Le pronostic à long-terme actuel après un accident ischémique transitoire (AIT) ou un infarctus cérébral reste mal connu. Ainsi, j’ai déterminé les risques absolus à long-terme de récidive d’infarctus cérébral et d’évènement coronarien aigu après un AIT ou un infarctus cérébral et identifié les individus qui restent à haut risque absolu de récidive ischémique malgré la prévention secondaire actuelle.Dans une cohorte populationnelle contemporaine de patients ayant eu un AIT ou un infarctus cérébral (OXVASC study, 2002-2014), les risques absolus de récidive d’infarctus cérébral et d’infarctus du myocarde après un AIT/infarctus cérébral ont significativement diminué au cours de la période d’étude, très probablement du fait de l’amélioration de la prévention secondaire avec le temps. Cependant, malgré la prévention secondaire actuelle les sous-groupes de patients avec un antécédent de pathologie coronarienne et ceux sans antécédent coronaire mais avec un score Essen 4 sont exposés à un risque absolu de récidive d’évènement ischémique suffisamment élevé pour justifier d’une intensification du traitement. Néanmoins, les thérapeutiques de prévention secondaire futures nécessitent de permettre d’obtenir une réduction absolue du risque de récidive d’évènement ischémique importante pour compenser un risque augmenté d’effets indésirables ou de surcoût par rapport aux thérapeutiques actuelles. En effet, chez ces sous-groupes de patients à haut risque de récidive ischémique, une réduction plus intensive du taux de cholestérol avec les inhibiteurs des PCSK-9 parait tout à fait justifiée, cependant nous avons montré que le coût de ces traitements excède la limite du rapport coût-efficacité généralement accepté tandis que le bénéfice d’une majoration du traitement antithrombotique semble contrebalancé par l’augmentation du risque hémorragique extracrânien. / The current long-term prognosis after transient ischaemic attack (TIA) or ischaemic stroke is not well known. I aimed to determine the long-term absolute residual risks of recurrent stroke and coronary events after TIA or ischaemic stroke and identify individuals who remain at high absolute risk of recurrent ischaemic events despite current secondary prevention management.In a population-based cohort of consecutive TIA or ischaemic stroke patients (OXVASC study, 2002-2014), the overall absolute risks of recurrent ischaemic stroke and coronary events after TIA/ischaemic stroke have decreased over the study period, and are likely to be explained by the improvement of secondary prevention over time. However, despite current secondary prevention, the subgroups of patients with prior coronary artery disease and those without prior coronary artery disease but with an Essen score of 4 remain at sufficiently high absolute risk of recurrent ischaemic events to justify more intensive treatment. Nevertheless, future secondary prevention therapies would need to achieve a substantial absolute risk reduction to outweigh increased side effects or cost compared to current therapies. Indeed, in these high-risk subgroups, more intensive lipid-lowering therapies might be justified, but we showed that the total cost of PCSK-9 inhibitors seems to exceed the generally accepted cost-effectiveness threshold while benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding.

Zusammenfassung der Arbeit Dissertation zur Erlangung des akademischen Grades Dr. med. Zusammenhang zwischen dem sozioökonomischem Status und der Entwicklung akuter ST – Strecken – Elevations – Myokardinfarkte eingereicht von Susanne Seide, geb. Gärtner, 02.12.1979 in München angefertigt am Institut für Herz- und Kreislaufforschung des Klinikum Links der Weser Bremen Klinik für Kardiologie und Angiologie Senator Wessling Strasse 1 28277 Bremen Betreuer: Prof. Dr. med. Rainer Hambrecht eingereicht im Februar 2015 An der Entwicklung der koronaren Herzkrankheit und dem damit verbundenen Auftreten akuter ST – Strecken – Elevations – Myokardinfarkte sind neben klassischen Risikofaktoren wie Bluthochdruck, Rauchen, Diabetes mellitus, Übergewicht und Fettstoffwechselstörungen andere Faktoren, wie Alter, Geschlecht, Bewegungsmangel und der psychosoziale Status beteiligt. Frühere Untersuchungen haben darüber hinaus gezeigt, dass die Entwicklung kardiovaskulärer Erkrankungen in einem Zusammenhang mit dem sozioökonomischen Hintergrundes steht. Inwieweit die Zugehörigkeit zu einer bestimmten sozialen Schicht Einfluss auf die Infarktrate der Bremer Bevölkerung hat, und ob es Unterschiede im Risikoprofil, in der Behandlung und Prognose von Patienten aus unterschiedlichen sozialen Milieus gibt, sollte mit dieser Arbeit untersucht werden. Hierzu wurden Daten von 2062 Patienten aus dem STEMI Register des Herzzentrums Bremen ausgewertet. Die Patienten aus dem Stadtgebiet Bremen wurden anhand der Postleitzahl ihrer Heimatadresse einer von vier Gruppen zugeordnet. Hiernach wurde für sie ein hoher sozioökonomischer Status (G1), ein intermediär hoher sozioökonomischer Status (G2), ein intermediär niedrig sozioökonomischer Status (G3) oder ein niedriger sozioökonomischer Status (G4) ermittelt. Der sozioökonomische Status der jeweiligen Gruppe wurde mit Hilfe des so genannten „Bremer Benachteiligungsindexes“, einem Maß für die soziale Stellung eines Stadtteiles, und anhand von Einkommensstatistiken der Bremer Stadtteile bestimmt. Die vier Gruppen wurden hinsichtlich ihrer Infarktinzidenzen verglichen. Innerhalb der Patientengruppen wurden Baselinecharakteristika (Alter zum Infarktzeitpunkt, Geschlecht, Vorerkrankungen, kardiovaskuläre Risikofaktoren), Surrogat – Parameter der Krankheitsausprägung (Mehrgefäßerkrankung, hämodynamische Stabilität, linksventrikuläre Ejektionsfraktion nach Myokardinfarkt), und der Therapie (PTCA, ACVB – Operation, Door – to – balloon Zeiten und Medikamentengabe) sowie Prognosedaten (30 Tage – Mortalität, 5 Jahres – Überleben) erhoben und die Gruppen anhand dieser Ergebnisse miteinander verglichen. Die wesentlichen Ergebnisse lassen sich wie folgt zusammenfassen: ➢ Die alters- und geschlechtsadjustierte Inzidenz akuter transmuraler Myokardinfarkte war in den sozial benachteiligten Bremer Stadtteilen signifikant höher als in Stadtbezirken mit geringerer Benachteiligung (G1: 47 ± 5 STEMIs pro 100.000 Einwohner pro Jahr versus G4: 66 ± 5 STEMIs pro 100.000 Einwohner pro Jahr; p < 0,01). ➢ Insbesondere junge Menschen waren von diesem sozialen Abwärtsgradienten betroffen (18 – 49 Jahre RR G4 2,01 versus 65 – 79 Jahre RR G4: 1,39). ➢ Herzinfarktpatienten aus sozial benachteiligten Stadtteilen waren zum Infarktzeitpunkt signifikant jünger (G1: 67±13 Jahre versus G4: 63±13 Jahre; p = 0,026), häufiger Raucher (G1: 35,9% versus G4: 51,2%; p < 0,01) und übergewichtig (G1:.15,3% BMI > 30 kg/qm versus G4: 26,1% BMI > 30 kg/qm; p < 0,01). ➢ Bezüglich der Infarktschwere und der Therapie zeigten sich keine wesentlichen Unterschiede zwischen den Gruppen (Mehrgefäßerkrankung G1: 62,4% versus G4: 57,0%; p = 0,27; Killip – Stadium III/IV G1: 12,5% versus G4: 13,0%; p = 0,84; LVEF nach Myokardinfarkt < 30% G1: 6,0% versus G4: 7,6%; p = 0,4; primäre PTCA G1: 89,8% versus G4: 89,8%; p = 0,92; ACVB - Operation G1: 11,6% versus G4: 12,6%; p = 0,13; Door – to – balloon Zeit G1: 54±38 min. versus G4 52±41 min.; p = 0,74; ASS G1: 94,4% versus G4: 94,7%; p = 0,64; ADP – Antagonist G1: 90,0% versus G4: 93,8%;p = 0,23; Betablocker G1 82,8% versus G4 83,9%; p = 0,25; Statin G1: 85,8% versus G4: 86,4%; p = 0,97; ACE – Hemmer oder AT1 – Rezeptorantagonisten G1: 77,4% versus G4: 79,3%; p = 0,90). ➢ Die alters– und geschlechtsadjustierte inhospitale Mortalität war in allen Gruppen vergleichbar hoch (G1: 4,8% versus G4: 3,9%; p = 0,3), für Patienten aus den sozioökonomisch am stärksten benachteiligten Stadtgebieten zeigte sich aber ein starker Trend hin zu einem geringeren 5 Jahres – Überleben (G4 versus G1: HR 1,55, 95% KI 0,98-2,5, p = 0,067). Die Ergebnisse dieser Studie demonstrieren, dass das relative Risiko für einen ST – Strecken – Elevations – Myokardinfarkt mit abnehmendem sozioökonomischem Status der Bevölkerung steigt, und dass das kardiovaskuläre Risikoprofil von Patienten aus sozioökonomisch benachteiligten Stadtteilen ausgeprägter ist. Trotz gleicher Initialtherapie aller STEMI Patienten, unabhängig von der sozialen Herkunft, haben diejenigen aus sozioökonomisch benachteiligten Wohnbezirken eine deutlich schlechtere Prognose. Daher besteht unseres Erachtens vor allem in den sozioökonomisch benachteiligten Stadtteilen nicht nur in Bremen ein erhöhter Handlungsbedarf hinsichtlich konsequenter primär– und sekundärpräventiver Maßnahmen.

Bakgrund: En hjärtinfarkt är en irreversibel ischemisk skada i hjärtmuskeln orsakad av en ocklusion. I Sverige är hjärt- och kärlsjukdomar den största folksjukdomen och årligen drabbas cirka 26 400 människor, av de avlider ungefär 5 900. För att uppnå en god livskvalitet är aspekterna gemenskap, mening, trygg identitet och en känsla av glädje grundläggande. Syfte: Syftet var att beskriva hur patienter upplever sin livskvalitet efter en hjärtinfarkt. Metod: En allmän litteraturöversikt baserad på 13 studier med deskriptiv kvalitativ ansats. Studierna identifierades med hjälp av databasen PubMed och dess kvalitet granskades genom SBU:s (2014) granskningsmall. Resultat: Resultatet sammanställdes utifrån sju kategorier och fem subkategorier vilka beskrev att: Patienterna drabbades primärt av chock och en nära-döden-upplevelse som resulterade i tacksamhet över att leva. Oro, rädsla, osäkerhet, ångest, depression, bröstsmärta, andfåddhet och fatigue var vanliga psykologiska och fysiologiska följder som kom att påverka patienterna i det dagliga livet. Relationen till familjemedlemmar blev negativt påverkad och de kände sig socialt begränsade. För att klara av den förändrade livssituationen var stöd och bearbetning nödvändigt. I efterförloppet ledde händelsen till nya prioriteringar och en förändrad syn på livet. Slutsats: Efter en hjärtinfarkt påverkas livskvaliteten negativt ur ett socialt, psykologiskt, emotionellt, fysiologiskt och existentiellt perspektiv. Då människan dagligen begränsas samt ställs inför utmaningar och påfrestningar krävs det en stor ansträngning för att klara av och hantera det dagliga livet. Denna information kan tillsammans med vidare forskning kring området användas som grund för utökade riktlinjer. / Background: A myocardial infarction is an occlusion-caused, irreversible ischemic injury in the heart muscle. In Sweden cardiovascular disease is the largest public health disease and approximately 26 400 people suffer from a myocardial infarction annually, of which about 5 900 die. To achieve a good quality of life it’s fundamental to have community, meaning, a secure identity and a sense of joy. Aim: The aim was to describe how patients experience their quality of life after a myocardial infarction. Method: A general literature review of 13 studies with descriptive and qualitative approaches. The studies were identified using the PubMed database and their quality was assessed using the SBU (2014) review template. Results: The result was compiled on the basis of seven categories and five sub-categories which described that: Patients were primarily affected by shock and a near-death experience that resulted in a gratitude for being alive. Concerns, fears, insecurities, anxiety, depression, chest pain, shortness of breath and fatigue were common psychological and physiological consequences that affected the patients in their daily life. The relationship with family members was negatively affected and they felt socially restricted. In order to cope with the changed life situation, it was of the utmost importance to get support and to process the consequences of the disease. In the aftermath, the event led to new priorities and a changed view of life. Conclusion: A myocardial infarction affects the patient's quality of life in a negative way from a social, psychological, emotional, physiological and existential perspective. Mainly because they are limited and daily faced with challenges and stress, which means that a great deal of effort is required in order for them to be able to carry out and manage their daily life. This information can together with further research be used as a basis for extended guidelines.

Objective: Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. Approaches and results: To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phospho-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. Conclusions: miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression.

Restoring blood flow, improving perfusion, reducing clinical symptoms, and augmenting ventricular function are the goals after acute myocardial infarction. Other than cardiac transplantation, no standard clinical procedure is available to restore damaged myocardium. Since we first reported cellular cardiomyoplasty in 1989, successful outcomes have been confirmed by experimental and clinical studies, but definitive long-term efficacy requires large-scale placebo-controlled double-blind randomized trials. On meta-analysis, stem cell-treated groups had significantly improved left ventricular ejection fraction, reduced infarct scar size, and decreased left ventricular end-systolic volume. Fewer myocardial infarctions, deaths, read-missions for heart failure, and repeat revascularizations were additional benefits. Encouraging clinical findings have been reported using satellite or bone marrow stem cells, but understanding of the benefit mechanisms demands additional studies. Adult mammalian ventricular myocardium lacks adequate regeneration capability, and cellular cardiomyoplasty offers a new way to overcome this; the poor retention and engraftment rate and high apoptotic rate of the implanted stem cells limit outcomes. The ideal type and number of cells, optimal timing of cell therapy, and ideal cell delivery method depend on determining the beneficial mechanisms. Cellular cardiomyoplasty has progressed rapidly in the last decade. A critical review may help us to better plan the future direction.

Purpose: The aim of this study was to determine whether the combination of 2 angiogenic growth factor, vascular endothelial growth factor 165(VEGF165) and angiopoietin-1 (Ang1), could increase angiogenesis and cardiomyocyte(CM) proliferation in an infarcted myocardium. Methods: Myocardial ischemia was induced in rats by ligation of the left anterior descending (LAD) coronary artery. Replication-deficient adenoviruses encoding VEGF165 (Ad-VEGF165), Ang1 (Ad-Ang1) or enhanced green fluorescence protein (Ad-EGFP) was injected into the ischemic myocardium immediately. Bromodexyuridine (BrdU) was administered intraperitoneally 1 week after ligation. One week later, the hearts were harvested and sectioned for hematoxylin-eosin (HE) and immunohistochemistry to evaluate densities of capillary, arteriole and double labelled BrdU(+) CM. M-mode echocardiography was used to evaluate the cardiac function. Results: Ang1 significantly increased collateral vessel formation. Both VEGF165 and Ang1 significantly increased densities of capillary and arteriole, as well as the number of double labelled BrdU(+) CM, and improved cardiac function. Conclusion: Our results suggest that the combination of VEGF165 and Ang1 can increase both myocardial angiogenesis and CM proliferation following myocardial ischemia in rats, leading to improved cardiac function.

Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (α1-adrenoceptor blockade), or 3) timolol (β-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 ± 9.5% (SD). Preemptive SCS reduced IS to 21.8 ± 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 ± 8.8%) and blunted by timolol (29.4 ± 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons.

Asthma affects 5%-10% of adults in the United States. Older adults (< 65 years) with asthma have higher rates of fatal asthma than younger adults. The occurrence of a respiratory emergency, such as status asthmaticus, would seem likely to create a situation of cardiopulmonary dysfunction conducive to myocardial ischemia. However, multiple studies of fatal or near-fatal asthma have failed to incriminate myocardial infarction as a contributing factor. We report a patient without underlying coronary artery disease who sustained myocardial injury consistent with myocardial ischemia and infarction during status asthmaticus while receiving recommended treatment without intravenous sympathomimetics or theophylline.

To determine the mechanism by which AMP 579, an adenosine A1/A2 agonist, administered at reperfusion protects ischemic myocardium, buffer-perfused rabbit hearts were subjected to 30 min of global ischemia and 2 h of reperfusion. AMP 579 (500 nM) was included in the reperfusate for the first 70 min. Average left ventricular diastolic pressure during reperfusion in hearts receiving AMP 579 was lower than that in control hearts (17.9 ± 2.4 vs. 39.0 ± 6.5 mm Hg, p < 0.05), indicating attenuation of contracture. Left ventricular developed pressure and coronary flow during reperfusion were also significantly improved with AMP 579 treatment. AMP 579's anti-contracture effect was blocked by the adenosine A2-receptor antagonist 8-(3-chlorostyryl)caffeine (CSC), but not by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). CSC, but not DPCPX, also blocked AMP 579's ability to preserve developed pressure and coronary flow in these hearts. AMP 579 significantly reduced infarction in isolated hearts subjected to regional ischemia. The anti-infarct effect again was abolished by CSC but not by DPCPX. Finally, we tested whether 5′-(N-ethylcarboxamido)adenosine (NECA), another A1/A2 agonist, also administered for the initial 70 min of reperfusion, could duplicate the anti-infarct effect of AMP 579. One-hundred-nanomolar NECA duplicated the protection, but neither 50 nM CGS21680, a selective A2 agonist, nor 100 μM adenosine was protective. Therefore, AMP 579 given at reperfusion reduces contracture and infarction. Anti-contracture and anti-infarct effects require the adenosine A2, but not the A1, receptor suggesting that prevention of contracture and tissue salvage are mechanistically related. Not all A2 agonists were able to duplicate the anti-infarct effect, suggesting something unique about AMP579.

Aims: There are limited data on the management and outcomes of chronic liver disease (CLD) patients presenting with acute myocardial infarction (AMI), particularly according to the subtype of CLD. Methods: Using the Nationwide Inpatient Sample (2004-2015), we examined outcomes of AMI patients stratified by severity and sub-types of CLD. Multivariable logistic regression was performed to assess the adjusted odds ratios (aOR) of receipt of invasive management and adverse outcomes in CLD groups compared with no-CLD. Results: Of 7 024 723 AMI admissions, 54 283 (0.8%) had a CLD diagnosis. CLD patients were less likely to undergo coronary angiography (CA) and percutaneous coronary intervention (PCI) (aOR 0.62, 95%CI 0.60-0.63 and 0.59, 95%CI 0.58-0.60, respectively), and had increased odds of adverse outcomes including major adverse cardiovascular and cerebrovascular events (1.19, 95%CI 1.15-1.23), mortality (1.30, 95%CI 1.25-1.34) and major bleeding (1.74, 95%CI 1.67-1.81). In comparison to the non-severe CLD sub-groups, patients with all forms of severe CLD had the lower utilization of CA and PCI (P <.05). Among severe CLD patients, those with alcohol-related liver disease (ALD) had the lowest utilization of CA and PCI; patients with ALD and other CLD (OCLD) had more adverse outcomes than the viral hepatitis sub-group (P <.05). Conclusions: CLD patients presenting with AMI are less likely to receive invasive management and are associated with worse clinical outcomes. Further differences are observed depending on the type as well as severity of CLD, with the worst management and clinical outcomes observed in those with severe ALD and OCLD.