Fragestellung Die Prognose eines akuten Hirninfarktes bei Verschluss einer proximalen Hirnarterie ist trotz der intravenösen Thrombolyse mit rtPA ungünstig. Kann die kombinierte pharmaco-mechanische Rekanalisation von proximalen Gefäßverschlüssen bei akutem Hirninfarkt zu einer Verbesserung des klinischen Ergebnisses führen? Methoden Wir analysierten retrospektiv 66 konsekutiv aufgenommene Patienten (36m, 30w; mittleres Alter 61 Jahre (23-86 Jahre), die von 2010 bis 2012 kombiniert pharmako-mechanisch intra-arteriell behandelt wurden. 32 Patienten wiesen einen kombinierten ACI-/M1-Verschluss, 23 einen M1-Verschluss und 11 eine Basilaristhrombose auf. Mittlerer NIHSS lag bei 23. 57 Patienten erhielten eine kombinierte pharmaco-mechanische Therapie, 3 Patienten wurden lediglich pharmakologisch und 6 Patienten rein mechanisch rekanalisiert. Rekanalisierung bei 35 Patienten mit einem Stent-Retriever (32 Patienten mit pREset, 3 Patienten mit SOLITAIRE) erfolgt. Bei 46 Patienten wurde rtPA und bei 32 Patienten Tirofiban als Bridging Verfahren eingesetzt. Eine Stentanlage erfolgte in 28,78% der Fälle. Ergebnisse Die erzielten Rekanalisationsraten lagen bei 89,4% bei einer mittleren Dauer der Intervention von 96 Minuten (53,03% unter 90 Min.). Ein günstiges klinisches Ergebnis nach mRS (mRS 0-2) wurde bei 48% der Patienten erreicht. Die Rate an symptomatischen intrazerebralen Blutungen lag bei 4,55%. Die Mortalität war 19,7%. Die multivariate Regressionsanalyse ergab als modifizierbare Prediktoren für ein günstiges Outcome die Dauer bis zur Rekanalisation und die Gabe von rtPA. Schlussfolgerungen Die kombinierte endovaskuläre pharmako-mechanische Therapie kann die Mortalität und Morbidität von Schlaganfallpatienten mit Verschlüssen einer proximalen Hirnarterie reduzieren. / Background The prognosis of ischemic stroke due to occlusion of proximal intracranial arteries is poor, even with intravenous rt-PA thrombolysis. Can a combined pharmaco-mechanical thrombolysis lead to a better Outcome in this patients? Materials and methods We analysed 66 consecutive patients (36m, 30f; mean age 61, range 23 - 86 years), treated with a combined pharmaco-mechanical intra-arterial thrombolysis from 2010 to 2012. 32 patients presented with ICA and MCA tandem occlusions, 23 with occlusion of the main trunk of the MCA, and 11 of the BA. The mean NIH-Stroke-Scale (NIHSS) at admission was 23. 57 patients underwent combined pharmaco-mechanical thrombolisys, 3 patients were only pharmacological and 6 patients only mechanical recanalised. In 35 patients were Stent-Retriever-Systems utilized (32 patients pREset, 3 patients SOLITAIRE). A bridging therapie with rtPA was in 46 patients used and with tirofiban in 32 patients. Stenting were performed as well in 28,78%. Results The Rekanalizationrate was 89,4%. The mean duration of the intervention was 96 minutes (53,03% under 90 minutes). After rehabilitation had 48% of our patient a favorable outcome measured with the mRS (mRS 0-2).The procent of sICH in our patients was 4,55. The Mortality was 19.7%. The modifiable Predictors for a favorable Outcome detected with a multivariate logistic regression analysis were the time to recanalisation and the bridging therapy with rtPA. Conclusion The combined intra-arterial pharmaco-mechanical thrombolysis may reduce mortality and morbidity after occlusions of the proximal intracranial arteries in acute stroke patients.

No description available.

Les techniques de thérapie par ultrasons sont apparues très récemment avec la découverte des ultrasons de haute intensité focalisée. La thrombolyse ultrasonore extracorporelle en fait partie et se base sur la destruction mécanique du thrombus causée par la cavitation acoustique. Cependant, c'est un phénomène mal contrôlé. Ainsi, un meilleur contrôle de l'activité de cavitation et sa localisation pendant la thérapie est essentiel pour considérer le développement d'un dispositif thérapeutique. Un prototype a déjà été conçu et amélioré avec une boucle de rétroaction en temps réel afin de contrôler l'activité de puissance de cavitation. Cependant, pour surveiller le traitement en temps réel, un système d'imagerie ultrasonore doit être incorporé dans le dispositif thérapeutique. Il doit être capable de localiser le thrombus, de positionner la focale du transducteur thérapeutique, de contrôler la destruction complète du thrombus et d'évaluer en temps réel l'activité de cavitation. Le travail actuel se focalise principalement sur le développement de techniques d'imagerie ultrasonore passive utilisées pour reconstituer les cartographies d'activité de cavitation. Différents algorithmes de formation de voies ont été examinés et validés par des simulations de sources ponctuelles, des expériences in vitro sur fil et des expériences de cavitation dans une cuve d'eau. Il a été démontré que l'algorithme de formation de voie le plus précis pour la localisation du point focale de cavitation est la technique de cartographie passive acoustique pondérée avec le facteur de cohérence de phase (PAM-PCF). En outre, des tests in vivo sur un modèle animal d'ischémie des membres aigus ont été évalués. Enfin, certaines optimisations du système d'imagerie développé précédemment ont été réalisées comme l'imagerie 3D, l'implémentation en temps réel et l'imagerie hybride combinant l'imagerie active anatomique avec les cartographies de cavitation passive / Ultrasound therapy techniques emerged very recently with the discovery of high intensity focused ultrasound (HIFU) technology. Extracorporeal ultrasound thrombolysis is one of these promising innovative low-invasive treatment based on the mechanical destruction of thrombus caused by acoustic cavitation mechanisms. Yet, it is a poorly controlled phenomenon and therefore raises problems of reproducibility that could damage vessel walls. Thus, better control of cavitation activity during the ultrasonic treatment and especially its localization during the therapy is an essential approach to consider the development of a therapeutic device. A prototype has already been designed and improved with a real-time feedback loop in order to control the cavitation power activity. However, to monitor the treatment in real-time, an ultrasound imaging system needs to be incorporated into the therapeutic device. It should be able to first spot the blood clot, to position the focal point of the therapy transducer, control the proper destruction of the thrombus, and evaluate in real-time the cavitation activity. Present work focusses mainly on the development of passive ultrasound techniques used to reconstruct cavitation activity maps. Different beamforming algorithms were investigated and validated through point source simulations, in vitro experiments on a wire, and cavitation experiments in a water tank. It was demonstrated that an accurate beamforming algorithm for focal cavitation point localization is the passive acoustic mapping weighted with the phase coherence factor (PAM-PCF). Additionally, in vivo testing on an animal model of acute limb ischemia was assessed. Finally, some optimizations of the previous developed imaging system were carried out as 3D imaging, real-time implementation, and hybrid imaging combining active anatomical imaging with passive cavitation mapping

Optimal induction of coronary thrombolysis depends in part upon the nature of the specific plasminogen activator used. The two general classes of plasminogen activators available clinically differ in a fundamental respect delineated by the term, clot selectivity. Clot selective agents are less prone to induce plasminemia and consequent occult activation of the coagulation cascade than are non-selective agents. However, under clinical conditions, all plasminogen activators result in some activation of the cascade with consequent generation of thrombin. Accordingly, optimal therapy requires the use of conjunctive anticoagulation to preclude the deleterious effects of rebound generation of thrombin, which has been well documented biochemically. The potential value of antiplatelet agents that can attenuate the positive feedback loop between activation of platelets and markedly amplified generation of thrombin in the setting of coronary thrombolysis is under active exploration. With appropriate monitoring of the efficacy of such agents in vivo it should be possible to enhance even further the benefits that can be conferred by pharmacologically induced coronary thrombolysis.

No description available.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the degree of Master of Science in Medicine, 2014 / The earliest possible initiation of reperfusion therapy is necessary to reduce morbidity and mortality from acute STEMI. Therefore improving the time to thrombolysis where percutaneous coronary interventional facilities are limited or do not exist is critical. The most effective system would integrate three key components to deliver continuous patient care, including: 1) from time of call for help through to emergency response; 2) transportation to and admission to hospital; 3) assessment and initiation of thrombolytic therapy. The purpose of this prospective study is: to develop a chest pain awareness education programme appropriate for the South African context; to assess safe initiation of thrombolytic therapy by emergency care practitioners for STEMI; and to compare the performance of emergency care practitioner thrombolysis with historical control data.

Background: Platelets provide the initial haemostatic plug at sites of vascular injury. They also participate in pathological thrombosis that leads to myocardial infarction, stroke and peripheral vascular disease. The outcome of an acute myocardial infarction depends not only on the formation and stability of an occlusive thrombus, but also on the efficacy of the endogenous thrombolytic process, which allows reperfusion of the infarct related artery and prevents recurrent ischaemic episodes. Various platelet function tests are available to measure the thrombogenic potential of an individual, but the sensitivity of these tests remain questionable as most of these tests use citrated blood and measure response to a particular agonist. Endogenous thrombolysis has been a neglected entity, and its beneficial effects on cardiovascular outcomes has not been studied in depth in the past, possibly as until recently there has been no available technique to measure spontaneous thrombolytic activity in native blood. The Global Thrombosis Test (GTT) is a new point of care tests that allows us to measure time to thrombus formation (Occlusion time: OT) using native blood, avoiding the use of agonists and making the test results more physiological. The GTT also measures the time to lyse this formed thrombi without use of any lytic agents (Lysis time: LT), allowing us to measure the patient’s endogenous thrombolytic potential. Aim: Our aim in this study was to detect patients who are at risk of future thrombotic events despite dual antiplatelet therapy, either due to prothrombotic tendency or due to impaired endogenous thrombolysis, and to determine if these two parameters were correlated. Methods: GTT was used to assess the thrombotic and thrombolytic activity in healthy volunteers, and in different patient populations. 100 healthy volunteers were tested using the GTT, and a normal range was established. 300 patients admitted to hospital with a diagnosis of acute coronary syndrome (ACS) were included in the study, and tested using the GTT after they had been stabilized on dual antiplatelet therapy (Aspirin and Clopidogrel). All these patients were followed up for a year, to determine if their baseline GTT results were a predictor of recurrent cardiac events. The primary endpoint of the study was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, nonfatal myocardial infarction, or stroke at 12 months. Results: All results were analysed using statistical package SPSS version 16.0 (SPSS Inc., Chicago, Illinois). The 100 healthy volunteers were all non-smokers, and were not taking any medications. There were 55 males and 45 females, and mean age was 38±11 years (range 22-76, IQR 11). OT was normally distributed with mean OT 377.80s, and using mean ± 2SD, we derived a normal range of 185-569s (200-550s). LT demonstrated a skewed distribution with values ranging between 457 – 2934s. Using log transformation, a normal range of 592 – 1923 (600- 2000s) was established for LT. OT and LT were both prolonged in ACS patients compared to normal volunteers (p< 0.001). No association was observed between OT and risk of major adverse cardiovascular events. LT was noted to be a significant and independent predictor of MACE in a multivariate model adjusted for cardiovascular risk factors. LT ≥ 3000 s was the optimal cutoff value for predicting 6 month MACE [hazard ratio (HR): 2.48, 95% CI: 1.2-4.8, P= 0.008] and cardiovascular death [HR: 4.04, 95% CI : 1.3-12.0, P= 0.012 ] and 12 month MACE [HR:1.9, 95% CI: 1.04- 3.5,P= 0.03] and cardiovascular death [HR: 3.9,95% CI: 1.34-11.9, P= 0.013 ]. LT ≥ 3000 s was observed in 23% of ACS patients. Conclusions: Our study suggests that endogenous thrombolytic activity based on lysis of platelet rich thrombi can be assessed by the point of care GTT assay, which can help in identification of ACS patients at high risk of future cardiac events. Prolongation of OT may be explained by the antiplatelet effects of Aspirin and Clopidogrel, as both these drugs prolong time to thrombus formation and hence increase OT. Further large studies are required to study factors which can reduce thrombogenic potential, and improve endogenous thrombolytic activity, which can be monitored using the GTT to improve cardiovascular outcomes.

Introdução:embora seja mundialmente conhecida a correlação entre os escores tomográficos de avaliação isquêmica cerebral com achados e desfechos clínicos em pacientes com acidente vascular cerebral (AVC) isquêmico, são limitadas as evidencias em pacientes do subtipo cardioembólico. Objetivo: avaliar e correlacionar o perfil e desfechos clínicos de pacientes com AVC isquêmico do subtipo cardioembólico com os achados tomográficos de isquemia, segundo escores tomográficos. Métodos:estudo retrospectivo de um grupo de pacientes com AVC do tipo cardioembólico segundo a classificação TOAST, selecionados através de uma amostra de conveniência dos pacientes que foram atendidos em um centro de referência de emergências cerebrovasculares (março de 2014 a março de 2015). Os exames tomográficos destes pacientes foram avaliados por dois observadores (um radiologista com 10 anos e outro com 2 anos de experiência em exames tomográficos) treinados na avaliação de escores tomográficos relacionados a alterações isquêmicas encefálicas e cegados para os dados clínicos e laboratoriais dos pacientes. A análise estatística correlacionou os achados clínicos que incuíram fatores e preditores de risco, bem como transformação hemorrágica com os escores tomográficos que avaliam a isquemia cerebral. Resultados:o grupo com escore ASPECTS ≤7 apresentou significativamente maior uso de antiarrítmico, exclusão de trombólise, maior NIHSS, escala Rankin em 24h mais elevada e mais dias de internação quando comparado ao ASPECTS >7. Os pacientes com transformação hemorrágica apresentaram proporção significativamente maior de escore ASPECTS ≤ 7, mais do que um terço de acometimento do território da artéria cerebral média e AVC maior considerado pelo escore BASIS. Conclusão:os pacientes avaliados com AVC isquêmico cardioembólico que apresentaram transformação hemorrágica têm valores piores nos escores tomográficos de isquemia, com NHISS mais elevado e maior número de dias de internação. Houve uma correlação positiva entre o escore ASPECTS e os escores tomográficos regra de um terço e BASIS. / Introduction: although known worldwide, the correlation between tomographic cerebral ischemia evaluation scores and clinical outcome in patients with ischemic cerebral vascular accident (CVA), the evidences on patients with cardioembolic subtype are limited. Objective: evaluate and correlate the profile and clinical outcomes of patients with embolic subtype ischemic CVA with ischemia tomographic findings, according to tomographic scores. Methods: retrospective study of a patients group with cardioembolic subtype CVA according to TOAST classification, selected through a convenience sample from the patients that were treated at the cerebral vascular disease reference center emergency, (March 2014 to March 2015). These patients tomographic exams were evaluated by two observers (a radiologist with 10 years of expertise and another with 2 years of expertise in tomographic exams) trained in the assessment of tomographic scores related to encephalic ischemia alterations and blinded for the patients clinical and laboratorial data. The statistical analysis correlated the clinical findings, which included risk factors and predictors, as well as hemorrhagic transformation with the tomographic scores that evaluate cerebral ischemia. Results: groups with ASPECTS score ≤7 presented significantly higher use of antiarrhythmics, thrombolysis exclusion, higher NIHSS, higher 24 hours Rankin scale and more days of hospitalization when compared to ASPECTS >7. Patients with hemorrhagic transformation presented a significantly higher proportion of ASPECTS score ≤7. Conclusion: evaluated patients with cardioembolic ischemic CVA that had hemorrhagic transformation have worse tomographic ASPECTS score for ischemia, with higher NHISS and more hospitalization days. There was positive correlation between ASPECTS score and one third rule and BASIS tomographic scores.

Pulmonary embolism as a part of venous thromboembolic disease has a broad spectrum of clinical presentations from minimal disease to life-threatening right heart failure. Therapy has to be guided by the risk associated with the individual clinical state of the patient. As long as hemodynamics are entirely stable, anticoagulation is given in order to prevent early or late recurrence, thereby allowing for endogeneous thrombolysis and recovery. In hemodynamically instable patients, i.e. patients under cardiopulmonary resuscitation or in shock, there is the need for a rapid reduction of thrombus mass in order to restore right ventricular function. Systemic thrombolysis is the most feasible modality to reduce the thrombus burden of the pulmonary circulation in the short term. For hemodynamically stable patients with right ventricular dysfunction as assessed by echocardiography, there is still some controversy as to whether thrombolysis improves the long-term outcome. At the least, thrombolysis may positively modify the short-term course of acute disease in patients with an extremely low risk of bleeding. When the acute phase has been overcome, secondary prophylaxis with vitamin K antagonists has to be given. The duration of secondary prophylaxis requires an individual assessment of both the risk of recurrence and the risk of bleeding. In the near future, new anticoagulant drugs such as direct thrombin and factor Xa inhibitors will offer new treatment modalities for the acute phase as well as for secondary prophylaxis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Introdução: Diversas condições clínicas podem modificar a resposta ao tratamento trombolítico no acidente vascular isquêmico agudo. O grau de comorbidade dos pacientes medido pelo Índice de Charlson, um índice que mede o grau de comorbidades clínicas em AVC, tem valor prognóstico na incapacidade pós-AVC tanto em populações com acidente vascular do tipo hemorrágico como isquêmico. Objetivo: Avaliar o efeito do grau de comorbidade aferido pelo índice de Charlson na resposta ao tratamento trombolítico no acidente vascular isquêmico e a incapacidade na alta hospitalar. Métodos: Estudo de coorte prospectivo de 96 pacientes tratados com trombólise para o acidente vascular isquêmico, avaliando o impacto das comorbidades clínicas na resposta ao tratamento trombolítico no AVC isquêmico. Os pacientes foram divididos em dois grupos, aqueles com alto ou baixo grau de comorbidades clínicas, conforme o índice de Charlson. A evolução após o tratamento foi aferida pelo escore de gravidade dos sintomas de acordo com a escala do NIHSS medido antes da infusão, imediatamente após o tratamento, 24horas e 7 dias após a trombólise. A incapacidade na alta foi avaliada pela escala modificada de Rankin sendo, considerada boa resposta a pontuação 0-1 e sua frequência comparada entre os dois grupos de pacientes. Resultados: A comparação dos escores médios do NIHSS mostraram diferenças significativas nos diferentes momentos entre os grupos de alta e baixa comorbidade (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Pacientes com índice de comorbidade baixo apresentaram redução do escore do NIHSS de 10.13 para 2.9, enquanto que no grupo com alta comorbidade, o tratamento trombolítico demostrou pouco efeito. Uma boa evolução, definida como incapacidade 0 e 1 na escala modificada de Rankin, foi observada em (73%) dos pacientes com baixo índice de comorbidade, enquanto somente (15%) dos pacientes com alto índice de comorbidade apresentaram essa evolução favorável, uma diferença clinicamente muito significativa (RR 5.62; 95% CI = 2.97 a 10.65; p< 0.001). Conclusão: A presença de comorbidades clínicas medida peloíndice de Charlson foi associada a uma menor resposta neurológica no tratamento trombolítico do AVC isquêmico e a um maior grau de incapacidade funcional na alta. / Background and purpose: Clinical comorbidities modify prognosis in haemorrhagic and ischaemic stroke. Charlson Comorbidity index is a validated and useful tool for evaluating comorbidity in stroke. In this study we evaluated the effect of clinical comorbidities as measured by Charlson Comorbidity Index in the in ischaemic stroke thrombolysis. Methods: Prospective cohort study of 96 thrombolysis treated ischaemic stroke patients. The cohort population was divided in two groups according with severity of Charlson Comorbidity Index. During study, NIHSS score was evaluated four times (pre, post, 24 hours and 7 days after thrombolysis) and lower or higher comorbidities groups were compared using repeated measures ANOVA. Response to thrombolysis in both groups was also analysed with disability modified Rankin scale. Results: We observed differences in evolution of mean NIHSS scores between higher and lower clinical comorbidity groups. Patients with low clinical comorbidities experiencing a significant reduction of NIHSS score that ranged from 10.13 to 2.9 points, while patients in the HIC group had initial NIHSS score of 14.75 and final NIHSS score of 13.78 (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Lack of response to thrombolysis had direct relation with disability at hospital discharge. Better clinical outcome, as evaluated by modified Rankin scale of 0 and 1, was markedly different between groups, with 23 (73%) versus 9 (15%) in low and high clinical comorbidities patients respectively (RR=5.62; 95%CI=2.97 to 10.65; p< 0.001). Conclusion: High level of clinical comorbidities negatively influences response to thrombolysis, attenuating treatment related reduction of stroke symptoms severity and increasing the frequency of disabled patients at discharge.