Bakgrund: Akut koronart syndrom (AKS) är ett samlingsnamn för akut hjärtinfarkt med ST-höjning (STEMI), akut hjärtinfarkt utan ST-höjning (NSTEMI) samt instabil angina pectoris (kärlkramp). AKS är ett livshotande tillstånd som behöver akutsjukvård utan fördröjning och är en av de vanligaste hälsoproblem globalt. Tidig identifiering av sjuksköterskan har en avgörande roll för behandlingsalternativen. Personcentrerad vård har även en central roll i mötet med patienter som drabbas av AKS samt har gynnsamma effekter genom förbättrad upplevelse av vården. Syfte: Syftet var att identifiera patienters symtom, riskfaktorer och upplevelse av att drabbas av akut koronart syndrom.  Metod: En litteraturöversikt med systematisk ansats valdes som metod för att få en sammanställning av redan befintlig forskning som är relevant för syftet. PubMed och CINAHL användes som databaser vid sökning av artiklar och totalt inkluderades 26 artiklar. Dataanalysen genomfördes med integrerad analys.  Resultat: I resultatet framkom två kategorier med 10 underkategorier. Första kategorin: Symtom relaterat till AKS. Det visade att bröstsmärta var det vanligaste symtomet men även att flertal andra symtom uppkom med stor variation och prodromala symtom vid AKS presenteras i stort. Symtom kopplat till kardiovaskulära riskfaktorer var även en viktig del i presentationen av resultatet samt att försöka tyda och hitta koppling till debuterade symtom. Andra kategorin: Upplevelser relaterat till AKS. Upplevelse av ångest, oro och rädsla av att dö i samband med AKS var inte ovanligt och många deltagare förstod inte att de upplevda symtomen var kopplat till AKS.  Slutsats: Det dominerande symtomet vid AKS var bröstsmärta, prodromal symtom presenterades dagar till månader innan insjuknande i AKS. Symtom hade även en stor individuell variation där debut, karaktär och varaktighet skiljde sig åt. Sjuksköterskan har en betydande roll i vården av patienter med AKS där personcentrerad vård har en central roll. / Background: Acute coronary syndrome (ACS) is a name for acute myocardial infarction with ST elevation (STEMI), acute myocardial infarction without ST elevation (NSTEMI) and unstable angina pectoris. ACS is a life-threatening condition that needs emergency medical attention without delay and is one of the most common health problems globally. Early identification by the nurse has a decisive role in the treatment options. Person- centred care has also a central role in the meeting with patients who suffer from ACS and the experience of the care.  Aim: The aim was to identify the patients' symptoms, risk factors and experience of suffering from acute coronary syndrome.  Methods: A literature review with systematic approach was chosen. PubMed and CINAHL were databases used when searching for articles and a total of 26 articles were included. The data analysis was carried out using integrated analysis.  Results: The results revealed two categories with 10 subcategories. First category: Symptoms related to ACS. Chest pain was the most common symptom, but other symptoms appeared with great variation and prodromal symptoms in ACS were presented widely. Symptoms linked to cardiovascular risk factors were an important part of the presentation of the results and trying to decipher and find a connection to the first symptoms. Second category: Experiences related to ACS. Experiencing anxiety, worry and fear of dying associated with ACS was not uncommon and many participants did not understand that the symptoms were linked to ACS. Conclusion: The predominant symptom was chest pain, prodromal symptoms were presented days to months before the onset of ACS. Symptoms also had a large individual variation where onset, character and duration differed. The nurse has a significant role in the care of patients with ACS where person- centred care has a central role.

Ischemisk hjärtsjukdom där akut koronart syndrom ingår är den främsta dödsorsaken i världen och är en stor utmaning inom global hälsa och sjukvård. Sekundärprevention är en väsentlig del av behandlingen vid akut koronart syndrom och innefattar både farmakologisk behandling samt livsstilsåtgärder. För patienter med akut koronart syndrom utgör ohälsosamma levnadsvanor en större risk för återinsjuknande, därför är det viktigt att hälso- och sjukvården stödjer dem till förbättrade levnadsvanor.  Syftet var att belysa faktorer som påverkar livsstilsförändringar hos patienter efter att ha insjuknat i ett akut koronart syndrom.  En allmän litteraturöversikt med systematisk sökmetod valdes som metod för att besvara syftet. Sökningar i två databaser samt manuell sökning utfördes. Femton vetenskapliga artiklar publicerade mellan 2014-2020 inkluderades efter kvalitetsgranskning. En integrerad analys utfördes, huvudkategorier och underkategorier identifierades.  I resultatet framkom fyra huvudkategorier och åtta underkategorier som kunde vara både främjande och hindrande för att genomföra livsstilsförändring. Där huvudkategorierna utgjordes av sjukdomsinsikt, självinsikt, hälsopåverkan samt social påverkan. Underkategorierna var förstå allvaret, kunskap, den egna viljan, tro på sin egen förmåga, kroppslig betydelse, känslomässig innebörd, socialt stöd samt socioekonomins styrande. De mest framträdande underkategorierna var kunskap, socialt stöd samt tro på sin egen förmåga.  Slutsatsen är att hälso- och sjukvården behöver bli bättre på att ge en konkret och individanpassad information till patienter med akut koronart syndrom för att möjliggöra livsstilsförändringar. Anhöriga bör involveras mer i vården för att kunna vara ett stöd för att genomföra livsstilsförändringar. För att patienten ska tro på sin förmåga är det viktigt att utgå från patientens resurser och sätta realistiska mål. Vården behöver bli mer personcentrerad för att ge patienten bättre förutsättningar att lyckas med livsstilsförändringar. / Ischemic heart disease, including acute coronary syndrome, is the leading cause of death worldwide and represents a significant challenge to global health and healthcare. Secondary prevention, consisting of pharmacological treatment and lifestyle changes, is an essential component of acute coronary syndrome treatment. Unhealthy lifestyle habits present a major risk for recurrent illness in acute coronary syndrome patients. Therefore, it is important for healthcare providers to support patients in improving their lifestyle habits. The aim of this study was to highlight the factors that influence lifestyle changes in acute coronary syndrome patients. A literature review with a systematic search method was selected to answer the aim. The article searches in two databases and a manual search were conducted. Fifteen articles published between 2014-2020 were included after quality review. An integrated analysis was conducted, main categories and subcategories were identified. In the result four main categories and eight subcategories of factors that could either facilitate or hinder lifestyle changes appeared. The main categories were disease awareness, selfawareness, health impact and social impact. The subcategories were realising the seriousness, knowledge, the own will, belief in one's ability, physical meaning, emotional meaning, social support and the impact of the socioeconomy. The most prominent subcategories were knowledge, social support and belief in one’s ability. In conclusion, healthcare providers need to offer more personalised information to acute coronary syndrome patients to enable lifestyle changes. Family members should be more involved in the care process to be able to support lifestyle changes. For the patient to believe in their own ability is it important to focus on their resources and setting realistic goals. The healthcare providers need to be more person-centred to provide the patient better conditions to succeed in making lifestyle changes.

(1) Background: Patients with severe chronic kidney disease (CKD G4–G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75–0.87 versus 0.85, 0.80–0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

Bakgrund: Akut Koronart Syndrom (AKS) är ett samlingsnamn för tre olika kliniska tillstånd som förorsakas av en ruptur på ett ateromatösa plack vilket leder till en trombosbildning som okluderar hjärtats kranskärl helt eller delvis. Den äldre populationen utgör en stor andel av patienterna som drabbas av AKS sjukdom. AKS är en diagnos som påverkar patienten både fysiskt och psykiskt och Akutsjuksköterskor ska bemöta och vårda dessa patienter under hela dygnets timmar oavsett om det är ett stort eller lågt inflöde på akutmottagningen. Enligt statistik från Socialstyrelsen ökar antalet patienter på akutmottagningarna och tiden för den erbjudna vården minskar vilket gör att vårdbehov måste tidigt kunna identifieras för att kunna sätta in rätt omvårdnadsåtgärder för dessa. Syfte:  Att belysa upplevelser av att som patient bli vårdad för akut koronart syndrom på akutmottagning.   Metod: Metoden som valts är en systematisk integrativ litteraturöversikt. Datainsamlingen har gjorts med hjälp av den femstegsprocess som beskrivits av Oermann och Knafl (2021) där analysfasen bytts ut mot en tematisk innehållsanalys enligt Braun och Clarkes (2008).  Resultat: Resultatet presenteras som tre övergripande teman (Fysiska upplevelser, Psykiska upplevelser och Vårdupplevelser) respektive åtta subteman (Smärtlindring vid koronar bröstsmärta. Rädsla, ångest och en osäkerhet över situationen. Upplevelse av hotad hälsa. Utsatthet vid hög belastning på akutmottagningen. Effekter av psykisk belastning vid AKS. Orsaker till upplevelsen av god vård. Bristande information och kommunikation. Självbestämmande och beslutstagande under vården.).  Slutsatser: Patienter som vårdas för AKS på akutmottagning har komplexa upplevelser med stor variation som alla behöver sin vård där akutsjuksköterskans kompetens är av stor vikt. Behov för information beskrevs i stora delar av resultatet. / Background: Acute coronary syndrome (ACS) is a collective name for three different clinical conditions which are caused by a rupture on a atherosclerothic plaque. This situation leads to the creation of a thrombos that occludes a coronary artery in the heart partially or completely. The older generation makes up for a greater part of the patients treated for ACS. ACS is a condition that affects the patient both physically and psychologically and emergency nurses care for these patients during every hour of the day no matter if the patient flow is high or low at the emergency department. According to statistics from Socialstyrelsen, the number of patients at the emergency department is increasing and the time for care decreasing which further notes the importance of being able to early identify care-needs to be able to provide the correct care for these.    Aim: To enlighten the experiences of patients getting care for acute coronary syndrome at the emergency department  Method: The method that was chosen was a systematic integrative literature review.  Datacollection has been done with the assistance of the five-step process described by Oermann och Knafl (2021) where the data analytic step has been replaced by a thematic content analysis described by Braun och Clarkes (2008).  Results: The result section presents three general themes (Physical experiences, Psychological experiences and care-experiences) together with eight sub-themes (Painrelief during coronary chest pain.  Fear, anxiety and uncertainty over the situation. An experience of threat towards health. Vulnerability during crowding at the emergency department. Effects of psychological burden during ACS. Reasons for experiencing good care. Lack of information and communication. Self-determination and decisionmaking during care.). Conclusions: Patients receiving care for AKS at the emergency department inhibit complex experiences with great variation which all need their own personal caring where the competence of the emergency nurse is of great importance. A need for information was described in greater parts of the result.

BACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Στο συγκεκριμένο ερευνητικό πρωτόκολλο μελετήθηκαν οι πιθανές ένοχες βλάβες σε φλεβικά μοσχεύματα ασθενών με οξέα στεφανιαία σύνδρομα με τη μέθοδο της Οπτικής Συνεκτικής Τομογραφίας (OCT). • Οι αθηροσκληρωτικές βλάβες των φλεβικών μοσχευμάτων έχουν μελετηθεί in vivo με τη μέθοδο της αγγειοσκόπησης και της ενδαγγειακής υπερηχογραφίας (IVUS). Απεναντίας, η απεικόνιση των μοσχευμάτων με τη μέθοδο της OCT, η οποία χαρακτηρίζεται από σημαντικά μεγαλύτερη διακριτική ικανότητα σε σχέση με το IVUS και βελτιωμένη διεισδυτική ικανότητα συγκρινόμενη με την αγγειοσκόπηση, δεν έχει μελετηθεί συστηματικά. • Μέθοδος: Η απεικόνιση των ένοχων βλαβών των μοσχευμάτων πραγματοποιήθηκε, κατόπιν αγγειογραφίας τους, με τη μέθοδο χωρίς απόφραξη της OCT σε ασθενείς με ασταθή στηθάγχη (UA), έμφραγμα μυοκαρδίου με ανάσπαση του διαστήματος ST (STEMI) και έμφραγμα μυοκαρδίου χωρίς ανάσπαση του διαστήματος ST (non-STEMI). Ο ινώδης ιστός, ο λιπώδης ιστός, οι εναποθέσεις ασβεστίου, ο θρόμβος και η ρήξη της πλάκας ορίστηκαν σύμφωνα με τα κριτήρια απεικόνισης στοιχείων για την OCT, όπως περιγράφηκαν και στο γενικό μέρος. • Αποτελέσματα: Απεικονίστηκαν 28 φλεβικά μοσχεύματα (μέσης ηλικίας 14.6 ετών) σε 26 ασθενείς. Οι βλάβες χαρακτηρίστηκαν ως σύμπλοκες αγγειογραφικά σε ποσοστό 96.4%, ενώ εμφάνιζαν εξέλκωση σε ποσοστό 32.1% και θρόμβο σε ποσοστό 21.4%. Η OCT αποκάλυψε ινολιπώδη σύσταση σε όλες τις βλάβες, εναπόθεση ασβεστίου στο 32.1% των βλαβών, ρήξη πλάκας σε ποσοστό 60.7% και παρουσία θρόμβου σε ποσοστό 46.4%. Η παρουσία του θρόμβου ήταν προοδευτικά συχνότερη ανάμεσα στις ομάδες ανάλογα με το κλινικό τους σύνδρομο (UA έως STEMI, p=0.003, UA έναντι εμφράγματος μυοκαρδίου, p=0.006). Η λεπτή ινώδης κάψα καταγράφηκε οριακά συχνότερα στους ασθενείς με οξύ έμφραγμα μυοκαρδίου (UA έναντι εμφράγματος μυοκαρδίου, p=0.06, STEMI 100% έναντι non-STEMI 53.3% έναντι UA 20%, p=0.03). Βλάβες με στοιχεία ευθρυπτότητας, όπως απεικονίζονταν στην OCT παρουσιάζονταν σε ποσοστό 67.9%, χωρίς όμως συσχέτιση με την κλινική εικόνα. • Συμπέρασμα: Οι ένοχες βλάβες φλεβικών μοσχευμάτων μεγάλης ηλικίας ασθενών με οξέα στεφανιαία σύνδρομα, όπως αυτές απεικονίζονται στην OCT, εμφανίζουν ινολιπώδη σύσταση, σχετικά λεπτή ινώδη κάψα, ρήξη πλάκας και θρόμβο που συσχετίζονται με το κλινικό φάσμα των οξέων στεφανιαίων συνδρόμων. Αυτά οδηγούν στο συμπέρασμα ότι οι ίδιοι μηχανισμοί αθηροσκλήρωσης που οδηγούν στην εμφάνιση οξέων στεφανιαίων συνδρόμων στα γηγενή στεφανιαία αγγεία, είναι πιθανόν να ενέχονται και στην πρόκληση οξέων στεφανιαίων συνδρόμων λόγω αποτυχίας των φλεβικών μοσχευμάτων. / This study sought to assess, with optical coherence tomography (OCT), presumably culprit atherosclerotic lesions of saphenous vein grafts (SVGs) in patients with acute coronary syndromes (ACS). Background: Atherosclerotic lesions of SVGs have been studied in vivo with angioscopy and intravascular ultrasound. However, imaging with OCT, which has a higher resolution than intravascular ultrasound and better penetration than angioscopy, has not been conducted systematically. Methods Using a nonocclusive OCT technique, we performed angiography and OCT of culprit SVG lesions in patients with unstable angina (UA), ST-segment elevation myocardial infarction (STEMI), and non-STEMI. Fibrous and fatty tissue, calcification, thrombus, and plaque rupture were defined according to OCT objective criteria. Results: Twenty-eight SVGs (average age 14.6 years) in 26 patients were imaged. Lesions on angiography were complex (96.4%), with ulceration in 32.1% and thrombus in 21.4%. OCT disclosed a fibrofatty composition in all lesions, calcification in 32.1%, plaque rupture in 60.7%, and thrombus in 46.4%. Thrombus was progressively more frequent across groups (UA to STEMI, p=0.003; UA vs. myocardial infarction, p=0.006). A thin fibrous cap was marginally more frequent in myocardial infarction patients (UA vs. myocardial infarction, p=0.06; STEMI 100% vs. non-STEMI 53.3% vs. UA 20%, p=0.03). OCT features of friability were present in 67.9% of SVGs not correlating with clinical presentation. Conclusions: OCT of culprit lesions of old SVGs in patients with ACS demonstrates fibrofatty composition, relatively thin fibrous cap, plaque rupture, and thrombus, which correlate with the clinical spectrum of ACS. This suggests that similar mechanisms with native vessels’ atherosclerosis may be involved in SVG-related ACS.

Les traitements antiplaquettaires représentent la pierre angulaire du traitement des patients admis pour syndrome coronaire aigu et/ou bénéficiant d’une angioplastie coronaire. L’association d’une bithérapie antiplaquettaire par aspirine et clopidogrel représente aujourd’hui le gold standard dans la prise en charge de ces patients. Malgré l’efficacité de ces molécules, les récidives d’événements ischémiques restent fréquentes, de l’ordre de 10% dans l’année suivant l’épisode clinique, et le concept de mauvaise réponse biologique au clopidogrel a été proposé comme une des hypothèses à ces récidives. En effet, de nombreuses études biologiques ont fait état d’une large variabilité interindividuelle de réponse biologique au clopidogrel, avec environ 20 à 30% des patients présentant un niveau d’inhibition plaquettaire sous traitement insuffisant. Dans ces travaux, cette réponse biologique a été évaluée par différents tests plaquettaires, les plus utilisés étant les tests de laboratoires (test d’agrégation et test VASP) et le test ‘minute’ Verify Now. Les mécanismes expliquant cette variabilité de réponse restent imparfaitement connus, mais des facteurs ont pu être clairement identifiés : polymorphismes génétiques, interactions médicamenteuses et facteurs cliniques comme le poids ou le diabète. Plus récemment, cette entité biologique a pu être reliée au pronostic clinique de nos patients avec un pronostic ischémique péjoratif chez les patients identifiés biologiquement comme mauvais répondeurs, et à l’inverse, un risque de complications hémorragiques accru chez les patients présentant la plus forte inhibition plaquettaire sous traitement. Devant ces constations, des solutions ont été proposées pour lutter contre cette mauvaise réponse comme une augmentation des doses de clopidogrel ou l’utilisation d’inhibiteurs de la glycoprotéine IIbIIIa. Ces stratégies ont apportés des résultats encourageants dans des études monocentriques, d’assez faibles effectifs. Toutefois, l’individualisation du traitement antiplaquettaire sur la base de ces tests n’est pas d’actualité, et devra attendre les résultats de larges essais multicentriques, actuellement en cours. Dans ce cadre, l’arrivée de nouveaux inhibiteurs de la voie de l’ADP, comme le prasugrel et le ticagrelor, pourront représenter des alternatives intéressantes chez ces patients à haut risque de récidive ischémique. / Antiplatelet therapy is the cornerstone therapy for patients admitted for acute coronary syndrome and/or undergoing percutaneous coronary intervention. Dual antiplatelet therapy with aspirin and clopidogrel is now the gold standard therapy for these patients. In spite of this effective association, recurrent events still occur and low response to clopidogrel has been proposed as one of the responsible factors. Indeed, numerous biological studies have described a broad interindividual variability of platelet response to clopidogrel, assessed with various platelet function tests such as light transmittance aggregometry, VASP phosphorylation index and the bed-side Verify Now assay. Mechanisms underlying this variability of response remain unclear and probably multifactorial, but factors have been clearly identified: genetic polymorphisms, medications interactions and clinical factors (diabetes, weight…). More recently, the clinical impact of this biological entity has been described with worse clinical outcome in patients non responder to clopidogrel, presenting a higher rate of recurrent ischemic events, including stent thrombosis. Meanwhile, a higher rate of bleeding complications have been found in patients with the highest on-treatment platelet inhibition, suggesting a ‘soft’ therapeutic window to avoid both types of recurrent events. Thus, several strategies have been proposed to overcome this poor response to the drug such as higher clopidogrel doses or additional GPIIbIIIa inhibitors in non responders. However, benefit of tailored therapy has been yet established in properly sized, prospective, randomized trial, which are currently ongoing. New comers in the class of P2Y12 inhibitors, prasugrel and ticagrelor, might represent a good alternative for these high-risk patients.

Les efforts investis pour diminuer les risques de développer un infarctus du myocarde sont nombreux. Aujourd’hui les médecins prennent connaissance des divers facteurs de risque connus prédisposant aux syndromes coronariens aigus (SCA) dans le but de prendre en charge les patients «à risque» [1]. Bien que le suivi rigoureux et le contrôle de certains facteurs de risque modifiables aient permis une meilleure gestion des cas de SCA, les cas d’infarctus persistent de manière encore trop fréquente dans le monde. Puisque d’importantes études ont démontré que les SCA pouvaient survenir sans même la présence des facteurs de risque conventionnels [2, 3], les chercheurs se sont penchés sur un autre mécanisme potentiellement responsable de l’avènement des SCA : l’inflammation. L’inflammation joue un rôle prépondérant dans l’initiation, la progression et les complications de l’athérosclérose [4, 5] mais aussi dans les situations post-infarctus [6, 7]. Au cours des dernières années, le contrôle du processus inflammatoire est devenu une cible de choix dans la prévention et le traitement des SCA. Cependant, malgré les efforts investis, aucun de ces traitements ne s’est avéré pleinement efficace dans l’atteinte du but ultime visé par une diminution de l’inflammation : la diminution de la mortalité. Le complément est un système complexe reconnu principalement pour son rôle primordial dans l’immunité [2]. Cependant, lorsqu’il est activé de manière inappropriée ou excessive, il peut être à l’origine de nombreux dommages cellulaires caractéristiques de plusieurs pathologies inflammatoires dont font partie les complications de l’athérosclérose et des événements post-infarctus. Le travail effectué dans le cadre de mon doctorat vise à établir les rôles physiopathologiques du complément dans les interactions de l’axe thrombose-inflammation caractéristiques des SCA dans le but ultime d’identifier des cibles thérapeutiques permettant le développement de nouvelles approches pour la prévention et le traitement de ces pathologies. Les principaux résultats obtenus durant mon cursus suggèrent d’abord que la voie alterne du complément peut représenter une cible thérapeutique de choix dans les maladies coronariennes aiguës puisque l’activation terminale du complément semble y être principalement causée par l’activation du cette voie. De faibles niveaux sériques de MBL (mannan-binding lectin) et une activation terminale négligeable du complément caractérisent plutôt la maladie coronarienne stable. En comparant l’activité relative de chacune des voies du complément chez des cohortes de patients traités ou non par un anticorps spécifique à la protéine C5 du complément (pexelizumab), un second volet démontre quant à lui qu’une inhibition de l’activation du C5 n’a pas d’effet bénéfique majeur sur l’inhibition de la formation du complexe sC5b-9 ou sur les événements cliniques subséquents. Par conséquent, nous avons exploré, à l’aide d’un modèle in vitro, les raisons de l’inefficacité du traitement. Les résultats révèlent que le blocage du C5 avec le pexelizumab inhibe la production de l’anaphylatoxine pro-inflammatoire C5a et du complexe terminal du complément sans toutefois avoir d’effet sur l’apoptose des cellules endothéliales produites induite par le sérum des patients atteints de STEMI. Finalement, une autre section stipule que l’atorvastatine diminue l’activation du complément induite par les plaquettes sanguines chez des patients hypercholestérolémiques, mettant en évidence l’importance du rôle de cette statine dans la réduction des effets délétères de l’activation du système du complément médié par les plaquettes. Ensemble, l’étude du rôle spécifique des différentes voies d’activation du complément dans des contextes pathologiques variés, l’analyse des effets d’une inhibition spécifique de la protéine C5 du complément dans la progression des SCA et la mise en évidence des interactions entre l’activation du complément et les plaquettes activées ont contribué au développement d’une meilleure connaissance des rôles physiopathologiques du complément dans la progression de la maladie coronarienne. / Many efforts have been made in lowering the risk of myocardial infarction in the general population. Most clinicians are knowledgeable of the several identified risk factors leading to the development of acute coronary syndromes (ACS), and in turn, insure a better follow-up for “at risk” patients [1]. Despite the fact that intensive efforts in controlling modifiable risk factors have led to a better management of new cases of ACS, myocardial infarction and its deleterious consequences are still a world plague. Because it as been shown that ACS can occur without the presence of traditional risk factors [3, 4], researchers have been interested in modifying new ACS biological pathways such as inflammation. Inflammation plays a key role in the initiation, progression, and complications of atherosclerosis [5, 6], but also in post-infarction situations [7, 8]. In the past years, inflammation markers have become important targets for the prevention and treatment of ACS. Despite intensive efforts, none of the yet tested drug was found to be effective in decreasing mortality. The complement system is mainly known for its fundamental role in innate and adaptive immunity [2]. However, excessive activation of the complement can lead to a significant number of deleterious effects such as inflammation, apoptosis, necrosis and cell lysis. Earlier findings have shown that complement is extensively activated in atherosclerotic lesions, particularly in vulnerable and ruptured plaques. The objective of my doctoral project was to establish the pathophysiological roles of complement in the axis inflammation-thrombosis of ACS with the ultimate goal of identifying new therapeutic targets leading to the development of new drugs for the prevention and treatment of these diseases. The main results obtained first suggest that the complement alternative pathway represents a potential therapeutic target in acute coronary disease since terminal complement activation occurs mainly by this specific pathway. Low MBL levels (mannan-binding lectin) in serum and negligible terminal complement activation rather characterize stable coronary artery disease. By comparing the relative activity of each pathway of the complement in patients treated or not by an antibody specific to the C5 protein of the complement (pexelizumab), other results show that an inhibition of C5 activation does not have a major beneficial effect on the inhibition of the sC5b-9 complex expression or on the subsequent clinical events. Consequently, we explored, using an in vitro model of endothelial cells, the reasons of this inefficiency. This work reveals that C5 inhibition by pexelizumab inhibits the production of the pro-inflammatory anaphylatoxin C5a and of the terminal complement complex without, however, effecting endothelial cell apoptosis induced by the serum of patients with STEMI. Finally, another section stipulates that atorvastatin decreases platelet-induced complement activation in hypercholesterolemic patients, highlighting the importance of statins in the reduction of the deleterious effects of platelets-induced complement activation. All together, the study of the specific role of the various pathways of complement activation in different pathological contexts, the analysis of the effects of a specific inhibition of the C5 complement protein in the progression of ACS and the highlighting of the interactions between complement and platelet activation contribute to the development of a better knowledge of the pathophysiological roles of the complement system in ACS.

Introdução: O tratamento da Síndrome Coronária Aguda (SCA) sem supradesnivelamento do segmento ST (SSST) sofreu grandes avanços nos últimos 20 anos, com a introdução de novos medicamentos e intervenções invasivas, que reduziram significativamente os eventos clínicos graves como morte e re(infarto), em curto, médio e longo prazos, a despeito dessa entidade ainda representar uma alta taxa de mortalidade no mundo ocidental. Entre os medicamentos, os inibidores da enzima conversora da angiotensina (IECA) tiveram um papel fundamental, demonstrando redução desses eventos em pacientes com alto risco cardiovascular. Nesse período, as troponinas cardíacas consolidaram-se como os biomarcadores de necrose miocárdica de escolha para o diagnóstico e avaliação prognóstica nesses pacientes, devido às suas altas sensibilidade e especificidade. Objetivo: Determinar o efeito do uso prévio de IECA na mensuração da troponina I cardíaca em pacientes com SCASSST, e avaliar os desfechos clínicos em até 180 dias. Casuística e métodos: Estudo prospectivo, observacional, em um único centro de cardiologia, realizado entre 8 de setembro de 2009 e 10 de outubro de 2010, com 457 pacientes, consecutivamente internados no Pronto-Socorro com SCASSST. Os pacientes deveriam apresentar sintomas isquêmicos agudos, nas últimas 48 horas. Foram excluídos os que apresentassem elevação do segmento ST, ou qualquer alteração confundidora ao ECG, como ritmo de marcapasso, bloqueio de ramo esquerdo ou fibrilação atrial. Foram selecionados para análise exploratória, dados de história clínica, exame físico, eletrocardiográficos e laboratoriais, com ênfase à troponina I cardíaca. As variáveis com nível de significância menor que 10% nesta análise, foram submetidas a um modelo de regressão logística múltipla. Resultados: Na população estudada, observou-se que a idade média era de 62,1 anos (DP=11,04) e 291 pacientes (63,7%) do gênero masculino. Fatores de risco como hipertensão arterial sistêmica (85,3%) e dislipidemia (75,9%) foram os mais prevalentes, além da presença de SCA prévia em 275 (60,2%) pacientes; com 49,5% dos pacientes já submetidos a alguma revascularização prévia (Intervenção Coronária Percutânea(ICP) ou Revascularização do Miocárdio (RM), além de 35,0% de diabéticos. Na avaliação de eventos em 180 dias, ocorreram 28 óbitos (6,1%): 11 por choque cardiogênico, 8 por infarto agudo do miocárdio, 3 por choque séptico, além de outras causas. Foi elaborado um modelo de análise estatística, onde foram analisadas as variáveis que interferiam com a liberação de troponina. Por esse modelo, observou-se que cada 1mg/dL a mais na glicemia de admissão, aumentava a chance da troponina ser maior que 0,5 ng/mL em 0,8% (p=0,0034);o uso de IECA previamente à internação reduzia a chance da troponina ser maior que 0,5 ng/mL em 40,6% (p=0,0482) e a presença de infradesnivelamento do segmento ST igual ou maior a 0,5 mm, em uma ou mais derivações, aumentava a chance da troponina ser maior que 0,5 ng/mL em 2,6 vezes (p=0,0016). A estatística C para este modelo foi de 0,77. Conclusão: Os dados apresentados nesta pesquisa em um centro terciário de cardiologia, mostraram uma correlação inequívoca entre o uso de IECA e a redução do marcador de necrose miocárdica troponina I cardíaca, utilizado como medida qualitativa.Porém, ainda não há dados disponíveis para se afirmar que esta redução poderia levar a um número menor de eventos clínicos graves como morte e re(infarto), no período de 180 dias. / Introduction: The last 20 years have seen great advances in the management of non-ST elevation acute coronary syndrome (NSTE-ACS). The introduction of novel drugs and invasive interventions significantly reduced major clinical events such as death and (re)infarction in the short, medium and long term. Yet, mortality rates remain high in the Western world. Among these drugs, angiotensin-converting enzyme (ACE) inhibitors have played a critical role in reducing these events in patients at high cardiovascular risk. In the meantime, cardiac troponins became firmly established as the myocardial necrosis biomarkers of choice to make the diagnosis and prognosis of these patients, due to their high sensitivity and specificity. Objective: To determine the effect of prior use of ECA inhibitors in serum levels of cardiac troponin I in patients with NSTE-ACS and to assess the clinical outcomes up to 180 days. Patients and methods: This was a prospective, observational study conducted at a single tertiary cardiology center from September 8, 2009 to October 10, 2010 with 457 consecutive patients admitted to the emergency department for NSTE-ACS. Only patients with acute ischemic symptoms within the past 48 hours were included in the study. Those with ST-segment elevation or any confounding ECG factor, such as pacemaker rhythm, left bundle branch block, or atrial fibrillation, were excluded. Study population underwent exploratory analysis, clinical history, physical examination, ECG, and laboratory tests, particularly for cardiac troponin I. Variables with a significance level less then 10% were entered into a multiple logistic regression model. Results: The mean age of the study population was 62.1 years (SD = 11.04), and 291 patients (63.7%) were male. Risk factors such as hypertension (85.3%) and dyslipidemia (75.9%) were the most prevalent, followed by previous ACS in 275 (60.2%) patients; 49.5% of the patients had already undergone previous revascularization procedures (either percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]). Diabetes was present in 35% of the patients. At the 180-day assessment, 28 patients (6.1%) had died: 11 as a result of cardiogenic shock, 8 of acute myocardial infarction, and 3 of septic shock, among other causes. In this study, a statistical model was developed to determine which variables affected troponin release. This model showed that each 1mg/dL increase in admission blood glucose increased the likelihood of troponin being higher than 0.5 ng/mL by 0.8% (p=0.0034); the use of ACE inhibitors prior to admission reduced the likelihood of troponin being higher than 0.5 ng/mL by 40.6% (p=0.0482), and the presence of ST-segment depression >= 0.5 mm in one or more ECG leads increased 2.6 times the likelihood of troponin being higher than 0.5 ng/mL (p=0.0016). The C-statistic for this model was 0.77. Conclusion: The data from this study conducted at a tertiary cardiology center show an unequivocal relationship between the use of ACE inhibitors and decreased levels of cardiac troponin I, a biomarker of myocardial necrosis used as a qualitative measure. However, there is no available data to determine whether or not this decrease would result in a lower number of major clinical events, such as death and re(infarction) within 180 days.

Estimativas nacionais e internacionais indicam que a síndrome coronariana aguda é uma das principais causas de internação hospitalar e óbito. A maioria desses pacientes tem diagnóstico de síndrome coronariana aguda sem supradesnivelamento do segmento ST (SCASSSST) e possui amplo espectro de gravidade, que varia de acordo com características clínicas e laboratoriais. A estratificação de risco é essencial para auxiliar na decisão clínica, discriminando quais pacientes se beneficiam de estratégias mais agressivas. Os escores TIMI e GRACE são os mais utilizados e com valor prognóstico estabelecido por estudos de coorte prospectiva. O strain longitudinal bidimensional (S2DL) permite a quantificação da deformidade miocárdica por meio do rastreamento de \"marcas acústicas\" naturais do músculo cardíaco pelo ultrassom, apresentando valores reduzidos na presença de isquemia miocárdica. O objetivo principal desse trabalho foi identificar, por meio do S2DL do ventrículo esquerdo, quais pacientes com SCASSSST apresentam estenose coronariana maior ou igual a 70%. Os objetivos secundários foram: 1) Identificar a porcentagem de pacientes categorizados como de baixo risco e moderado risco, segundo os escores TIMI e GRACE, que apresentaram estenose coronária maior ou igual a 70%; 2) Determinar um valor de corte do S2DL e número mínimo de segmentos adjacentes acometidos que se correlacionem com o território irrigado pela coronária comprometida (com estenose maior ou igual a 70%) nos pacientes portadores de SCASSSST. Total de 100 pacientes com Idade de 60±11,4, 62% do sexo masculino e predomínio de pacientes (p) de baixo e moderado risco cardiovascular (80% pelo escore TIMI e 99% pelo escore GRACE). Divididos em grupo A (34p) com estenose coronária < 70% e grupo B (66p) com estenose coronária >=70%. Os escores clínicos foram maiores no grupo B (TIMI 3,59±1,4; p=0,008 e GRACE 88,7±24,18; p=0,040). O strain longitudinal global (SLG) permitiu identificar os pacientes com estenose coronária >=70% (AUC=0,72, sensibilidade=50%, especificidade=90%, valor preditivo positivo= 75,1% e valor preditivo negativo=74,9%). No grupo B, 72,8% e 98,5% foram categorizados como de baixo e moderado risco pelos escores TIMI e GRACE, respectivamente. O strain longitudinal segmentar (SLS) permitiu identificar a coronária culpada pelo evento isquêmico, com valor de cut-off e número mínimo de segmentos estimados em: -14 e 4 segmentos para coronária descendente anterior, -16 e 3 segmentos para a coronária circunflexa e coronária direita. Concluímos que o SLG mostrou ser acurado em discriminar pacientes com estenose coronária grave, mesmo naqueles com escore de risco baixo e moderado pelos escores TIMI e GRACE. O SLS permite estimar a área de miocárdio isquêmico por meio do número de segmentos com deformidade alterada, e conhecer a coronária culpada mais provável. / National and international estimates indicate that acute coronary syndrome is one of the major causes of hospitalization and death. Most of these patients have a diagnosis of non-ST-elevation acute coronary syndrome (NSTE-ACS) and have wide spectrum of severity. Risk stratification is essential to assist in clinical decision. The TIMI and GRACE risk scores are the most used and the prognostic values were established by prospective cohort study. Myocardial strain by speckle tracking is a technique based on widely available two-dimensional grayscale echocardiography, enabling the accurate evaluation of global and regional myocardial function, and it is has been shown to be sensitive to abnormalities caused by ischemia. The main objective of this study was to identify, through global longitudinal strain, whose patients (p) with NSTE-ACS had >= 70 % coronary stenosis. The secondary objectives were: 1) Identify the percentage of p categorized as low or moderate risk according to the TIMI and GRACE risk scores , who showed coronary stenosis >= 70 % ; 2) Determine a cutoff value of regional strain and the minimum number of segments allowing the identification of the culprit coronary artery in p with NSTE-ACS. Hundred (p) with diagnosis NSTE-ACS were stratified according to TIMI and GRACE risk scores, and all p underwent coronary angiography. Global longitudinal strain (GLS) and territorial strain (TS) were calculated. Age 60 ± 11.4, 62% male. Majority were low and moderate cardiovascular risk (TIMI score by 80 % and 99 % by the GRACE score). They were divided into group A (34p) with coronary stenosis < 70 % and group B (66p) with coronary stenosis >= 70 %. Clinical scores were higher in group B (TIMI 3.59 ± 1.4, p = 0.008 and 88.7 ± GRACE 24.18, p = 0.040). SLG was accurate identifying p with coronary stenosis >= 70 % (AUC = 0.72, p=0.001, sensitivity = 50 %, specificity = 90 %, positive predictive value = 75.1 % and negative predictive value = 74.9 %). Group B were low and moderate cardiovascular risk 72.8 % by TIMI risk score and 98.5 % by GRACE risk scores. TS was able to identify the culprit coronary in an ischemic event with cutoff values and minimum number of damaged segments as follow: -14 and 4 segments for anterior descending coronary, -16 and 3 segments to the circumflex coronary and right coronary. SLG has proved accurate in discriminating patients with severe coronary stenosis, even in those with low and moderate risk by TIMI and GRACE risk scores. TS estimates the area of ischemic myocardium by the number of segments with abnormal deformity, and suggests the most likely culprit coronary.