<p dir="ltr">Fibromuscular Dysplasia (FMD) is a non-inflammatory, non-atherosclerotic blood vessel disorder characterized by a series of narrowed and dilated regions of vasculature. These patients are prescribed blood thinners or anti-platelet therapeutics as treatment to this systemic disease. Current image-based diagnostic methods cannot reliably predict a patient’s risk of stroke in order to properly manage medication. There are also challenges in distinguishing FMD from other diseases that can cause arterial obstructions, like atherosclerosis or vasculitis.</p><p dir="ltr">The ultimate goal of this research is to develop a methodology for evaluating the risk of mechanical platelet activation based on medical imaging. Our hypothesis is that subject-specific assessment of platelet activation due to hemodynamic stress can improve risk stratification of FMD patients. The aims of the projects were therefore to 1) Develop a CFD-based methodology for estimating platelet activation state, and 2) Test this methodology on a small cohort of subjects with FMD, carotid artery stenosis, and healthy controls. A modeling workflow was developed, combining Eulerian and Lagrangian approaches to compute flow fields and evaluate shear stress history of particles advected through the vascular geometries. From this stress history, predictive estimates of mechanical platelet activation can be calculated utilizing a platelet activation state (PAS) metric. We applied this modeling workflow to assess platelet activation in segments of carotid arteries of patients with Fibromuscular Dysplasia, Carotid Artery Stenosis, and healthy controls for comparison against experiments performed at the Cleveland Clinic assessing mechanical platelet activation in patients with each of these conditions. This work supports the development of a patient-specific determination of these same metrics, in order to more precisely assess patient risk of stroke.</p>

Made available in DSpace on 2016-01-26T12:51:26Z (GMT). No. of bitstreams: 1 luisdomingosfornitano_tese.pdf: 1565670 bytes, checksum: acedd7e7a18ad6dcdbdc6b72c97ae59d (MD5) Previous issue date: 2008-09-26 / Obesity is an independent risk factor for cardiovascular disease, especially in its morbid form. Bariatric surgery is an effective therapeutic option for sustained weight loss. However, there is no consensus in these cases regarding the performance of functional tests for preoperative evaluations. Objective: The aim of the present study was to analyze clinical, electrocardiographic and hemodynamic response variables using a conventional exercise test on individuals with morbid obesity in comparison to overweight individuals. Materials and Method: Six hundred seventeen cases were included. Group I had 290 patients with morbid obesity and Group II had 327 overweight patients. All were submitted to a conventional treadmill exercise test. Classic positivity criteria were used. Results: Both groups tolerated the test well. There was no statistically significant difference in terms of positivity of the test [ST segment abnormality or angor (p=0.3863) or ST segment abnormality alone (p=0.1000)]. The significantly higher values in the obese individuals were basal heart rate (HR), basal sistolic arterial pressure (SAP), maximum SAP, basal diastolic arterial pressure (DAP), maximum DAP, chronotropic incompetence (p<0.0001) and maximum double product (p<0.0421). The significantly lower values in the obese individuals were exercise time, maximum HR and METs values (p<0.0001). Conclusions: Hemodynamic parameters were significantly different between the two groups. However, there were no differences in terms of ST segment abnormalities or effort-induced angina. The very low functional capacity and complex arrhythmia found in some obese individuals draws attention to the need for complementary investigation with the aim of diminishing the risk of postoperative heart complications. / A obesidade é fator de risco independente para doença cardiovascular, particularmente em sua forma mórbida. A cirurgia bariátrica é opção terapêutica eficaz para o emagrecimento sustentado nesses casos não havendo, entretanto, consenso sobre a realização de testes funcionais para avaliação pré-operatória. Objetivo: Analisar as respostas clínicas, eletrocardiográficas e hemodinâmicas por teste ergométrico convencional, em portadores de obesidade mórbida em comparação a indivíduos com sobrepeso. Casuística e Método: Foram incluídos 617 casos sendo o Grupo I, com 290 pacientes obesos mórbidos e o Grupo II, com 327 pacientes com sobrepeso, todos submetidos a teste ergométrico convencional em esteira. Foram utilizados os critérios clássicos de positividade. Resultados: A prova foi bem tolerada por ambos os grupos. Não houve diferença estatisticamente significante em termos de positividade do Teste (por alteração do segmento ST ou angor) [P = 0,3863] ou somente por alteração do segmento ST [P= 0,1000]. As variáveis significantemente maiores nos obesos foram: Freqüência cardíaca (FC) basal, Pressão arterial sistólica (PAS) basal; PAS máxima; Pressão arterial diastólica (PAD) basal; PAD máxima; Déficit cronotrópico (P <0,0001) e o Duplo Produto (DP) máximo (P =0,0421). Os valores significantemente menores nos obesos foram: tempo de exercício, FC máxima e valores em METS (P<0,0001). Conclusões: Os parâmetros hemodinâmicos mostraram-se significantemente diferentes entre os dois grupos não havendo, porém, diferenças em termos de anormalidades do segmento ST ou angina induzida por esforço. A capacidade funcional muito baixa e as arritmias complexas observadas em alguns dos obesos alertam para a necessidade de investigação complementar no sentido de diminuir o risco de complicações cardíacas pós-operatórias.

ABSTRACT Purpose: The purpose of this study was to examine the relationship between self-reported sedentary time (ST) and the cumulative risk of preserved ejection fraction heart failure (HFpEF) and reduced ejection fraction heart failure (HFrEF) using a diverse cohort of U.S. adults 45-84 years of age. Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects (52.9% female). All were free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with baseline ST and risk of overall heart failure (HF), HFpEF, and HFrEF. Weekly self-reported ST was dichotomized based on the 75th percentile (1,890 min/wk). Results: During an average of 11.2 years of follow-up there were 178 first incident HF diagnoses; 74 HFpEF, 69 HFrEF and 35 with unknown EF. Baseline ST >1,890 min/wk was significantly associated with an increased risk of HFpEF (HR [95% CI]; 1.87 [1.13 – 3.09], p= 0.01), but not HFrEF (HR [95% CI]; 1.30 [0.78 – 2.15], p= 0.32). The relationship with HFpEF remained significant in separate fully adjusted models including either waist circumference (HR [95% CI]; 2.16 [1.23 – 3.78], p < 0.01) or body mass index (HR [95% CI]; 2.17 [1.24 – 3.80], p < 0.01). Additionally, every 60 minute increase in weekly ST was associated with a significant 3% increased risk of HFpEF (HR [95% CI]; 1.03 [1.01 – 1.05], p < 0.01). Conclusions: Sedentary time > 1,890 min/wk (~4.5 h/d) is a significant independent predictor of HFpEF, but not HFrEF.

L'utilisation de stents actifs (DES) a révolutionné le traitement de l'athérosclérose. Le relargage contrôlé de médicaments anti-prolifératifs dans la paroi artérielle (PA) a permis de réduire fortement le taux de resténose intra-stent. Mais le risque de thromboses intra-stents tardives demeure un enjeu majeur des DES en partie lié au retard de cicatrisation de la PA endommagée lors de l'implantation. Cette thèse présente une méthode d'optimisation du design des DES afin d'inhiber la resténose sans affecter la cicatrisation. Pour quantifier la performance des différents designs, un modèle numérique décrivant l'écoulement sanguin et le transport de médicaments dans les artères stentées a été développé. Il prend en compte la structure multi-couches de la PA et les interactions du médicament avec les cellules. Un algorithme d'optimisation est couplé au modèle afin d'identifier les DES optimaux. L'optimisation du temps de relargage ainsi que de la concentration initiale du médicament dans le revêtement du DES ont un effet significatif sur la performance. Lorsque le médicament utilisé est le paclitaxel, les solutions optimales consistent à relarguer le produit à des concentrations nettement inférieures à celles des DES actuels soit pendant quelques heures, soit pendant une durée d'un an. Pour le sirolimus, un relargage lent est nécessaire. Les formes optimales des spires du DES sont toujours allongées mais profilées seulement lorsque le relargage est rapide. Ces résultats permettent d'expliquer en partie les performances des différents DES récents et révèlent un fort potentiel d'amélioration dans la conception des DES par rapport aux dispositifs commerciaux actuels.

During catheterized x-ray interventions the patient and medical staff is exposed to scatter radiation, as a consequence of tissue interactions. Ionizing radiation for medical purpose is potentially dangerous and can cause malignancy, skin damage and more. Studies have suggested an increase in the prevalence of eye lens cataract, thyroid cancer and left sided brain tumors in doctors. Therefore, it is mandatory to reduce the radiation dose in medicine, a principle known as ALARA (as low as Reasonably Achievable). Lead aprons, collars and shieldings are safety precautions to protect the team in the operating room. The x-ray equipment and surgical techniques are constantly evolving and the interventions become more complex which may increase the x-ray dose. Although x-ray imaging is required in interventional procedures endeavors of reducing radiation exposure to staff is of high interest. There is a need to increase the awareness about scatter radiation and radiation protection efforts are gaining momentum. Initiative to train a dose reducing behavior by education and awareness are key documents within the European Union’s guidelines on Radiation protection. The aims of this thesis were to create a 3D model for representation of real-time exposure and accumulated scatter radiation to staff performing interventional x-ray procedures and identify parameters that affect the scatter radiation. Extensive measurements were made with real time dosimeters while irradiating an anthropomorphic phantom. For five lateral C-arm projections, 68 - 80 data points each were used to measure scatter dose distribution around the patient. In the typical operator position, the effect of craniocaudal projection angle, patient size, field size, image detector height and pulse rate on scatter radiation dose was also investigated. It was possible to create a 3D model from interpolated measurement data that can generate dose rate with promising results. Six out of eight modelled doses deviated +/- 26.6 % from the validation cases. A model that delivers relative dose is an intuitive approach in education for interventional x-ray radiation safety. The staff position in relation to the x-ray source and the patient size have a significant correlation to the dose rate. Additional measurements are needed to ensure the reliability of the model. This work completes the effect of scatter radiation distribution around the patient table, which is not yet evaluated as thoroughly by other authors.

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

Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.

Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

BackgroundThe prompt seeking of medical care after the onset of symptoms suggestive of acute coronary syndromes (ACS)/acute myocardial infarction (AMI) is associated with the receipt of coronary reperfusion therapy, and effective cardiac medications in patients with an ACS/AMI and is crucial to reducing mortality and the risk of serious clinical complications in these patients. Despite declines in important hospital complications and short-term death rates in patients hospitalized with an ACS/AMI, several patient groups remain at increased risk for these adverse outcomes, including women and the elderly. However, recent trends in age and sex differences in extent of pre-hospital delay, hospital management practices, and short-term outcomes associated with ACS/AMI remain unexplored. The objectives of this study were to examine the overall magnitude, and changing trends therein, of age and sex differences in duration of pre-hospital delay (1986-2005), hospital management practices (1999-2007), and short-terms outcomes (1975-2005) in patients hospitalized with ACS/AMI. MethodsData from 13,663 residents of the Worcester, MA, metropolitan area hospitalized at all greater Worcester medical centers for AMI 15 biennial periods between 1975 and 2005 (Worcester Heart Attack Study), and from 50,096 patients hospitalized with an ACS in 106 medical centers in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007 were used for this investigation. Results In comparison with men years, patients in other age-sex strata exhibited significantly longer pre-hospital delay, with the exception of women < 65 years; had a significantly lower odds of receiving aspirin, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers, statins, and undergoing coronary artery bypass graft surgery (CABG) surgery or percutaneous coronary intervention (PCI), and were significantly more likely to develop atrial fibrillation, cardiogenic shock, heart failure, and to die during hospitalization and in the first 30 days after admission. There was a significant interaction between age and sex in relation to the use of several medications and the development of several of these outcomes; in patients Conclusions Our results suggest that the elderly were more likely to experience longer prehospital delay, were less likely to be treated with evidence-based treatments during hospitalization for acute coronary syndrome, and were more likely to develop adverse outcomes compared to younger persons. Younger women were less likely to be treated with effective treatments and were more likely to develop adverse outcomes compared with younger men while there was no sex difference in these outcomes. Interventions targeted at older patients, in particular, are needed to encourage these high-risk patients to seek medical care promptly to maximize the benefits of currently available treatment modalities. More targeted treatment approaches during hospitalization for ACS/AMI for younger women and older patients are needed to improve their hospital prognosis.

Background: Every year, more than 2 million people undergo cardiac surgery including 15 000 Canadians (1). Acute kidney injury remain a frequent complication in this setting which can affect up to 39% of patients (2). This complication is associated with a significant increase in the risk of short-term and long-term mortality after cardiac surgery (1). Multiple mechanisms can lead to acute kidney injury in the peri-operative period which complexify prevention and treatment. Among them, multiple clinical factors can result in an increase in venous pressure leading to a state of systemic congestion deleterious to kidney function in addition to other organs. The detection of congestion at the bedside of patients after cardiac surgery could be used to identify patients at risk of developing congestive complications such as congestive acute kidney injury as well as opening possibilities for prevention and treatment. Doppler ultrasound is a non-invasive technology enabling the assessment of blood flow velocity within the venous system. A reduction of systemic venous compliance lead to the appearance of alterations in portal vein flow and intra-renal venous flow. The objectives of the work presented in this thesis were the following: To determine the prevalence and predictive factor associated with the appearance of venous flow alterations during the intra-operative and post-operative period, to determine if their detection is associated with acute kidney injury in the post-operative period and to determine the clinical significance of their detection in the immediate post-operative period. Main results: This thesis is comprised of 3 cohort studies including a total of 1497 ultrasound asessments in 362 patients. Alterations in venous Doppler signals were observed in a subtantial proportion of patients during the per-operative period, from 10.8% to 24.3% depending on the time of assessment and the site assessed. We observed significant correlations between venous Doppler alterations and other clinical markers of congestion including central venous pressure, NT-pro-BNP and fluid balance. Furthermore, we observed that portal flow pulsatility and abnormal patterns of intrarenal venous flow were correlated. Using repeated assessments in a cohort of 145 patients, we observed that portal flow pulsatility and severe alterations in intrarenal venous flow were associated with the subsequent development of acute kidney injury in the post-operative period. A re-analysis of this data suggested that a grading system combining mutliple Doppler assesments at intensive care admission after cardiac surgery including heaptic veins, the portal vein and intrarenal veins may be able to identify patients at risk of developping acute kidney injury with high specificity. Conclusions: In the context of cardiac surgery, Doppler ultrasound can be used to identify alterations in peripheral venous Doppler signals suggestive of a congestion phenomenon and may be able to anticipate complications related to venous congestion such as acute kidney injury. / Contexte : Chaque année, plus de 2 millions de personnes subissent une chirurgie cardiaque, dont 15 000 Canadiens (1). L’insuffisance rénale aiguë demeure une complication fréquente chez les patients subissant une chirurgie cardiaque atteignant une incidence jusqu’à 39 % dans la période postopératoire (2). Cette complication est associée à une augmentation du risque de mortalité à court et long termes. Plusieurs mécanismes peuvent engendrer l’insuffisance rénale aiguë dans la période peropératoire, ce qui complexifie la prévention et le traitement. Parmi ceux-ci, divers facteurs peuvent engendrer une augmentation des pressions veineuses menant à un état de congestion systémique qui affecte la fonction des reins ainsi que celle des autres organes vitaux. La détection de la congestion au chevet des patients durant la période intraopératoire et postopératoire pourrait permettre d’identifier les individus à risque de développer des complications de nature congestive telles que l’insuffisance rénale aiguë ainsi que de mettre en place des stratégies de prévention et de traitement. L’échographie Doppler est une technologie non invasive qui permet d’évaluer la vélocité du sang dans le réseau veineux. La diminution de la compliance veineuse entraine l’apparition d’altérations du flot veineux de la veine porte et des veines intrarénales. Les objectifs des travaux présentés dans cette thèse étaient les suivants : déterminer la prévalence ainsi que les facteurs prédicteurs de l’apparition de ces altérations durant la période peropératoire; déterminer si la détection de ces altérations est en mesure de prédire l’apparition d’insuffisance rénale aiguë dans la période postopératoire; et déterminer quelle est la signification clinique de l’apparition de ces signes dans la période postopératoire immédiate. Résultats principaux : Les travaux contenus dans cette thèse comportent trois études de cohorte comprenant 1497 examens échographiques chez 362 patients. La présence d’altération du flot veineux a été observée chez une proportion substantielle des patients durant la période post-opératoire, allant de 10.8% à 24.3% selon le site intérrogé et le moment où l’examen est effectué. Nous avons observé des associations entre les altérations du flot veineux et les autres marqueurs de congestion incluant la pression veineuse centrale, la mesure du NT-pro-BNP et la balance liquidienne. De plus, nous avons observé que la pulsatilité du flot portal est corrélée aux altérations du signal Doppler dans les veines intrarénales. Grâce à des examens répétées effectuées dans une cohorte de 145 patients, nous avons observé que la pulsatilité du flot portal et la présence d’un profil compatible avec une anomalie sévère du flot intrarénal veineux étaient associées indépendamment avec la survenue subséquente d’insuffisance rénale aiguë durant la période postopératoire. Une réanalyse de ces données nous a permis de constater qu’un système de gradation combinant la présence des altérations du flot veineux à plusieurs sites, incluant les veines hépatiques, la veine porte et les veines intrarénales, au moment de l’admission aux soins intensifs permet d’indentifier les patients qui développeront une insuffisance rénale aiguë avec une spécificité élevée. Conclusions : Dans le contexte de la chirurgie cardiaque, l’échographie Doppler peut être utilisée au chevet afin d’indentifier des altérations du flot veineux périphérique suggestives d’un phénomène de congestion et d’anticiper les complications de nature congestive tel que l’insuffisance rénale aiguë.