L'objectif de la présente thèse était d'examiner dans une large population non sélectionnée au Québec, l'impact du diabète sur la mortalité suite à une hospitalisation pour un premier infarctus aigu du myocarde (IAM) survenue dans des centres hospitaliers de la province de Québec entre 1995 et 2001. La réalisation de ce projet de thèse s'est basée sur le jumelage de trois bases de données médico-administratives, soit 1) le fichier québécois des hospitalisations, 2) le registre des décès et 3) la base de données du Programme québécois de surveillance du diabète. L'analyse des données a permis dans un premier temps de mettre en évidence l'influence du diabète dans l'augmentation de la mortalité à long terme chez les groupes les plus à risque, en l'occurrence les jeunes femmes âgées de moins de 65 ans, chez qui, le risque de mortalité à cinq ans était 1,5 fois plus élevé que chez les hommes diabétiques et 3 fois plus élevé que chez les femmes non diabétiques de même tranche d'âge, et ce, indépendamment des facteurs sociodémographiques, des co-morbidités, des complications hospitalières et du traitement invasif par revascularisation reçu pendant le séjour hospitalier. Dans un deuxième temps, nous avons examiné l'évolution temporelle dans la létalité hospitalière et à 1 an suite à l'admission pour IAM et dans le recours à la revascularisation (pontage coronarien et angioplastie) chez les patients diabétiques et non diabétiques. Les résultats de cette étude descriptive ont démontré une augmentation significative dans le recours à la revascularisation chez les patients diabétiques durant la période de l'étude. Cette amélioration était accompagnée d'un déclin significatif dans la létalité, similaire à la population non diabétique. Par ailleurs, malgré cette baisse significative de la létalité, le risque de mortalité à 1 an demeure toutefois 1,21 fois plus élevé chez les diabétiques que chez les non diabétiques, et ce même après ajustement pour les caractéristiques des patients et les co-morbidités. Par la suite, nous avons démontré que cette baisse de mortalité chez la population diabétique était restreinte aux groupes appartenant à une classe socio-économique favorisée. Chez les plus démunis, matériellement et socialement, la létalité est demeurée relativement stable dans le temps. Enfin, les résultats de l'étude de validation de la définition de cas de diabète utilisée dans la présente thèse ont démontré que la définition de cas de diabète est associée à une sensibilité de 94,6% et à une valeur prédictive positive de 87,9%. Ces résultats indiquent que les bases de données administratives constituent une source valide et fiable pour identifier l'ensemble de la population diagnostiquée diabétique au Québec.

<p>In unstable coronary artery disease (CAD) it still is a matter of debate which patients should undergo early revascularisation. In the FRISC II study (n=2457) an early invasive strategy was, compared to a primarily non-invasive strategy, associated with reduced mortality and myocardial infarction (MI) rates. However, in this heterogeneous group of patients, tools for an appropriate selection to revascularisation are needed.</p><p>From the FRISC II study we evaluated the prognosis, the angiographic extent of CAD and the effects of an early invasive strategy in relation to risk variables on admission.</p><p>The occurrence of ST depression and/or elevated levels of Troponin T were associated with a higher risk for death and MI, more severe CAD and also with a reduction of death or MI by the early invasive strategy.</p><p>Elevated levels of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (Il-6) were associated with a higher mortality but an unchanged MI rate. Elevated levels of Il-6, but not CRP, identified patients with a large reduction of mortality by the invasive strategy.</p><p>Age ≥ 70 years, male gender, diabetes, previous MI, ST depression and elevated levels of troponin and markers of inflammation were independently associated with an adverse outcome. The FRISC-score was constructed using these 7 variables. At FRISC-score ≥ 5 an early invasive strategy markedly reduced mortality and MI, at FRISC–score 3-4 death/MI was reduced, whereas in patients with a FRISC-score 0-2 neither mortality nor death/MI was influenced.</p><p>In unstable CAD, a non-invasive strategy seems justified only for patients at low risk, i.e. FRISC score < 2. In patients with intermediate and high risk, i.e. FRISC-score ≥ 3, an early invasive strategy is recommended.</p>

In unstable coronary artery disease (CAD) it still is a matter of debate which patients should undergo early revascularisation. In the FRISC II study (n=2457) an early invasive strategy was, compared to a primarily non-invasive strategy, associated with reduced mortality and myocardial infarction (MI) rates. However, in this heterogeneous group of patients, tools for an appropriate selection to revascularisation are needed. From the FRISC II study we evaluated the prognosis, the angiographic extent of CAD and the effects of an early invasive strategy in relation to risk variables on admission. The occurrence of ST depression and/or elevated levels of Troponin T were associated with a higher risk for death and MI, more severe CAD and also with a reduction of death or MI by the early invasive strategy. Elevated levels of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (Il-6) were associated with a higher mortality but an unchanged MI rate. Elevated levels of Il-6, but not CRP, identified patients with a large reduction of mortality by the invasive strategy. Age ≥ 70 years, male gender, diabetes, previous MI, ST depression and elevated levels of troponin and markers of inflammation were independently associated with an adverse outcome. The FRISC-score was constructed using these 7 variables. At FRISC-score ≥ 5 an early invasive strategy markedly reduced mortality and MI, at FRISC–score 3-4 death/MI was reduced, whereas in patients with a FRISC-score 0-2 neither mortality nor death/MI was influenced. In unstable CAD, a non-invasive strategy seems justified only for patients at low risk, i.e. FRISC score &lt; 2. In patients with intermediate and high risk, i.e. FRISC-score ≥ 3, an early invasive strategy is recommended.

Suite à une ischémie, de nombreux acteurs moléculaires et cellulaires concourent pour promouvoir la revascularisation post-ischémique afin de limiter les lésions tissulaires. Des cellules progénitrices et inflammatoires originaires de la moelle osseuse sont notamment recrutées au niveau du tissu ischémique où elles activent et participent à la régénération vasculaire et tissulaire. Leurs capacités pro-angiogéniques et pro-vasculogéniques suscitent d'ailleurs un grand intérêt pour l'élaboration de nouvelles stratégies thérapeutiques. L'objectif de ce travail de thèse aura été d'améliorer notre compréhension des mécanismes qui régissent la mobilisation et le recrutement des cellules progénitrices originaires de la moelle osseuse et de mettre en évidence l'efficacité d'un traitement basée sur l'utilisation de cellules souches pour promouvoir la revascularisation post-ischémique. Dans un premier travail nous avons mis en évidence que les catécholamines (dopamine -DA- et norépinephrine -NE-) du système nerveux sympathique régulent la mobilisation des cellules progénitrices originaires de la moelle osseuse via une signalisation dépendante de la eNOS. Nous avons montré que la DA et la NE augmentent le nombre de cellules médullaires recrutées dans le tissu ischémique et stimulent leur différenciation en cellules à phénotype endothéliale ou inflammatoire favorisant ainsi la revascularisation post-ischémique. Le recrutement des cellules médullaires dépend également des chimiokines, et plus particulièrement de CXCL12 qui est connue pour attirer les cellules exprimant son récepteur CXCR4. Le deuxième travail de cette thèse a montré que le pouvoir chimioattractant de CXCL12 est également régulé par sa capacité à se lier aux héparan-sulfates (HS), et donc à adhérer à la matrice extracellulaire. En effet, de fortes interactions CXCL12/HS induisent une augmentation de la régénération vasculaire post-ischémique corrélée à un meilleur recrutement des cellules d'origine médullaires dans le tissu lésé.Une fois recrutées dans le tissu ischémique, les cellules souches, de part leurs capacités remarquables d'auto-renouvellement, de prolifération, de différenciation et leur activité paracrine sont d'excellents activateurs de la revascularisation post-ischémique. La troisième étude de cette thèse met en évidence l'efficacité des cellules souches embryonnaires humaines multipotentes pour traiter l'ischémie critique du membre inférieur. Nous avons également révélé que ce potentiel thérapeutique dépend du miR-21.Ces travaux ont permis de démontrer que la régulation de la mobilisation et du recrutement des cellules souches contrôle la revascularisation post-ischémique et de souligner l'efficacité d'un traitement basé sur l'utilisation de cellules souches pour promouvoir la revascularisation post-ischémique.

Introduction Bypass surgery for infrainguinal disease is indicated when a patient presents with chronic (disabling claudication or chronic limb-threatening ischaemia) or acute ischemia. Duplex ultrasound surveillance can be used in the follow-up period to detect grafts in risk of failure. If detected before occlusion occurs an intervention can prolong patency. Aim The purpose of this study was to evaluate the outcome of the procedure, whether there are factors associated with no improvement, and to elucidate the value of routine ultrasound surveillance. Methods Patients who underwent lower extremity bypass surgery at Falu hospital between 2010 and 2020 were identified from the national registry Swedvasc. Clinical outcome was based on change in the Rutherford classification. Duplex ultrasound measured peak systolic velocities. A significant stenosis was defined as a 2-3.5-fold increase in ratio of adjacent velocities in the bypass. For a non-significant stenosis, the ratio had to be increased but by less than 2 times. Results 114 patients underwent bypass surgery. Mean age was 70 years. Postoperative surveillance was carried out for 78 patients. Of these, 40 (51.3%) presented with an abnormality and further 30 of them (75%) received further intervention. There was a correlation between cardiac risk and outcome at the 30-day follow-up. For the majority of the not-surveilled, a major adverse event occurred within 1 year. Conclusions Bypass surgery was beneficial for the majority. Cardiac risk was a negative predictor for outcome. Most patients attending the surveillance benefited from early detection of risk of graft failure. To improve its value and efficacy, guidelines are needed within the clinic.

No description available.

<p>Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. </p><p>Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.</p><p>Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.</p><p>A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.</p><p>Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.</p>

Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease. Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor. A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions. Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

The main goal of this dissertation was to assess prospectively the value of two cardiovascular magnetic resonance methodises (the transmural extent of an late gadolinium enhancement and the contractile reserve during low dose dobutamine administration) as predictors of left ventricular segmental and global functional recovery in patients with left ventricular systolic dysfunction undergoing surgical or percutaneous revascularisation. Taking into account previous studies, revascularisation of the viable myocardium results in an improvement of patient’s symptoms and prognosis. This finding emphasized the need for and importance of noninvasive tests to quantify the amount of viable myocardium in patients with left ventricular dysfunction in order to define the optimal management strategy. On the basis of the research described in the dissertation, the diagnostic value of different cardiovascular magnetic resonance based viability prediction methods was assessed. The superiority of combined viability prediction model incorporating an late gadolinium enhancement and the contractile reserve during low dose dobutamine administration was confirmed. The optimal predictors of the significant improvement of left ventricular ejection fraction were found: the percentage of viable segments from all dysfunctional and revascularised segments in a patient and the absolute value of left ventricular ejection fraction measured during low dose dobutamine administration. On the basis of the... [to full text] / Disertacijoje nagrinėta dviejų magnetinio rezonanso metodikų (vėlyvojo kontrastinės medžiagos kaupimo transmuralumo bei mažų dobutamino dozių sukeliamo miokardo kontraktilinio rezervo) bei šių metodikų derinio vertė, prognozuojant bendrosios bei segmentinės kairiojo skilvelio funkcijos atsistatymą po revaskuliarizacijos (perkutaninės vainikinių arterijų intervencijos ar vainikinių arterijų apeinamųjų jungčių suformavimo operacijos), pacientams, turintiems išeminės kilmės kairiojo skilvelio sistolinę disfunkciją. Kadangi yra nustatyta, jog sėkminga gyvybingo miokardo revaskuliarizacija pagerina kairiojo skilvelio sistolinę disfunkciją turinčių pacientų simptomus bei prognozę, todėl gyvybingo miokardo nustatymas yra svarbus, siekiant parinkti optimalią tokių pacientų gydymo taktiką. Disertacijoje aprašomo tyrimo pagalba buvo nustatyta širdies magnetinio rezonanso vertė, prognozuojant miokardo bendrosios bei segmentinės kontrakcijos atsistatymą bei pagrįsta vėlyvojo kontrastinės medžiagos kaupimo transmuralumo bei mažų dobutamino dozių sukeliamo kontraktilinio rezervo nustatymo metodikų derinimo nauda. Disertacijoje aptarti optimalūs reikšmingo bendrosios kairiojo skilvelio sistolinės funkcijos pagerėjimo prognostiniai rodikliai: gyvybingų segmentų procentas nuo visų išeityje disfunkcinių bei revaskuliarizuotų paciento segmentų bei absoliuti kairiojo skilvelio išstūmimo frakcija, išmatuota mažų dobutamino dozių skyrimo metu. Disertacijos rezultatų pagrindu buvo sukurtas... [toliau žr. visą tekstą]

Disertacijoje nagrinėta dviejų magnetinio rezonanso metodikų (vėlyvojo kontrastinės medžiagos kaupimo transmuralumo bei mažų dobutamino dozių sukeliamo miokardo kontraktilinio rezervo) bei šių metodikų derinio vertė, prognozuojant bendrosios bei segmentinės kairiojo skilvelio funkcijos atsistatymą po revaskuliarizacijos (perkutaninės vainikinių arterijų intervencijos ar vainikinių arterijų apeinamųjų jungčių suformavimo operacijos), pacientams, turintiems išeminės kilmės kairiojo skilvelio sistolinę disfunkciją. Kadangi yra nustatyta, jog sėkminga gyvybingo miokardo revaskuliarizacija pagerina kairiojo skilvelio sistolinę disfunkciją turinčių pacientų simptomus bei prognozę, todėl gyvybingo miokardo nustatymas yra svarbus, siekiant parinkti optimalią tokių pacientų gydymo taktiką. Disertacijoje aprašomo tyrimo pagalba buvo nustatyta širdies magnetinio rezonanso vertė, prognozuojant miokardo bendrosios bei segmentinės kontrakcijos atsistatymą bei pagrįsta vėlyvojo kontrastinės medžiagos kaupimo transmuralumo bei mažų dobutamino dozių sukeliamo kontraktilinio rezervo nustatymo metodikų derinimo nauda. Disertacijoje aptarti optimalūs reikšmingo bendrosios kairiojo skilvelio sistolinės funkcijos pagerėjimo prognostiniai rodikliai: gyvybingų segmentų procentas nuo visų išeityje disfunkcinių bei revaskuliarizuotų paciento segmentų bei absoliuti kairiojo skilvelio išstūmimo frakcija, išmatuota mažų dobutamino dozių skyrimo metu. Disertacijos rezultatų pagrindu buvo sukurtas... [toliau žr. visą tekstą] / The main goal of this dissertation was to assess prospectively the value of two cardiovascular magnetic resonance methodises (the transmural extent of an late gadolinium enhancement and the contractile reserve during low dose dobutamine administration) as predictors of left ventricular segmental and global functional recovery in patients with left ventricular systolic dysfunction undergoing surgical or percutaneous revascularisation. Taking into account previous studies, revascularisation of the viable myocardium results in an improvement of patient’s symptoms and prognosis. This finding emphasized the need for and importance of noninvasive tests to quantify the amount of viable myocardium in patients with left ventricular dysfunction in order to define the optimal management strategy. On the basis of the research described in the dissertation, the diagnostic value of different cardiovascular magnetic resonance based viability prediction methods was assessed. The superiority of combined viability prediction model incorporating an late gadolinium enhancement and the contractile reserve during low dose dobutamine administration was confirmed. The optimal predictors of the significant improvement of left ventricular ejection fraction were found: the percentage of viable segments from all dysfunctional and revascularised segments in a patient and the absolute value of left ventricular ejection fraction measured during low dose dobutamine administration. On the basis of the... [to full text]