Thèses : « Aortic valve stenosis (AVS) »

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Ma, Qixiang. « Deep learning based segmentation and detection of aorta structures in CT images involving fully and weakly supervised learning ». Electronic Thesis or Diss., Université de Rennes (2023-....), 2024. http://www.theses.fr/2024URENS029.

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La réparation endovasculaire des anévrismes aortiques abdominaux (EVAR) et l’implantation valvulaire aortique transcathéter (TAVI) sont des interventions endovasculaires pour lesquelles l’analyse des images CT préopératoires est une étape préalable au planning et au guidage de navigation. Dans le cas de la procédure EVAR, les travaux se concentrent spécifiquement sur la question difficile de la segmentation de l’aorte dans l’imagerie CT acquise sans produit de contraste (NCCT), non encore résolue. Dans le cas de la procédure TAVI, ils abordent la détection des repères anatomiques permettant de prédire le risque de complications et de choisir la bioprothèse. Pour relever ces défis, nous proposons des méthodes automatiques basées sur l’apprentissage profond (DL). Un modèle entièrement supervisé basé sur la fusion de caractéristiques 2D-3D est d’abord proposé pour la segmentation vasculaire dans les NCCT. Un cadre faiblement supervisé basé sur des pseudo-labels gaussiens est ensuite envisagé pour réduire et faciliter l’annotation manuelle dans la phase d’apprentissage. Des méthodes hybrides faiblement et entièrement supervisées sont finalement proposées pour étendre la segmentation à des structures vasculaires plus complexes, au-delà de l’aorte abdominale. Pour la valve aortique dans les CT cardiaques, une méthode DL de détection en deux étapes des points de repère d’intérêt et entièrement supervisée est proposée. Les résultats obtenus contribuent à l’augmentation de l’image préopératoire et du modèle numérique du patient pour les interventions endovasculaires assistées par ordinateur
Endovascular aneurysm repair (EVAR) and transcatheter aortic valve implantation (TAVI) are endovascular interventions where preoperative CT image analysis is a prerequisite for planning and navigation guidance. In the case of EVAR procedures, the focus is specifically on the challenging issue of aortic segmentation in non-contrast-enhanced CT (NCCT) imaging, which remains unresolved. For TAVI procedures, attention is directed toward detecting anatomical landmarks to predict the risk of complications and select the bioprosthesis. To address these challenges, we propose automatic methods based on deep learning (DL). Firstly, a fully-supervised model based on 2D-3D features fusion is proposed for vascular segmentation in NCCTs. Subsequently, a weakly-supervised framework based on Gaussian pseudo labels is considered to reduce and facilitate manual annotation during the training phase. Finally, hybrid weakly- and fully-supervised methods are proposed to extend segmentation to more complex vascular structures beyond the abdominal aorta. When it comes to aortic valve in cardiac CT scans, a two-stage fully-supervised DL method is proposed for landmarks detection. The results contribute to enhancing preoperative imaging and the patient's digital model for computer-assisted endovascular interventions

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Lopez, Marco Ana. « Low-flow low-gradient aortic stenosis : outcomes after aortic valve replacement ». Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667817.

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Aortic stenosis is the commonest valve disorder in the Western World. The natural history of the disease is very well described; with a decreased survival once symptoms occur. There is currently, no medical therapy available to reduce the natural progression of the aortic stenosis, and therefore, aortic valve replacement has been recognised as the standard of care treatment for symptomatic aortic stenosis, with TAVI having merged as alternative for those cases with high/prohibitive surgical risk. All types of aortic stenosis have in common a reduced valve area (AVA <1.0cm2), but depending on the mean gradients and the stroke volume index, there are different types: Normal-Flow High-Gradient (NFHG AS) and Low-Flow Low-Gradient (LFLG AS) aortic stenosis. The latter is further subdivided into Classical and Paradoxical forms depending on the ejection fraction value. NFHG AS is the most common type. The left ventricle is capable of generating a normal flow through the stenotic valve, that it is translated onto high gradients. This type has been thoroughly studied and has an excellent prognostic with aortic valve replacement, with very low in-hospital mortality and long-term survival similar to the age-matched population. LFLG AS, on the other hand, is defined by a reduced stroke volume (SVi < 35 ml/min) and a low gradient (mean gradient < 40mmHg). The Classical form (CLFLG AS) has impaired ventricular function. These patients have dilated ventricles that are not able to generate enough flow through the stenotic valve and hence the low gradient. Dobutamine stress echocardiography is key for the diagnosis of this subtype, as it differentiates it from the Pseudo-Severe aortic stenosis (in which the problem is not in the aortic valve but in the left ventricle, and therefore there is no benefit from aortic valve replacement) and it has also prognostic value by determining the contractile reserve. These patients have been reported to have the highest mortality post aortic valve replacement and a reduced long-term survival; however, those who survive achieve excellent functional class. The other subtype of LFLG, the Paradoxical form (PLFLG AS) has a preserved ventricular function. These patients have a ventricular restrictive physiology, with reduced SVi due to a combination of mechanism such as subendocardial fibrosis, concentric remodeling, impaired diastolic filling and high afterload. It is paramount here to confirm the diagnosis by accurate echocardiography, ruling out measurement errors and other causes of reduced SVi. PLFLG AS patients have worse prognosis than NFHG AS but better prognosis than CLFLG AS patients. The primary hypothesis of our research project was that aortic valve replacement could be performed in patients with LFLG AS with low in-hospital mortality. Therefore, with the objectives of determining operative and mid-term outcomes of surgical intervention in LFLG AS compared to NFHG AS, we conducted a retrospective analysis of all patients who underwent isolated aortic valve replacement in our centre. Primary end-points were mortality (in-hospital, at one and five years) and the secondary end-points analysed were postoperative complications and clinical status at follow-up. Patients in the LFLG AS group were significantly older and had more cardiovascular risk factors and comorbidities than the NFHG AS group. Despite those differences, in-hospital mortality was equivalent and remarkably low in both groups. As expected, LFLG AS patients had a reduced mid-term survival but those who survived remained in an excellent functional class. With the separate analysis of the LFLG AS subgroups, we confirmed that CLFLG AS had higher in-hospital and mid-term mortality than PLFLG AS patients. In both groups, the in-hospital mortality was remarkably low compared to previous literature reports. Aortic valve replacement provided symptomatic relief and excellent functional class during the mid-term follow-up as well as recovery of the ventricular function in most of the patients. Based on our results, we concluded that aortic valve replacement should be recommended for symptomatic severe LFLG AS.
La estenosis aórtica es la enfermedad valvular más frecuente en el tercer mundo. La historia natural de la enfermedad es bien conocida desde hace décadas, siendo una enfermedad con mal pronóstico a medio-corto plazo que hace necesario someter a estos pacientes a recambio valvular aórtico tras la aparición de síntomas. La forma mas común de estenosis aórtica, con flujo normal y gradiente alto, tiene un pronóstico excelente tras el recambio valvular aórtico, con una supervivencia similar a la de la población normal. Sin embargo, la estenosis aórtica de bajo-flujo y bajo-gradiente, es una entidad menos conocida y de peor pronóstico. Estos pacientes tienen una mortalidad mucho mayor tras recambio valvular aórtico y menor supervivencia a largo plazo. El diagnóstico en el bajo-flujo bajo-gradiente es vital para seleccionar correctamente los pacientes con estenosis aórtica que se beneficiarán de tratamiento quirúrgico, teniendo también valor pronóstico, dependiendo de la categoría de bajo flujo (Clásica o Paradójica) y otros determinantes como la presencia/ausencia de reserva contráctil del ventrículo izquierdo. Nuestra hipótesis fue que la estenosis aórtica de bajo-flujo y bajo-gradiente, pueden ser tratada con recambio valvular aórtico con una mortalidad hospitalaria similar a aquellos con flujo normal y alto gradiente. Los objetivos del proyecto fueron el análisis de resultados hospitalarios y a medio plazo (mortalidad hospitalaria, a 1 y 5 años) así como la clase funcional y recuperación de la función ventricular, en pacientes con estenosis aórtica de bajo-flujo bajo-gradiente sometidos a recambio valvular aórtico comparado con flujo normal alto-gradiente. Nuestros resultados nos llevan a la conclusión de que el recambio valvular aórtico en pacientes con estenosis aórtica de bajo-flujo bajo-gradiente se puede lograr con baja mortalidad quirúrgica, comparable con pacientes con flujo normal y alto gradiente. A pesar de que tener una mayor mortalidad a medio-plazo, los supervivientes exhiben una excelente clase funcional y desaparición de síntomas, que apoyan la indicación quirúrgica en estos pacientes.

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Paul, Anup K. « Assessment of the Severity of Aortic Stenosis using Aortic Valve Coefficient ». University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470672658.

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Rubino, A. S. (Antonino S. ). « Efficacy of the Perceval sutureless aortic valve bioprosthesis in the treatment of aortic valve stenosis ». Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526212289.

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Abstract Aortic valve stenosis (AS) is one of the most diffuse valvular diseases in developed countries. AS is a progressive disease, which usually results in serious life-threatening adverse events. Defining a treatment strategy for AS is a focus of cardiovascular research, although the topic is still controversial because of its related clinical and economical implications. Surgical aortic valve replacement (AVR),which is regarded as the gold standard for the treatment of severe symptomatic AS, affords excellent results, particularly in asymptomatic patients with good functional status. AVR requires the institution of cardiopulmonary bypass and aortic cross-clamping, and the duration of these procedures is directly associated with increasing morbidity and mortality, especially in patients with preoperative comorbidities. Accordingly, techniques aimed at decreasing the duration of cardiopulmonary bypass and aortic cross-clamping have the potential to improve postoperative outcomes of AVR. In the present study, we demonstrated that the Perceval sutureless bioprosthesis could significantly reduce the duration of the surgical procedure. This was associated with improved immediate postoperative outcomes and long-term freedom from adverse events. The use of a Perceval sutureless bioprosthesis can facilitate AVR through minimally invasive approaches and is associated with fewer transfusions of packed red cells compared to full sternotomy approaches, even with traditional stented bioprostheses. It could be expected that patients at intermediate-high risk would benefit more from the combination of a fast surgical procedure, performed with reduced surgical invasiveness. When compared to transcatheter aortic valve implantation (TAVI), the Perceval sutureless bioprosthesis was associated with increased incidence of device success as well as less paravalvular leak, with similar immediate and 1-year outcomes. Finally, AVR with the Perceval sutureless bioprosthesis provided excellent hemodynamics at rest and under high workload. The significant increase of effective orifice area under stress suggests that the Perceval sutureless bioprosthesis is the valve of choice for patients with small aortic annuli or when prosthesis-patient mismatch is anticipated
Tiivistelmä Aorttaläpän ahtauma on yksi yleisimmistä läppävioista kehittyneissä maissa. Aorttaläpän ahtauma on etenevä sairaus, joka yleensä johtaa vakaviin henkeä uhkaaviin haittatapahtumiin. Aorttaläpän ahtauman hoitotavasta keskustellaan kiivaasti sydän- ja verisuonitautien tutkimuksessa siihen liittyvien kliinisten ja taloudellisten vaikutusten vuoksi. Aorttaläppäleikkausta, jossa aorttaläppä korvataan proteesilla, on aina pidetty vaikean oireisen aorttaläpän ahtauman hoidon kultaisena standardina, koska sen tulokset ovat erinomaisia, etenkin oireettomilla potilailla, joilla sydämen toiminta on hyvä. Leikkaus vaatii sydän-keuhkokoneen käyttöä ja aortan sulkemista, joiden kesto on suoraan yhteydessä kasvavaan sairastavuuteen ja kuolleisuuteen erityisesti potilailla, joilla on muitakin sairauksia. Niinpä tekniikat, jotka lyhentävät sydän-keuhkokoneen käyttöaikaa ja aortan sulkuaikaa, voivat mahdollisesti parantaa aorttaläppäleikkauksen tuloksia. Tässä tutkimuksessa osoitettiin, että ompeleettoman biologisen Perceval-läppäproteesin käyttö vähensi merkittävästi leikkauksen kestoa. Tämä oli yhteydessä parantuneisiin lyhyen ja pitkän aikavälin tuloksiin leikkauksen jälkeen. Ompeleettoman biologisen Perceval-läppäproteesin käyttö voi helpottaa aorttaläppäleikkausta, koska se voidaan asentaa vähemmän kajoavasta avauksesta, ja siihen liittyy vähemmän punasolusiirtoja rintalastan kokoavaukseen verrattuna, myös silloin kun käytetään kokoavausta ja perinteisiä stenttibioproteeseja. Voisi olla odotettavaa, että keskisuuren tai suuren riskin potilaat hyötyisivät enemmän leikkauksesta, jossa yhdistyvät toimenpiteen nopeus ja vähäisempi kajoavuus. Katetriteitse asennettuun biologiseen keinoläppään (TAVI) verrattuna ompeleeton biologinen Perceval-läppäproteesi oli yhteydessä parempaan laitteen toimimiseen ja pienempään paravalvulaariseen vuotoon. Muut tulokset heti leikkauksen jälkeen ja yhden vuoden seurannassa olivat samanlaisia. Lopuksi voidaan todeta, että aorttaläppäleikkaukseen ompeleettomalla biologisella Perceval-läppäproteesilla liittyi erinomainen hemodynamiikka levossa ja korkean työkuorman aikana. Stressin aikaisen tehokkaan aorttaläpän aukon pinta-alan merkittävä kasvu osoittaa, että ompeleeton biologinen Perceval-läppäproteesi on hyvä valinta potilaille, joilla on pieni aorttaläpän aukko tai kun on odotettavissa proteesin ja potilaan yhteensopimattomuutta

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Peltonen, T. (Tuomas). « Endothelial factors in the pathogenesis of aortic valve stenosis ». Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514289880.

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Abstract Calcified aortic valve disease represents a spectrum of disease spanning from mild aortic valve sclerosis to severe aortic valve stenosis (AS), being an actively regulated disease process and showing some hallmarks of atherosclerosis. The calcified aortic valve lesion develops endothelial injury and is characterized by inflammation, lipid accumulation, renin-angiotensin system activation and fibrosis. There is no approved pharmacological treatment available in AS. This study was aimed to characterize gene expression of endothelial factors in aortic valves in patients representing different stages of calcified aortic valve disease to reveal new targets for pharmacological interventions in AS. Aortic valves obtained from 75 patients undergoing valve replacement surgery were studied. Expression of natriuretic peptides (ANP, BNP and CNP), their processing enzymes (corin and furin), natriuretic receptors (NPR-A, NPR-B and NPR-C), endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE-1), endothelin receptors A and B (ETA and ETB), and apelin pathway (apelin and its receptor APJ) was characterized by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. AS was characterized by distinct downregulation of gene expression of CNP, its processing enzyme furin and the target receptor NPR-B. Furthermore, increased amount of ET-1 and its target receptor ETA as well as imbalance between ETA and ETB receptors and downregulated endothelial nitric oxide synthase (eNOS) gene expression were observed. Finally, gene expression of apelin and APJ receptor were significantly upregulated in stenotic valves when compared to controls in combination with disequilibrium between expression of angiotensin II receptors AT1 and AT2. The study provides a better understanding of molecular mechanisms associated with calcific aortic valve disease and suggest potential targets for novel therapeutic interventions.

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MOSCHETTA, DONATO. « UNRAVELLING SEX-DEPENDENT MECHANISMS IN CALCIFIC AORTIC VALVE STENOSIS ». Doctoral thesis, Università degli Studi di Milano, 2022. https://hdl.handle.net/2434/947275.

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Calcific aortic valve stenosis (CAVS) is the most common form of heart valve disease and affects about 3% of the population. Its prevalence increases with age, without a causal relation between ageing and CAVS development. To date, CAVS is a slow, progressive, multifactorial disorder considered to be actively driven by several cellular and molecular processes. Its natural history consists of a long clinically silent phase of non-uniform leaflet thickening with or without minimal calcification, known as aortic valve sclerosis (AVSc), without significant obstruction of blood flow, followed by the symptomatic stage, the aortic valve stenosis (AS). Currently, there is no pharmacological therapy preventing CAVS progression nor treating patients with AS. As a result, surgical or percutaneous aortic valve replacement remain the only treatments for severe AS, leaving the pathological molecular and cellular mechanisms unsolved. One of the first trigger of the pathology due to the oxidative stress is the endothelial dysfunction, followed by local inflammation and interstitial cells (VIC) differentiation into myofibroblasts and osteoblasts. Activated valve endothelial cells, undergoing endothelial to mesenchymal transition (EndMT), begin to express mesenchymal adhesion molecules and facilitate monocytes infiltration and local inflammation. These environmental changes induce VIC trans-differentiation into myofibroblast- and osteoblast-like cells. Activated VICs carry out a progressive extracellular matrix (ECM) pathological rearrangement characterized by the activation of fibrosis and calcification processes, which ultimately drive to fibro-calcific deposit formation. In the last years different studies reported sex-related difference in molecular mechanisms in the context of CAVS. In particular, it was shown that men with AS show a higher aortic valve calcium (AVC) load than women. Recently, it has been described that woman aortic valve leaflets were more fibrotic than man ones. Hence, it has been hypothesized that the mechanisms underlying CAVS progression could be different between the two sexes. We confirmed the evidence on sex-related calcium load in a meta-analysis performed on almost three thousand AS patients. Based on our results, AVC load, evaluated by computed tomography, is higher in man AS patients than in woman ones, even normalizing the data for the state of the pathology and for the aortic 9 annulus area. By the CT scan images analysis, we confirmed also the higher prevalence of fibrotic tissue in woman AS patients, than in men. In silico analysis of whole tissue RNA microarray revealed that the cellular composition of the aortic valve was different between men and women with CAVS. In particular, women showed a prevalence of mesenchymal cells, while in men there was a prevalence of inflammatory cells. This finding was in line with the analysis of circulating cytokines: pro inflammatory cytochines such as IL1β, TNFα, INFβ, and INFγ were upregulated in men CAVS patients. Based on these premises, we isolated and characterized VICs from AS patients and performed RNA sequencing to evaluate the differentially expressed molecular mechanisms. Among pathways overactivated in men there was the mitochondrial gene expression and this finding was confirmed by the higher mitochondrial damage in AS VICs from men respect to the one from women. We hypothesized that the mitochondrial damage caused a lower ATP production, therefore we evaluated the effects of a synthetic ATP equivalent, the 2ThioUTP, on the extracellular calcification of VICs from CAVS men. The in vitro 2ThioUTP administration showed indeed lower extracellular calcification of CAVS VICs both in normal and pro-calcifying conditions. All these data, taken together with robust literature evidences, shed light on the influence of sex in the development and progression of CAVS disease. Further studies are needed to better define the sexual dimorphism of this detrimental pathology. The recognition of sex-specific molecular mechanisms, linked to AS onset, may help in the identification of a gender-specific targeted therapy. In this direction, novel pharmacological therapies intended to reduce or even halt CAVS progression could be discovered, providing the basis for a personalized medicine approach in the context of CAVS.

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Pawade, Tania Ashwinikumar. « Imaging calcification in aortic stenosis ». Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/29589.

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BACKGROUND Aortic stenosis is a common and potentially fatal condition in which fibro-calcific changes within the valve leaflets lead to the obstruction of blood flow. Severe symptomatic stenosis is an indication for aortic valve replacement and timely referral is essential to prevent adverse clinical events. Calcification is believed to represent the central process driving disease progression. 18F-Fluoride positron emission tomography computed tomography (PET-CT) and CT aortic valve calcium scoring (CT-AVC) quantify calcification activity and burden respectively. The overarching aim of this thesis was to evaluate the applications of these techniques to the study and management of aortic stenosis. METHODS AND RESULTS REPRODUCIBILITY The scan-rescan reproducibility of 18F-fluoride PET-CT and CT-AVC were investigated in 15 patients with mild, moderate and severe aortic stenosis who underwent repeated 18F-fluoride PET-CT scans 3.9±3.3 weeks apart. Modified techniques enhanced image quality and facilitated clear localization of calcification activity. Percentage error was reduced from ±63% to ±10% (tissue-to-background ratio most-diseased segment (MDS) mean of 1.55, bias -0.05, limits of agreement - 0·20 to +0·11). Excellent scan-rescan reproducibility was also observed for CT-AVC scoring (mean of differences 2% [limits of agreement, 16 to -12%]). AORTIC VALVE CALCIUM SCORE: SINGLE CENTRE STUDY Sex-specific CT-AVC thresholds (2065 in men and 1271 in women) have been proposed as a flow-independent technique for diagnosing severe aortic stenosis. In a prospective cohort study, the impact of CT-AVC scores upon echocardiographic measures of severity, disease progression and aortic valve replacement (AVR)/death were examined. Volunteers (20 controls, 20 with aortic sclerosis, 25 with mild, 33 with moderate and 23 with severe aortic stenosis) underwent CT-AVC and echocardiography at baseline and again at either 1 or 2-year time-points. Women required less calcification than men for the same degree of stenosis (p < 0.001). Baseline CT-AVC measurements appeared to provide the best prediction of subsequent disease progression. After adjustment for age, sex, peak aortic jet velocity (Vmax) ≥ 4m/s and aortic valve area (AVA) < 1 cm2, the published CT-AVC thresholds were the only independent predictor of AVR/death (hazard ratio = 6.39, 95% confidence intervals, 2.90-14.05, p < 0.001). AORTIC VALVE CALCIUM SCORE: MULTICENTRE STUDY CT-AVC thresholds were next examined in an international multicenter registry incorporating a wide range of patient populations, scanner vendors and analysis platforms. Eight centres contributed data from 918 patients (age 77±10, 60% male, Vmax 3.88±0.90 m/s) who had undergone ECG-gated CT within 3 months of echocardiography. Of these 708 (77%) had concordant echocardiographic assessments, in whom our own optimum sex-specific CT-AVC thresholds (women 1377, men 2062 AU) were nearly identical to those previously published. These thresholds provided excellent discrimination for severe stenosis (c-statistic: women 0.92, men 0.88) and independently predicted AVR and death after adjustment for age, sex, Vmax ≥4 m/s and AVA < 1 cm2 (hazards ratio, 3.02 [95% confidence intervals, 1.83-4.99], p < 0.001). In patients with discordant echocardiographic assessments (n=210), CT-AVC thresholds predicted an adverse prognosis. BICUSPID AORTIC VALVES Within the multicentre study, higher continuity-derived estimates of aortic valve area were observed in patients with bicuspid valves (n=68, 1.07±0.35 cm) compared to those with tri-leaflet valves (0.89±0.36 cm p < 0.001,). This was despite no differences in measurements of Vmax (p=0.152), or CT-AVC scores (p=0.313). The accuracy of AVA measurments in bicuspid valves was therefore tested against alternative markers of disease severity. AVA measurements in bicuspid valves demonstrated extremely weak associations with CT-AVC scores (r2=0.08, p=0.02) and failed to correlate with downstream markers of disease severity in the valve and myocardium and against clinical outcomes. AVA measurements in bicuspid patients also failed to independently predict AVR/death after adjustment for Vmax ≥4 m/s, age and gender. In this population CT-AVC thresholds (women 1377, men 2062 AU) again provided excellent discrimination for severe stenosis. CONCLUSIONS Optimised 18F-fluoride PET-CT scans quantify and localise calcification activity, consolidating its potential as a biomarker or end-point in clinical trials of novel therapies. CT calcium scoring of aortic valves is a reproducible technique, which provides diagnostic clarity in addition to powerful prediction of disease progression and adverse clinical events.

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Zhao, Ying. « Effect of valve replacement for aortic stenosis on ventricular function ». Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-46809.

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Background：Aortic stenosis (AS) is the commonest valve disease in the West. Aortic valve replacement (AVR) remains the only available management for AS and results in improved symptoms and recovery of ventricular functions. In addition, it is well known that AVR results in disruption of LV function mainly in the form of reversal of septal motion as well as depression of right ventricular (RV) systolic function. The aim of this thesis was to study, in detail, the early and mid-term response of ventricular function to AVR procedures (surgical and TAVI) as well as post operative patients’ exercise capacity. Methods：We studied LV and RV function by Doppler echocardiography and speckle tracking echocardiography (STE) in the following 4 groups; (1) 30 severe AS patients (age 62±11 years, 19 male) with normal LV ejection fraction (EF) who underwent AVR, (2) 20 severe AS patients (age 79±6 years, 14 male) who underwent TAVI, (3) 30 healthy controls (age 63±11 years, 16 male), (4) 21 healthy controls (age 57±9 years, 14 male) who underwent exercise echocardiography. Results: After one week of TAVI, the septal radial motion and RV tricuspid annulus peak systolic excursion (TAPSE) were not different from before, while surgical AVR had significantly reversed septal radial motion and TAPSE dropped by 70% compared to before. The extent of the reversed septal motion correlated with that of TAPSE (r=0.78, p<0.001) in the patients as a whole after AVR and TAVI (Study I). Compared with controls, the LV twist function was increased in AS patients before and normalized after 6 months of surgical AVR. In controls, the LV twist correlated with LV fractional shortening (r=0.81, p<0.001), a relationship which became weak in patients before (r=0.52, p<0.01) and after AVR (r=0.34, p=ns) (Study II). After 6 months of surgical AVR, the reversed septal radial motion was still significantly lower than before. The septal peak displacement also decreased and its time became prolonged. In contrast, the LV lateral wall peak displacement increased and the time to peak displacement was early. The accentuated lateral wall peak displacement correlated with the septal peak displacement time delay (r=0.60, p<0.001) and septal-lateral time delay (r=0.64, p<0.001) (Study III). In 21 surgical AVR patients who performed exercise echocardiography, the LV function was normal at rest but different from controls with exercise. At peak exercise, oxygen consumption (pVO2) was lower in patients than controls. Although patients could achieve cardiac output (CO) and heart rate (HR) similar to controls at peak exercise, the LV systolic and early diastolic myocardial velocities and strain rate as well as their delta changes were significantly lower than controls. pVO2 correlated with peak exercise LV myocardial function in the patients group only, and the systolic global longitudinal strain rate (GLSRs) at peak exercise was the only independent predictor of pVO2 in multivariate regression analysis (p=0.03) (Study IV). Conclusion: Surgical AVR is an effective treatment for AS patients, but results in reversed septal radial motion and reduced TAPSE. The newly developed TAVI procedure maintains RV function which results in preservation of septal radial motion. In AS, the LV twist function is exaggerated, normalizes after AVR but loses its relationship with basal LV function. While the reversed septal motion results in decreased and delayed septal longitudinal displacement which is compensated for by the accentuated lateral wall displacement and the time early. These patients remain suffering from limited exercise capacity years after AVR.

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Bagur, Rodrigo Hernan. « Transcatheter aortic valve implantation for the treatment of patients with severe symptomatic aortic stenosis ». Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29420/29420.pdf.

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Fairbairn, Tim. « Severe aortic valve stenosis and the consequences of transcatheter and surgical aortic valve replacement : a cardiovascular magnetic resonance study ». Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/5853/.

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Background: Severe symptomatic aortic stenosis (AS) heralds a poor prognostic outlook and significant co-morbidity, with valve replacement the only definitive cure. Transcatheter aortic valve implantation (TAVI) has developed as an alternative to the standard treatment of surgical aortic valve replacement (SAVR) in high-risk or inoperable AS patients. The clinical and cost effectiveness of TAVI compared to SAVR requires further investigation. Methods: A prospective study of sixty seven TAVI and twenty seven SAVR patients, recruited from September 2009 to September 2011. Baseline assessments included a cerebral and cardiovascular magnetic resonance scan (1.5 Tesla MRI system) and the completion of two health surveys (EQ 5D and SF 12). Follow-up MRI was performed at 5±2 days (cerebral MRI) and 6 months (cardiovascular MRI) post AVR. Health status was assessed at 30 days, 6 months and one year. A cost-effectiveness analysis was performed using a 10 year Markov model with deterministic and probabilistic sensitivity analyses. Results: TAVI and SAVR resulted in similar levels of ventricular reverse remodelling. TAVI had a greater reduction in valvular impedance (21±8mmHg vs. 35±13mmHg, p=0.017) and myocardial fibrosis (10.9±6 % vs. 8.5±5%, p=0.03). Cerebral emboli occurred in 77% of TAVI patients. Age (r=0.37, p=0.042), severity of atheroma (r=0.91, p<0.001) and catheterisation time (r=0.45, p=0.02) were predictors of cerebral infarcts. HRQOL significantly improved over 12 months (PCS, p=0.02; EQ-5D, p=0.02; VAS, p=0.01 and SF6D p=0.03). Male gender (SF6D, p=0.01) and increased operator experience (PCS, EQ5D and VAS, p<0.05) predicted an improvement in HRQOL. Despite greater procedural costs, TAVI was cost-effective compared to SAVR over the 10 year model horizon (costs £52,593 vs. £53,943 and QALYs 2.81 vs. 2.75) indicating that TAVI dominated SAVR. Conclusions: TAVI has comparable cardiac and health benefits to SAVR, but greater cerebral complications. TAVI is likely to represent a clinical and cost effective alternative to SAVR.

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Taniguchi, Tomohiko. « Initial Surgical VersusConservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis ». 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225456.

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Kanamori, Norio. « Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction ». Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263349.

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Ahlén, Caroline. « Outcome of patients with severe aortic stenosis – A retrospective follow-up study ». Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9372.

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Aortic stenosis is the most common valvular disease in the adult population. A significant aortic stenosis is a serious condition, and if a symptomatic patient is not operated on, it may in most cases cause death. We have examined how many aortic stenoses that were diagnosed during one year, and a follow-up of the patients was also performed. We found 77 patients with significant aortic stenosis with a mean age of 76±13 years. At the time of follow-up 30 (39%) patients, aged between 29-85 years, had been surgically treated with implantation of a valve prosthesis within 2-23 months after the initial examination. At this initial examination 14 of the 30 patients who later underwent surgery had no symptoms. A coronary bypass operation was also performed on seven patients. Postoperative complications were observed in six patients, but none of them was fatal. At the initial examinations there were 26 (34%) patients with a significant aortic stenosis and symptoms who were not treated surgically. The main reason why these patients were not operated was high age, unwillingness, or severe left ventricular dysfunction. This study indicates the importance of repeated clinical and echocardiograpic examinations in patients with aortic stenosis. Almost half of the patients, that later underwent surgery, had no symptoms at the initial examination, but later developed symptoms which made surgery necessary. In one third of the patients no surgery was performed in spite of clinical symptoms.

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Musa, Tarique Al. « Transcatheter and surgical aortic valve replacement for severe aortic stenosis : insights from cardiovascular magnetic resonance imaging ». Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/15238/.

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Background: Surgical aortic valve replacement (SAVR) remains first-line treatment for symptomatic severe aortic stenosis, whereas transcatheter aortic valve implantation (TAVI) is indicated in patients who are inoperable or considered too high-risk for surgery. Current focus is centred on differences in the impact of valve replacement upon cardiovascular function to guide patient selection and the development of novel prosthetic valves to improve outcomes. Cardiovascular Magnetic Resonance (CMR) imaging is the investigative modality of choice for such a purpose. Objectives: To compare the impact of SAVR and TAVI upon aortic stiffness, right ventricular function and myocardial strain, and to compare two vendor designs in the quantity of post-TAVI aortic regurgitation and reverse remodelling. Methods: A prospective study of patients with severe aortic stenosis under surveillance and subsequently requiring SAVR or TAVI, recruited between September 2009 and December 2015. A 1.5 Tesla CMR study was performed pre and 6 months post SAVR, and pre, immediately and 6 months post implantation of Medtronic CoreValve and Boston Lotus TAVI. Aortic distensibility (AD), pulse wave velocity (PWV), right ventricular (RV) volumes, myocardial strain and aortic regurgitation (AR) were quantified. Results: At 6 months, SAVR was associated with a significant worsening in PWV (6.38±4.47 vs. 11.01±5.75ms-1, p=0.001) and ascending AD (1.95±1.15 vs. 1.57±0.68x10-3mmHg-1, p=0.044), whereas no change was seen following TAVI. A significant reduction in RV ejection fraction (58±8 vs. 53±8%, p=0.005) was seen flowing SAVR, with no change following TAVI. A significant and comparable decline in LV torsion and twist was observed. Baseline circumferential strain was significantly associated with all-cause mortality (hazard ratio, 1.03; 1.01–1.05; p=0.009). Significantly less AR was seen immediately following Lotus than CoreValve TAVI (4.3±3.4 vs.11.7±8.4%, p=0.001) with equivalent degrees of reverse remodelling observed at 6 months. Conclusion: Compared with TAVI, SAVR is more detrimental upon aortic stiffness and right ventricular function at 6 months. CMR derived circumferential strain is associated with survival following SAVR and TAVI.

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Bordoni, Barbara <1980&gt. « Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6892/1/Tesi_def_270315_3.pdf.

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Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.

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Bordoni, Barbara <1980&gt. « Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6892/.

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Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.

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Ding, Wenhong. « Survival and functional recovery following valve replacement in patients with severe aortic stenosis ». Doctoral thesis, Umeå universitet, Medicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-82644.

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Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome. Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient >40mmHg or valve area <1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) <50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients. Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p<0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p< 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p<0.001), presence of restrictive LV filling (p<0.001), raised PSPAP (p<0.001) and CABG (p=0.037). However, only EF<40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p<0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p<0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p<0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p<0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p<0.001 for both). LVEF increased (from 45±1 to 54±2%;p<0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p<0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p<0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index<=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p<0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p<0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p<0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p<0.001). Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.

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Hagen-Peter, Gayle Ann. « Living with Aortic Stenosis : A Phenomenological Study of Patients' Experiences and Subsequent Health Choices ». ScholarWorks @ UVM, 2015. http://scholarworks.uvm.edu/graddis/516.

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Symptomatic aortic stenosis (AS) is an increasing phenomenon as more adults live longer. The gold standard for treating AS is surgical aortic valve replacement (SAVR). Frequently, as older individuals with AS often have multiple comorbidities, a SAVR is determined to be too high risk. Therefore, a less invasive treatment option is available, namely a transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR). Such biomedical procedures have encouraged life extension and the decision to intervene commonplace with the aging population. Without an intervention, significant debilitating symptoms affect a person's quality of life (QoL). Multiple quantitative studies evaluating QoL before and after a TAVI have been performed. However QoL has multiple attributes and is not a single construct. By limiting practice to these defined QoL measures, we exclude the human experience and what values individuals describe as important to them. The dilemma in the present medical model is influenced by two paradigms, evidence based medicine and patient centered medicine. Some people opt not to have a TAVI. This study aims to understand what it is like living with aortic stenosis as perceived by the participant and to gain a more meaningful understanding of why some individuals with AS choose not to have this procedure performed. Using a convenience sample of patients who declined a TAVI, a telephone interview with the person focused on their perceived QoL and the implications determining not to pursue a TAVI. In this qualitative phenomenological design, open-ended questions included: 1) What is it like to live with Aortic Stenosis. 2) Why did you choose not to have the TAVI? Interviews will explore emerging themes. Advanced practice nurses are in ideal positions for performing research to gain greater insight on the complexity of people's health choices. As the incidence of AS occurs more frequently in the increasing aged population, TAVI offers a treatment option for those patients who are symptomatic with AS and are not surgical candidates. However, health care providers should focus on the illness, not the disease, and explore the patients' biopsychosocial values with their medical needs. The information gathered in this study will help guide heath care providers with offering holistic health care incorporating both paradigms of evidence based practice and patient centered medicine options on treatment for people with symptomatic AS.

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Näpänkangas, J. (Juha). « Pathogenesis of calcific aortic valve disease ». Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526223520.

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Abstract Calcific aortic valve disease (CAVD) represents a disease spectrum, ranging from mild aortic valve sclerosis to severe obstructive aortic stenosis (AS), associated with a high risk of myocardial infarction and cardiovascular death. It is a common disease in the Western countries, and with their aging populations, its prevalence is likely to increase. Today, CAVD is recognized as an actively regulated disease. Mechanical stress and endothelial injury are the initiating factors, followed by lipid accumulation and oxidation, leading to inflammation, fibrosis and calcification. Ultimately, the progressive calcification hinders the normal valvular function and obstructs the flow of blood through the valve. The only effective treatment for symptomatic AS is aortic valve replacement. The trials with pharmacological treatments, mainly with anti-atherosclerotic drugs, have not been successful in slowing the progression of the disease. This study was aimed to identify differentially expressed transcripts, and molecular markers taking part in the pathophysiology behind CAVD. In particular, factors related to the renin-angiotensin system, and the apelin – APJ pathway, were investigated during the development of CAVD. In addition, the expressions of granzymes and perforin, as well as podoplanin, were studied in different stages of CAVD. It was demonstrated that these molecules are expressed in aortic valves and dysregulated in AS. These results can help to clarify the mechanisms driving CAVD, thus being potential targets for pharmacological therapy. Furthermore, the studied molecules may reflect the stage and possible subgroups of CAVD
Tiivistelmä Aorttaläpän ahtauma edustaa tautijatkumoa, joka alkaa lievästä aorttaläpän paksuuntumisesta eli aorttaskleroosista ja jatkuu vaikeaan aorttaläpän kalkkeutuneeseen ahtaumaan eli aorttastenoosiin, johon liittyy korkea sydäninfarktin ja sydän- ja verisuonitatutiperäisen kuoleman riski. Aorttaläpän ahtauma on yleinen tauti länsimaissa, ja väestön ikääntyessä sen esiintyvyys on luultavimmin lisääntymässä. Nykyään aorttaläpän ahtauman tiedetään olevan aktiivisesti säädelty tauti. Mekaaninen rasitus ja endoteelivaurio käynnistävät tautiprosessin, läppäkudokseen kertyy lipidejä ja ne hapettuvat, mikä johtaa tulehdukseen, sidekudoksen lisääntymiseen ja kalkkeutumiseen. Lopulta etenevä kalkkeutuminen heikentää läpän normaalia toimintaa ja estää veren normaalia virtausta sydämestä aorttaan. Ainoa tehokas hoito oireiseen aorttastenoosiin on aorttaläpän korvausleikkaus. Lääkehoitoina on kokeiltu erityisesti ateroskleroosin hoitoon käytettäviä lääkkeitä, mutta niillä ei ole onnistuttu estämään taudin etenemistä. Tässä väitöskirjatyössä tutkittiin molekyylejä ja biokemiallisia reittejä, jotka liittyvät reniini-angiotensiinijärjestelmään ja apeliini-APJ-reittiin. Lisäksi tutkittiin grantsyymien ja perforiinin sekä podoplaniinin ilmentymistä aorttaläpän ahtauman eri kehitysvaiheissa. Tulosten perusteella näitä tekijöitä ilmennetään aorttaläpässä ja niiden määrä on muuttunut kalkkeutuneessa läpässä. Tulokset auttavat osaltaan ymmärtämään aorttaläpän ahtaumaan ja kalkkeutumiseen johtavia mekanismeja, joita voidaan hyödyntää uusia lääkehoidon kohteita suunniteltaessa. Tutkitut molekulaariset tekijät voivat kuvastaa aortan ahtaumataudin vaiheita ja mahdollisia alaryhmiä

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Poggio, P. « THE ROLE OF VALVE INTERSTITIAL CELLS IN THE PATHOGENESIS OF CALCIFIC AORTIC VALVE DISEASE ». Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229415.

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Calcific aortic valve disease (CAVD) is the most common etiology of acquired aortic valve disease. The early stage is characterized by thickening of the leaflets and none or marginal effect on the mechanical properties of the valve, while the end stage disease is associated with impaired leaflet motion and resistances to blood flow. These conditions are known as aortic valve sclerosis (AVSc) and calcific aortic valve stenosis (AVS), respectively. AVSc is present in 25–30% of patients over 65 years of age and in up to 40% of those over 75 years of age. Moreover, since AVSc hemodynamics are comparable to healthy controls, the presentation of the disease is largely asymptomatic and almost 10% of these patients will progress to AVS within 10 years from the diagnosis. Patients with severe AVS have a life expectancy of less than 10 years if untreated. Currently the main indication for AVS is aortic valve replacement (AVR). Over the last decade several clinical trials have been performed to halt the progression of CAVD with contradictory results. The early enthusiastic findings documenting a reduction in the progression of CAVD have been questioned by later randomized studies, which show substantial equivalence between treatments and placebo. It has been proposed that CAVD therapy may have been initiated too late in the course of the disease to have the desired effect. In conclusion, there is currently no definitive therapy supported by prospective and randomized studies to halt or delay the progression of CAVD, leaving AVR the treatment of choice. Therefore, the identification of high-risk patients at early stages of degeneration will open new perspectives for the appropriate timing of therapeutic intervention on future clinical trials. We implemented in vitro and ex vivo experiments to better characterize the early asymptomatic stage of CAVD and to evaluate osteopontin (OPN) as a potential biomarker in the progression of this degenerative disease. Moreover, we focused on OPN role in valve endothelial cells (VEC) migration, as well as valve interstitial cells (VIC) osteoblastic-like activation and biomineralization. Our results supported the correlation between CAVD progression and increased OPN levels in aortic valve tissue and blood. Interestingly, in advance stages of calcification, we demonstrated that the overexpressed OPN had different post-translational modification compared to healthy controls. Moreover, we analyzed bone morphogenetic protein 4 (BMP4) pathway and mechanical tensile stretch as cause of VIC osteogenic-like transdifferentiation and calcium accumulation.

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Ohukainen, P. (Pauli). « Molecular profiling of calcific aortic valve disease ». Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526211909.

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Abstract Calcific aortic valve disease (CAVD) is the most common valvular heart disease in the Western world. Although it shares mainly the same risk factors as coronary heart disease (CHD), i.e. similar initial events in both diseases but with time, they lead to different clinical outcomes. Thus, when it affects the coronary arteries, the disease leads to an obstructive or rupture-prone plaque whereas in the aortic valve, it causes massive calcification and ossification. This obstructs the blood flow from the left cardiac ventricle, causing myocardial hypertrophy, and if left untreated, heart failure and death. Many of the pathobiological differences between CAVD and CHD remain unknown. Currently, there are no effective lifestyle- or pharmacologic treatments for CAVD and the only therapy is a valve replacement operation. In this thesis, several studies utilizing large-scale methods were undertaken to profile the molecular events leading to CAVD. Surgically removed valves from patients in different stages of the disease were obtained and gene transcripts, microRNA-molecules and several proteins were identified as being differentially expressed. Several of these were investigated further, including two pro-inflammatory CC-type chemokine ligands 3 and 4 (CCL3 and CCL4), microRNA-125b, several granzyme-proteins and heat-shock protein 90. The results of this thesis provide a large dataset of hundreds of molecular changes associated with CAVD. It is proposed that they can be used as a basis for the generation of new hypotheses and assist in the design of experiments to clarify the mechanisms driving CAVD
Tiivistelmä Aorttaläpän kalkkeutuva ahtauma on länsimaiden yleisin sydänläppäsairaus. Riskitekijät ovat pääosin samat kuin sepelvaltimotaudissa, ja molemmat saavat alkunsa samalla tavalla. Ajan myötä ne kuitenkin johtavat varsin erilaisiin kliinisiin ilmenemismuotoihin: sepelvaltimoihin kasvaa ahtauttavia ja repeytymisherkkiä plakkeja, kun taas aorttaläppään muodostuu runsaasti kalkkia ja luuta. Se haittaa verenvirtausta sydämen vasemmasta kammiosta aorttaan, mikä aiheuttaa sydänlihaksen paksuuntumista. Hoitamattomana tauti johtaa lopulta sydämen vajaatoimintaan ja kuolemaan. Monet syyt eroihin sepelvaltimotaudin ja aorttaläpän ahtauman välillä ovat edelleen tuntemattomia. Tällä hetkellä aorttaläpän ahtaumaan ei ole olemassa tehokasta elintapa- tai lääkehoitoa, ja ainoa hoitomuoto onkin vioittuneen aorttaläpän korvaaminen proteesilla. Tässä väitöskirjatyössä tehtiin useita laaja-alaisia molekyylitason profilointitutkimuksia, joilla selvitettiin aorttaläpän ahtaumaan mahdollisesti johtavia mekanismeja. Aineistona oli leikkauksessa potilailta poistettuja, erilaisissa taudin vaiheissa olevia aorttaläppiä. Niistä kerättiin tietoja kaikkien geenien ilmentymisestä, mikroRNA-molekyyleistä sekä koko proteomitason muutoksista. Useat tunnistetuista molekyyleistä valittiin jatkotutkimuksiin niiden tarkempien ominaisuuksien selvittämiseksi. Näitä olivat tulehdusta välittävät kemokiinit CCL3 ja CCL4, mikroRNA-125b, useat grantsyymiproteiinit sekä lämpöshokkiproteiini 90. Väitöskirjatyön tuloksista voidaan muodostaa ainutlaatuinen aineisto sadoista erilaisista aorttaläpän ahtaumaan johtavista molekyylitason muutoksista. Sitä voidaan hyödyntää uusien tutkimushypoteesien muodostamisessa sekä aorttaläpän ahtauman tarkempien mekanismien selvittämiseen tähtäävien kokeellisten tutkimusten suunnittelussa

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Wang, Qian. « Patient-specific finite element modeling of biomechanical interaction in transcatheter aortic valve implantation ». Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54849.

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Transcatheter aortic valve implantation (TAVI) is an effective alternative treatment option for patients with severe aortic stenosis, who are at a high risk for conventional surgical aortic valve replacement or considered inoperable. Despite the short- and mid-term survival benefits of TAVI, adverse clinical events, such as paravalvular leak, aortic rupture, and coronary occlusion, have been reported extensively. Many of these adverse events can be explained from the biomechanics perspective. Therefore, an in-depth understanding of biomechanical interaction between the device and native tissue is critical to the success of TAVI. The objective of this thesis was to investigate the biomechanics involved in the TAVI procedure using patient-specific finite element (FE) simulations. Patient-specific FE models of the aortic roots were reconstructed using pre-procedural multi-slice computed tomography images. The models incorporated aged human aortic material properties with material failure criteria obtained from mechanical tests, and realistic stent expansion methods. TAV deployment and tissue-device interaction were simulated; and the simulation results were compared to the clinical observations. Additionally, parametric studies were conducted to examine the influence of the model input on TAVI simulation results and subsequently the potential clinical complications such as paravalvular leak, annular rupture, and coronary artery occlusion. The methodology presented in this thesis could be potentially utilized to develop valuable pre-procedural planning tools to evaluate device performance for TAVI and eventually improve clinical outcomes.

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Nyström-Rosander, Christina. « Chlamydia pneumoniae in aortic valve sclerosis and thoracic aortic disease : aspects of pathogenesis and therapy / ». Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5356-2/.

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Miyake, Makoto. « Early Surgery vs. Surgery After Watchful Waiting for Asymptomatic Severe Aortic Stenosis ». Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264637.

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Wallby, Lars. « Signs of inflammation in different types of heart valve disease : The VOCIN study ». Doctoral thesis, Linköping : Department of Medical and Health Sciences, Linköping University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11330.

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Muta, Eri. « Impact of the left ventricular mass index on the outcomes of severe aortic stenosis ». Kyoto University, 2019. http://hdl.handle.net/2433/242385.

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DELLA, ROSA FRANCESCO. « Impact of asymptomatic carotid stenosis on mid term outcome of transcatheter aortic valve replacement ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2016. http://hdl.handle.net/10281/105574.

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Introduction Stroke is a potential major complication of aortic valve replacement (AVR), transcatheter aortic valve implantation (TAVI), and balloon aortic valvuloplasty (BAV). Although its occurrence is rare, stroke significantly affects survival and quality of life. Peripheral vascular disease and carotid artery disease are independent risk factors that have been identified as predictors of operative death according to surgical risk scores. The presence of a significant carotid stenosis may increase the surgical risk leading to the choice of a percutaneous transaortic valve implantation rather than a surgical AVR. At present there is no evidence that describes the impact of asymptomatic significant carotid stenosis detected accidentally during preoperative evaluation on the onset of cerebrovascular periprocedural events after TAVI. Population In this first analysis we considered 521 patients with severe aortic stenosis (AS) and cardiac symptoms (New York Heart Association [NYHA] class II function or worse). A score of at least 20 % on the EuroSCORE (European System for Cardiac Operative Risk Evaluation) and 10% on the risk model developed by the Society for Thoracic Surgeons (STS)., Follow-up All patients underwent clinical surveillance, bio-chemical tests, electrocardiogram and echocardiogram before hospital discharge. The follow-up assessment included medical examination, electrocardiogram and echocardiogram to perform valve imaging and hemodynamic evaluation. It was performed at our Center or at the treating cardiologist ambulatory 30 days and one year after the procedure. The events considered were mortality (by all-cause and cardiovascular death), myocardial infarction, stroke and transient ischemic attack (TIA), bleeding (minor and life-threatening bleeding), acute renal failure, vascular complications, disturb of conduction and arrhythmias and the combined criteria of safety, according to VARC and VARC 2 definitions. Procedure The coexistence of carotid and peripheral artery diseases not only further increases risk and long-term mortality but influences also technical approaches since all centers adopt a policy of using the transfemoral approach first, with criteria for the use of non-transfemoral approaches that are based on the size and degree of tortuosity, calcifications, and atheroma of the aorto-iliofemoral arterial tree, as assessed by the multidisciplinary team. In our Center, preventive measures have been taken to limit the risk associated to the procedure in our patients presenting carotid artery stenosis. Results The main findings of the current study are the following: (a) no correlation has been observed about the presence of an asymptomatic carotid artery stenosis discovered before the TAVI procedure and mortality, rate of cerebrovascular events (stroke or TIA) and myocardial infarction during the first postoperative month; (b) no differences concerning all-causes and cardiovascular mortality and onset of cerebrovascular events (stroke/TIA) at long-term have been shown between patients with and without CAS. Conclusion The presence of asymptomatic carotid stenosis is not a risk factor for cerebrovascular events after percutaneous aortic valve implantation at 30 days and one-year follow-up. Cerebrovascular events after TAVI occur in a vulnerability period extending to 1 month post-procedure. No difference exists in the CVE rate with regard to the type of valve or the access route. Coronary, carotid, aortic, iliac and femoral artery disease are often found in elderly patients presenting with severe symptomatic AS undergoing TAVI. These patients are also affected by several clinical factors and frailty that correlate with the presence and severity of arterial pathologies and can impact on incidence of CVEs and longterm survival

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Heinrich, Russell Shawn. « Assessment of the fluid mechanics of aortic valve stenosis with in vitro modeling and control volume analysis ». Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/16664.

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Dellgren, Göran. « Aortic valve replacement with stentless bioprostheses : prospective long-term studies of the Biocor and the Toronto SPV / ». Stockholm : Karolinska institutet, 2002. http://diss.kib.ki.se/2002/91-7349-152-7.

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Van, Aswegen Karl. « Dynamic modelling of a stented aortic valve ». Thesis, Link to the online version, 2008. http://hdl.handle.net/10019/1747.

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Teien, Dag. « Assessment of aortic stenosis with special reference to Doppler ultrasound ». Doctoral thesis, Umeå universitet, Klinisk fysiologi, 1986. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103813.

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Ghotikar, Miheer S. « Aortic valve analysis and area prediction using bayesian modeling ». [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/fcla/etd/SFE0001369.

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Simpson, Michael S. « An in vitro investigation of systolic anterior motion of the mitral valve ». Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/33615.

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Yap, Choon Hwai. « The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification ». Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45742.

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Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our ability to prevent or cure the disease. Ex vivo investigations, however, have provided evidence that the aortic valve's biological response is sensitive to mechanical forces, including fluid shear stresses, leading to the hypothesis that adverse fluid shear stress environment play a role in leading to valve calcification. This thesis seeks to investigate this hypothesis. A method for performing experimental measurement of time-varying shear stress on aortic valve leaflets under physiologic flow conditions was first developed, based on the Laser Doppler Velocimetry technique, and was systematically validated. This method was then applied to both the aortic surface and the ventricular surface of a normal tricuspid the aortic valve, and then on a congenital bicuspid aortic valve, using suitable in vitro valve models and an in vitro pulsatile flow loop. It was found that in the tricuspid valve, the peak shear stress on the aortic surface under adult resting condition was approximately 15-19 dyn/cm². Aortic surface shear stresses were elevated during mid- to late-systole, with the development of the sinus vortex, and were low during all other instances. Aortic surface shear stresses were observed to increase with increasing stroke volume and with decreasing heart rate. On the ventricular surface, shear stresses had a systolic peak of approximately 64-71 dyn/cm² under adult resting conditions. During late systole, due to the Womersley effect, shear stresses were observed to reverse in direction to a substantial magnitude for a substantial period of time. Further, it was found that a moderately stenotic bicuspid aortic valve can experience excessive unsteadiness in shear stress experienced by its leaflets, most likely due to the turbulent forward flow resulting from the stenosis, and due to the skewed forward flow. To demonstrate that the measured shear stresses can have an effect on the aortic valve biology, ex vivo experiments were performed in specific to determine the effects of these various shear stress characteristics on the biological response of porcine aortic valve leaflets, using the cone and plate bioreactor. It was found that unsteady shear stress measured in the bicuspid valve resulted in increased calcium accumulation. Further, it was found that low shear stresses and high frequency shear stresses resulted in increased calcium accumulation. Thus, shear stress was found to affect aortic valve pathology, and low and unsteady fluid shear stresses can enhance pathology.

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Holliday, Casey Jane. « Discovery of shear- and side-dependent messenger RNAs and microRNAs in aortic valvular endothelium ». Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/47517.

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Aortic valve (AV) disease is a major cause of cardiovascular-linked deaths globally. In addition, AV disease is a strong risk factor for additional cardiovascular events; however, the mechanism by which it initiates and progresses is not well-understood. We hypothesize that low and oscillatory flow is present on the fibrosa side of the AV and stimulates ECs to differentially regulate microRNA (miRNA) and mRNAs and influence AV disease progression. This hypothesis was tested employing both in vitro and in vivo approaches, high throughput microarray and pathway analyses, as well as a variety of functional assays. First, we isolated and characterized side-dependent, human aortic valvular endothelial cells (HAVECs). We found that HAVECs express both endothelial cell markers (VE-Cadherin, vWF, and PECAM) as well as smooth muscle cell markers (SMA and basic calponin). Using microarray analysis on sheared, side-specific HAVECs, we identified side- and shear-induced changes in miRNA and mRNA expression profiles. More specifically, we identified over 1000 shear-responsive mRNAs which showed robust validation (93% of those tested). We then used Ingenuity Pathway Analysis to identify key miRNAs, including those with many relationships to other genes (for example, thrombospondin and I&B) and those that are members of over-represented pathways and processes (for example, sulfur metabolism). Furthermore, we validated five shear-sensitive miRNAs: miR-139-3p, miR-148a, miR-187, miR-192, and miR-486-5p and one side-dependent miRNA, miR-370. To prioritize these miRNAs, we performed in silico analysis to group these key miRNAs by cellular functions related to AV disease (including tissue remodeling, inflammation, and calcification). Next, to compare our in vitro HAVEC results in vivo, we developed a method to isolate endothelial-enriched, side-dependent total RNA and identify and validate side-dependent (fibrosa vs. ventricularis) miRNAs in porcine aortic valvular endothelium. From this analysis, we discovered and validated eight side-dependent miRNAs in porcine endothelial-enriched AV RNA, including one miRNA previously identified in vitro, miR-486-5p. Lastly, we determined the relationship between important miRNAs (specifically miR-187 and miR-486-5p) and AV disease by modulating levels of miRNAs and performing functional assays. Preliminary studies overexpressing miR-187 in HAVECs have shown a reduction in inflammatory state through monocyte adhesion (p<0.05). Further, miR-486-5p overexpression reveals an increase in migration (p<0.05) and a trend for a decrease in early apoptosis, linking miR-486-5p to tissue remodeling in the AV. Better understanding of AV biology and disease in terms of gene-regulation under different hemodynamic conditions will facilitate the design of a tissue-engineered valve and provide alternative treatment options.

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Alkhalil, Ahmad. « Outcomes Of Early Versus Late Discharge In Transfemoral Transcatheter Aortic Valve Replacement Via Minimally Invasive Strategy : A Propensity-Matched Analysis ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1465592493.

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Olsson, Karin. « Hope and life-struggle : patients' experiences with Transcatheter Aortic Valve Implantation ». Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127873.

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The overall aim of this thesis is to explore experiences and self-reported outcomes from Transcatheter Aortic Valve Implantation, TAVI, among people with severe aortic stenosis. The thesis includes four studies. Study I-II are based on interviews performed the day before TAVI and Qualitative Concept Analysis was used for analysis. Study III is based on interviews at six months’ follow-up and Grounded Theory was used for analysis. Study IV is quantitative and based on questionnaires at baseline and at six months’ follow-up. Nonparametric, descriptive statistics were used for the analysis. Study I described the vulnerable situation for patients with severe aortic stenosis before TAVI. They were facing death and at the same time struggling to cope with their symptoms and to maintain independent. TAVI offered hope but also caused uncertainty about the new method. Study II focused on the patients’ decision-making process. Three patterns were identified; ambivalent, obedient, and reconciled. The ambivalent patient is unsure of the value of treatment and aware of the risks; the obedient patient is unsure of the value of one's own decision and wants to leave the decision to others; the reconciled patient has reached a point where there is no choice anymore and is always sure that the decision to undergo TAVI is right. Study III offered a deeper understanding of the TAVI trajectory. A journey of balancing between hope and life-struggle was the core category of the analysis. Before TAVI patients felt threatened, but also experienced hope. The rehabilitation phase was described as demanding and depressing or surprisingly simple. At the six months’ followup patients described being pleased to return to life, however, many were still struggling with limitations. Study IV focused on quantifying the symptom burden, function and health related quality of life before and after TAVI. The results were reflected against that of patients treated with open surgery. Self-rated function and health related quality of life increased and symptoms were reduced at follow-up, but breathlessness and fatigue were still common. Conclusively, TAVI patients are struggling with limitations, both because of their comorbidities and because of their valve disease which also poses a threat to their lives. TAVI gives an opportunity to survive, to stay independent and to increase quality of life. To feel and preserve hope is essential for patients’ wellbeing, both before and during the recovery process.

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Kumar, Anirudh. « SAFETY AND EFFICACY OF BALLOON AORTIC VALVULOPLASTY STRATIFIED BY ACUITY OF PATIENT ILLNESS ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1623349720127583.

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Straiton, Nicola. « The acceptability of heart valve replacement procedures, and patient-reported outcomes in adults with aortic stenosis ». Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29843.

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The incidence of aortic stenosis (AS) is high and increasing alongside the aging of populations in developed countries. Yet the impact of severe AS and associated treatments on the lives of people and their carers who provide support, is poorly understood. This thesis aims to investigate patient-reported outcomes of severe AS and valve replacement for adults living with AS and the acceptability of these replacement procedures for individuals and their carers. A multi-method study was conducted, consisting of two systematic reviews one of which synthesised the evidence for functional capacity and health-related quality of life (HRQoL) outcomes after transcatheter aortic valve replacement (TAVR), and another determining the validity and reliability of consumer-grade wearables to monitor physical activity in older, community-dwelling adults. Additionally, a study (n=32) measuring AS patients' functional capacity, physical activity and HRQoL before and after AVR and a descriptive, qualitative study exploring the acceptability of TAVR to patients (n=18) and their carers (n=8) were conducted. Before valve replacement severe AS patients had poor functional capacity, physical activity and HRQoL. Evidence from the reviews and the study demonstrated that for most people with severe AS, AVR by any mode improves functional capacity and overall HRQoL and that wearable activity trackers can accurately measure physical activity amongst older adults. AS patients and their carers found TAVR to be an acceptable intervention to treat the condition, addressing pre-operative symptom-driven emotions of struggling and fear, and fostering post-operative feelings of confidence and an ability to get back to a sense of normal. Furthermore, TAVR aligned with participants’ values, preferences and needs. Understanding the impact of severe AS on the lives of patients and their carers will enable clinicians to tailor clinical support before and after treatment.

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Dobson, Laura Elizabeth. « Cardiovascular magnetic resonance imaging in severe aortic stenosis : impact of surgical and trans-catheter aortic valve replacement on reverse remodelling and fibrosis ». Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/12944/.

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Introduction: Aortic stenosis (AS) is the commonest valvular lesion in the developed world and is associated with adverse cardiac remodelling. With its excellent accuracy and reproducibility, cardiovascular magnetic resonance (CMR) imaging is an ideal tool to assess cardiac remodelling and reverse remodelling following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The aims of this thesis were: 1) to evaluate gender differences in AS and following aortic valve replacement, 2) to evaluate the incidence of post-procedural myocardial infarction following SAVR and TAVI, 3) to describe the immediate effect of TAVI on reverse remodelling and 4) to assess the impact of TAVI-induced left bundle branch block (LBBB) . Methods: Between January 2009 and April 2015, patients with severe AS undergoing either TAVI or SAVR were prospectively recruited. Patients underwent comprehensive 1.5T CMR evaluation pre-procedure, prior to hospital discharge and 6m post-procedure. Results: 1) Women with severe AS have a lower indexed left ventricular (LV) mass than men (65.3± 18.4 vs. 81.5±21.3g/m2, p < 0.001). 6m following valve replacement, LV mass regression is similar between genders (men 21.7±10.1 vs. women 18.4±11.0%, p=0.121). 2) Myocardial infarction (MI) is more frequent following SAVR than TAVI (n=10 (26%) vs. n=3 (5%), p=0.004). 3) Over 10% of LV mass regression occurs prior to hospital discharge following TAVI and is more pronounced in the absence of myocardial fibrosis (p=0.005). 4) TAVI-induced LBBB is associated with a reduced LVEF 6m following TAVI compared with those with a narrow QRS (-2.1±6.9 vs. +4.6±7.8%, p=0.002). Conclusions: TAVI and SAVR are associated with favourable cardiac reverse remodelling which does not differ according to gender and begins prior to hospital discharge. SAVR is associated with a higher incidence of post-procedural MI than TAVI. TAVI-induced LBBB should be avoided where possible due to its unfavourable effects on cardiac reverse remodelling.

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Vánky, Farkas. « Surgery for aortic stenosis : with special reference to myocardial metabolism, postoperative heart failure and long-term outcome / ». Linköping : Linköpings universitet, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-7471.

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D'Onofrio, Augusto. « Clinical and hemodynamic outcomes of trans-apical aortic valve implantation. insights from the i-ta registry ». Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423827.

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Senile degenerative calcific aortic valve stenosis (AVS) is a progressive disease characterized by a peculiar natural history. When symptoms begin (congestive heart failure and dyspnea, angina, syncope) mortality rate rapidly increase and quality of life dramatically worsen. It has been estimated that the overall survival of patients with severe symptomatic AVS is less than 50% 2 years after the onset of symptoms. The number of patients suffering from AVS worldwide will increase over time as life expectancy progressively extends. The treatment of choice for severe symptomatic AVS is aortic valve replacement (AVR) that is usually performed under general anesthesia, with median sternotomy and cardiopulmonary bypass. AVR is a well-established procedure, with excellent early and long-term results and valve prostheses have now reached optimal hemodynamic performance and duration. During the last few years, the development of sutureless aortic bioprosthesis has made easier the surgical procedure. In fact, aortic valve replacement with sutureless valves (SU-AVR) needs shorter cardiopulmonary bypass and aortic cross clamp times and can be safely performed through a minimally invasive approach. However, a recent survey showed that around 30% of patients with severe symptomatic AVS does not undergo AVR for several reasons: they are not referred for surgery by their family physician or by their cardiologist because of age, they are declined surgery for a high preoperative risk profile; they are inoperable for severe ascending aortic calcification (porcelain aorta). Trans-catheter aortic valve implantation (TAVI) is an alternative therapeutic option in high-risk or inoperable patients. TAVI can be performed through several accesses: trans-femoral (TF-TAVI), trans-apical (TA-TAVI), trans-aortic (TAo-TAVI) and trans-subclavian (TS-TAVI). This thesis will focus on TAVI and in particular on TA-TAVI in terms of, indications, technique and outcomes. We will show the results of the Italian Registry of Trans-Apical Aortic Valve Implantation (I-TA) that includes the great majority of patients who underwent TA-TAVI in Italy since this procedure became commercially available in 2008. Furthermore we will present the results of a propensity-matched study that compared all the three available surgical options for patients with severe symptomatic aortic valve stenosis: surgical aortic valve replacement (SAVR), SU-AVR and TA-TAVI. From the results of these two studies it clearly appears that TA-TAVI is an excellent therapeutic options in patients with aortic valve stenosis. The two main issues that still need to be solved are the incidence of paravalvular leak, and valve durability. Paravalvular leak has been demonstrated to have a significant impact on long term survival while the assessment of valve durability needs a longer observation of these patients in order to reach time points when structural valve deterioration is more likely to occur
La stenosi valvolare aortica (AVS) degenerativa senile è una malattia ad evoluzione progressiva caratterizzata da un significativo aumento della mortalità e da un drammatico peggioramento della qualità della vita dal momento in cui compare la sintomatologia specifica: dispnea (scompenso cardiaco congestizio), angina e sincopi. É stato dimostrato che, dalla comparsa dei sintomi, la sopravvivenza a due anni è inferiore al 50%. La diffusione di questa patologia è in aumento in seguito al progressivo incremento dell’aspettativa di vita, specialmente nei paesi più sviluppati. Il trattamento di prima scelta nei pazienti affetti da AVS severa sintomatica è rappresentato dall’intervento chirurgico di sostituzione valvolare. Questa procedura è generalmente eseguita in anestesia generale attraverso una sternotomia longitudinale mediana e con l’utilizzo della circolazione extracorporea. I risultati dell’intervento di sostituzione valvolare aortica sono ormai ben conosciuti, la sopravvivenza a breve e medio termine è eccellente e le protesi utilizzate hanno dimostrato delle ottime performance sia in termini di durata sia dal punto di vista emodinamico. Negli ultimi anni sono state introdotte sul mercato le bioprotesi aortiche sutureless che non richiedono punti di sutura per ancorarsi sull’anulus aortico. L’intervento di sostituzione valvolare aortica con le protesi sutureless (SU-AVR) richiede, infatti, dei tempi di clampaggio aortico e di circolazione extracorporea inferiori rispetto alle protesi tradizionali ed inoltre può essere più agevolmente eseguito attraverso un accesso mini-invasivo. Ciononostante, una recente analisi ha evidenziato che circa il 30% dei pazienti affetti da stenosi aortica non sono sottoposti all’intervento cardiochirurgico a causa dell’età molto avanzata o delle severe patologie associate da cui sono affetti. L’impianto valvolare aortico trans-catetere è un’alternativa terapeutica che può essere considerata nei pazienti ritenuti inoperabili con la tecnica tradizionale oppure per coloro che vengono considerati ad altissimo rischio a causa delle severe patologie coesistenti. La procedura di TAVI può essere eseguita attraverso diversi approcci: trans-femorale (TF-TAVI), trans-apicale (TA-TAVI), trans-aortico (Tao-TAVI) e trans-succlavio (TS-TAVI). L’argomento di questa Tesi sarà la procedura di TAVI e in particolare rivolgeremo la nostra attenzione alla TAVI trans-apicale in termini d’indicazioni, tecniche e risultati. In questa tesi saranno presentati i risultati del Registro italiano dell’Impianto Valvolare Aortico per via Trans-Apicale (I-TA registry), in cui sono stati arruolati la grande maggioranza dei pazienti sottoposti a TA-TAVI in Italia dal 2008, anno in cui questa tecnica è stata disponibile. Verranno inoltre presentati i risultati di uno studio propensity-matched in cui sono stati confrontati i risultati di tutte le tre tecniche chirurgiche attualmente disponibili per il trattamento dei pazienti con AVS: SAVR, TA-TAVI e SU-AVR. Dai risultati di questi studi appare chiaramente che la TA-TAVI è una valida alternativa terapeutica nei pazienti con AVS. Ci sono tuttavia ancora due aspetti che richiedono particolare attenzione: l’incidenza di leak paravalvolari e la durata di queste nuove bioprotesi. La presenza di un leak paravalvolare si è dimostrata un fattore prognostico negativo in termini di sopravvivenza a distanza mentre un’effettiva valutazione della durata di queste protesi richiede un’osservazione più prolungata in modo tale da arrivare ad intervalli di tempo in cui il verificarsi di una degenerazione strutturale sia più probabile

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De, Rui Marina. « Aortic valve replacement in elderly subjects : effects on physical performance, cognitive function and quality of life ». Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3425391.

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Background: aortic valve stenosis (AVS) is becoming more and more common in the elderly population, involving around 13.2% of subjects older than 75 years. In addition to worsening quality of life, untreated severe AVS has been associated with high short term mortality rate. However, these adverse outcomes could be modified by aortic valve replacement (AVR). In recent years, in particular, newer surgery procedures and anesthesiological techniques have allowed also older and frailer patients access to AVR procedures. Previous studies have evaluated the effectiveness of AVR in older subjects in terms of peri- and post-operative mortality, but its impact on frail patients’ global health has been scarcely investigated. Aim of the study: the aim of our study was to evaluate the impact of AVR procedure on older patients’ physical performance, cognitive status and quality of life at 45 days, three and six months after surgery. Subjects and methods: this prospective study included 46 patients over 70 years, enrolled in collaboration with the Department of Cardiac Surgery of the University of Padova. All subjects were affected by AVS, and were recommended to undergo AVR. Study participants were evaluated with a multidimensional geriatric assessment before AVR (T0) and 45 days (T1), three (T2) and six months (T3) after surgery. In particular, for each participant we collected data on clinical examination, self-sufficiency (using the Activites of Daily Living and Instrumental Activites of Daily Living scales), cognitive status (using the Mini Mental State Examination and the Montreal Cognitive Assessment), presence of depressive symptom (through the Geriatric Depression Scale), quality of life (using the Short-Form 36 items Health Survey) and physical performance (through the Short Physical Performance Battery, gait speed, 6-minute walking test, and measurements of upper and lower limbs strength). Results: of the initial sample of 46 patients, 22 reached the 6-month follow-up and were included in the study. Compared with the pre-operative evaluation, at T1 we observed a significant decline in nutritional status (BMI, arm circumference, MNA score) and in physical performance (SPPB, handgrip strength, lower limb flexion-extension and isometric strength). At T3, MMSE, MoCA, MNA and SPPB scores improved significantly from baseline. Upper and lower limbs strength at 6-month follow up was not significantly different from baseline. Quality of life remained nearly stable at T1, but improved significantly at T2 and T3. Considering the variation in gait speed from baseline to 6-month follow up, subjects that showed an improvement in this item compared to worsening subjects, at baseline had lower values of handgrip and limbs strength, gait speed and 6-MWT distance. Conclusions: our results show that in older AVS patients, AVR have a positive impact on nutrition, physical performance, cognitive functioning, mood and quality of life, whereas it does not have any significant impact on limbs muscle strength.
Premessa: la stenosi valvolare aortica (AVS) sta diventando sempre più frequente nella popolazione anziana, coinvolgendo circa il 13.2% dei soggetti sopra i 75 anni. Oltre a compromettere la qualità della vita, la AVS di grado severo non trattata porta alla morte in un tempo relativamente breve. La storia naturale della AVS può essere modificata dalla sostituzione della valvola aortica (AVR). I progressi nelle tecniche operatorie e anestesiologiche hanno ampliato negli ultimi anni l’accesso all’intervento chirurgico a pazienti sempre più anziani e sempre più fragili. In letteratura gli studi hanno finora valutato l’efficacia della AVR nel paziente anziano in termini di mortalità peri- e post-operatoria, mentre mancano dati circa l’esito dell’intervento sulla salute globale del paziente fragile a medio termine. Scopo dello studio: lo scopo del nostro studio era valutare nel soggetto anziano l’impatto dell’intervento di AVR sulla performance fisica, sullo stato cognitivo e sulla qualità di vita a distanza di 45 giorni, tre e sei mesi dall’intervento chirurgico. Soggetti e metodi: in collaborazione con l’U.O. Cardiochirurgia, secondo un disegno osservazionale longitudinale sono stati studiati 46 pazienti di età > 70 anni affetti da AVS per i quali era stata posta indicazione all’AVR. I soggetti sono stati valutati prima dell’intervento chirurgico (T0) e dopo l’intervento chirurgico a 45 giorni (T1), a tre mesi (T2) e a 6 mesi (T3). In tutte le visite i soggetti sono stati sottoposti a una valutazione geriatrica multidimensionale, comprensiva di esame clinico, valutazione dell’autonomia funzionale (Activites of Daily Living e Instrumental Activites of Daily Living Scales), dello stato cognitivo (Mini Mental State Examination, Montreal Cognitive Assessment), del tono dell’umore (Geriatric Depression Scale), della qualità di vita (Short-Form 36 items Health Survey, SF-36) e della performance fisica (Short Physical Performance Battery, Gait Speed, Six minute Walking Test, misurazione della forza massimale degli arti superiori e inferiori). Risultati: dei 46 pazienti inclusi nello studio in questo lavoro sono stati considerati solo i 22 soggetti che hanno completato il follow-up a 6 mesi. Rispetto alla valutazione preoperatoria, al follow-up dei 45 giorni era evidente un significativo peggioramento nei parametri nutrizionali (BMI,circonferenza del braccio, punteggio MNA) e dei test di performance fisica (forza massimale di prensione della mano, forza di flesso-estensione degli arti inferiori e test isometrico della forza degli arti inferiori). Al follow-up dei 6 mesi MNA, MMSE, MoCA, SPPB miglioravano significativamente, raggiungendo valori superiori a quelli basali. La forza degli arti superiori e inferiori non si modificava significativamente 6 mesi dopo l’intervento rispetto al basale. Per ciò che concerne la qualità di vita, i punteggi all’SF-36 rimanevano pressoché stabili a 45 giorni mentre miglioravano significativamente al controllo a 3 e a 6 mesi. Considerando la variazione della velocità del passo tra la valutazione basale e quella a 6 mesi, i soggetti che presentavano un miglioramento nel follow up, rispetto agli altri soggetti al basale presentavano valori più bassi di forza degli arti superiori e inferiori, di velocità del passo e percorrevano una distanza significativamente inferiore al 6-MWT. Conclusioni: i dati di questo studio evidenziano che nei pazienti anziani affetti da AVS, la sostituzione valvolare aortica migliora lo stato nutrizionale, le facoltà cognitive, il tono dell’umore, la performance fisica e la qualità di vita. La forza degli arti inferiori e superiori invece mantiene a 6 mesi valori non diversi da quelli pre-operatori. I soggetti che sembrano beneficiare maggiormente dal punto di vista funzionale della AVR sono quelli più compromessi a basale dal punto di vista della performance fisica.

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44

Abessi, Ovais. « Leaflet Material Selection for Aortic Valve Repair ». Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/30191.

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Leaflet replacement in aortic valve repair (AVr) is associated with increased long-term repair failure. Hemodynamic performance and mechanical stress levels were investigated after porcine AVr with 5 types of clinically relevant replacement materials to ascertain which material(s) would be best suited for repair. Porcine aortic roots with intact aortic valves were placed in a left-heart simulator mounted with a high-speed camera for baseline valve assessment. Then, the non-coronary leaflet was excised and replaced with autologous porcine pericardium (APP), glutaraldehyde-fixed bovine pericardial patch (BPP; Synovis™), extracellular matrix scaffold (CorMatrix™), or collagen-impregnated Dacron (HEMASHIELD™). Hemodynamic parameters were measured over a range of cardiac outputs (2.5–6.5L/min) post-repair. Material properties of the above materials along with St. Jude Medical™ Pericardial Patch with EnCapTM Technology (SJM) were determined using pressurization experiments. Finite element models of the aortic valve and root complex were then constructed to verify the hemodynamic characteristics and determine leaflet stress levels. This study demonstrates that APP and SJM have the closest profiles to normal aortic valves; therefore, use of either replacement material may be best suited. Increased stresses found in BPP, HEMASHIELD™, and CorMatrix™ groups may be associated with late repair failure.

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45

Madan, Ashish. « In vitro assessment of the effects of valvular stenosis on aorta hemodynamics and left ventricular function ». Wright State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1527085221854915.

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46

Facchin, Michela. « Clinical and Hemodynamic Results after Transcatheter Aortic Valve implantation (TAVI) : Early and Late (10-year) follow-up ». Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3424733.

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Transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with severe symptomatic aortic stenosis (AS) considered inoperable or at high surgical risk. More recently, TAVI has been performed also to lower risk patients based on the Heart Team decision. Few studies have studied interaction between surgical risk categories and outcomes. Aim of the study To analyze safety and efficacy (VARC-2 defined) TAVI treated patients as function of different preoperative risk. To assess independent predictors of death. Methods Four-hundred-eighty-two patients who underwent TAVI in our center between 2007 and 2017 were included in the study. According to Society of Thoracic Surgeons (STS) score and to other parameters, all the patients were retrospectively stratified into 4 groups: prohibitive (contraindications to aortic valve replacement, n = 124), high (STS > 8, n = 131), intermediate (4 ≤ STS ≤ 8, n = 112) and low (STS < 4, n = 115) risk. Early, 1-year and long-term outcomes have been evaluated in those 4 groups according the VARC 2 criteria. Results The TAVI procedure resulted to be safe because of low mortality rate throughout all risk groups. The lowest 30-days mortality rate was observed in low and prohibitive-risk patients (p=0.048). In the low risk group, in-hospital mortality was 0%. The results were similar at 1-year of follow-up, with a mortality rate of 6% and 7% in low- and prohibitive-risk patients vs 21% and 19% in intermediate- and high-risk groups, (p<0.008). At 5-year of follow-up the mortality rate was 52% and it appeared to be lower only in low-risk patients at long-term follow-up. Independent predictors of mortality were pre-procedural congestive heart failure (CHF), neoplastic disease, pre-procedural-creatinine, post-procedural major or life threatening bleeding and post-procedural acute kidney injury (AKI). Implanted prosthesis performed well with stable hemodynamic results over time and rare dysfunction (2.1%). Conclusions In our study population, TAVI was safe and effective, with low rates of mortality and adverse events regardless of the surgical risk. At longer follow-up mortality rate was significantly lower in low-risk patients. Pre-procedural CHF, neoplastic diseases, pre-procedural creatinine, post-procedural severe bleedings and post-procedural AKI were independent predictors of mortality. Transcatheter heart valves (THV) performance after the procedure was excellent and stable over time with low rate of late prosthesis dysfunction. Further studies should be addressed to confirm the promising long-term results among low-risk patients and the long-term durability of THV.

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Bachlah, Dana Mohamad. « Modeling of the inner structural band of the aortic valve bio prosthesis ». Bachelor's thesis, Igor Sikorsky Kyiv Polytechnic Institute, 2021. https://ela.kpi.ua/handle/123456789/43660.

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Обсяг дипломної роботи становить 73 сторінок, містить 28 ілюстрацій, 20 таблиць. Загалом опрацьовано 59 джерел. Актуальність: Захворювання аортального клапана призводять до серйозних дисфункцій, спричинених зворотним потоком клапана або підвищенням його опору. Наслідком цієї патології є важка серцева недостатність, скорочення тривалості та якість життя. Єдине лікування - хірургічна заміна клапана на штучний протез або пластику аортального клапана. Заміна хворого аортального клапана на штучний протез є ефективним методом профілактики серцевої недостатності, збільшення тривалості та поліпшення якості життя. Мета: Моделювання внутрішньої структурної смуги біопротезу аортального клапана. Завдання: переглянути літературу з анатомії судин та клапанів серця; проаналізувати та виявити проблему; побудувати внутрішню структурну клапанну модель клапана у винахіднику AutoCAD; Аналіз варіантів матеріалів для виготовлення клапанного корпусу показав прийнятні механічні характеристики та біосумісність. Основні результати: переглянуто літературу з суміжних тем; порівняльний аналіз існуючих прототипів штучних клапанів серця; вибір «біологічного нітинолу»; Розроблено 5 стандартних розмірів каркаса для біопротезування аортального клапана.
The volume of the graduation work is 73 pages, contains 28 illustrations, 20 tables. In total 59 sources have been processed. Relevance: Aortic valve diseases lead to its severe dysfunction caused backflow on the valve or increased its resistance. The consequence of this pathology is severe heart failure, reduced duration and quality of life. The only treatment is surgical replacement of the valve with an artificial prosthesis or aortic valve plastic. Replacing of a sick aortic valve with an artificial prosthesis is an effective method of preventing heart failure, increasing duration and improving quality of life. Purpose: Modeling of the inner structural band of the aortic valve bio prosthesis. Tasks: to review literature on anatomy of blood vessels and heart valves; analyze and identify the problem; build inner structural band valve model in AutoCAD inventor; analyze the material options for the manufacture of the valve frame showed acceptable mechanical characteristics and biocompatibility. Main results: literature on related topics has been reviewed; comparative analysis of existing prototypes of artificial heart valves; selection of “biological nitinol”; 5 standard sizes of frame for aortic valve bio prosthesis was designed.

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Conklin, Colleen. « Disparities in Survival and Mortality among Infants with Congenital Aortic, Pulmonary, and Tricuspid Valve Defects by Maternal Race/Ethnicity and Infant Sex ». Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3046.

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Background: The etiology of congenital heart valve defects is not well understood; little is known about the risk factors that contribute to the survival and mortality outcomes of children with these defects. Methods: Using data from the Texas Birth Defects Registry (TBDR) we conducted a retrospective cohort study of 2070 singleton infants with congenital aortic, pulmonary, or tricuspid valve atresia or stenosis born in Texas between January 1, 1996 and December 31, 2007 to Hispanic, Non-Hispanic (NH) black, and NH white women. TBDR data were death-to-birth matched by the Texas Vital Statistics Unit for deaths between January 1, 1996 and December 31, 2008. Using Kaplan-Meier survival estimates with log rank tests and Cox proportional hazards regression model hazard ratios (HR) with 95% confidence intervals (CI), we examined whether infant sex and maternal race/ethnicity affected early childhood survival or risk of mortality for children with congenital heart valve defects. Covariates included birth weight and gestational age, maternal age, maternal education, and number of co-occurring birth defects. Results: In children with aortic valve atresia and aortic valve stenosis, we found males had higher early childhood survival than females (55.0% vs. 41.5%, P=0.0451 and 91.6% vs. 82.5%, P=0.0492, respectively). Early childhood survival for males (94.9%) with pulmonary valve stenosis was slightly lower than females (97.1%, P=0.0116), and was also lower for NH black (94.1%) and Hispanic (95.3%) children than NH white children (97.8%, P=0.0340). After adjusting for covariates, early childhood mortality in children with pulmonary valve atresia with hypoplastic right ventricle was greater in NH black than NH white children (HR=2.93, CI 1.09-7.85, P=0.0329) and greater in NH black males than NH white males (HR=4.63, CI 1.12-19.19, P=0.0349). For children with tricuspid valve atresia, early childhood survival was lower in NH black males (35.7%) and Hispanic males (64.0%) than NH white males (81.0%, P=0.0269); after adjusting for covariates, risk for early childhood mortality was higher in NH black than NH white children (HR=3.39, CI 1.41-8.13, P=0.0062), and higher in NH black males than NH white males (HR=5.23, CI 133-20.58, P=0.0179). Conclusions: Our findings demonstrate there are disparities in early childhood survival and risk of mortality by infant sex and maternal race/ethnicity for children with congenital heart valve defects. These findings provide a foundation for further investigation to better understand why these disparities exist and what can be done to improve the outcomes for children with these defects.

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49

Chaloupková, Aneta. « Farmakoekonomická analýza distribuce zdravotnického produktu CoreValve ». Master's thesis, Vysoká škola ekonomická v Praze, 2011. http://www.nusl.cz/ntk/nusl-113239.

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This diploma work is focused on using economic analysis methods to compare cost-effectivness of an innovative technology for treating aortic stenosis that is transcatheter implantation of an artificial valve CoreValve by Medtronic with traditional treatments. During the analyses we utilized only publicly available data which are often too general while more specific data might not be available because they do not exist or are not publicly available. This work sets up a theoretical foundation for the analyses, performs the analyse sof the product, PEST analyses and cost analyses. Since pacient's willigness to pay index (WTP) in the Czech republic has not yet been measured for this treatment, it is not posible to confirm the cost-effectivness of CoreValve, even though it has been confirmed in several countries based on the literature search related to this topic.

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50

Pohjolainen, V. (Virva). « Characterization of non-collagenous extracellular matrix proteins in cardiac and aortic valve remodelling ». Doctoral thesis, Oulun yliopisto, 2012. http://urn.fi/urn:isbn:9789514299025.

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Abstract Heart failure (HF) and aortic valve stenosis (AS) are complex disorders affected by functional alterations and actively regulated remodelling of the heart and the aortic valve, respectively. In addition to structural proteins, such as collagens and elastin, the extracellular matrix (ECM) in the heart and the aortic valve comprises non-collagenous factors that are not strictly involved in the architecture but may modulate cardiac and valvular remodelling. In the present study the expression of non-collagenous fibrosis- and calcification-related ECM proteins was investigated in HF-associated cardiac remodelling from different origins as well as in fibrocalcific aortic valve disease leading to AS. The experimental models of pressure overload, myocardial infarction (MI) and chronic renal failure were used to study the cardiac expression of bone morphogenetic protein (BMP)-2, BMP-4, bone sialoprotein, matrix Gla protein (MGP), osteoactivin, osteopontin, periostin and/or pleiotrophin in vivo in cardiac remodelling. Human aortic valves, obtained from patients undergoing valve replacement, were studied to characterize the valvular expression of BMP-2, BMP-4, bone sialoprotein, MGP, osteoactivin, osteopontin, osteoprotegerin, periostin, pleiotrophin, and thrombospondins (TSPs) 1-4 in the different stages of fibrocalcific aortic valve disease. Left ventricular (LV) MGP expression was upregulated in vivo in non-uremic cardiac remodelling. In vitro results indicate that angiotensin II elevates MGP expression in cardiomyocytes and fibroblasts. Periostin gene expression was induced in cardiac but not in aortic valve remodelling and the cardiac induction in chronic renal insufficiency was associated with LV hypertrophy and blood pressure as well as the cardiac gene expression of other fibrosis-related genes. Bone sialoprotein and osteopontin were expressed in the aortic valves in parallel with calcification, and also in distinct models of cardiac remodelling. Osteoprotegerin protein expression in stenotic valves was weak regardless of a simultaneous increase in gene expression. BMPs were downregulated in AS and no change in LV gene expression was detected in uremic cardiac remodelling. All the studied TSPs were expressed in human aortic valves, and especially the expression of TSP-2 was shown to increase in fibrocalcific aortic valves simultaneously with decreased activation of the Akt/nuclear factor (NF)-κB-pathway. This study delineates distinct expression patterns of non-collagenous ECM proteins in pathological tissue remodelling in the heart and in the aortic valve, and thus emphasizes the role of ECM proteins as an important modulator of cardiac and aortic valve remodelling
Tiivistelmä Sydämen vajaatoiminnan ja aorttastenoosin taudinkuvaan kuuluvat toiminnallisten muutosten ohella aktiivisesti säädellyt soluväliaineen muutokset sydämen ja aorttaläpän rakenteessa. Soluväliaineen rakenteen muodostavien kollageenien ja elastiinin lisäksi soluväliaineessa on rakenteeseen kuulumattomia proteiineja. Tässä väitöskirjassa tutkittiin sidekudoksen kertymiseen ja kudosten kalkkiutumiseen osallistuvia soluväliaineen proteiineja sydämen vajaatoiminnassa sekä aorttastenoosiin johtavassa kalkkiuttavassa aorttaläppäviassa. Tutkimuksessa selvitettiin sydämen soluväliaineen proteiinien ilmentymistä painekuormituksen, sydäninfarktin ja pitkäaikaisen munuaisten vajaatoiminnan koemalleissa rotalla. Tutkittavia proteiineja olivat luun morfogeneettiset proteiinit 2 ja 4, luun sialoproteiini, matriksin Gla proteiini (MGP), osteoaktiviini, osteopontiini, periostiini ja pleiotropiini. Edellä mainittujen proteiinien lisäksi osteoprotegeriinin ja trombospondiinien 1-4 ilmentymistä tutkittiin kalkkiuttavan aorttaläppävian eri kehitysvaiheissa. Aorttaläpät oli kerätty tekoläppäleikkauspotilailta. Sydämessä MGP:n ilmentyminen lisääntyi kaikissa muissa paitsi munuaisten vajaatoiminnan koemallissa. Angiotensiini II nosti MGP:n ilmentymistä sydänlihassoluissa ja sidekudossoluissa. Periostiinin ilmentyminen lisääntyi sydämen uudelleenmuovautumisessa, muttei aorttaläppäviassa. Lisäksi munuaisten vajaatoiminnan aiheuttama periostiinin ilmentymisen muutos sydämessä liittyi sekä sydämen kasvuun, verenpaineen nousuun että muiden sidekudosta muokkaavien proteiinien ilmentymiseen. Luun sialoproteiinin ja osteopontiinin ilmentymiset erosivat toisistaan erilaisissa sydämen vajaatoiminnan malleissa, mutta aorttaläpissä niiden molempien ilmentyminen oli suhteessa läpän kalkkiutumiseen. Osteoprotegeriinin geenin ilmentyminen lisääntyi kalkkiutuneissa aorttaläpissä vaikkakin proteiinin määrä pysyi vähäisenä. Luun morfogeneettisten proteiinien ilmentyminen oli alentunut sairaissa läpissä, muttei sydämessä munuaisten vajaatoiminnan aikana. Aorttaläpissä ilmennettiin kaikkia trombospondiineita, joista trombospondiini-2:n ilmentyminen kasvoi sairaissa aorttaläpissä. Kalkkiutuneissa läpissä solunsisäinen Akt/NF-κB–signaalinvälitysjärjestelmä oli vaimentunut. Tutkimus osoittaa, että soluväliaineen proteiinien ilmentymistä säädellään eri tavoin sydämen vajaatoiminnassa ja aorttastenoosissa kudoksen uudelleenmuovautumisprosessin aikana

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Thèses sur le sujet « Aortic valve stenosis (AVS) »

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