Timely management in pre-hospital emergency care enhances the chances of patients' survival or clinical outcomes of an Acute Coronary Syndrome (ACS). In Botswana nurses serve in the frontline of pre-hospital emergency services as the initial recipients of the emergency reports and situations. Knowledge of the patient's characteristics will assist the nurses as well as the family/others to understand the patient's responses during an ACS situation and therefore enable prompt patient assessment and facilitation of early access to appropriate care. Patient and family involvement in care during cardiac emergencies also influences the patient outcomes. This is a non-experimental, quantitative, exploratory and descriptive study, designed to explore and describe the characteristics of patients with the experience of an ACS, and the available resources during the pre-hospital phase of emergency care, with the aim of improving patients' clinical outcomes. The results indicated that optimal care by nurses is essential in the chain of care influencing patients' chances of surviving ACS. / Health Studies / M.A. (Health Studies)

Rationnel : L’implication établie des progéniteurs endothéliaux circulants dans les phénomènes de néovascularisation chez l’adulte a stimulé la recherche de thérapeutiques angiogènes basées sur la greffe de ces cellules. Deux types cellulaires au phénotype endothélial sont actuellement définis entre autres par leur cinétique d’apparition en culture : les progéniteurs précoces (CFU-EC ou CAC) et tardifs (ECFC). Notre équipe a montré que l’injection thérapeutique de cellules mononucléées de moelle osseuse (BM-MNC) permettait la néovascularisation du site ischémié chez des patients atteints d’artériopathie des membres inférieurs, et que les néovaisseaux formés avaient le phénotype d’ECFC. Nous avons dans un premier temps mesuré les concentrations de différentes protéines modulant l’angiogenèse, chez des patients atteints de pathologies ischémiques et cardiovasculaires, ou impliquant des anomalies vasculaires associées à la fibrose. Ainsi, le transforming growth factor - β1 (TGF-β1) dans la fibrose pulmonaire idiopathique (FPI), la thrombospondine-1 (TSP-1) dans l’artériopathie des membres inférieurs (AMI), et le placental growth factor (PlGF) chez les patients atteints de pathologies cardiovasculaires [syndrome coronarien aigu (SCA), ou patients devant subir une chirurgie de la valve ou un pontage coronarien], se sont distingués comme potentiel biomarqueur plasmatique dans ces pathologies, et ont été étudiés dans la biologie des ECFC humaines.Résultats : Le taux plasmatique de TGF-β1 est augmenté chez les patients atteints de FPI par rapport à la population contrôle ; il a un effet pro-angiogène in vivo (vascularisation des implants de Matrigel®) et in vitro (prolifération et migration des ECFC) via les récepteurs ALK-1, ALK-5 et TGF-βRII. Le taux plasmatique de TSP-1 est augmenté chez les patients artéritiques par rapport à la population contrôle. Par ailleurs les néovaisseaux formés de patients artéritiques ayant été traités par injection locale de BM-MNC expriment la TSP-1. Dans les modèles murins de Matrigel®-plugs et d’ischémie du membre inférieur (IMI), la TSP-1 induit une diminution de la vascularisation des implants ainsi qu’une diminution de la revascularisation du membre ischémié. In vitro, la TSP-1 augmente l’adhésion via un mécanisme N-Terminal dépendant, et diminue le potentiel angiogène (prolifération et migration) des ECFC via sa liaison au récepteur CD47, ce qui active la voie de signalisation SDF-1/CXCR4. Le taux plasmatique de PlGF est augmenté chez les patients atteints de SCA par rapport à 2 populations contrôles ; il est également augmenté chez les patients ayant subit une chirurgie cardiaque. Les PlGF-1 et -2 potentialisent la tubulogenèse des ECFC in vitro via la phosphorylation du récepteur VEGFR1. Cet effet est aboli lorsque le VEGFR1 est inhibé par ARN interférence ou par le composé chimique « 4321 ». De plus ce composé « 4321 » inhibe la vascularisation des implants de Matrigel®, ainsi que la revascularisation du membre ischémié dans le modèle d’IMI.Conclusions : Le TGF-β1 joue un rôle dans le remodelage vasculaire de la FPI via les ECFC ; la TSP-1 est un potentiel biomarqueur de l’angiogenèse induite par les ECFC dans l’AMI ; l’inhibition de la voie PlGF/VEGFR1 module la tubulogenèse induite par les ECFC, cellules impliquées dans la formation de nouveaux vaisseaux. Nous avons ainsi mis en évidence 3 protéines modulant l’angiogenèse dans 3 contextes pathologiques différents, caractérisés par un remodelage vasculaire et où les ECFC sont impliquées dans leurs mécanismes physiopathologiques. Ces 3 protéines se présentent donc comme de potentiels biomarqueurs plasmatiques, modulant les propriétés angiogènes des ECFC et pouvant influencer leur efficacité en tant que produit de thérapie cellulaire. Ces protéines jouent un rôle probable dans l’équilibre homéostatique au décours des pathologies concernées. / Rationale: The pro-angiogenic capacities of endothelial progenitor cells are now well established, and their involvement in neovascularization events in adults has stimulated the research in the field of angiogenic therapy based on transplant of these cells. Current data converge towards the notion of two cell types with endothelial phenotype, defined at least by their kinetics of appearance in culture: early endothelial progenitor cells (CFU-EC or CAC) and late (ECFC). Our team has shown that the therapeutic injection of bone marrow mononuclear cells (BM-MNC) led to neovascularization of the ischemic site in patients with critical limb ischemia, and that the new vessels formed bore the phenotype of ECFC. We initially measured the concentrations of different proteins modulating angiogenesis in patients with ischemic and cardiovascular diseases, or involving vascular abnormalities associated with fibrosis. Thus, the transforming growth factor - ß1 (TGF-ß1) in idiopathic pulmonary fibrosis, the thrombospondin-1 (TSP-1) in peripheral artery disease, and the placental growth factor (PlGF) in patients with cardiovascular diseases [acute coronary syndrome (ACS), patients undergoing valve surgery or coronary artery bypass surgery], emerged as potential plasmatic biomarkers in these pathological settings, and have been studied in the biology of human ECFC.Results: TGF-ß1 plasma level is increased in patients with idiopathic pulmonary fibrosis (IPF) compared to the control population; it exerts a pro-angiogenic effect in vivo (vascularization of Matrigel ®-plugs) and in vitro (proliferation and migration of ECFC) via ALK-1, ALK-5 and TGF-ßRII receptors. TSP-1 plasma level is increased in patients with peripheral artery disease (PAD) compared to the control population. In addition, the new vessels formed in PAD patients treated by local injection of BM-MNC express TSP-1. In murine models of Matrigel ®-plugs and hindlimb ischemia, TSP-1 induces a decrease in plugs vascularization and impaired revascularization of ischemic limb. In vitro, TSP-1 increases ECFC adhesion via an N-terminal dependent mechanism and reduces their angiogenic potential (proliferation and migration) via its binding to CD47 receptor, which activates the SDF-1/CXCR4 signaling pathway. PlGF plasma level is increased in ACS patients compared with the control population and stable angina patients and is also increased in patients undergoing cardiac surgery. PlGF-1 and -2 potentiate ECFC tubulogenesis in vitro via phosphorylation of the VEGFR1 receptor. This effect was abolished when the ECFC VEGFR1 is inhibited by RNA interference or by the chemical compound "4321". In addition this compound "4321" inhibits the vascularization of Matrigel ®-plugs, and revascularization of the ischemic limb in the hindlimb ischemia model.Conclusions: TGF-ß1 is involved in the IPF vascular remodeling through ECFC; TSP-1 is a potential biomarker of angiogenesis induced by ECFC in PAD; the inhibition of the PlGF/VEGFR1 pathway modulates ECFC tubulogenesis, cells involved in the formation of new vessels. We thus identified three proteins that modulate angiogenesis in three different pathological settings characterized by a vascular remodeling and where ECFC are involved in their pathophysiology. These three proteins therefore state as potential plasmatic biomarkers, modulating ECFC angiogenic properties and are able to influence their efficacy as a cell therapy product. These plasmatic biomarkers likely play a role in the homeostasis of those pathologies progress.

INTRODUÇÃO: Em pacientes com síndromes isquêmicas miocárdicas instáveis (SIMI), tanto a hiperatividade simpática quanto a resposta inflamatória exacerbada se associam a pior prognóstico. No entanto, ainda é desconhecido se existe alguma correlação entre esses dois marcadores de evolução desfavorável. OBJETIVOS: Correlacionar a atividade nervosa simpática muscular com marcadores inflamatórios nas fases precoce e tardia de pacientes portadores de SIMI. MÉTODOS: Pacientes hospitalizados com diagnóstico de SIMI e evolução favorável foram incluídos de forma prospectiva desde que apresentassem idade entre 18 e 65 anos e aterosclerose coronária comprovada por cinecoronariografia. Logo após a inclusão no estudo foram coletadas informações basais, e no quarto dia (± 1 dia) de internação os pacientes foram submetidos à avaliação da ANSM e coleta concomitante de amostra sanguínea para dosagem de proteína CReativa ultrassensível (PCR-us), interleucina-6 (IL6), e fosfolipase A2 associada à lipoproteína (Lp-PLA2). ANSM foi obtida pela técnica de microneurografia do nervo fibular. As medidas e respectivas análises de correlação foram repetidas em 1, 3 e 6 meses após a hospitalização. Correlações entre ANSM e marcadores inflamatórios foram analisadas por meio do teste de Pearson (variáveis de distribuição não-paramétrica foram transformadas logaritmicamente). Modelos de regressão linear múltipla foram criados para avaliar os efeitos independentes. RESULTADOS: Foram estudados 34 pacientes com idade média de 51,7±7,0 anos, sendo 79,4% do sexo masculino. A prevalência de hipertensão arterial foi de 64,7%, diabetes mellitus 8,8%, e doença arterial coronária prévia de 20,6%. A apresentação foi IAM com supradesnível de ST em 18 pacientes (52,9%), IAM sem supra de ST em 14 (41,2%) e angina instável em 02 pacientes (5,9%). Tanto ANSM quanto biomarcadores inflamatórios estavam elevados durante a fase aguda das SIMI e diminuíram ao longo do tempo. Na fase hospitalar, a mediana da PCR-us foi 17,75 (8,57; 40,15) mg/L, e IL-6 6,65 (4,45; 8,20) pg/ml, a Lp- PLA2 média foi 185,8 ± 52,2 nmol/min/ml, e ANSM média 64,2 ± 19,3 impulsos/100bpm. Após 6 meses, houve diminuição significativa de todas essas variáveis quando comparadas com a fase hospitalar. Entretanto, não houve correlação significativa entre a atividade simpática e qualquer dos marcadores inflamatórios analisados, em nenhuma das fases analisadas (p > 0,05), Por outro lado, ANSM se correlacionou independentemente com níveis de CKMB na fase aguda (p=0,027), e com fração de ejeção do VE na fase crônica (p=0,026). CONCLUSÃO: Apesar do aumento inicial dos níveis de marcadores inflamatórios e da atividade simpática em pacientes com SIMI, não houve correlação significativa entre esses parâmetros em nenhuma das fases analisadas, sugerindo que as alterações dessas variáveis estariam relacionadas a diferentes vias fisiopatológicas / INTRODUCTION: Previous publications have shown that both sympathetic hyperactivity and enhanced inflammatory response are associated with worse outcomes during acute coronary syndromes (ACS). However, little is known about the correlation between these two pathologic pathways. OBJECTIVE: To correlate muscle sympathetic nerve activity with inflammatory biomarkers in both acute and chronic phase of ACS. METHODS: Patients hospitalized with uncomplicated ACS were enrolled if they were 18-65 years old and have significant atherosclerosis. Baseline characteristics information were collected and at fourth day (± 1 day) of hospitalization they were submitted to muscle sympathetic nerve activity (MSNA) analysis and blood sample were collected for ultrasensitive C-reactive protein (usCRP), interleukin-6 (IL-6) and Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) measurements. MSNA was recorded directly from the peroneal nerve using the microneurography technique. Measurements were repeated at 1, 3 and 6 months after hospitalization. Correlations between MSNA and inflammatory markers and baseline characteristics were made using Pearson\'s test (nonnormally distributed variables were logarithmically transformed) and multivariate regression models were performed to assess the independent effects. RESULTS: Thirty-four patients were included, 79.4% male, mean age 51.7 (SD 7.0 years). The prevalence of hypertension was 64.7%, diabetes mellitus 8.8%, and previous coronary heart disease 20.6%. The ACS presentation was STEMI in 18 patients (52.9%), NSTEMI in 14 (41.2%) and UA in 02 patients (5.9%). Both MSNA and inflammatory markers were elevated during acute phase of ACS and decreased over time. In the hospitalization phase the median usCRP was 17.75 (8.57; 40.15) mg/L, median IL-6 6.65 (4.45; 8.20), mean Lp-PLA2 185.8 ± 52.2 nmol/min/mL, and mean MSNA 64.2 ± 19.3 bursts/100heart beats. All of these variables decreased significantly over 6 months when compared to in-hospital phase. However, there were no significant correlations between the sympathetic activity and inflammatory markers in any of the analyzed phases (p>0.05). After adjusted analyzes, MSNA was independently associated with CKMB levels at acute phase (p=0.027) and with left ventricular ejection fraction at 6 months (p=0.026). CONCLUSION: Despite the increased levels of inflammatory markers and sympathetic activity among patients with ACS, there was no correlation between these assessments, suggesting that although they may be present concomitantly during an ACS they might follow different pathological pathways

Contexte L’occlusion d’une artère du cœur cause un syndrome coronarien aigu (SCA) soit avec une élévation du segment ST (IAMEST) ou sans élévation du segment ST (1). Le traitement des patients avec un IAMEST requiert soit une intervention coronarienne d’urgence (ICP primaire) ou une thérapie fibrinolytique (FL). La thérapie FL peut être administrée soit dans un contexte pré-hospitalier (PHL) ou à l’hôpital. Une prise en charge précoce des patients avec SCA peut être améliorée par un simple indice de risque. Objectifs Les objectifs de cette thèse étaient de : 1) comparer l’ICP primaire et la thérapie FL (2); décrire plusieurs systèmes internationaux de PHL; (3) développer et valider un indice de risque simplifié pour une stratification précoce des patients avec SCA. Méthodes Nous complétons des méta-analyses, de type hiérarchique Bayésiennes portant sur l’effet de la randomisation, d’études randomisées et observationnelles; complétons également un sondage sur des systèmes internationaux de PHL; développons et validons un nouvel indice de risque pour ACS (le C-ACS). Résultats Dans les études observationnelles, l’ICP primaire, comparée à la thérapie FL, est associée à une plus grande réduction de la mortalité à court-terme; mais ce sans bénéfices concluants à long terme. La FL pré-hospitalière peut être administrée par des professionnels de la santé possédant diverses expertises. Le C-ACS a des bonnes propriétés discriminatoires et pourrait être utilisé dans la stratification des patients avec SCA. Conclusion Nous avons comblé plusieurs lacunes importantes au niveau de la connaissance actuelle. Cette thèse de doctorat contribuera à améliorer l’accès à des soins de qualité élevée pour les patients ayant un SCA. / Background Acute occlusion of an artery of the heart results in acute coronary syndromes (ACS), either with ST-segment elevation (STEMI) or without ST-segment elevation (1). STEMI requires urgent treatment to restore coronary artery flow either by primary percutaneous coronary intervention (PCI) or fibrinolytic therapy (FL) (2). Although several randomized controlled trials (RCTs) demonstrate the superiority of primary PCI in reducing mortality compared to FL (2), the benefit of primary PCI over FL remains uncertain in unselected “real-life” patients (3,4). FL can be administered either in the pre-hospital setting (i.e., pre-hospital FL (PHL)) or at the hospital. PHL is rarely available outside Europe (5,6). Insights into the organization of PHL systems of care may promote more widespread use of PHL. Risk stratification of ACS patients should be prompt to ensure timely PCI for high-risk patients and to avoid unnecessary intervention in low-risk patients (7). Despite the availability of numerous ACS risk scores, there is still no simple risk score that can be easily applied in the initial management of ACS patients (8). Objectives The objectives of this doctoral dissertation were to address these current knowledge gaps in the optimal management of ACS. The objectives were to: 1) evaluate the efficacy, effectiveness, and safety of primary PCI and FL, (2) describe the infrastructure, processes and outcomes of several international PHL systems; and (3) develop and validate a novel clinical risk score for early risk stratification of ACS patients. Methods To address these objectives, I completed Bayesian hierarchical random-effects meta-analyses of published RCTs and observational studies which compare primary PCI and FL in patients with STEMI. I undertook a survey of the infrastructure, processes and outcomes of PHL in several European and North American pre-hospital emergency systems. Finally, I developed and validated an ACS risk score called the Canadian ACS (C-ACS). Results Primary PCI was superior to FL in reducing short-term mortality in RCTs and observational studies. However, the long-term survival benefit of primary PCI was noted only in RCTs, and not in the observational studies. PHL can be effectively delivered by health care professionals with variable levels of expertise. The new risk score, C-ACS, has good discriminant properties for short- and long-term mortality in patients with ACS. Conclusions The first manuscript of this dissertation has been recognized as one of the most valuable recent publications in STEMI management and has contributed to reorganization of STEMI care in Ontario. The other two manuscripts in this dissertation provide practical information and tools for health professionals caring for patients with ACS. In summary, this doctoral dissertation has and will continue to contribute to improve access to high quality care for patients with ACS.

La première partie de cette thèse porte sur l'étude du no-reflow ou obstruction microvasculaire en IRM cardiaque. Dans une première étude, nous avons mesuré l'incidence du no-reflow dans une population de 25 patients pris en charge pour infarctus du myocarde sans sus-décalage du segment ST. Nous avons trouvé que 32% de ces patients présentaient un no-reflow et que la présence de no-reflow était associée à une taille d'infarctus significativement plus importante ainsi qu'une élévation plus importante des enzymes cardiaques. Dans une deuxième étude nous avons comparé la performance diagnostique du myocardial blush grade (MBG) pour le diagnostic du no-reflow avec l'IRM cardiaque sur les séquences de rehaussement tardif post-gadolinium. Cette étude a été réalisée dans une population de 39 patients pris en charge pour un premier épisode de STEMI. Nous avons trouvé que le MBG sous-estimait la présence de no-reflow à la phase aiguë de l'infarctus après reperfusion optimale en comparaison avec l'IRM. La deuxième partie de cette thèse concerne la quantification de l'infarctus du myocarde en IRM cardiaque de rehaussement tardif post-gadolinium. Nous avons comparé une technique d'évaluation semi-quantitative visuelle rapide avec la planimétrie manuelle classique sur une population de 103 patients pris en charge pour syndrome coronarien aigu. La taille de l'infarctus était évaluée par ces deux méthodes en IRM cardiaque réalisée 4 jours après admission. Nous avons trouvé une excellente corrélation et un bon niveau de concordance entre les deux méthodes d'évaluation de la taille d'infarctus, avec des temps de posttraitements beaucoup plus courts pour l'analyse visuelle rapide. Enfin, la troisième partie de cette thèse aborde le sujet de l'utilisation de l'IRM cardiaque comme outil de mesure dans les essais thérapeutiques sur la reperfusion myocardique. Nous avons utilisé l'IRM cardiaque pour évaluer l'efficacité de l'utilisation de la cyclosporine A à la phase aigüe de l'infarctus reperfusé et son effet sur remodelage ventriculaire à 6 mois. Dans cette étude 28 patients ont été étudiés en IRM cardiaque 5 jours et 6 mois après un infarctus du myocarde. Nous avons trouvé une persistance de la réduction significative de 23% de taille de l'infarctus à 6 mois dans le groupe traité par cyclosporine par rapport au groupe contrôle. Il n'y avait pas d'effet négatif de la cyclosporine A sur le processus de remodelage ventriculaire gauche / We assessed the presence and extent of microvascular obstruction (MVO) and its relationship with infarct size and left ventricular (LV) functional parameters after acute non-ST elevated myocardial infarction (NSTEMI). 25 patients with first acute NSTEMI underwent a complete cardio magnetic resonance (CMR) study 72 hours after admission. MO was detected in 32% of patients and was significantly associated with a larger infarct size. There were no significant difference between both groups for the LV functional parameters but patients with MO showed a higher troponin-I and CK release. We studied the relation between Myocardial Blush Grade (MBG) and gadolinium-enhanced CMR for the assessment of MVO in 39 patients with acute ST elevated myocardial infarction (STEMI) treated by primary PCI. No statistical relation was found between MBG and MVO extent at CMR (p=0.63). MBG underestimates MVO after an optimal revascularization in AMI compared to CMR.We compared the performance and post-processing time of a global visual scoring method to standard quantitative planimetry and we compared both methods to the peak values of myocardial biomarkers. 103 patients admitted with reperfused AMI to our intensive care unit had a complete CMR study 4±2 days after admission. There was an excellent correlation between quantitative planimetry and visual global scoring for the hyperenhancement extent’s measurement (r=0.94; y=1.093x+0.87; SEE=1.2; P<0.001) and there was also a good concordance between the two approaches with significantly shorter mean post-processing time for the visual scoring method. There was also significant levels of correlation between the enzymatic peak values and the visual global scoring method. The visual global scoring method allows a rapid and accurate assessment of the myocardial global delayed enhancement. This study examined the effect of a single dose of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and 6 months after AMI.28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. There was a persistent 23% reduction of the absolute infarct size at 6 months without any dementrial effect in the cyclosporine A group compared with the control group of patients. Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling

Contexte L’occlusion d’une artère du cœur cause un syndrome coronarien aigu (SCA) soit avec une élévation du segment ST (IAMEST) ou sans élévation du segment ST (1). Le traitement des patients avec un IAMEST requiert soit une intervention coronarienne d’urgence (ICP primaire) ou une thérapie fibrinolytique (FL). La thérapie FL peut être administrée soit dans un contexte pré-hospitalier (PHL) ou à l’hôpital. Une prise en charge précoce des patients avec SCA peut être améliorée par un simple indice de risque. Objectifs Les objectifs de cette thèse étaient de : 1) comparer l’ICP primaire et la thérapie FL (2); décrire plusieurs systèmes internationaux de PHL; (3) développer et valider un indice de risque simplifié pour une stratification précoce des patients avec SCA. Méthodes Nous complétons des méta-analyses, de type hiérarchique Bayésiennes portant sur l’effet de la randomisation, d’études randomisées et observationnelles; complétons également un sondage sur des systèmes internationaux de PHL; développons et validons un nouvel indice de risque pour ACS (le C-ACS). Résultats Dans les études observationnelles, l’ICP primaire, comparée à la thérapie FL, est associée à une plus grande réduction de la mortalité à court-terme; mais ce sans bénéfices concluants à long terme. La FL pré-hospitalière peut être administrée par des professionnels de la santé possédant diverses expertises. Le C-ACS a des bonnes propriétés discriminatoires et pourrait être utilisé dans la stratification des patients avec SCA. Conclusion Nous avons comblé plusieurs lacunes importantes au niveau de la connaissance actuelle. Cette thèse de doctorat contribuera à améliorer l’accès à des soins de qualité élevée pour les patients ayant un SCA. / Background Acute occlusion of an artery of the heart results in acute coronary syndromes (ACS), either with ST-segment elevation (STEMI) or without ST-segment elevation (1). STEMI requires urgent treatment to restore coronary artery flow either by primary percutaneous coronary intervention (PCI) or fibrinolytic therapy (FL) (2). Although several randomized controlled trials (RCTs) demonstrate the superiority of primary PCI in reducing mortality compared to FL (2), the benefit of primary PCI over FL remains uncertain in unselected “real-life” patients (3,4). FL can be administered either in the pre-hospital setting (i.e., pre-hospital FL (PHL)) or at the hospital. PHL is rarely available outside Europe (5,6). Insights into the organization of PHL systems of care may promote more widespread use of PHL. Risk stratification of ACS patients should be prompt to ensure timely PCI for high-risk patients and to avoid unnecessary intervention in low-risk patients (7). Despite the availability of numerous ACS risk scores, there is still no simple risk score that can be easily applied in the initial management of ACS patients (8). Objectives The objectives of this doctoral dissertation were to address these current knowledge gaps in the optimal management of ACS. The objectives were to: 1) evaluate the efficacy, effectiveness, and safety of primary PCI and FL, (2) describe the infrastructure, processes and outcomes of several international PHL systems; and (3) develop and validate a novel clinical risk score for early risk stratification of ACS patients. Methods To address these objectives, I completed Bayesian hierarchical random-effects meta-analyses of published RCTs and observational studies which compare primary PCI and FL in patients with STEMI. I undertook a survey of the infrastructure, processes and outcomes of PHL in several European and North American pre-hospital emergency systems. Finally, I developed and validated an ACS risk score called the Canadian ACS (C-ACS). Results Primary PCI was superior to FL in reducing short-term mortality in RCTs and observational studies. However, the long-term survival benefit of primary PCI was noted only in RCTs, and not in the observational studies. PHL can be effectively delivered by health care professionals with variable levels of expertise. The new risk score, C-ACS, has good discriminant properties for short- and long-term mortality in patients with ACS. Conclusions The first manuscript of this dissertation has been recognized as one of the most valuable recent publications in STEMI management and has contributed to reorganization of STEMI care in Ontario. The other two manuscripts in this dissertation provide practical information and tools for health professionals caring for patients with ACS. In summary, this doctoral dissertation has and will continue to contribute to improve access to high quality care for patients with ACS.