Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke

Background Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. Methods We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). Results The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). Conclusions In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days.

An improved simple rat model for global cerebral ischaemia by induced cardiac arrest

OBJECTIVES Cerebral hypoxic-ischaemic injury following cardiac arrest is a devastating disease affecting thousands of patients each year. There is a complex interaction between post-resuscitation injury after whole-body ischaemia-reperfusion and cerebral damage which cannot be explored in in vitro systems only; there is a need for animal models. In this study, we describe and evaluate the feasibility and efficiency of our simple rodent cardiac arrest model. METHODS Ten wistar rats were subjected to 9 and 10 minutes of cardiac arrest. Cardiac arrest was introduced with a mixture of the short-acting beta-blocking drug esmolol and potassium chloride. RESULTS All animals could be resuscitated within 1 minute, and survived until day 5.General health score and neurobehavioural testing indicated substantial impairment after cardiac arrest, without differences between groups. Histological examination of the hippocampus CA1 segment, the most vulnerable segment of the cerebrum, demonstrated extensive damage in the cresyl violet staining, as well as in the Fluoro-Jade B staining and in the Iba-1 staining, indicating recruitment of microglia after the hypoxic-ischaemic event. Again, there were no differences between the 9- and 10-minute cardiac arrest groups. DISCUSSION We were able to establish a simple and reproducible 9- and 10-minute rodent cardiac arrest models with a well-defined no-flow-time. Extensive damage can be found in the hippocampus CA1 segment. The lack of difference between 9- and 10-minute cardiac arrest time in the neuropsychological, the open field test and the histological evaluations is mainly due to the small sample size.

Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment.

BACKGROUND AND PURPOSE Lesion volume on diffusion-weighted magnetic resonance imaging (DWI) before acute stroke therapy is a predictor of outcome. Therefore, patients with large volumes are often excluded from therapy. The aim of this study was to analyze the impact of endovascular treatment in patients with large DWI lesion volumes (>70 mL). METHODS Three hundred seventy-two patients with middle cerebral or internal carotid artery occlusions examined with magnetic resonance imaging before treatment since 2004 were included. Baseline data and 3 months outcome were recorded prospectively. DWI lesion volumes were measured semiautomatically. RESULTS One hundred five patients had lesions >70 mL. Overall, the volume of DWI lesions was an independent predictor of unfavorable outcome, survival, and symptomatic intracerebral hemorrhage (P<0.001 each). In patients with DWI lesions >70 mL, 11 of 31 (35.5%) reached favorable outcome (modified Rankin scale score, 0-2) after thrombolysis in cerebral infarction 2b-3 reperfusion in contrast to 3 of 35 (8.6%) after thrombolysis in cerebral infarction 0-2a reperfusion (P=0.014). Reperfusion success, patient age, and DWI lesion volume were independent predictors of outcome in patients with DWI lesions >70 mL. Thirteen of 66 (19.7%) patients with lesions >70 mL had symptomatic intracerebral hemorrhage with a trend for reduced risk with avoidance of thrombolytic agents. CONCLUSIONS There was a growing risk for poor outcome and symptomatic intracerebral hemorrhage with increasing pretreatment DWI lesion volumes. Nevertheless, favorable outcome was achieved in every third patient with DWI lesions >70 mL after successful endovascular reperfusion, whereas after poor or failed reperfusion, outcome was favorable in only every 12th patient. Therefore, endovascular treatment might be considered in patients with large DWI lesions, especially in younger patients.

Mechanical endovascular thrombectomy for acute ischemic stroke: a retrospective multicenter study in Belgium.

Clinical trials have shown a beneficial effect of mechanical thrombectomy in acute ischemic stroke patients treated within six up to even 12 h after symptom onset. This treatment was already performed in selected hospitals in Belgium before completion of the randomized controlled trials. Outcome data on these procedures in Belgium have not been published. We performed a retrospective multicenter study of all patients with acute ischemic stroke treated with mechanical endovascular therapy in four hospitals in Belgium. Clinical outcomes, as measured by the modified Rankin Scale (mRS), site of arterial occlusion, reperfusion and the association between these variables were studied. The study included 80 patients: 65 patients with an occlusion in the anterior circulation and 15 with an occlusion in the posterior circulation. Good functional outcome (GFO) rates, defined as mRS 0-2 at 90 days, were 42 % in all patients, 44 % in anterior circulation stroke and 34 % in posterior circulation stroke. Reperfusion was achieved in 78 % of patients; more (100 %) in patients with posterior compared to patients with anterior circulation stroke (72 %; p = 0.02). The rate of GFO was greater in patients with reperfusion versus patients in whom reperfusion was not achieved (adjusted OR 8.2, 95 % CI 2.0-34.2). Symptomatic intracerebral hemorrhage was documented in 5 % of all patients. Endovascular treatment with mechanical devices for acute ischemic stroke in Belgium results in GFO and reperfusion rates similar to recently published results in the endovascular-treated arms of randomized clinical trials. Rates of symptomatic intracranial hemorrhage are low and comparable to other cohort studies and clinical trials.

Mechanical Thrombectomy for Isolated M2 Occlusions: A Post Hoc Analysis of the STAR, SWIFT, and SWIFT PRIME Studies.

BACKGROUND AND PURPOSE Mechanical thrombectomy is beneficial for patients with acute ischemic stroke and a proximal anterior occlusion, but it is unclear if these results can be extrapolated to patients with an M2 occlusion. The purpose of this study was to examine the technical aspects, safety, and outcomes of mechanical thrombectomy with a stent retriever in patients with an isolated M2 occlusion who were included in 3 large multicenter prospective studies. MATERIALS AND METHODS We included patients from the Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), Solitaire With the Intention For Thrombectomy (SWIFT), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) studies, 3 large multicenter prospective studies on thrombectomy for ischemic stroke. We compared outcomes and technical details of patients with an M2 with those with an M1 occlusion. All patients were treated with a stent retriever. Imaging data and outcomes were scored by an independent core laboratory. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b/3. RESULTS We included 50 patients with an M2 and 249 patients with an M1 occlusion. Patients with an M2 occlusion were older (mean age, 71 versus 67 years; P = .04) and had a lower NIHSS score (median, 13 versus 17; P < .001) compared with those with an M1 occlusion. Procedural time was nonsignificantly shorter in patients with an M2 occlusion (median, 29 versus 35 minutes; P = .41). The average number of passes with a stent retriever was also nonsignificantly lower in patients with an M2 occlusion (mean, 1.4 versus 1.7; P = .07). There were no significant differences in successful reperfusion (85% versus 82%, P = .82), symptomatic intracerebral hemorrhages (2% versus 2%, P = 1.0), device-related serious adverse events (6% versus 4%, P = .46), or modified Rankin Scale score 0-2 at follow-up (60% versus 56%, P = .64). CONCLUSIONS Endovascular reperfusion therapy appears to be feasible in selected patients with ischemic stroke and an M2 occlusion.

TICI and Age: What's the Score?

BACKGROUND AND PURPOSE Previous studies have suggested that advanced age predicts worse outcome following mechanical thrombectomy. We assessed outcomes from 2 recent large prospective studies to determine the association among TICI, age, and outcome. MATERIALS AND METHODS Data from the Solitaire FR Thrombectomy for Acute Revascularization (STAR) trial, an international multicenter prospective single-arm thrombectomy study and the Solitaire arm of the Solitaire FR With the Intention For Thrombectomy (SWIFT) trial were pooled. TICI was determined by core laboratory review. Good outcome was defined as an mRS score of 0-2 at 90 days. We analyzed the association among clinical outcome, successful-versus-unsuccessful reperfusion (TICI 2b-3 versus TICI 0-2a), and age (dichotomized across the median). RESULTS Two hundred sixty-nine of 291 patients treated with Solitaire in the STAR and SWIFT data bases for whom TICI and 90-day outcome data were available were included. The median age was 70 years (interquartile range, 60-76 years) with an age range of 25-88 years. The mean age of patients 70 years of age or younger was 59 years, and it was 77 years for patients older than 70 years. There was no significant difference between baseline NIHSS scores or procedure time metrics. Hemorrhage and device-related complications were more common in the younger age group but did not reach statistical significance. In absolute terms, the rate of good outcome was higher in the younger population (64% versus 44%, P < .001). However, the magnitude of benefit from successful reperfusion was higher in the 70 years of age and older group (OR, 4.82; 95% CI, 1.32-17.63 versus OR 7.32; 95% CI, 1.73-30.99). CONCLUSIONS Successful reperfusion is the strongest predictor of good outcome following mechanical thrombectomy, and the magnitude of benefit is highest in the patient population older than 70 years of age.

Molecular control of cardiac sodium homeostasis in health and disease.

INTRODUCTION Cardiac myocytes utilize three high-capacity Na transport processes whose precise function can determine myocyte fate and the triggering of arrhythmias in pathological settings. We present recent results on the regulation of all three transporters that may be important for an understanding of cardiac function during ischemia/reperfusion episodes. METHODS AND RESULTS Refined ion selective electrode (ISE) techniques and giant patch methods were used to analyze the function of cardiac Na/K pumps, Na/Ca exchange (NCX1), and Na/H exchange (NHE1) in excised cardiac patches and intact myocytes. To consider results cohesively, simulations were developed that account for electroneutrality of the cytoplasm, ion homeostasis, water homeostasis (i.e., cell volume), and cytoplasmic pH. The Na/K pump determines the average life-time of Na ions (3-10 minutes) as well as K ions (>30 minutes) in the cytoplasm. The long time course of K homeostasis can determine the time course of myocyte volume changes after ion homeostasis is perturbed. In excised patches, cardiac Na/K pumps turn on slowly (-30 seconds) with millimolar ATP dependence, when activated for the first time. In steady state, however, pumps are fully active with <0.2 mM ATP and are nearly unaffected by high ADP (2 mM) and Pi (10 mM) concentrations as may occur in ischemia. NCX1s appear to operate with slippage that contributes to background Na influx and inward current in heart. Thus, myocyte Na levels may be regulated by the inactivation reactions of the exchanger which are both Na- and proton-dependent. NHE1 also undergo strong Na-dependent inactivation, whereby a brief rise of cytoplasmic Na can cause inactivation that persists for many minutes after cytoplasmic Na is removed. This mechanism is blocked by pertussis toxin, suggesting involvement of a Na-dependent G-protein. Given that maximal NCX1- and NHE1-mediated ion fluxes are much greater than maximal Na/K pump-mediated Na extrusion in myocytes, the Na-dependent inactivation mechanisms of NCX1 and NHE1 may be important determinants of cardiac Na homeostasis. CONCLUSIONS Na/K pumps appear to be optimized to continue operation when energy reserves are compromised. Both NCX1 and NHE1 activities are regulated by accumulation of cytoplasmic Na. These principles may importantly control cardiac cytoplasmic Na and promote myocyte survival during ischemia/reperfusion episodes by preventing Ca overload.

Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model

Gebiet: Chirurgie Abstract: OBJECTIVES: – The number of heart transplantations is limited by donor organ availability. Donation after circulatory determination of death (DCDD) could significantly improve graft availability, however, organs undergo warm ischaemia followed by reperfusion, leading to tissue damage. Laboratory studies suggest that mechanical postconditioning [(MPC), brief, intermittent periods of ischaemia at the onset of reperfusion] can limit reperfusion injury, however, clinical translation has been disappointing. We hypothesized that MPC-induced cardioprotection depends on fatty acid levels at reperfusion. – – METHODS: – Experiments were performed with an isolated rat heart model of DCDD. Hearts of male Wistar rats (n = 42) underwent working-mode perfusion for 20 min (baseline), 27 min of global ischaemia and 60 min reperfusion with or without MPC (two cycles of 30 s reperfusion/30 s ischaemia) in the presence or absence of high fat [(HF), 1.2 mM palmitate]. Haemodynamic parameters, necrosis factors and oxygen consumption (O2C) were assessed. Recovery rate was calculated as the value at 60 min reperfusion expressed as a percentage of the mean baseline value. The Kruskal-Wallis test was used to provide an overview of differences between experimental groups, and pairwise comparisons were performed to compare specific time points of interest for parameters with significant overall results. – – RESULTS: – Percent recovery of left ventricular (LV) work [developed pressure (DP)-heart rate product] at 60 min reperfusion was higher in hearts reperfused without fat versus with fat (58 ± 8 vs 23 ± 26%, P < 0.01) in the absence of MPC. In the absence of fat, MPC did not affect post-ischaemic haemodynamic recovery. Among the hearts reperfused with HF, two significantly different subgroups emerged according to recovery of LV work: low recovery (LoR) and high recovery (HiR) subgroups. At 60 min reperfusion, recovery was increased with MPC versus no MPC for LV work (79 ± 6 vs 55 ± 7, respectively, P < 0.05) in HiR subgroups and for DP (40 ± 27 vs 4 ± 2%), dP/dtmax (37 ± 24 vs 5 ± 3%) and dP/dtmin (33 ± 21 vs 5 ± 4%, P < 0.01 for all) in LoR subgroups. – – CONCLUSIONS: – Effects of MPC depend on energy substrate availability, MPC increased recovery of LV work in the presence, but not in the absence, of HF. Controlled reperfusion may be useful for therapeutic strategies aimed at improving post-ischaemic recovery of cardiac DCDD grafts, and ultimately in increasing donor heart availability.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging

Purpose. The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). Methods. We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions () were prestratified into enhancing lesions with increased permeability (EL+; ) and enhancing lesions with subtle permeability (EL−; ). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. Results. Significant differences () were found between EL+ and EL− and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL− and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL− and EL+ versus NEL), while EL− and NEL differed only in their SD during outflow. Conclusion. DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL− were similar to NEL, while EL+ differed significantly from EL− and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

Upstream clopidogrel, prasugrel, or ticagrelor for patients treated with primary angioplasty: Results of an angiographic randomized pilot study.

OBJETIVES The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood. METHODS A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration. RESULTS Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022). CONCLUSIONS In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.

Minimally invasive extracorporeal circulation resuscitation in hypothermic cardiac arrest.

Current guidelines for the treatment of hypothermic cardiocirculatory arrest recommend extracorporeal life support and rewarming, using cardiopulmonary bypass or extracorporeal membrane oxygenation circuits. Both have design-related shortcomings which may result in prolonged reperfusion time or insufficient oxygen delivery to vital organs. This article describes clear advantages of minimally invasive extracorporeal circulation systems during emergency extracorporeal life support in hypothermic arrest. The technique of minimally invasive extracorporeal circulation for reperfusion and rewarming is represented by the case of a 59-year-old patient in hypothermic cardiocirculatory arrest at 25.3°C core temperature, with multiple trauma. With femoro-femoral cannulation performed under sonographic and echocardiographic guidance, extracorporeal life support was initiated using a minimally invasive extracorporeal circulation system. Perfusing rhythm was restored at 28°C. During rewarming on the mobile circuit, trauma surveys were completed and the treatment initiated. Normothermic weaning was successful on the first attempt, trauma surgery was completed and the patient survived neurologically intact. For extracorporeal resuscitation from hypothermic arrest, minimally invasive extracorporeal circulation offers all the advantages of conventional cardiopulmonary bypass and extracorporeal membrane oxygenation systems without their shortcomings.

Plasma Heme Oxygenase-1 in Patients Resuscitated from out-of-Hospital Cardiac Arrest

Heme oxygenase-1 (HO-1) is an enzyme induced by hypoxia and reperfusion injury, and is associated with organ dysfunction in critically ill patients. Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are subjected to hypoxemia, brain injury, and organ dysfunction. Accordingly, we studied HO-1 among these patients. A total of 143 OHCA patients resuscitated from a shockable initial rhythm and admitted to an ICU were included, with plasma HO-1 measured at ICU admission and at 24 h. We analyzed the associations between plasma HO-1 and time to return of spontaneous circulation (ROSC), 90-day mortality, and 12-month Cerebral Performance Category (CPC). HO-1 plasma concentrations were higher after OHCA compared with controls. HO-1 concentrations at admission and on day 1 associated with ROSC (P = 0.002 to P = 0.003). Admission and day 1 HO-1 plasma concentrations were higher in 90-day non-survivors than in survivors (P = 0.017, 0.026). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (P = 0.024). Admission plasma HO-1 levels had an AUC of 0.623 to predict 90-day mortality and an AUC of 0.611 to predict CPC 3 to 5. In conclusion, we found that higher HO-1 plasma levels are associated with longer ROSC and poor long-term outcome.