPc (p<0.0001 for comparison of partial r values). In both men and in women Pb contributed more than Pf (p<0.05) to variations in LVM. Although in men Pa (partial r=0.33, p<0.0001) contributed to a similar extent as Pi ((partial r=0.34, p<0.0001) to variations in LVMI, in women Pa (partial r=0.05, p=0.36) failed to contribute to LVM, whilst Pi was significantly associated with LVM (partial r=0.30, p<0.0001). Similar results were obtained with AIx as opposed to Pa in the regression models. Therefore, in both women and in men, Pb is more closely associated with PPc and LVM than Pf, but indices of aortic pressure augmentation markedly underestimate these effects, particularly in women. As the relative impact of aortic Pb as compared to Pf on cardiovascular damage independent of brachial BP is uncertain, in 1174 participants from a community sample I subsequently assessed the relative impact of Pb and Pf on variations in LVM (n=786), aortic pulse wave velocity (PWV)(n=1019), carotid intima-media thickness (IMT)(n=578), transmitral early-to-late LV diastolic velocity (E/A)(n=779) and estimated glomerular filtration rate (eGFR)(n=1174). Independent of mean arterial pressure and confounders, PPc and both Pb and Pf were associated with end-organ measures or damage (p<0.05 to <0.0001). With adjustments for brachial PP and confounders, Pb remained directly associated with LVM (partial r=0.10, p<0.01), PWV (partial r=0.28, p<0.0001), and IMT (partial r=0.28, p<0.0001), and inversely associated with E/A (partial r=-0.31, p<0.0001) and eGFR (partial r=-0.14, p<0.0001). Similar relations were noted with the presence of end-organ damage (p<0.05 to <0.0001). In contrast, with adjustments for brachial PP and confounders, Pf no longer retained direct relations with LVM, PWV, and IMT or inverse relations with E/A and eGFR. Adjustments for Pb, but not Pf diminished brachial PP-independent relationships between PPc and end-organ measures. Thus, although both Pf and Pb contribute to end-organ measures and damage, independent of brachial iv BP, the impact of aortic BP is accounted for largely by Pb. PPamp is independently associated with cardiovascular outcomes. However, the aortic functional change most likely to account for this effect is uncertain. In 706 community participants I subsequently aimed to identify the aortic functional change that accounts for relations between PPamp and LVM. In multivariate models with the inclusion of brachial PP, 1/PPamp (partial r=0.12, p<0.005), Pb (partial r=0,09, p<0.05), and aortic PWV (partial r=0.09, p<0.05) were independently associated with LVMI. Similarly, in multivariate models with the inclusion of brachial PP, 1/PPamp (p<0.005), Pb (p<0.01), and aortic PWV (p<0.01) were independently associated with LV hypertrophy (LVH). With adjustments for Pb, the brachial PP-independent relationships between 1/PPamp and LVMI or LVH were abolished (p>0.08 for both). However, adjustments for PWV failed to modify brachial PP-independent relations between 1/PPamp and LVMI or LVH. Hence, independent relations between PPamp and LVM or LVH are largely accounted for by Pb. In conclusion, in the present thesis I show that the use of augmented pressures underestimates the impact of reflected pressure wave effects on end-organs, particularly in women; that brachial BP-independent relations between aortic BP and end organs is determined largely by Pb and that relations between PPamp and end organ measures is largely accounted for by Pb. These findings add to our understanding of the adverse effects of aortic functional changes on the cardiovascular system and suggest cost-effective approaches to add to risk prediction. / LG2018

In calcific aortic valve disease, the early sclerotic valve lesion is similar to the atherosclerotic arterial plaque, but at the later stage calcification prevails. Our aim was to assess the association of several new potential risk factors, eg. systemic inflammation, neurohormonal activation and altered calcium metabolism with aortic stenosis (AS) in patients with significant coronary artery disease..

La sténose aortique à bas débit et bas gradient (SA-BD-BG) peut s’accompagner d’une fraction d’éjection ventriculaire gauche altérée (SA-BD-BG classique) ou préservée (SA-BD-BG paradoxale). Elles constituent un sous-ensemble de patients très difficile à caractériser. En effet, le défi chez les patients avec une SA-BD-BGest de distinguer entre une SA sévère d’une SA pseudo-sévère. L’établissement de la sévérité exacte de la SA est importante, car les patients ayant une SA réellement sévère bénéficient généralement d’un remplacement valvulaire aortique, mais sans intervention, ceux-ci auront un très mauvais pronostic. Malheureusement, les critères mesurés à l’échocardiographie au repos et à l’effort, utilisés pour détecter la sévérité de la SA selon les guides de pratique actuels, ne sont pas optimaux et par conséquent, une certaine proportion de patients ne sont pas bien diagnostiqués et ne reçoivent pas la thérapie appropriée. Il a été démontré dans notre groupe que chez les patients atteints d’une SA-BD-BG, l’aire valvulaire aortique projetée (AVAProj), mesurée à l’aide d’une échocardiographie au repos et à l’effort, est un meilleur prédicteur de sévérité de la SA et de mortalité que les critères habituels mesurés lors de l’échocardiographie au repos et à l’effort. Par contre, l’échocardiographie à l’effort ne peut être faite chez tous les patients et parfois, elle conduit à des résultats qui sont non concluants.Le degré de calcification de la valve aortique, mesuré par tomodensitométrie, est un autre paramètre utilisé pour confirmer la sévérité de la SA, mais les seuils diagnostiques et pronostiques ne sont pas encore optimisés chez les patients atteints d’une SA-BD-BG. Les hypothèses sont que l’aire valvulaire aortique projetée est équivalent au degré de calcification de la valve aortique pour 1) évaluer la sévérité de la SA et 2) pour prédire la mortalité toute cause chez les patients atteints d’une SA-BD-BG. L’objectif général de ce projet de maîtrise est de comparer l’aire valvulaire aortique projetée et le degré de calcification de la valve aortique pour évaluer la sévérité de la SA et prédire le devenir des patients atteints d’une SA-BD-BG. / Low flow, low gradient aortic stenosis (LF-LG-AS) may occur with depressed (classical LF-LG-AS) or with preserved (paradoxical LF-LG-AS) left ventricular ejection fraction. This entity is really difficult to characterize. Indeed, the challenge in this subgroup is to discriminate between a true-severe versus a pseudo-severe AS. It is important to determine the exact severity of AS, because patients with a true-severe AS will benefit from anaortic valve replacement and without intervention, their prognostic will be extremely poor. Unfortunately, rest and stress echocardiographic criteria recommended by the actual guidelines for patients with LF-LG-AS to assess AS severity are far from being optimal, and consequently, a substantial proportion of these patients stays misevaluated and may thus not receive the optimal therapy. Our group found that in patients with LF-LG-AS,projected aortic valve area (AVAProj), measured under rest and stress echocardiography, better predicts underlying AS severity and survival compared to traditional echocardiographic parameters. However, stress echocardiography is not possible in some patients and AS severity often remains indeterminate. The degree of aortic valve calcification, calculated by multi-detector computed tomography may be useful to confirm AS severity, but the optimal cut off values are not well established in patients with LF-LG-AS. The hypotheses related to this study are that projected aortic valve area is equivalent to the degree of aortic valve calcification to 1) evaluate AS severity and 2) to predict all-cause mortality in patients with LF-LG-AS. The general objective is to compare the projected aortic valve area and the degree of aortic valve calcification to evaluate AS severity and to predict mortality in patients with LF-LG-AS.