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1
Peacock, Jacqueline D. "The Role of Sox9 in Heart Valve Development and Disease." Scholarly Repository, 2011. http://scholarlyrepository.miami.edu/oa_dissertations/543.
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Heart valve structures open and close during the cardiac cycle to provide unidirectional blood flow through the heart, critical for efficient cardiovascular function. Valve dysfunction results in either incomplete opening or incomplete closure of the valve. Both types of valve dysfunction decrease efficiency of blood flow, increasing the load on the myocardium and leading to secondary heart disease such as pathological hypertrophy and heart failure. There are currently no effective treatments to prevent or slow the progression of valve disease, and there are no pharmacological treatments for advanced valve disease. Although most valve disease is associated with aging, increasing evidence suggests that valve disease often has origins in development. Congenital valvuloseptal defects affect many newborns, ranging from life-threatening malformations requiring immediate repair to more subtle, often undiagnosed defects that increase susceptibility to valve disease later in life. Therefore, an improved understanding of the mechanisms of heart valve formation and maintenance of adult valves may serve as an important step in improving valve disease treatment options. In this work, the mechanisms of normal valve development and the role of Sox9 in developing and mature valves are further studied. The temporal and spatial expression of extracellular matrix genes and proteins are examined throughout normal murine valve development. Sox9 function in the processes of valve development and valve maintenance is examined using mouse models of conditional Sox9 loss-of-function. Heart valve phenotypes in mice with reduced Sox9 function are examined throughout development and in adult mice with resultant calcific valve disease. The possible causative mechanisms of calcific valve disease in mice with reduced Sox9 function are further investigated by identification of novel possible targets of Sox9 transcriptional regulation. Together these studies improve our understanding of heart valve development, characterize a model of heart valve calcification with genetic etiology, and identify and characterize novel targets of Sox9.
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Sharma, Vishal. "Natriuretic peptides in valvular heart disease." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23463.
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Plasma natriuretic peptide concentrations rise in response to either atrial or ventricular wall stretch and have been found to be useful in the diagnosis and assessment of patients with congestive cardiac failure. Although previous studies have suggested that plasma natriuretic peptides may offer some prognostic information in patients with valvular heart disease, it is unclear whether concentrations reflect disease severity and how plasma concentrations vary across different valve lesions. The aim of this research was to identify the factors that affect natriuretic peptide releases in valvular heart disease (VHD) and to investigate whether natriuretic peptides can be used in clinical practice to identify those patients who may benefit from early intervention. Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in patients with normal left ventricular (LV) systolic function and isolated VHD (mitral regurgitation, MR, n=33; aortic regurgitation, AR, n=39; aortic stenosis, AS, n=34; mitral stenosis, MS, n=30), and age and sex matched controls (n=39) immediately prior to exercise stress echocardiography. Peptide levels were compared against age and sex matched controls and against markers of severity for each valve lesions and across different valve lesions. Compared to controls, patients with all types of VHD had elevated plasma BNP concentrations [(MR median 35(inter quartile range 23-52), AR 34(22-45), AS 31(22-60), MS 58(34-90); controls 24(16-33) pg/mL; p < 0.01 for all]. LV end diastolic volume index varied by valve lesion; [MR (mean ± standard deviation 77±14), AR (91±28), AS (50±17), MS (43±11), controls (52±13) mL/m2; p < 0.0001]. There were no associations between LV volume and BNP. Left atrial (LA) area index varied [MR (18±4cm2/m2), AR (12±2), AS (11±3), MS (19±6), controls (11±2); p < 0.0001], but correlated with plasma BNP concentrations: MR (r=0.42,p=0.02), MS (r=0.86,p < 0.0001), AR (r=0.53,p=0.001), AS (r=0.52, p=0.002). Higher plasma BNP concentrations were associated with increased pulmonary artery pressure and reduced exercise capacity. Despite adverse cardiac remodelling, 81(60%) patients had a BNP concentration within the normal range. In patients with MS BNP was strongly associated with left atrial area index (r=0.86; p < 0.0001) and a BNP level of greater than 2 times the upper limit of normal identified patients who fulfilled guideline criteria for intervention (Area under the curve (AUC) 0.87 [0.74,0.99], p =0.006) and lower exercise capacity (AUC 0.82 [0.67,0.97]; p=0.004). In AR patients significant remodelling could occur whilst BNP remained within the normal range and in general BNP appeared less useful in assessing disease severity. However raised levels of BNP was associated with more severe AR as assessed by left ventricular outflow tract:AR Jet area ratio (r=0.43 p=0.0007). AR patients with an abnormal BNP had signs of early LV dysfunction on exercise with a lower LV longitudinal strain rate post exercise compared to AR patients with a normal BNP (0.68±0.31 vs. 1.06±0.45 1/sec; p=0.02). In MR patients, higher plasma BNP concentrations were associated with larger left atrial area index (r=0.42, p=0.02), higher pulmonary artery pressure (r=0.53, p=0.002) and a lower exercise time (r=-0.60, p=0.0002). BNP was not associated with any marker of left ventricular size or function in MR. These findings suggest that despite significant LV remodelling, plasma BNP concentrations are often normal in patients with VHD. Consequently, plasma BNP concentrations should be interpreted with caution when assessing patients with VHD. However natriuretic peptide levels offer complementary information to the standard assessment of patients with VHD and an unexplained finding of an elevated BNP in an otherwise asymptomatic patient should prompt further investigation.
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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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Tseng, Yuan-Tsan. "Heart valve tissue engineering." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:e67c780d-d60f-42e7-9311-dd523f9141b3.
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Since current prosthetic heart valve replacements are costly, cause medical complications, and lack the ability to regenerate, tissue-engineered heart valves are an attractive alternative. These could provide an unlimited supply of immunological-tolerated biological substitutes, which respond to patients' physiological condition and grow with them. Since collagen is a major extra cellular matrix component of the heart valve, it is ideal material for constructing scaffolds. Collagen sources have been shown to influence the manufacturing of collagen scaffolds, and two commercial sources of collagen were obtained from Sigma Aldrich and Devro PLC for comparison. Consistencies between the collagens were shown in the primary and secondary structures of the collagen, while inconsistencies were shown at the tertiary level, when a higher level of natural crosslinking in the Sigma collagen and longer polymer chains in the Devro collagen were observed. These variations were reduced and the consistency increased by introducing crosslinking via dehydrothermal treatment (DHT). Collagen scaffolds produced via freeze-drying (FD) and critical point-drying with cross-linking via DHT or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide /N-hydroxysuccinimide (EDC/NHS) were investigated. All the scaffolds were compatible with mesenchymal stem cells (MSCs) according to the proliferation of the cells and their ability to produce ECM, without differentiating between osteogenic, chondrogenic or endothelial lineages. The FD EDC/NHS scaffold demonstrated the most suitable physical property of all. This result illustrates that FD EDC/NHS crosslinking is the most suitable scaffold investigated as a start for heart valve tissue engineering. To prepare a scaffold with a controlled local, spatial and temporal delivery of growth factor, a composite scaffold comprising poly (lactic-co-glycolic acid) (PLGA) microspheres was developed. This composite scaffold demonstrated the same compatibility to the MSCs as untreated scaffold. However, the PLGA microspheres showed an increase in the deterioration rate of Young's modulus because of the detachment of the microspheres from the scaffold via cellular degradation.
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Hadian, Mojtaba. "Study of collagen structure in canine myxomatous mitral valve disease." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4383.
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Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs, and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. Realising the importance of collagen fibres in mitral heart valves and considering the paramount significance of myxomatous mitral valve disease, a better understanding of the pathogenesis of MMVD is essential. Thus, this study was designed to investigate the changes in collagen molecules, including fibril structure, fibril orientation, d-spacing, collagen density, collagen content, thermal stability, and the status of mature and immature crosslinks. A combination of biophysical and biochemical tools such as x-ray diffraction, neutron diffraction, HPLC were utilised in order to fulfil the objectives. Biochemical assay of hydroxyproline revealed a 10% depletion of collagen in mildly affacted (grade I and II) leaflets, while a 20% depletion of fibrillar collagen was revealed by mapping the collagen fibrils onto the anatomy of cardiac leaflets using x-ray data. Differential scanning calorimetry showed that there were no significant differences in the onset temperature of denaturation of collagen between the healthy and affected leaflets. However, in affected areas of leaflets, the enthalpy of denaturation significantly dropped by 20%. In the affected regions, neutron diffraction results showed an increase in the immature reducible cross-links though the low number of the samples can be considered a limiting factor in this regard. However, the HPLC results showed a 25% decrease in the number of mature cross-links. Additionally, the recently introduced imaging technologies to biology and medicine such as differential enhancing imaging (DEI) and coherent anti-Stokes Raman scattering spectroscopy (CARS) were, to the author’s best knowledge, applied for the first time to this disease. In doing so, this thesis furthers our understanding of the pathogenesis of MMVD, especially in relation to the collagen. The thesis provides new findings about MMVD and demonstrates the potential of biophysical tools for studying similar conditions.
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Menciotti, Giulio. "Advanced Echocardiographic Imaging In Dogs With Myxomatous Mitral Valve Disease." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/77704.
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Myxomatous mitral valve degeneration (MMVD) is the most common canine cardiac disease.
In the studies presented in this dissertation, we used advanced echocardiographic techniques to elucidate several aspects of MMVD in dogs. Our hypothesis was that the mitral valve (MV) morphology could have a role in the development of MMVD. First, we tested whether we could use real time three-dimensional transthoracic echocardiography (RT-3DTTE), and an offline software for MV analysis to evaluate canine MV. We described that the technique was feasible and repeatable, we evaluated the morphology of the MV in healthy dogs, and we provided reference values for MV morphologic variables in this species. Then, we used the same technique to compare healthy dogs to dogs affected by MMVD. We found that dogs affected by MMVD have more circular and flatter valve. We then analyzed the MV of healthy Cavalier King Charles Spaniels (CKCSs), given the high predisposition of this breed for MMVD. Our findings indicate that compared to healthy dogs of other breeds, the MV of healthy CKCSs is flatter and has less leaflet tenting, corroborating our hypothesis that an altered MV morphology could represent a predisposing factor for disease development. We also used RT–3DTTE to characterize the area of the regurgitant MV orifice of dogs affected with MMVD, finding that the technique requires further standardization in order to become clinically useful.
The elevation of pulmonary venous pressure caused by MMVD can, in some dogs, cause pulmonary arterial hypertension (PH), which is a risk factor associated with worse outcome in dogs with MMVD. Diagnosis of PH in dogs with MMVD is usually made by estimating pulmonary pressure using Doppler echocardiography. We are currently evaluating the accuracy of this technique, compared to invasive measurement of pulmonary pressure. Only preliminary data are presented regarding this study, as the disclosure of the blinding would have infringed the power of the study. Our preliminary results demonstrate that there is only moderate agreement between the two techniques, indicating that caution should be used when deriving the non-invasive estimation of systolic pulmonary pressure in order to make clinical decisions.Ph. D.
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Kim, Andrew. "Targeted macrophage depletion is protective against heart valve disease in Marfan syndrome." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1562059861013629.
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Lopez-Alvarez, Jordi. "Evaluation of early indicators of disease progression in dogs with degenerative mitral valve disease." Thesis, Royal Veterinary College (University of London), 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669194.
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Weinberg, Eli 1979. "Multiscale simulations of the aortic heart valve : applications in disease and surgery." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44797.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (p. 136-148).
This thesis presents mathematical models describing the mechanical behavior of the human aortic heart valve over a range of length and time scales. In the human heart, the valves perform the vital function of controlling the direction of blood flow. Each valve is an intricate mechanical structure, with distinct features and functions at multiple scales. This effort first develops a framework of reference configurations that enables communication between simulations of the different length scales. Three simulations are created within that framework. At the cell scale, the interaction between a single valvular interstitial cell and its surrounding matrix is described. At the tissue scale, a model is created for the valve cusp tissue mechanical behavior, including the multilayered, nonuniform geometry and nonlinear, anisotropic material properties. At the organ scale, a dynamic, three-dimensional model with fluid-structure interaction predicts the motion of the valve, blood, and surrounding tissue. Each simulation is verified against a number of experimental measures. These three simulations together constitute a model for the dynamic, three-dimensional, multiscale mechanical behavior of the healthy human aortic heart valve throughout the cardiac cycle. The model is employed to perform multiscale investigation into the mechanisms of the disease calcific aortic stenosis in three ways. First, the model of the healthy valve is extended to describe disease progression on the decade time scale. Calcification is introduced at the tissue level and the effects on valve function are monitored at the organ level. Second, the role of mechanical deformations in the disease process is examined by comparing multiscale deformations between the normal valve case and a known disease-prone case.
(cont.) Finally, a combined computational and experimental study investigates the role of fluid shear in calcific disease. Shears computed in the organ-scale simulation are applied to endothelial cells in vitro. The cells express disease-related genes in a manner consistent with the region-specific nature of calcific disease, providing evidence for a role of shear in the disease process. The multiscale model presented in this thesis has further utility in investigating function, disease, and therapy of the human aortic valve.
by Eli J. Weinberg.
Ph.D.
10
LaHaye, Stephanie Donna. "Discovering and Modeling Genetic Causes of Congenital Heart Disease." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492610446228702.
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Liu, Yin. "Role Of Nitric Oxide In Embryonic Heart Development And Adult Aortic Valve Disease." Scholarship@Western, 2014. http://ir.lib.uwo.ca/etd/2108.
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Congenital heart disease (CHD) is the most common birth defect in infants. Identifying factors that are critical to embryonic heart development or CHDs in general could further our understanding of the disease and may lead to new strategies of its prevention and treatment. Endothelial nitric oxide synthase (NOS3/eNOS) is known for many important biological functions including vasodilation, vascular homeostasis and angiogenesis. Previous studies have shown that deficiency in NOS3 results in congenital septal defects, cardiac hypertrophy and postnatal heart failure. In addition, NOS3 is pivotal to morphogenesis of aortic valve and myocardial capillary development. The aim of my thesis was to investigate the role of NOS3 in the embryonic and adult heart. I discovered that NOS3 deficiency resulted in coronary artery hypoplasia in fetal mice and spontaneous myocardial infarction in postnatal hearts. Coronary artery diameters, vessel density and volume were significantly decreased in NOS3-/- mice at postnatal day 0. Lack of NOS3 also down-regulated the expression of Gata4, Wilms tumor-1, vascular endothelial growth factor, basic fibroblast growth factor and erythropoietin in the embryonic heart at E12.5, and inhibited migration of epicardial cells into the myocardium. In addition, my data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3-/- compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3-/- mice. Immunostaining of Snail1 was performed in the embryonic heart. Snail1 positive and total mesenchymal cells in the AV cushion were decreased in NOS3-/- compared with WT mice at E10.5 and E12.5. Finally, in the adult aortic valves, NOS3 is important in inhibition of thrombosis formation. Deficiency in NOS3 leads to aortic valve thrombosis and calcification. At 12 months old, 72% (13/18) of NOS3-/- mice showed severe spontaneous aortic valve thrombosis compared with WT mice (0/12). Ex vivo culture of aortic valves showed that platelet aggregation and adhesion were significantly increased in NOS3-/- aortic valves compared with WT aortic valves. There was also a significant regurgitation of the aortic valve during systole in the NOS3-/- compared with WT mice. In addition, NOS3 deficiency resulted in significant aortic valve stenosis, calcification and fibrosis. In summary, these data suggest NOS3 plays a critical role in embryonic heart development and morphogenesis of coronary arteries and inhibits thrombosis formation in the adult aortic valves.
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Gharibeh, Lara. "Gata6 Haploinsufficiency Leads to Aortic Valve, Conduction System and Limbs Defects." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37584.
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Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Congenital heart disease (CHD) is a risk factor for premature cardiovascular complications. Great advances have occurred in the past years leading to the identification of several genes essential for proper cardiac formation such as GATA4/5/6 mutated in some individuals with CHD. GATA6 is a zinc finger transcription factor whose presence is crucial for early embryonic development. GATA6 is expressed in many cell types of the heart including myocardial, endocardial, neural crest, and vascular smooth muscle. In human, mutations in GATA6 result in variable cardiac phenotypes. The objective of this thesis was to determine the roles that GATA6 play in the different cell types of the heart and to elucidate the molecular basis of the cardiac defects associated with Gata6 haploinsufficiency. For this, a combination of cell and molecular techniques were used in vitro and in vivo. First, we show that Gata6 heterozygozity leads to RL-type bicuspid aortic valve (BAV)- the most common CHD affecting 2% of the population. GATA6-dependent BAV is the result of disruption of valve remodeling and extracellular matrix composition in Gata6 haploinsufficient mice. Cell-specific inactivation of one Gata6 allele from Isl-1 positive cells, but not from endothelial or neural crest cells, recapitulates the phenotype of Gata6 heterozygous mice revealing an essential role for GATA6 in secondary heart field myocytes during valvulogenesis. We further uncovered a role for GATA6 as an important regulator of the cardiac conduction system and revealed that GATA6 expression regulates the activity of the cardiac pacemaker. GATA6 exerts its role via regulation of the cross-talk among the different cell types of the SAN. Lastly, some CHDs are characterized by abnormalities of both the limbs and the heart such as the Holt Oram syndrome (caused by mutation in TBX5 transcription factor). The molecular basis for limb-heart defects remain poorly understood. In the course of this work, we discovered that Gata6 haploinsufficiency resulted in a partially penetrant polysyndactyly (extra digits fused together) phenotype. Together, the data provide novel molecular and cellular insight into GATA6 role in normal and pathologic heat development. Our results also suggest that GATA6 should be added to the list of genes whose mutations are potentially associated with heart and limb abnormalities. Better knowledge of the molecular basis of CHD is a prerequisite for the development of diagnostic and therapeutic strategies to improve care of individuals with congenital heart disease.
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Antoniali, Fernando. "Determinação da proporção entre os segmentos do anel da valva tricuspide : estudo anatomico em corações de humanos." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311156.
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Orientador: Domingo Marcolino BraileDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-07T03:55:43Z (GMT). No. of bitstreams: 1 Antoniali_Fernando_M.pdf: 4775200 bytes, checksum: 8361f227d501574e0c98c3965065c58b (MD5) Previous issue date: 2006
Resumo: Objetivo: Determinar a proporção existente entre os segmentos do anel da valva tricúspide normal em humanos. Método: Foram estudados 30 corações de cadáveres humanos não formolizados, com menos de 6h de período ¿post-mortem¿, sem lesões congênitas ou adquiridas e com valvas tricúspides sem deformidades e continentes. A continência desta valva foi confirmada por injeção de água sob pressão no interior do ventrículo direito estando a valva pulmonar fechada. Foram realizadas fotos digitais da valva tricúspide com o anel valvar íntegro e após secção na comissura póstero-septal e retificação do anel valvar. Estas fotos contendo escalas milimetradas foram avaliadas por programa específico de computador. Foram feitas medidas computadorizadas do perímetro, segmento septal e segmento ântero-posterior do anel valvar íntegro. Nesta condição também foram feitas medidas da distância linear entre as comissuras ântero-septal e póstero-septal. Na condição de anel valvar retificado, foram realizadas medidas computadorizadas e manuais do perímetro e dos segmentos septal, anterior e posterior do anel valvar tricuspídeo. Compararam-se as medidas médias e as razões entre elas nas condições de anel íntegro e retificado. Compararam-se, também, a forma computadorizada e manual de mensuração do anel. Resultados: Nas medidas computadorizadas realizadas com imagens digitais do anel valvar íntegro, os valores médios do perímetro, segmento septal e ântero-posterior foram 105mm (±12,7), 30,6mm (±3,7) e 74mm (±9,4), respectivamente. A distância linear média entre as comissuras ântero-septal e póstero-septal foi de 28,9mm (±3,4). Nas medidas computadorizadas realizadas com imagens digitais do anel valvar retificado, os valores médios foram 117,5mm (±13,3), 32mm (±3,7), 46,3mm (±8,3) e 39,1mm (±8,5), respectivamente para perímetro, segmento septal, anterior e posterior. A razão média entre o segmento ântero-posterior e o septal foi 2,43 (±0,212) e 2,67 (±0,304) respectivamente em anéis íntegros e retificados. Houve diferenças significantes entre as medidas do perímetro (p<0,0001), do segmento septal (p=0,003) e do segmento ântero-posterior (p<0,0001) quando realizadas em anéis íntegros e retificados. As razões entre segmento ântero-posterior e septal também apresentaram diferença significante (p=0,0005). As medidas manuais do anel valvar retificado apresentaram os valores médios de 118,5mm (±12,7), 32,6mm (±3,4), 46,6mm (±7,7) e 39,3mm (±7,9), respectivamente para perímetro, segmento septal, anterior e posterior. Não houve diferenças significantes entre medidas manuais e computadorizadas. Conclusões: A proporção existente entre os segmento septal e o segmento ântero-posterior, do anel da valva tricúspide normal em humanos, é igual a 1 : 2,43. A secção e retificação do anel tricuspídeo altera as medidas de seus segmentos e suas relações
Abstract: Objective: The purpose of this study was to determine the proportion among the segments of the human tricuspid valve annulus. Methods: Descriptive autopsy study of 30 human hearts, without fixation, with less than six hours of post-mortem period, without congenital or acquired lesions and without tricuspid regurgitation. The tricuspid valve insufficiency was excluded by infusion of pressured water in the right ventricle with closed pulmonary valve. Digital images of the tricuspid ring on anatomical position and on flattened state were analyzed by specific software. Computerized measurements of the perimeter, septal segment, anteroposterior segment and the linear distance between the anteroseptal and posteroseptal commissures were obtained on anatomical position. Computerized and manual measurements of the perimeter, septal, anterior and posterior segments were obtained on flattened state. The measurements were demonstrated and compared on the two different situations, anatomical position and flattened. The computerized measurements were compared with the manual ones. Results: The mean values of the perimeter, septal and anteroposterior segments of the tricuspid ring, obtained by computerized measurements on anatomical position were: 105mm (±12.7), 30.6mm (±3.7) e 74mm (±9.4), respectively. The mean linear distance between the anteroseptal and posteroseptal commissures was 28.9mm (±3.4). On the flattened state and by computerized measurements, the mean value of the perimeter was 117.5mm (±13.3) and of the septal, anterior e posterior segments were respectively: 32mm (±3.7), 46.3mm (±8.3) e 39.1mm (±8.5). The mean ratio between the antero-posterior and septal segments was 2.43 (±0.212) on the anatomical position and on flattened state was 2.67 (±0.304). Statistical differences were observed in the measurements of perimeter (p<0.0001), septal segment (p=0.003) e antero-posterior segment (p<0.0001) on the two situations. Statistical difference also occurred on the ratios between the antero-posterior and septal segments (p=0.0005). The mean values obtained by manual measurements of the tricuspid ring on flattened state were: 118.5mm (±12.7), 32.6mm (±3.4), 46.6mm (±7.7) e 39.3mm (±7.9), respectively for perimeter, septal, anterior and posterior segments. There weren¿t statistical differences on computerized and manual measurements. Conclusions: The proportion between the septal and antero-posterior segments of the normal human tricuspid valve is 1 : 2.43. The attitude of flatting the tricuspid ring to measure the segments, changes their values and the ratios between them
Mestrado
Cirurgia
Mestre em Cirurgia
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Hezzell, Melanie Jane. "Identification of clinical variables associated with ventricular remodelling and survival in canine mitral valve disease." Thesis, Royal Veterinary College (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572459.
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Akram, Abawi. "Transcatheter aortic valve implantation for patients with aorticstenosis and concomitant ischemic heart disease: : A five-yearfollow-up." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-76214.
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Introduction: Transcatheter aortic valve implantation (TAVI) is an established procedure to treat severe aortic stenosis (AS). This study investigates the impact of ischemic heart disease (IHD) on survival in patients undergoing TAVI. Aim: Five-year all-cause mortality stratified according to the presence or absence of IHD. Methods: Retrospective register study including all patients that underwent a TAVI-procedure 2009 to 2018. Patients were stratified according to the presence or absence of IHD. Our primary end-point was five-year all-cause mortality. Survival was analyzed using Kaplan-Meier curve. Data were acquired through the SWENTRY registry and patient files. Results: A total of 264 patients were included in the study, with 139 (52.7 %) patients in the IHD group vs 125 (47.3 %) patients in the non-IHD group. Mean follow-up time was 40 ±30 months. At baseline, there was a higher proportion of males, patients with hypertension, peripheral arterial disease, left ventricular ejection fraction <50 % and, a higher EuroSCORE I in the IHD-group. Transfemoral approach was most common in both groups. No differences were noted in respect to peri- and postoperative complications. Five-year all-cause mortality was 17/38 (44.7 %) vs 18/30 (60.0 %), p = 0,232, in the IHD and non-IHD group respectively. Non-adjusted cumulative five-year survival was not significantly different between the groups (Log-Rank, p = 0,056). Conclusions: In patients with severe AS undergoing TAVI, the five-year all-cause mortality was not statistically different between patients with or without IHD.
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Zuo, Heng. "3D Multi-Physics MRI-Based Human Right Ventricle Models for Patients with repaired Tetralogy of Fallot: Cardiac Mechanical Analysis and Surgical Outcome Prediction." Digital WPI, 2017. https://digitalcommons.wpi.edu/etd-dissertations/478.
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Introduction. Computational modelling has been used widely in biological and clinical applications, but relatively less in surgical design and optimization. Magnetic resonance image (MRI)-based right ventricle (RV) models were introduced for patients with repaired Tetralogy of Fallot (rTOF) to assess ventricle cardiac function, and to identify morphological and mechanical parameters which can be used to predict and optimize post-surgery cardiac outcome. Tetralogy of Fallot is a common congenital heart defect which includes a ventricular septal defect and severe right ventricular outflow obstruction, account for the majority of cases with late onset RV failure. The current surgical approach for the patients with repaired ToF including pulmonary valve replacement/insertion (PVR) has yielded mixed results. It is of great interest to identify parameters which may be used to predict surgical cardiac function outcome after PVR. Data, Model, and Methods. Cardiac Magnetic Resonance (CMR) data from 20 healthy volunteers (11 males, mean year : 22.8) and 56 TOF patients (37 males, mean year : 25.3) were provided by Children's Hospital - Boston, Harvard Medical School from our NIH-funded project (R01 HL089269). RV wall thickness (WT), circumferential and longitudinal curvature (C-cur and L-cur), surface area (SA) and surface to volume ratio (SVR) were obtained based on CMR data for morphological analysis. 6 healthy volunteers and 16 TOF patients were chosen to construct 3D computational models for mechanical analysis. The 3D CMR-based RV/LV/Patch combination models included a) isotropic and anisotropic material properties, b) myocardial fiber orientation, c) active contraction with two zero-load geometries, and d) fluid-structure interactions. The models were used to obtain the assessment for RV mechanical conditions, which might be helpful for PVR surgical outcome prediction. All the computational models were built and solved in a commercial finite element software ADINA. Statistical methods including Linear Mixed- effort Method and Logistical regression were used in the morphological and mechanical analysis to find out potential indicators for predicting PVR outcome from the morphological and mechanical parameters. Results. In morphological analysis, statistically significant differences were found in RV SA and SVR between better-outcome patient group (BPG) and worse-outcome patient group (WPG). At begin of ejection, mean RV SA of BPG was 13.6% lower than that from WPG (241.1 cm2 v.s. 279.0 cm2, p =0.0161). Mean RV SVR of BPG was 13.1% lower than that from WPG (1.26 cm2/ml v.s. 1.45 cm2/ml, p =0.0271). Similar results were also found in RV SA and SVR at begin of filling. Furthermore, RV EF change from pre- to post-PVR were found negatively correlated with RV SA and SVR. In mechanical analysis, 22 structure-only models with one zero-load geometry (1G) were constructed to obtain stress/strain distributions. Stress-P1 from BPG was found to be closer to that from HG, compared to Stress- P1 of WPG. At the beginning of ejection, mean Stress-P1 of BPG was only 6.8% higher than that from healthy group (p =0.6889), while average Stress-P1 of WPG was 84.1% higher than that of healthy group (p =0.0418). Similar results were also found at begin of filling. The results suggested that comparing patients' RV stress values with healthy RV stress values may help identify patients with possible better outcome. The models with two zero-load geometries (2G models) and FSI models were also constructed. Their numerical results indicated that 2G models can provide end-ejection and end-filling results which were not available in 1G models, and FSI models can provide flow velocity, pressure and shear stress information which lacked in structure-only models (1G and 2G models). Conclusion. In vivo image-based 3D patient- specific computational models could lead to considerable potential gain not only in surgical design and outcome prediction, but also in understanding the mechanisms of RV failure for patients with repaired TOF.
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Aherne, Michael. "Evaluation of right ventricular function using conventional and real-time 3-dimensional echocardiography in normal dogs and dogs with myxomatous mitral valve disease." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/77929.
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Objectives: To investigate the feasibility of real-time three-dimensional (3D) echocardiographic analysis of right ventricular (RV) function in healthy dogs and to compare conventional and 3D echocardiographic (3DE) indices of RV function in dogs with various stages of myxomatous mitral valve disease (MMVD), classified per the guidelines of the American College of Veterinary Internal Medicine, to those from healthy dogs.
Animals: Twenty-two healthy dogs and 56 dogs with MMVD
Methods: All dogs underwent conventional and 3D echocardiographic examinations. Measurements of 3DE RV function indices including RV end-diastolic volume (EDV), RV end-systolic volume (ESV), RV stroke volume (SV), and RV ejection fraction (EF) were recorded. Measurements of conventional indices of RV function were also obtained. RV EDV, ESV, and SV were indexed to bodyweight (BW) and analyzed using commercially available software.
Results: Three-dimensional RV datasets could be acquired and analyzed in all dogs. Intra- and inter-observer coefficents of variation were > 20% for all 3D RV indices. Right ventricular EDV and ESV were decreased and RV EF was increased in dogs with advanced MMVD when compared to controls. Several conventional echocardiographic indices of RV function also differed between the control group and various MMVD groups.
Conclusions: Real-time 3DE RV assessment is feasible in normal dogs with acceptable intra- and inter-observer variability. Several 3DE indices of RV systolic function differ between dogs with advanced MMVD when compared to normal dogs. Further investigation is required to determine if these differences have clinical implications.Master of Science
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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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Ogunrombi, Akinwumi Babatunde. "Sixteen year retrospective analysis of rheumatic and non-rheumatic heart disease patients undergoing valve procedures at Groote Schuur Hospital first incidence single aortic and mitral valve replacement." Master's thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/11525.
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Includes abstract.Includes bibliographical references.
Rheumatic heart disease is still the most common cause of valvular heart lesions requiring replacement or repair procedures worldwide. In South Africa, where there is an interesting mix of first and third world dynamics, factors sustaining the epidemic of rheumatic disease are still commonplace. The choice of appropriate valve procedure and prosthesis in our setting will depend on an adequate knowledge of short and long term outcomes of valve replacement and repair. The aim of this thesis was to evaluate the demographics and presentation of our rheumatic and non-rheumatic patients and to determine if our current implantation choices could be validated.
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Geldenhuys, Agneta. "Ten-year propensity matched cohort analysis of mitral valve repair and replacement for rheumatic heart disease at Groote Schuur Hospital." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/2779.
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Fang, Ming. "Wnt/ß-catenin signaling pathway in non-myocyte lineages in the heart." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1458299605.
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Oliveira, Francisco Artur Forte. "Molecular analysis of oral bacteria in dental plaque, saliva and cardiac valve of patients with cardiovascular disease." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9733.
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FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoCoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Over the past few years, there has been increasing evidence of the effect of the oral health over the general health of individuals, supported by a series of biological and epidemiological studies that show a relation between the mouth and many diseases, including cardiovascular diseases. Structural deficiencies and functional abnormalities of heart valves represent an important cause of cardiovascular morbidity and mortality in Brazil, and a few defects have been recently associated with infectious agents. The aim of this study was to identify cariogenic and periodontopathogenic bacteria in dental plaque, saliva and heart valves, without clinical endocarditis, of patients with heart valve diseases, and correlate these findings with the oral health status of the patients. Oral exams using the DMTF (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes to evaluate caries and periodontal disease, respectively, were performed. Samples of supragingival and subgingival dental plaque, saliva and cardiac valves were evaluated, through Real Time Polymerase Chain Reaction, for the presence of DNA of Streptococcus mutans (S. mutans), Prevotella intermedia (P. intermedia), Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola). A total of 114 samples were collected from 42 patients with a mean age of 55.6 Â 13.8 years. The average number of missing teeth due to caries was 23.52 Â 9.41 teeth per patient, and according to the highest score of periodontal disease observed for each patient, excluding edentulous patients (44.0%), periodontal pockets over 4mm (43.4%) and dental calculus (34.7%) were detected in a higher number of patients. The molecular analysis of the oral samples revealed high frequency of S. mutans and P. intermedia in supragingival dental plaques, subgingival dental plaques and saliva of dentate and edentulous patients (variation 60.0% - 100.0%), while P. gingivalis and T. denticola were detected in a smaller number of oral samples (variation 17.6% - 64.0%). The microorganism most frequently detected in heart valve samples was the S. mutans (89.3%), followed by P. intermedia (19.1%), P. gingivalis (4.2%) e T. denticola (2.1%). Significant difference was observed between the frequency of P. intermedia, P. gingivalis and T. denticola in the heart valve and dental plaque, as oposed to S. mutans. The identification of oral bacteria, especially S. mutans, in heart valves of patients with a previous history of dental caries and gingivitis/periodontitis suggests the possible involvement of these pathogens in the etiopathogenesis of heart valve diseases.
Atualmente, cada vez mais se tem evidÃncias do efeito da condiÃÃo oral na saÃde geral dos indivÃduos, atravÃs de uma sÃrie de estudos epidemiolÃgicos e biolÃgicos que mostram uma relaÃÃo entre a boca e diversas doenÃas, incluindo as doenÃas cardiovasculares. Desordens estruturais e nas funÃÃes das vÃlvulas cardÃacas representam uma importante causa de morbidade e mortalidade cardiovascular no Brasil, sendo alguns processos, como a estenose aÃrtica degenerativa, mais recentemente associados a agentes infecciosos. O objetivo desta pesquisa foi identificar bactÃrias cariogÃnicas e periodontopatogÃnicas na placa dental, saliva e vÃlvulas cardÃacas, sem endocardite clÃnica, de pacientes com doenÃa valvar, correlacionando esses achados à condiÃÃo bucal dos indivÃduos. AvaliaÃÃo, quanto Ãs doenÃas cÃrie e periodontal, foi realizada, atravÃs dos Ãndices CPO-D (Dentes Permanentes Cariados, Perdidos e Obturados) e PSR (Registro Periodontal Simplificado), respectivamente. Amostras de placa dental supragengival, subgengival, saliva e vÃlvula cardÃaca foram coletadas para investigaÃÃo da presenÃa de DNA, atravÃs de PCR (ReaÃÃo em Cadeia de Polimerase) em tempo real, de Streptococcus mutans (S. mutans), Prevotella intermedia (P. intermedia), Porphyromonas gingivalis (P. gingivalis) e Treponema denticola (T. denticola). Um total de 114 amostras foi coletado de 42 pacientes com mÃdia de idade de 55.6  13.8 anos. A mÃdia de dentes perdidos devido à cÃrie, por paciente, foi em torno de 23.52  9.41 e, segundo o maior grau de doenÃa periodontal observado no indivÃduo, excluindo-se os pacientes desdentados totais (44.0%), bolsa superior a 4 mm (43.4%) e o cÃlculo dental (34.7%) esteve presente em um maior nÃmero de pacientes. A anÃlise molecular das amostras bucais revelou alta frequÃncia de S. mutans e P. intermedia nas placas supragengival, subgengival e saliva de pacientes dentados e desdentados (variando entre 60.0% e 100.0%), enquanto que P. gingivalis e T. denticola estiveram presentes em menor nÃmero de amostras bucais (variando entre 17.6% e 64.0%). O micro-organismo mais frequentemente encontrado nas amostras valvares foi o S. mutans (89.3%), seguido da P. intermedia (19.1%), P. gingivalis (4.2%) e T. denticola (2.1%). DiferenÃa significativa foi encontrada entre a presenÃa de P. intermedia, P. gingivalis e T. denticola na vÃlvula e na placa dental, diferentemente do S. mutans. A identificaÃÃo de bactÃrias orais, principalmente S. mutans, em vÃlvulas cardÃacas de pacientes com elevada experiÃncia prÃvia de cÃrie e ocorrÃncia de gengivite/periodontite, sugere o possÃvel envolvimento desses patÃgenos nas doenÃas valvares.
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Mantovani, Matheus Matioli. "Função mecânica do átrio esquerdo em cães com degeneração valvar crônica de mitral." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07102016-103144/.
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O objetivo desse estudo foi determinar se os índices de função, volume (VAE) e área (AAE) do átrio esquerdo (AE) podem ser utilizados para avaliar a gravidade da degeneração valvar crônica de mitral (DVCM) em cães, bem como diagnosticar a insuficiência cardíaca congestiva (ICC) nestes pacientes. A hipótese é que o aumento dos volumes e decréscimo da função atrial esquerda possa estar associado com a gravidade da DVCM e também com a ICC. Oitenta cães foram incluídos em um estudo clínico transversal observacional e prospectivo, sendo agrupados de acordo com a gravidade DVCM. Os cães foram igualmente distribuídos nos grupos A, B1, B2 e C + D, de acordo com o estadiamento para DVCM proposto pelo American College of Veterinary Internal Medicine. A mudança fracional da área (FAC) e a fração de ejeção atrial esquerda (FEAE) foram calculados com as seguintes equações: FAC total = 100 x (AAEmáxima AAEmínima) / AAEmáxima, FAC passiva = 100 x (AAEmáxima AAEpa) / AAEmáxima e FAC ativa = 100 x (AAEpa AAEminima) / AAEpa, cujas as mensurações foram realizadas no corte apical quatro câmaras; e FEAE Total = 100 x (VAEmáxima VAEmínima) / VAEmáxima, FEAE passiva = 100 x (VAEmáxima VAEpa) / VAEmáxima e FEAE ativa = 100 x (VAEpa VAEminima) / VAEpa, calculadas por meio do método biplanar área-comprimento, no corte apical quatro e duas câmaras. A FAC total, FAC ativa, FEAE total e FEAE ativa foram significativamente menores nos pacientes do grupo C+D do que as observadas nos demais grupos. Também foi observado que com o agravamento da DVCM ocorreu o aumento do VAEmáximo/kg, VAEpa/kg, VAEmínimo/kg, AAEmáximo/m2, AAEpa/m2, AAEmínimo/m2. Os volumes do AE, bem como suas áreas, apresentaram grande acurácia e aumentaram a capacidade para diagnosticar a ICC nos cães do DVCM. Conclui-se que a função atrial esquerda total e ativa é reduzida nos cães com ICC secundária a DVCM quando comparados aos cães saudáveis e naqueles com DVCM sem ICC. Além disso, os volumes e as áreas atriais podem ser utilizados para diagnosticar a ICC nesses pacientesThis study aimed to determine whether left atrial (LA) function indices, volume (LAV) and area (LAA) can be used to assess severity of mitral valve chronic degeneration (MVCD) in dogs, as well as to diagnose congestive heart failure (CHF) in these patients. The hypothesis stated that the increase in left atrial volumes and decrease in function are associated with the severity of MVCD and also with CHF. Eigthy dogs were included in a cross sectional prospective observational clinical study, grouped according to the severity of MVCD based on clinical signs and echocardiographic evaluation. Dogs were equitatively distribuited among groups A, B1, B2 and C + D, according to MVCD staging proposed by the American College of Veterinary Internal Medicine. The fractional area change (FAC) and left atrial ejection fraction (LAEF) were calculated based on the following equations: total FAC = 100 x (LAAmaximum LAAminimum) / LAAmaximum, passive FAC = 100 x (LAAmaximum LAApa) / LAAmaximum and active FAC ativa = 100 x (LAApa LAAminimum) / LAApa, which measurements were performed in four chamber apical view; and total LAEF = 100 x (LAVmaximum LAVminimum) / LAVmaximum, passive LAEF = 100 x (LAVmaximum LAVpa) / LAVmáximum and active LAEF = 100 x (LAVpa LAVminimum) / VLAVpa , calculated by biplanar arealength method in four and two-chambers apical view. The total and active FAC, total LAEF and active LAEF were significantly smaller in pacients from group C+D than the observed in the other groups. With increasing severity of MVCD there was increase in LAVmaximum/kg, LAVpa/kg, LAVminimum/kg, LAAmaximum/m2, LAApa/m2, LAAminimum/m2. LA volumes, as well as LA areas had a good performance as diagnostic methods, with high accuracy and increased capacity for heart failure detection in dogs with MVCD. In conclusion, left atrial total and active function are reduced in dogs with HF secondary to MVCD when compared with healthy dogs and dogs with MVCD without HF. Moreover, atrial volumes and areas can be used to diagnose HF in these patients
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Mekontso, Dessap Armand. "Sérotonine et pathologie cardiovasculaire : implication dans les valvulopathies cardiaques, la maladie coronaire et le remodelage vasculaire." Thesis, Paris Est, 2008. http://www.theses.fr/2008PEST0046.
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En plus de sa fonction de neurotransmetteur, la sérotonine (5-HT) jouerait un rôle clé dans le système cardio-vasculaire, via ses effets vasoactif, prolifératif et trophique. Nous avons étudié son implication dans les valvulopathies cardiaques, la coronaropathie, et le remodelage vasculaire. La surproduction et l’absence d’inactivation de 5-HT sont des mécanismes possibles des valvulopathies associées au syndrome carcinoïde et à la prise d’anorexigènes. Nous avons démontré que l’inactivation du gène du transporteur de 5-HT (5-HTT, responsable de la capture cellulaire de 5-HT), conduit à la fibrose cardiaque et valvulaire chez la souris. Bien que le récepteur 5-HT1B médie les effets trophiques de 5-HT sur les myofibroblastes cardiaques humains, la contribution de ce récepteur à la valvulopathie a été écartée car les souris doublement déficientes en 5-HTT et 5-HT1B présentaient les mêmes altérations cardiaques que celles déficientes en 5-HTT. Le 5-HTT (ainsi que le récepteur 5-HT2A) serait aussi impliqué dans les effets de 5-HT observés chez les patients coronariens. Nous avons évalué l’association éventuelle reliant les polymorphismes fonctionnels du 5-HTT (L/S) et du 5-HT2A (C/T) au risque et la gravité de la coronaropathie sur un total de 830 sujets d’âge différent. L’allèle L était un facteur de risque indépendant de coronaropathie chez les sujets jeunes (mais pas chez les sujets âgés). Le polymorphisme du 5-HT2A n’était pas associé avec la survenue de coronaropathie, et aucun des génotypes n’était associé à la resténose clinique. Les occlusions tardives des greffons coronaires après chirurgie de pontage ont été attribuées au remodelage vasculaire par hyperplasie néointimale des cellules musculaires lisses (CML) sous l’effet de divers facteurs de croissance dont 5-HT. Nous avons observé que le remodelage vasculaire en organoculture, ainsi que la prolifération et la migration des CML vasculaires en réponse au sérum de veau foetal étaient nettement plus élevées pour les greffons de veine saphène que pour l’artère radiale et l'artère mammaire interne. Ces différences pourraient expliquer la variabilité de perméabilité angiographique des greffons coronaires à long terme. Ces trois études confirment le rôle important de la sérotonine dans les pathologies cardiovasculairesSerotonin (5-HT) may play a key role in the cardiovascular system, with vasoactive, proliferative and trophic properties. We aimed at studying its implication in cardiac valve disease, coronary artery disease, and vascular remodelling of coronary grafts. 5-HT overproduction and reduced inactivation are possible mechanisms responsible for cardiac valvular disease in patients with carcinoid tumors and those treated with appetite suppressants, respectively. We found that deficiency of the 5-HT transporter (5-HTT, which is responsible for 5-HT uptake) gene leads to cardiac fibrosis and valvulopathy in mice. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. 5-HTT may also mediate the effects of the high blood serotonin levels seen in patients with premature coronary artery disease (CAD), along with 5-HT2A receptor. We prospectively evaluated associations linking functional polymorphisms of 5-HTT (L/S) and 5-HT2A (C/T) to the risk and severity of premature versus late-onset CAD in a total of 830 individuals. The L allele was an independent risk factor for premature CAD (but not late-onset CAD). 5-HT2A genotypes were not associated with CAD and neither 5-HTT nor 5-HT2A genotypes were associated with clinical restenosis. Late graft occlusions after coronary artery bypass grafting have been ascribed to vascular remodelling with neointimal hyperplasia of smooth muscle cells (SMC), which is mediated by various growth factors including 5-HT. We found that the ex vivo vascular-wall remodelling in organ cultures, as well as SMC proliferation and migration in response to fetal calf serum were significantly higher for saphenous vein rings than for radial artery and internal thoracic artery rings. These differences might shed light on reported dissimilar angiographic patency rates of these coronary grafts
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MIRAOUI, MONGI. "Etude et realisation d'une valve a feuillets souples : application a la mecanique valvulaire cardiaque." Paris 6, 1986. http://www.theses.fr/1986PA066420.
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Hoşcan, Yeşim Altınbaş Ahmet. "Romatizmal mitral kapak hastalığında mekanik kapak replasmanı sonrası sol atriyal apendisk fonksiyonlarının araştırılması /." Isparta : SDÜ Tıp Fakültesi, 2003. http://tez.sdu.edu.tr/Tezler/TT00100.pdf.
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Pinto, Inês Isabel Ramos. "Comparison of heart measurements in thoracic radiographs before and after the treatment of pulmonary edema in dogs with degenerative mitral valve disease : a retrospective study of 18 clinical cases." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2019. http://hdl.handle.net/10400.5/18204.
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Dissertação de Mestrado Integrado em Medicina VeterináriaThe Degenerative Mitral Valve Disease (DMVD) has the highest prevalence of all canine heart diseases accounting for 75-80% of the cases of dogs with cardiac disease. DMVD is characterized by having an evolutive nature. As the disease progresses the microscopic and macroscopic alterations of the mitral valve’s apparatus become more severe and gradually start preventing the valve’s normal function. One of the complications that may occur is the development of pulmonary edema. Overt pulmonary edema occurs when the capacity of the pulmonary lymphatic system is exceeded, leading to an increase in the extravascular water content of the lungs. The etiology and consequently the cure for DMVD are not currently known, hence the importance of understanding and developing tools that allow the monitoring of the disease. Even though the best way to assess and confirm the diagnosis of DMVD is through echocardiography, this exam requires additional expertise to be performed and interpreted, as well as substantial financial costs to the owner. Simultaneously, radiography of the thorax is widely available and cost-effective, which justifies the interest in studying the evolution of the radiographic measures Vertebral Heart Score (VHS) and Vertebral Left Atrium Size (VLAS) in dogs with DMVD. This retrospective study aims to compare heart measurements in thoracic radiographs before and after the treatment of pulmonary edema in 18 dogs with DMVD that were submitted to consultation in a french veterinary referral center. The main conclusion of this study is that the size of the left atrium and the cardiac silhouette decreases after the resolution of cardiogenic pulmonary edema when compared to the dimensions during its occurrence. Furthermore, this decrease in the left atrium’s size is detectable using the VLAS method, which confirms its value in monitoring the progression of the disease. Consequently, it is possible for those who do not have access to an echocardiographic exam, to use the VLAS method to follow the evolution of the left atrium’s size throughout the progression of DMVD. It was also verified that VLAS measurements have a positive correlation with echocardiographic measures of the left atrium, implying that when one increases the other does so as well, and vice-versa.
RESUMO - Comparação de medições cardíacas em radiografias torácicas antes e depois do tratamento de edema pulmonar em animais com Doença Degenerativa da Válvula Mitral: um estudo retrospetivo de 18 casos clínicos - A Doença Degenerativa da Válvula Mitral (DDVM) tem a prevalência mais alta de todas as doenças cardíacas caninas, representando 75-80% dos casos destes doentes. A DDVM é caracterizada pela sua natureza evolutiva. Assim à medida que a doença progride, as alterações microscópicas e macroscópicas da válvula mitral tornam-se mais graves e começam gradualmente a impedir o seu normal funcionamento. Uma das complicações que pode ocorrer é o desenvolvimento de edema pulmonar que sucede quando a capacidade do sistema linfático do pulmão é excedida, levando, por isso, à acumulação de conteúdo aquoso no compartimento extravascular dos mesmos. A etiologia e consequentemente a cura da DDVM não são atualmente conhecidas, dai a importância em perceber e desenvolver ferramentas que permitam a monitorização da doença. Embora a melhor maneira de determinar e confirmar o diagnóstico de DDVM seja através de uma ecocardiografia, este exame de diagnóstico representa um investimento para o proprietário, necessita de material caro e exige um nível de competência mais elevado para o realizar e interpretar. Simultaneamente, a realização de radiografias do tórax é uma técnica amplamente disponível e económica, o que justifica o interesse em estudar a evolução das medidas radiográficas Vertebral Heart Score (VHS) e Vertebral Left Atrium Size (VLAS) em cães com DDVM. O objetivo deste estudo retrospetivo prende-se com a comparação de medidas cardíacas, em radiografias da cavidade torácica, antes e depois do tratamento de edema pulmonar em 18 cães com DDVM que foram apresentados em consulta num centro hospitalar veterinário de referência francês. A principal conclusão deste estudo indica que o tamanho do átrio esquerdo e da silhueta cardíaca diminui depois da resolução do edema pulmonar de origem cardíaca, quando comparado com as dimensões durante a sua ocorrência. Adicionalmente, esta diminuição de tamanho do átrio esquerdo é detetável utilizando o método VLAS, o que confirma o seu valor na monitorização da progressão da doença. Consequentemente, é possível para aqueles que não têm acesso a um exame ecocardiográfico, utilizarem o método VLAS para seguir a evolução do tamanho do átrio esquerdo durante a progressão da DDVM. Também se verificou que as medições VLAS têm uma correlação positiva com as medidas ecocardiográficas do átrio esquerdo, o que implica que quando uma medida aumenta a outra aumenta também, e vice-versa.
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Yu, Mengyao. "Exploitation des données issues d'études d'association pangénomiques pour caractériser les voies biologiques associées au risque génétique du prolapsus de la valve mitrale GWAS-driven gene-set analyses, genetic and functional follow-up suggest GLIS1 as a susceptibility gene for mitral valve prolapse Up-dated genome-wide association study and functional annotation reveal new risk loci for mitral valve prolapse." Thesis, Sorbonne Paris Cité, 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2203&f=17890.
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Le prolapsus de la valve mitrale (MVP) est une valvulopathie fréquente qui touche près de 1 personne sur 40 dans la population générale. Il s'agit de la première indication de réparation et / ou de remplacement de la valve. De nombreux gènes comme FLNA, DCHS1 pour les formes familiales et TNS1 et LMCD1 pour les formes sporadiques ont récemment été décrit comme associés au MVP. Cependant, les défauts génétiques touchant ces gènes n'expliquent pas tous les cas du MVP. De plus, les mécanismes biologiques expliquant la susceptibilité génétique au MVP, notamment pour les formes sporadiques les plus fréquentes restent mal compris. Dans cette thèse, mon objectif était 1) de caractériser globalement les mécanismes biologiques impliqués dans le risque génétique du MVP dans le contexte des études d'association pangénomique (GWAS), et 2) d'améliorer la résolution du génotypage par l'imputation génétique et par l'addition d'une nouvelle étude cas témoins, (UKBioBank) afin de permettre la découverte de nouveaux loci de prédisposition. Dans la première partie, j'ai appliqué des outils d'enrichissement de voies biologiques ou sets de gènes (i-GSEA4GWAS, DEPICT) aux données GWAS. J'ai pu montrer que les gènes présents autour des loci GWAS sont impliqués dans l'organisation des filaments d'actine, l'organisation du cytosquelette et le développement cardiaque. Nous avons également décrits de nombreux régulateurs de la transcription impliqués le développement, la prolifération cellulaire et la migration, comme le gène GLIS1 qui joue un rôle dans les transitions morphologiques cellulaires (EndoMT, MET). Afin de confirmer le rôle de GLIS1 dans l'association avec le MVP, j'ai réalisé une analyse génétique dans UKBiobank et, en combinaison avec les données françaises, l'association a atteint le seuil de significativité génomique. Des expériences d'immunohistochimie ont indiqué que Glis1, la protéine orthologue de la souris est exprimée au cours du développement embryonnaire principalement dans les noyaux des cellules endothéliales et interstitielles des valves mitrales. D'autre part, l'inactivation de Glis1 à l'aide d'oligonucléotides de type Morpholinos ont été l'origine d'une régurgitation atrio-ventriculaire chez le poisson zèbre. Dans la deuxième partie, j'ai généré des données de génotypage plus dense à l'aide d'une imputation basée sur Haplotype Reference Consortium (HRC) et TOPMed. J'ai d'abord comparé la précision d'imputation entre les données utilisant les différents panels et constaté qu'aucun panel n'atteignait une précision optimale pour les variants rares (MAF <0,01) dans nos échantillons. La précision d'imputation s'améliorait pour les variants fréquents (MAF> 0,05), en particulier pour les cohortes dont le génotypage étaient réalisé avec des puces identiques. J'ai pu ainsi cartographier avec plus de précision les loci déjà confirmés (ex. Chr 2 autour de TNS1). J'ai également identifié 6 nouveaux loci associés au MVP prometteurs. Les nouveaux variants associés sont tous fréquents. L'annotation fonctionnelle fine à l'aide de données publiques a indiqué leurs rôles potentiels dans la régulation transcriptionnelle de plusieurs gènes candidats (ex. PDGFD et ACTN4). En résumé, mes travaux de thèse ont apporté des résultats génétiques originaux mettant en lumière de nouveaux mécanismes biologiques en rapport avec la biologie et le développement de la valve. Ces travaux ont fait appel à de nombreuses stratégies génétiques d'association et d'enrichissement, d'imputation haute densité et d'annotations fonctionnelles. Mes travaux ont également été renforcés par des validations dans des modèles animaux en collaboration. Il sera nécessaire toutefois de confirmer par réplication, et potentiellement par des expériences biologiques, les résultats nouveaux issus des travaux d'imputation haute densité afin de déclarer ces nouveaux gènes de prédispositions au MVPMitral valve prolapse (MVP) is a common heart valve disease affecting nearly 1 in 40 individuals in the general population. It is the first indication for valve repair and/or replacement and moreover, a risk factor for mitral regurgitation, an established cause of endocarditis and sudden death. MVP is characterized by excess extracellular matrix secretion and cellular disorganization which leads to bulky valves that are unable to coapt correctly during ventricular systole. Even though several genes including FLNA, DCHS1 TNS1, and LMCD1 were reported to be associated with MVP, these explain partially its heritability. However, understanding the biological mechanisms underlying the genetic susceptibility to MVP is necessary to characterize its triggering mechanisms. In this thesis, I aimed 1) to characterize globally the biological mechanisms involved in the genetic risk for MVP in the context of genome-wide association studies (GWAS), and 2) improve the genotyping resolution using genetic imputation, which allowed the discovery of additional risk genes for MVP. In the first part of my study, I applied pathway enrichment tools (i-GSEA4GWAS, DEPICT) to the GWAS data. I was able to show that genes at risk loci are involved in biological functions relevant to actin filament organization, cytoskeleton biology, and cardiac development. The enrichment for positive regulation of transcription, cell proliferation, and migration motivated the follow-up of GLIS1, a transcription factor that regulates Hedgehog signalling. I followed up the association with MVP in a dataset of cases and controls from the UK Biobank and, in combination with previously available data, I found a genome-wide significant association with MVP (OR=1.22, P=4.36 ×10-10). Through collaborative efforts, immunohistochemistry experiments in mouse indicated that Glis1 is expressed during embryonic development predominantly in nuclei of endothelial and interstitial cells of mitral valves, while Glis1 knockdown using morpholinos caused atrioventricular regurgitation in zebrafish. In the second part of my work, I generated larger genotyping datasets using a imputation based on Haplotyp Refernece Consortium and TOPMed, two large and highly dense imputation panels that were recently made available. I first compared the imputation accuracy between data using HRC and TopMED and found that both panels have low imputation accuracy for rare allele (MAF<0.01). However, the imputation accuracy increased with the input sample size for common variants (MAF>0.05), especially when genotyping platforms were harmonised. I was able to fine map established loci (e.g Chr 2) and also able to identify six novel and promising associated loci. All new loci are driven by common variants that I confirmed as high profile regulatory variants through an extensive computationally-based functional annotations at promising loci that pointed at several candidate genes for valve biology and development (e.g PDGFD and ACTN4). In summary, my PhD work applied up-to-data high throughput genetic association methods and functional enrichment and annotation to GWAS data. My results provide novel insights into the genetics, molecular and cellular basis of valve disease. Further genetic confirmation through replication, but also through biological experiments are expected to consolidate these statistically and computationally supported results
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Roubertie, François. "Identification de substrats arythmogènes et des mécanismes de décompensation dans une population de tétralogie de Fallot à l’âge adulte et perspectives de prise en charge ultérieure." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0421/document.
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Le nombre d’adultes porteurs d’une tétralogie de Fallot opérée dans l’enfance est en constante augmentation. Initialement, ces patients étaient considérés comme guéris. A l’âge adulte, ils présentent en fait des complications d’ordre rythmique, responsables de morts subites, et des complications d’ordre mécanique : dilatation du ventricule droit (VD) liée à l’insuffisance pulmonaire chronique, séquellaire de la première chirurgie de réparation de la cardiopathie. Les mécanismes de l’arythmie ainsi qu’une éventuelle interaction entre la dysfonction VD et la survenue de ces arythmies ne restent que partiellement élucidés. Dans ce travail, en couplant les données d’études cliniques et les données expérimentales issues d’un modèle animal (MA) mimant une tétralogie de Fallot réparée, nous avons montré que 1) l’échocardiographie ne pouvait pas se substituer à l’IRM pour la surveillance des patients avec tétralogie de Fallot réparée 2) la valvulation pulmonaire restait une intervention à risque de mortalité 3) une bioprothèse non stentée était une bonne solution pour effectuer cette valvulation 4) en cas de fuite tricuspidienne sévère lors de cette valvulation, une plastie était indispensable 5) plusieurs gènes participaient au remodelage ventriculaire droit (analyse génétique effectuée sur le MA) 6) le remodelage électrophysiologique du VD (MA) s’accompagnait de propriétés pro-arythmogènes. Les mécanismes de décompensation sont intriqués : un lien entre dysfonction VD et arythmie paraît bien établi. D’autres analyses électrophysiologiques sont en cours au niveau du ventricule gauche (MA), pour rechercher d’autres mécanismes pro-arythmogènesThe number of adults with a repaired tetralogy of Fallot is increasing. In the past, those patients were considered healed. Nonetheless, they present arrhythmogenic issues, with frequent sudden death, and mechanical complications: right ventricular dilation due to long lasting pulmonary valve regurgitation, secondary to surgical repair. The origin of arrhythmia and its interaction with right ventricular dysfunction is only partially understood. In this study, combining clinical with experimental data, we pointed out: 1) concerning the follow-up of this population, echocardiography is not a substitute to MRI 2) operative mortality of pulmonary valve replacement (PVR) still exists 3) a stentless bioprosthesis represents a valid solution for PVR 4) a valve repair is mandatory for severe tricuspid valve regurgitation at PVR 5) the genetic analysis carried out in an animal model of repaired tetralogy of Fallot, demonstrated the involvement of numerous genes in right ventricular remodeling 6) remodeling of the right ventricle in this animal model generates pro-arrhythmic substrate. Heart failure mechanisms in repaired tetralogy of Fallot are complex: a link between right ventricular dysfunction and arrhythmias is demonstrated. Further studies are needed to investigate other pro-arrhythmic mechanisms involving the left ventricle
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Junior, José de Lima Oliveira. "Influência da doença aterosclerótica arterial coronária crítica na mortalidade hospitalar de pacientes portadores de estenose aórtica submetidos à substituição valvar." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5156/tde-05112008-110349/.
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Com o aumento da expectativa de vida nas últimas décadas, tem ocorrido aumento concomitante da prevalência da estenose aórtica degenerativa e da doença aterosclerótica arterial coronária. O presente estudo visa avaliar a influência da doença ateroslerótica arterial coronária crítica na mortalidade hospitalar de pacientes portadores de estenose aórtica submetidos à substituição valvar isolada ou combinada à revascularização do miocárdio. No período de janeiro de 2001 a março de 2006, no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram analisados 448 pacientes submetidos à substituição valvar aórtica isolada (grupo GI) e 167 pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio (grupo GII). Os dados pré-operatórios eleitos para análise foram: sexo, idade, índice de massa corpórea, antecedentes de: acidente vascular cerebral, diabete melito, doença pulmonar obstrutiva crônica, febre reumática, hipertensão arterial sistêmica, endocardite, infarto agudo do miocárdio, tabagismo, fração de ejeção do ventrículo esquerdo, doença aterosclerótica arterial coronária crítica, fibrilação atrial crônica; operação valvar aórtica prévia (conservadora), classe funcional de insuficiência cardíaca congestiva, valor sérico de creatinina e de colesterol total, tamanho da prótese utilizada, extensão (completa ou incompleta) e número de anastomoses distais da revascularização do miocárdio, tempo de circulação extracorpórea e tempo de pinçamento aórtico. No estudo estatístico empregou-se análise univariada (teste Qui-Quadrado e teste t de Student) e multivariada (regressão logística) para avaliação da influência da doença aerosclerótica arterial coronária crítica na mortalidade hospitalar dos dois grupos estudados. No grupo GI (substituição valvar aórtica isolada), a mortalidade hospitalar foi 14,3% (64 óbitos), sendo 14,5% (58 óbitos) nos pacientes sem doença aterosclerótica arterial coronária crítica associada (grupo GIB) e 12,8% (6 óbitos) nos que apresentavam essa associação (grupo GIA). No grupo GII (substituição valvar aórtica combinada à revascularização do miocárdio), a mortalidade hospitalar foi 17,6% (29 óbitos), sendo 16,1% (20 óbitos) nos pacientes submetidos à substituição valvar aórtica combinada à revascularização completa do miocárdio (grupo GIIA) e 20,9% (9 óbitos) nos com revascularização incompleta do miocárdio (grupo GIIB). Nos pacientes submetidos à substituição valvar aórtica isolada, a presença de doença aterosclerótica arterial coronária crítica associada, em pelo menos duas artérias, influenciou a mortalidade hospitalar (p= 0,016). Nos pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio, o número de artérias coronárias com doença aterosclerótica crítica e a extensão da revascularização do miocárdio realizada não influenciaram a mortalidade hospitalar (p>0,05), mas a realização de mais de três anastomoses distais influenciou (p= 0,03).With the increase in life expectancy in recent decades has occurred concomitant increase in the prevalence of degenerative aortic stenosis and atherosclerotic coronary artery disease. This study aim to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of patients with aortic stenosis underwent isolated valve replacement or combined coronary artery bypass grafting. In the period of january 2001 to March 2006, at the Heart Institute University of Sao Paulo Medical Center were examined 448 patients underwent isolated aortic valve replacement (GI group) and 167 patients underwent combined aortic valve replacement and coronary artery bypass grafting (GII group). Preoperative data analised were: sex, age, body mass index, history of stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, myocardial infarction, smoking, chronic atrial fibrillation. Left ventricular ejection fraction, concomitant critical atherosclerotic coronary artery disease, previous surgical aortic valvuloplasty, congestive heart failure functional class, serum creatinine and cholesterol level, aortic valve prosthesis size, concomitant complete or incomplete coronary artery bypass grafting and number of bypass grafts, cardiopulmonary bypass and aortic cross clamping time. Univariate statistical analysis (Chi-square and Student\'s t test) and multivariate (logistic regression) were used to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of two groups. GI group (isolated aortic valve replacement) hospital mortality was 14.3% (64 deaths), and 14.5% (58 deaths) in patients without associated critical atherosclerotic coronary artery disease (GIB group) and 12.8% (6 deaths) in patients with that association (GIA group). GII group (combined aortic valve replacement and coronary artery bypass grafting) hospital mortality was 17.6% (29 deaths), and 16.1% (20 deaths) in patients underwent combined aortic valve replacement and complete coronary artery bypass grafting (GIIA group) and 20.9% (9 deaths) in patients with combined incomplete coronary artery bypass grafting (GIIB group). In patients underwent isolated aortic valve replacement, associated critical atherosclerotic coronary artery disease, of at least two arteries, influenced hospital mortality (p = 0016). In patients underwent combined aortic valve replacement and coronary artery bypass grafting, the number of coronary arteries with critical atherosclerotic disease and coronary artery bypass grafting extension didnt influenced hospital mortality (p> 0.05), but more than three coronary distal anastomoses influenced the hospital mortality (p = 0.03).
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Moraes, Ricardo Casalino Sanches de. "Validação do EuroSCORE em valvopatas submetidos à cirurgia cardíaca." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-25112013-101041/.
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Introdução: A estratificação de risco pré-operatória é elemento essencial para a decisão cirúrgica, assim foram desenvolvidos alguns sistemas de pontuações para predizer mortalidade após cirurgia cardíaca em adultos. O EuroSCORE (ES) é um dos mais difundidos mundialmente sendo considerado um bom preditor de mortalidade em pacientes que foram submetidos à cirurgia cardíaca e foi considerado um sistema de pontuação de fácil uso e boa aplicabilidade. Racional: O ES já é usado assistencialmente em nossa instituição, entretanto, não foi realizada uma validação local em uma coorte específica de portadores de valvopatias. Sabemos das importantes diferenças epidemiológicas entre nossa população e pacientes citados na literatura mundial. Objetivos: O objetivo desse estudo é validar o ES como ferramenta preditora de mortalidade após cirurgia valvar. Métodos: Foram incluídos no trabalho 540 pacientes portadores de Valvopatia, com indicação de substituição da função valvar. O período de inclusão foi de fevereiro a dezembro de 2009. Todos os pacientes tiveram o cálculo da mortalidade estimada, baseada no EuroSCORE no pré-operatório, foram seguidos até alta hospitalar ou 30 dias após cirurgia. A capacidade discriminativa do modelo foi calculada utilizando a área sobre a curva receiver operating Characteristic (ROC) e a para o cálculo calibração utilizou-se o teste de Hosmer-Lemeshow (H-L). Resultados: A média etária da população foi de 56 ± 12 anos, 50% do sexo feminino, com etiologia predominante de Doença reumática. As variáveis: endocardite infecciosa, hipertensão pulmonar e o histórico de cirurgia prévia foram mais prevalentes em nossa coorte quando comparada com o banco de dados original do ES. A mortalidade observada global foi de 16% (6% em cirurgias eletivas e 34% em cirurgia de emergência), já a mortalidade predita foi de 6.1%, 8.7% e 4.31% para ES aditivo, ES logístico e ESII, respectivamente. Na avaliação da capacidade discriminativa a área sobre a curva ROC (ASCR) foi considerada boa com valores de 0,81 ; 0,76 ; 0,76 respectivamente para ES II; ES aditivo e logístico. A calibração do modelo foi considerada ideal com P > 0,05 para os modelos de ES. Conclusão: Os modelos do ES foram validados como ferramentas preditoras de risco de mortalidade após cirurgia cardíaca valvarIntroduction: Preoperative risk stratification is essential for surgical decision, and some scoring systems have been developed to predict mortality after cardiac surgery in adults. The European System for Cardiac Operative Risk Evaluation (EuroSCORE), developed in European states, aims to predict 30-day mortality of patients undergoing cardiac surgery. Although already used in our institution we not been performed a local validation. We know the epidemiological difference between Brazilian and European population. Therefore, the aim of this study was to evaluate the validation of the EuroSCORE models in our institution. Methods: Between February 1st 2009 and December 30th 2009, a total of 540 consecutive patients with valvular heart disease and indication for surgical treatment were evaluated before and after this treatment. Patient demographics, risk factors, surgery details, length of hospital stay and 30-day mortality were collected. The EuroSCORE algorithms were calculated according to the published guidelines (http://www.euroscore.org) on the entire patient sample prior to the time of surgery. Performance of the models was assessed by comparing the observed and predicted mortality. The area under the receiver operating characteristic curve (AUCR) evaluated the predictive performance. The calibration was analyzed by Hosmer-Lemeshow goodness-of-fit statistic. Results: The mean age was 56±12 years and 50% of patients were female. The most common etiology of valvular heart disease was Rheumatic disease. Main differences between the present cohort and the original EuroSCORE cohort were: Age, gender, previous cardiac surgery, pulmonary hypertension and active endocarditis. The mean of Aditive and logistic EuroSCORE were 6 ± 3 and 8.66 ± 10.35 respectively. For EuroSCORE II the mean logistic value was 4.2 ± 5.95. Mortality rate of 16% (6% in elective surgery and 34 % in emergency/urgency surgery), with estimated mortalities according to additive, logistic EuroSCORE and EuroSCORE II of 6.1%, 8.7% and 4.31%, respectively. The AUC for additive EuroSCORE was 0.76, for logistic EuroSCORE 0.76, was lower than that for EuroSCORE II 0.81. Conclusion: EuroSCORE models demonstrated good discriminative capacity and calibration in these valvular heart disease patients undergoing cardiac surgery
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Calcutteea, Avin. "New insights in the assessment of right ventricular function : an echocardiographic study." Doctoral thesis, Umeå universitet, Medicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-66725.
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Background: The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined. Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function. Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software. Results: 1- Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls: p<0.01 & p<0.01, Group 1: p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract. 2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell (p=0.04). 3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls. Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.
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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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Butkuvienė, Irena. "Koronarine širdies liga ir ryškiai sumažinta kairiojo skilvelio sistoline funkcija sergančių ligonių chirurginio gydymo klinikinis įvertinimas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2009. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2009~D_20090611_130708-29100.
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Disertacijos objektas yra koronarine širdies liga ir ryškiai sumažinta kairiojo skilvelio sistoline funkcija sergančių ligonių klinikinės būklės pokyčiai ir išgyvenimas vėlyvuoju pooperaciniu laikotarpiu po izoliuotų aorto-vainikinių arterijų apeinamųjų jungčių suformavimo operacijų (AVAJSO), bei kairio skilvelio tūrio ir formos atkūrimo operacijų (TFAO). Tai retrospektyvinis tyrimas. Analizuoti 216 ligonių sergančių koronarine širdies liga, kuriems atliktos AVAJSO ir 139 ligonių, kuriems kartu su revaskuliarizacija atliktos kairio skilvelio TFAO, duomenys. Nustatyta, kad ligonių, sergančių IŠL su KS sistoline disfunkcija, išgyvenimas vėlyvuoju – iki 7 metų laikotarpiu po AVAJSO bei 6 metų laikotarpiu po KS TFAO, yra geras. Nustatėme, kad operacijų, kurias nuspręsta atlikti ligoniams, turintiems krūtinės anginos simptomus, be miokardo gyvybingumo požymių įrodymo echokardiografiniu mažų dozių dobutamino krūvio mėginiu, pirmųjų 30 parų mirties rizika nebuvo didesnė. Rasta, kad ligonių, kurių funkcinė klasė vienerių metų laikotarpiu po AVAJSO buvo blogesnė, iki operacijos buvo EKG ilgesnė QRS komplekso trukmė, didesni KS galiniai diastoliniai dydžiai ir operacijos metu jiems buvo suformuota mažiau AVA jungčių. Išaiškinta, kad KS tūrio ir formos atkūrimo operacijos ligoniams su toli pažengusia KS remodeliacija atliekamos saugiai, su ne didesne pirmųjų 30 parų mirties rizika nei atliekant vien AVAJSO. Išaiškinta, kad tų ligonių, kurių funkcinė būklė nepagerėjo vienerių metų... [toliau žr. visą tekstą]ANNOTATION OF DISERTATION Subject of disertation: Surgical treatment of patients suffering from ischemic heart disease with significantly decreased left ventricle systolic function: clinical evaluation. Objective - evaluation of clinical status and long-term postoperative survival of patients suffering from ischemic heart disease and decreased left ventricle systolic function (LV EF ≤ 35%) after isolated coronary by-pass grafting and left ventricle volume and shape surgical restoration operations. Retrospective study. The study group included 216 patients for whom coronary artery bypass grafting (CABG) and 139 patients who underwent surgical ventricular restoration (SVR). It was postulated that the long-term survival (up to 7 years) in patients after CABG and long-term survival (6 years) in patients after SVR is good. It was found out that the risk of fatal outcome during the first 30 days after CABG in patients 0suffering from ischemic LV dysfunction and symptoms of angina pectoris with viable myocardium, statistically reliably did not differ from patients with nonviable myocardium. It was stated that patients with greater functional class during one year after CABG, preoperatively had longer duration of ECG QRS complex, higher end-diastolic findings and had lower number of by-passes during the operation. We also demonstrated that LV shape and volume restoration operations were being performed for patients with highly advanced LV remodeling safely and postoperative risk... [to full text]
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Odelin, Gaëlle. "Etude du rôle du facteur de transcription Krox20 dans le développement et la maturation des valves cardiaques chez la souris." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5014.
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Les pathologies valvulaires aortiques sont des pathologies plurifactorielles, comportant un déterminisme génétique indiscutable mais peu caractérisé. Ma thèse a pour but d’étudier le rôle du facteur de transcription Krox20 au cours du développement et de la maturation valvulaire à travers l’analyse de modèles murins. Nous avons montré que ce gène est nécessaire au développement et à la maturation de la valve aortique. L’invalidation de Krox20 chez la souris conduit à une hypertrophie des feuillets aortiques dès les stades fœtaux et à des insuffisances aortiques chez l’adulte. Ces anomalies sont associées à des défauts d’organisation de la matrice extracellulaire en partie liée à une régulation directe de l’expression des collagènes de type I et III. 25% des souris déficientes pour Krox20 présentent une bicuspidie de la valve aortique. Nous avons observé une diminution de l’expression de eNos chez ces mutants et pu mettre en évidence une interaction génétique entre Krox20 et eNos. De plus, nous avons identifié une sous population de cellules des crêtes neurales cardiaques impliquées dans l’apparition de la bicuspidie chez les mutants Krox20. Afin d’explorer le rôle de Krox20 dans la calcification de la valve aortique, nous avons étudié les conséquences de la surexpression de ce gène dans un modèle et montré que lcela induisait une activation de gènes pro-fibrotiques et pro-ostéogénique sans conduire à des dépôts calciques. Krox20 est donc un facteur de transcription important pour la valvulogenèse et à l’homéostasie valvulaire chez l’adulte. Mes travaux ont contribué à l’identification de Krox20 comme gène candidat potentiel aux valvulopathies rencontrées chez l’hommeLong seen as a consequence of aging and mechanical wear of aortic cusps, aortic valve diseases are currently considered multifactorial diseases, with an indisputable genetic determinism but not well characterized. My thesis aims to study the role of the transcription factor Krox20 during development and maturation of the valve through the analysis of mouse models. We have shown that this gene is necessary for the development and maturation of the aortic valve. Indeed, the deletion of Krox20 in the mouse leads to thickened aortic leaflets from the fetal stage and the onset of aortic valve disease in adults. These anomalies are associated with defects in the organization of the extracellular matrix and more particularly to direct regulsation of collagen type I and type III expression. Our analysis showed that 25% Krox20-/- mice have a bicuspid aortic valve. The analysis of this model has allowed us to identify a population of cardiac neural crest cells involved in the occurrence of this phenotype. In addition, we were able to observe a down regulation of eNos in Krox20-/- embryos and show a genetic interaction between Krox20 and eNos. To address the role of Krox20 in the process of calcification of the aortic valve, we have studied the effects of its overexpression. Our preliminary results indicate that this overexpression leads to activation of pro-fibrotic and pro-osteogenic genes, however, this is not sufficient to induce calcification of aortic valve leaflets.Therefore Krox20 is important for valvulogenesis but also for valvular homeostasis in the adult. My work has contributed to the identification of a potential candidate gene involved in human valve diseases
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Lefebvre, Xavier. "Systolic anterior motion of the mitral valve in obstructive hypertrophic cardiomyopathy : an in-vitro study." Diss., Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/11712.
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Gieseking, Elizabeth Robinson. "Control mechanism for the papillary muscles of the mitral valve : an In Vitro study." Thesis, Georgia Institute of Technology, 1989. http://hdl.handle.net/1853/10912.
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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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Martins, Carlo de Oliveira. "Análise proteômica diferencial em válvula mitral na doença reumática cardíaca." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-02082013-142739/.
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A Doença Reumática Cardíaca (DRC) é uma séria complicação de orofaringite causada por determinados sorotipos de Streptococcus pyogenes não tratada adequadamente em indivíduos suscetíveis. É um grande problema de saúde pública, principalmente nos países não desenvolvidos e em desenvolvimento, como Brasil, Índia, países da África, regiões de população aborígine da Austrália, e Egito. É altamente debilitante e com alta taxa de mortalidade devido ao comprometimento cardíaco. As lesões miocárdicas iniciais regridem, mas as lesões valvares, principalmente a mitral e a aórtica, são irreversíveis e progressivas. Muitos estudos já caracterizaram a resposta imune celular (linfócitos T) e humoral nos indivíduos acometidos pela doença. Mimetismo molecular e espalhamento de epítopo são os principais mecanismos que se pensa estar envolvidos na patogênese da DRC. Avaliamos, nesta pesquisa, o perfil de expressão proteica em valvas mitrais de indivíduos acometidos por DRC. Para detectar alterações específicas desta doença, comparamos as expressões de proteínas nos grupos portadores de DRC com insuficiência (DRC-INS) e com estenose (DRC-EST) a um grupo de indivíduos com degeneração mixomatosa de valva mitral (DMX) e outro sem valvulopatias (CTL). Alterações especificamente observadas em tecido mitral na DRC-INS ou DRC-EST em fases avançadas da doença podem explicar o mecanismo de desenvolvimento desses dois tipos de lesão. Foram encontradas 25 \"spots\", correpondendo a 29 proteínas diferencialmente expressas nos grupos com valvulopatias, refletindo principalmente alterações na matriz extracelular. Encontramos importante clivagem diferencial da vimentina, cuja proteína íntegra possui 54 kDa, formando fragmentos com ~40 e ~45 kDa, aumentados na DRC, principalmente na DRC-INS. O colágeno do tipo VI, com aproximadamente 95 kDa, encontrou-se com expressão diminuída exclusivamente no grupo DRC-INS. A Vitronectina foi encontrou-se aumentada em na DMX e na DRC-EST, em relação ao grupo controle, principalmente na DRC-EST. Lumican, por sua vez, teve expressão diminuída na DMX e na DRC-EST, apesar de possuir um único \"spot\" com expressão aumentada na DRC. Utilizando métodos de análise de padrões de expressão protéica in silico foram identificados conjuntos de proteínas capazes de discriminar as amostras de valva mitral por etiologia da doença. O presente trabalho pode auxiliar na elucidação dos mecanismos de desenvolvimento da doença e de alterações estruturais do tecido mitral em resposta às lesões autoimunes, bem como no diagnósticoda DRC.Rheumatic Heart Disease (RHD) is a serious complication of oropharingitis caused by some serotypes of Streptococcus pyogenes not properly treated in susceptible individuals. It is a public health concern, mainly for undeveloped and developing countries, such as Brazil, India, some countries in Africa, aboriginal regions in Australia, and Egypt. It is highly debilitating with a high mortality rate due to cardiac commitment. Initial myocardial lesions disappear, but valvar lesions, mainly mitral and aortic, are irreversible and progressive. Many studies have characterized cellular (T lymphocytes) and humoral responses in individuals affected by the disease. Molecular mimicry and epitope spreading are the main mechanisms thought to be involved in the pathogenesis of RHD. We evaluated, in this research, the profile of protein expression in mitral valves from individuals affected by RHD. To detect alterations specific of this disease, we compared protein expression in the group of RHD with regurgitation (RHD-RGT) and stenosis (RHD-STN) to a group of individuals with mitral valve myxomatous degeneration (MXD) and another group without valvulopathies (CTL). Alterations specifically observed in the mitral tissue of RHD-RGT and RHD-STN in advanced stages of the disease can explain the mechanism of development for these two kinds of lesions. Twenty-five spots, corresponding to 29 proteins were found to be differentially expressed in the valvulopathy groups, reflecting mainly alterations in extracellular matrix. We found important differential cleavage of vimentin, the whole protein having 54 kDa, in fragments with ~40 and ~45 kDa, increased in RHD, mainly in RHD-RGT. Collagen type-VI, with approximatelly 95 kDa, was found to have decreased expression exclusivelly in the RHD-RGT group. Increased expression of Vitronectin was detected in DMX and RHD-EST groups, compared to the CTL group, mainly in the RHD-STN. Lumican, in turn, had decreased expression in the MXD and RHD-STN groups. By using in silico methods for analysis of patterns of protein expression, we identified sets of proteins capable of discriminating mitral valve samples by disease etiology. The present study might help elucidating the mechanisms of disease development and structural alterations in the mitral tissue in response to the autoimmune lesions, as well as in the diagnosis of RHD.
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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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Palermo, Thierry. "Etude de l'effondrement d'un tube elastique encastre : modelisation d'une prothese valvulaire cardiaque." Paris 7, 1988. http://www.theses.fr/1988PA077132.
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Jimenez-Mejia, Jorge Hernan. "The loading and function of the mitral valve under normal, pathological and repair conditions : an in vitro study /." Diss., Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-11102006-003456/.
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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007.Ajit Yoganathan, Committee Chair ; Thomas Vassiliades, Committee Member ; Joseph Gorman, Committee Member ; Marc Levenston, Committee Member ; John N. Oshinski, Committee Member.
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Burleson, Armelle Cagniot. "Analysis of turbulent jets for the determination of heart valve leakage." Diss., Georgia Institute of Technology, 1993. http://hdl.handle.net/1853/11307.
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Leung, Wing-ki Vikki, and 梁頴琪. "The implications of transcatheter aortic valve implantation (TAVI) adoption." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48424031.
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Aortic stenosis is a life-threatening valvular heart disease. At the onset of symptoms, a patient’s prognosis becomes poor and the risk of death rapidly increases. Aortic valve replacement surgery remains the gold standard in treatment for aortic stenosis. However, in the total population of patients with severe aortic stenosis, about one third are deemed inoperable due to their high surgical risk. In recent years, the development of transcatheter aortic valve implantation (TAVI), a non-invasive heart valve replacement procedure brought hope for the elderly, high-risk and inoperable aortic stenosis patient population pool. A literature review was performed to examine the safety, efficacy and effectiveness evidence for transcatheter aortic valve treatment option. The results showed that TAVI is a safe treatment option, however the effectiveness for the whole patient population is unknown. The adoption of this alternative treatment option is certainly coupled with multiple dimension of impact from a public health perspective. It remains inconclusive whether TAVI is an effective treatment option to be adopted.published_or_final_version
Public Health
Master
Master of Public Health
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Spinner, Erin M. "Tricuspid valve mechanics: understanding the effect of annular dilatation and papillary muscle displacement." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45754.
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Tricuspid regurgitation (TR), back flow of blood from the right ventricle to the right atrium, has been reported in approximately 85% of the population, with 16% having mild or severe TR. Patients with untreated moderate to severe TR are likely to experience decreased exercise capacity and have increased morbidity and mortality, thus affecting the patient's quality of life. Current methods of repair offer limited rates of success, and many patients require further operations to correct returning levels of TR. Incomplete repair may be due to incomplete understanding of the functional anatomy and mechanics of the TV and the underlying causes of TR.
It was hypothesized that alterations in the geometry of tricuspid valve annular and subvalvular apparatus induced by ventricular dilatation determine the severity of TR. In vivo measurements of papillary muscle (PM) position in patients with single or biventricular dilatation revealed PM displacement away from the center of the annulus as compared to control patients. Additionally, pulmonary arterial pressure, annulus area, ventricular size and apical displacement of the anterior PM were highly correlated with the severity of TR. An in vitro right-heart simulator was developed to investigate isolated mechanics of TR. Through these in vitro studies it was demonstrated that the tricuspid valve begins to leak at only 40% dilation, much lower than the mitral valve. Additionally, it was shown that isolated PM displacement resulted in significant TR. The highest levels of TR were achieved with a combination of annular dilatation and PM displacement. Alterations in leaflet coaptation, as quantified by measuring the amount of leaflet available for coaptation and leaflet mobility were observed with annular dilatation and PM displacement, both isolated and combined. The changes in leaflet coaptation resulted in redistribution of the forces on the chords originating from the anterior PM and inserting into the anterior and posterior leaflets.
The findings herein provide the clinical and scientific community with a mechanistic understanding of the tricuspid valve to further improve intervention and repair of TV disease.
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Smith, Benjamin Hutchinson. "Prognostic value of serial exercise test results in physically active coronary artery disease patients." Thesis, This resource online, 1987. http://scholar.lib.vt.edu/theses/available/etd-04272010-020259/.
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Hopmeyer, Joanne. "Effect of physiologic parameters on the quantification of mitral regurgitation using the flow convergence method." Diss., Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/10969.
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Vesier, Carol Cockerham. "The role of papillary muscle-mitral valve geometry in systolic anterior motion of the mitral valve." Diss., Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/10279.
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Wilkerson, Patrick Wayne. "Quantification of mitral regurgitation using corrected doppler measurements." Thesis, Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/17302.
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Grande, Kathryn Jane. "The aortic root-aortic valve relationship in the normal, diseased, and surgically repaired states /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/8114.
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