Long term outcome after endovascular treatment for large ischemic core acute stroke is associated with hypoperfusion intensity ratio and onset-to-reperfusion time.

BACKGROUND: Endovascular treatment (EVT) is effective for large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined core. However, the influence of perfusion imaging during thrombectomy on the functional outcomes of patients with large ischemic core (LIC) stroke at both early and late time windows is uncertain in real-world practice. METHOD: A retrospective analysis was performed on 99 patients who underwent computed tomography angiography (CTA) and CT perfusion (CTP)-Rapid Processing of Perfusion and Diffusion (RAPID) before EVT and had a baseline ischemic core ≥ 50 mL and/or Alberta Stroke Program Early CT Score (ASPECTS) score of 0-5. The primary outcome was the three-month modified Rankin Scale (mRS) score. Data were analyzed by binary logistic regression and receiver operating characteristic (ROC) curves. RESULTS: A fair outcome (mRS, 0-3) was found in 34 of the 99 patients while 65 had a poor prognosis (mRS, 4-6). The multivariate logistic regression analysis showed that onset-to-reperfusion (OTR) time (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.007; p = 0.008), ischemic core (OR, 1.066; 95% CI, 1.024-1.111; p = 0.008), and the hypoperfusion intensity ratio (HIR) (OR, 70.898; 95% CI, 1.130-4450.152; p = 0.044) were independent predictors of outcome. The combined results of ischemic core, HIR, and OTR time showed good performance with an area under the ROC curve (AUC) of 0.937, significantly higher than the individual variables (p < 0.05) using DeLong's test. CONCLUSIONS: Higher HIR and longer OTR time in large core stroke patients were independently associated with unfavorable three-month outcomes after EVT.

Impact of reperfusion therapies on clot resolution and long-term outcomes in patients with pulmonary embolism.

OBJECTIVE: Major progress in reperfusion strategies has substantially improved the short-term outcomes of patients with pulmonary embolism (PE), however, up to 50% of patients report persistent dyspnea after acute PE. METHODS: A retrospective study of the PE response team registry and included patients with repeat imaging at 3 to 12 months. The primary outcome was to determine the incidence of residual pulmonary vascular obstruction following acute PE. Secondary outcomes included the development of PE recurrence, right ventricular (RV) dysfunction, chronic thromboembolic pulmonary hypertension, readmission, and mortality at 12 months. RESULTS: A total of 382 patients were included, and 107 patients received reperfusion therapies followed by anticoagulation. Patients who received reperfusion therapies including systemic thrombolysis, catheter-directed thrombolysis, and mechanical thrombectomy presented with a higher vascular obstructive index (47% vs 28%; P < .001) and signs of right heart strain on echocardiogram (81% vs 43%; P < .001) at the time of diagnosis. A higher absolute reduction in vascular obstructive index (45% vs 26%; 95% confidence interval, 14.0-25.6; P < .001), greater improvement in RV function (82% vs 65%; P = .021), and lower 12-month mortality rate (2% vs 7%; P = .038) and readmission rate (33% vs 46%; P = .031) were observed in the reperfusion group. No statistically significant differences were found between groups in the development of chronic thromboembolic pulmonary hypertension (8% vs 5%; P = .488) and PE recurrence (8% vs 6%; P = .646). CONCLUSIONS: We observed a favorable survival and greater improvement in clot resolution and RV function in patients treated with reperfusion therapies.

Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open-label, controlled trial.

BACKGROUND AND PURPOSE: Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours. METHODS AND DESIGN: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days. STUDY OUTCOMES: Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days. DISCUSSION: TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours. TRIAL REGISTRATION NUMBER: NCT05141305.

Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center.

INTRODUCTION: Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce. OBJECTIVE: To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes. METHODS: In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan-Meier method. Differences stratified by reperfusion were assessed using the log-rank test. RESULTS: Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7-52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2-87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4-42.9, p=0.020). At a mean follow-up of 2.5±3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE. CONCLUSIONS: In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.

Role of perfusion medium in rewarming machine perfusion from hypo- to normothermia.

BACKGROUND: Gradual warming up of cold stored organ grafts using a controlled machine perfusion protocol facilitates restitution of cellular homeostasis and mitigates rewarming injury by adapted increase of temperature and metabolism. The aim of the present study was to compare intra- and extracellular type perfusion media for the use in machine perfusion-assisted rewarming from hypo- to normothermia. METHODS: Rat livers were retrieved 20 min after cardiac arrest. After 18 h of cold storage (CS) with or without additional 2 h of rewarming machine perfusion from 8°C up to 35°C with either diluted Steen solution or with Belzer MPS, liver functional parameters were evaluated by an established ex vivo reperfusion system. RESULTS: Rewarming machine perfusion with either solution significantly improved graft performance upon reperfusion in terms of increased bile production, less enzyme release, and reduced lipid peroxidation compared to CS alone. Cellular apoptosis (release of caspase-cleaved keratin 18) and release of tumor necrosis factor were only reduced significantly after machine perfusion with Belzer MPS. Histological evaluation did not disclose any major morphological damage in any of the groups. CONCLUSION: Within the limitation of our model, the use of Belzer MPS seems to be an at least adequate alternative to a normothermic medium like Steen solution for rewarming machine perfusion of cold liver grafts.

Implications of Post-recanalization Perfusion Deficit After Acute Ischemic Stroke: a Scoping Review of Clinical and Preclinical Imaging Studies.

The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. Unfortunately, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear. This scoping review provides an overview of clinical and preclinical findings on post-ischemic reperfusion, aiming to elucidate the pattern and consequences of PRPD from a translational perspective. The MEDLINE database was searched for quantitative clinical and preclinical studies of AIS reporting PRPD based on cerebral circulation parameters acquired by translational tomographic imaging methods. PRPD and stroke outcome were mapped on a charting table, creating an overview of PRPD after AIS. Twenty-two clinical and twenty-two preclinical studies were included. Post-recanalization hypoperfusion is rarely reported in clinical studies (4/22) but unequivocally associated with detrimental outcome. Post-recanalization hyperperfusion is more commonly reported (18/22 clinical studies) and may be associated with positive or negative outcome. PRPD has been replicated in animal studies, offering mechanistic insights into causes and consequences of PRPD and allowing delineation of possible courses of PRPD. Complex relationships exist between PRPD and stroke outcome. Diversity in methods and lack of standardized definitions in reperfusion studies complicate the characterization of reperfusion patterns. Recommendations are made to advance the understanding of PRPD mechanisms and to further disentangle the relation between PRPD and disease outcome.

Intra-Arterial Thrombolysis is Associated with Delayed Reperfusion of Remaining Vessel Occlusions following Incomplete Thrombectomy.

BACKGROUND AND PURPOSE: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging. MATERIALS AND METHODS: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion. RESULTS: The median age of the final study population (n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics (n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1). CONCLUSIONS: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials.

Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen Gas Treatment Reduces Ischemia-Reperfusion Injury in Rat Livers.

We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and a subsequent 90-minute reperfusion in an isolated perfused rat liver system. The experimental groups were the immediately reperfused control group (CT), the CS with University of Wisconsin solution (UW) group, the CS with Dsol group, the CS with UW and post-reperfusion H2 treatment group (UW-H2), and the CS with Dsol and post-reperfusion H2 group (Dsol-H2). We first compared the Dsol-H2, UW, and CT groups to evaluate this alternative method to conventional CS. The protective potential of the Dsol-H2 group was superior to that of the UW group, as evidenced by lower portal venous resistance and lactate dehydrogenase leakage, a higher oxygen consumption rate, and increased bile production. Multiple comparison tests among the UW, Dsol, UW-H2, and Dsol-H2 groups revealed that both treatments, during CS and after reperfusion, conferred a similar extent of protection and showed additive effects in combination therapy. Furthermore, the variance in all treatment groups appeared smaller than that in the no-treatment or no-stress groups, with excellent reproducibility. In conclusion, combination therapy with Dsol during CS and hydrogen gas after reperfusion additively protects against graft injury.

Continued Infarction Growth and Penumbral Consumption After Reperfusion in Vaccine-Naive Patients With COVID-19: A Case-Control Study.

BACKGROUND. Neurologic sequelae of SARS-CoV-2 include potentially malignant cerebrovascular events arising from complex hemodynamic, hematologic, and inflammatory processes occurring in concert. OBJECTIVE. This study concerns the hypothesis that despite angiographic reperfusion COVID-19 promotes continued consumption of at-risk tissue volumes after acute ischemic stroke (AIS), yielding critical insights into prognostication and monitoring paradigms in vaccine-naive patients experiencing AIS. METHODS. This retrospective study compared 100 consecutive COVID-19 patients with AIS presenting between March 2020 and April 2021 with a contemporaneous cohort of 282 AIS patients without COVID-19. Reperfusion classes were dichotomized into positive (extended thrombolysis in cerebral ischemia [eTICI] score = 2c-3) and negative (eTICI score < 2c) groups. All patients underwent endovascular therapy after initial CT perfusion imaging (CTP) to document infarction core and total hypoperfusion volumes. RESULTS. Ten COVID-positive (mean age ± SD, 67 ± 12 years; seven men, three women) and 144 COVID-negative patients (mean age, 71 ± 16 years; 76 men, 68 women) undergoing endovascular reperfusion, with antecedent CTP and follow-up imaging, comprised the final dataset. Initial infarction core and total hypoperfusion volumes (mean ± SD) were 1.5 ± 18 mL and 85 ± 100 mL in COVID-negative patients and 30.5 ± 34 mL and 117 ± 80.5 mL in COVID-positive patients, respectively. Final infarction volumes were significantly larger in patients with COVID-19, with median volumes of 77.8 mL versus 18.2 mL among control patients (p = .01), as were normalized measures of infarction growth relative to baseline infarction volume (p = .05). In adjusted logistic parametric regression models, COVID positivity emerged as a significant predictor for continued infarct growth (OR, 5.10 [95% CI, 1.00-25.95]; p = .05). CONCLUSION. These findings support the potentially aggressive clinical course of cerebrovascular events in patients with COVID-19, suggesting greater infarction growth and ongoing consumption of at-risk tissues, even after angiographic reperfusion. CLINICAL IMPACT. SARS-CoV-2 infection may promote continued infarction progression despite angiographic reperfusion in vaccine-naive patients with large-vessel occlusion AIS. The findings carry potential implications for prognostication, treatment selection, and surveillance for infarction growth among revascularized patients in future waves of infection by novel viral strains.

Reperfusion by endovascular thrombectomy and early cerebral edema in anterior circulation stroke: Results from the SITS-International Stroke Thrombectomy Registry.

BACKGROUND: A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. AIM: To investigate the association of reperfusion with development of early CED after stroke thrombectomy. METHODS: From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. RESULTS: In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. CONCLUSION: In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Endovascular thrombectomy of large ischemic strokes: Reimagining the boundaries of reperfusion.

The cumulative results of the SELECT-2, ANGEL-ASPECTS, and RESCUE-JAPAN LIMIT clinical trials suggest that endovascular thrombectomy performed within 24 h of symptom onset, in patients presenting with large ischemic strokes, defined by parenchymal and/or perfusion imaging, is safe and is associated with better functional outcomes with a treatment effect that persisted across all subgroups of patients. Our aim was to review these studies and to discuss the implications that these studies may have on patient selection, systems of care, and the utility of our imaging modalities.

Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis.

BACKGROUND: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). METHODS: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015-2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. RESULTS: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03-4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50-10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16-2.06]; Pinteraction=0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00-8.05] versus absent: aOR, 1.98 [95% CI, 0.65-6.03]; Pinteraction=0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25-11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01-3.83]; Pinteraction=0.16). CONCLUSIONS: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.

Futile reperfusion of endovascular treatment for acute anterior circulation large vessel occlusion in the ANGEL-ACT registry.

BACKGROUND: Some patients with large vessel occlusion (LVO) still cannot achieve functional independence despite successful reperfusion after endovascular treatment (EVT), named futile reperfusion. We aimed to explore the incidence and predictors of futile reperfusion of EVT for anterior circulation LVO in the Chinese population based on a nationwide prospective multicenter registry. METHODS: We selected patients from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) registry. Successful reperfusion was defined as modified Treatment In Cerebral Ischemia (mTICI) 2b-3 after EVT, and functional independence was defined as 90-day modified Rankin Scale (mRS) 0-2. A multivariable regression model was performed to identify the independent predictors of futile reperfusion in anterior circulation LVO patients. RESULTS: A total of 1158 anterior circulation LVO patients were included in our study. 600 of the 1158 patients (51.8%) suffered futile reperfusion. Age ≥69 (adjusted OR (aOR) 1.69, 95% CI 1.21 to 2.35, P=0.002), baseline National Institutes of Health Stroke Scale (NIHSS) ≥14 (aOR 2.36, 95% CI 1.71 to 3.27, P<0.001), baseline serum glucose ≥6.5 mmol/L (aOR 1.73, 95% CI 1.27 to 2.36, P=0.001), drip and ship (aOR 1.56, 95% CI 1.11 to 2.18, P=0.011), and general anesthesia (aOR 2.28, 95% CI 1.66 to 3.14, P<0.001) were associated with a high risk of futile reperfusion in the anterior LVO patients after EVT, whereas baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥8 (aOR 0.65, 95% CI 0.47 to 0.91, P=0.011) and complete reperfusion (aOR 0.62, 95% CI 0.43 to 0.89, P=0.010) were associated with a low risk of futile reperfusion in the anterior LVO patients after EVT. CONCLUSIONS: In the ANGEL-ACT registry, 51.8% of anterior circulation LVO patients suffered futile reperfusion after EVT. Age ≥69 years, baseline NIHSS ≥14, baseline serum glucose ≥6.5 mmol/L, drip and ship, general anesthesia, baseline ASPECTS <8, and incomplete reperfusion were the independent predictors of futile reperfusion.

Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHODS: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Spontaneous Reperfusion in Patients with Transient ST-Elevation Myocardial Infarction-Prevalence, Importance and Approaches to Management.

Patients with transient ST-elevation myocardial infarction (STEMI) or spontaneous resolution (SpR) of the ST-segment elevation on electrocardiogram could potentially represent a unique group of patients posing a therapeutic management dilemma. In this review, we discuss the potential mechanisms underlying SpR, its relation to clinical outcomes and the proposed management options for patients with transient STEMI with a focus on immediate versus early percutaneous coronary intervention. We performed a structured literature search of PubMed and Cochrane Library databases from inception to December 2020. Studies focused on SpR in patients with acute coronary syndrome were selected. Available data suggest that deferral of angiography and revascularization within 24-48 h in these patients is reasonable and associated with similar or perhaps better outcomes than immediate angiography. Further randomized trials are needed to elucidate the best pharmacological and invasive strategies for this cohort.

Acute Ischemic Stroke in Pregnancy : A Practical Focus on Neuroimaging and Reperfusion Therapy.

INTRODUCTION: Pregnancy increases the risk of acute ischemic stroke (AIS) among young women and is responsible for about 5% of maternal deaths and significant disability. Concerns of potential adverse events of imaging and reperfusion therapies in this group of patients can lead to a substantial delay or omission of treatment that can significantly worsen outcomes. OBJECTIVE: The objective of this study is to discuss main concerns of diagnosis and therapy of pregnant patients with AIS regarding neuroimaging and reperfusion treatment. RESULTS: The cumulative radiation dose of computed tomography (CT)-based entire diagnostic procedure (noncontrast CT, CT-angiography and CT-perfusion) is estimated to be below threshold for serious fetal radiation exposure adverse events. Similarly, magnetic resonance imaging(MRI)-based imaging is thought to be safe as long as gadolinium contrast media are avoided. The added risk of intravenous thrombolysis (IVT) and mechanical thrombectomy during pregnancy is thought to be very low. Nevertheless, some additional safety measures should be utilized to reduce the risk of radiation, contrast media and hypotension exposure during diagnostic procedures or reperfusion treatment. CONCLUSION: Fetal safety concerns should not preclude routine diagnostic work-up (except for gadolinium contrast media administration) in childbearing AIS women, including procedures applied in unknown onset and late onset individuals. Due to rather low added risk of serious treatment complications, pregnancy should not be a sole contraindication for neither IVT, nor endovascular treatment.

Prognostic accuracy and impact of cerebral collateral status on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy: a systematic meta-analysis.

BACKGROUND: Cerebral collateral status has a potential role in mediating postreperfusion clinical and safety outcomes in acute ischemic stroke (AIS). PURPOSE: To investigate the prognostic accuracy and impact of collateral status on clinical and safety outcomes in patients with AIS receiving reperfusion therapy. MATERIAL AND METHODS: Studies with AIS patients treated with reperfusion therapy, collateral status assessed using Tan, ASITN/SIR, or similar collateral grading methods and data stratified according to collateral status were included. Relevant data on clinical outcomes, such as functional outcome at 90 days, mortality at 90 days, angiographic reperfusion, symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT), were collated and analyzed. RESULTS: A meta-analysis of 18 studies involving 4132 patients with AIS was conducted. Good collateral status was significantly associated with angiographic reperfusion (odds ratio [OR]=1.97, 95% confidence interval [CI]=1.38-2.80; P < 0.0001), sICH (OR=0.67, 95% CI=0.46-0.99; P = 0.042), and 90-day functional outcome (OR=3.05, 95% CI=1.78-5.24; P < 0.0001). However, its association with HT (OR=0.76, 95% CI=0.38-1.51; P = 0.425) and three-month mortality (OR=0.53, 95% CI=0.17-1.69; P = 0.280) did not reach statistical significance. The prognostic accuracy of collaterals for predicting angiographic reperfusion, HT, functional outcome (at 90 days), and mortality (at 90 days) were 63%, 49%, 66%, and 48%, respectively. CONCLUSION: Cerebral collaterals are significantly associated with clinical and safety outcomes, albeit with a prognostic accuracy range of 48%-66%; thus, evaluation of their patency is a useful prognostic tool in patients with AIS receiving reperfusion therapy.

Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body.

BACKGROUND: Regarding the overall inadequate results after cardiopulmonary resuscitation, the development of new treatment concepts is urgently needed. Controlled Automated Reperfusion of the whoLe body (CARL) represents a therapy bundle to control the conditions of reperfusion and the composition of the reperfusate after cardiac arrest (CA). The aim of this study was to investigate the plasma expander's role in the CARL priming solution and examine its mechanism of action. METHODS: Viscosity, osmolality, colloid osmotic pressure (COP), pH and calcium binding of different priming solutions were measured in vitro and compared to in vivo data. N = 16 pigs were allocated to receive CARL following 20 min of untreated CA with either human albumin 20% (HA, N = 8) or gelatin polysuccinate 4% (GP, N = 8). Blood gas analyses were performed during the first hour of reperfusion and catecholamine and fluid requirements were recorded. Neurological outcome was assessed by neurological deficit scoring (NDS) on the seventh day. RESULTS: In vitro, addition of HA to the CARL priming solution resulted in higher COP and higher calcium-binding than GP. In vivo, treatment with HA led to greater reduction of ionized calcium and higher extracorporeal flows within the first 30 min of reperfusion with no difference in catecholamine support and fluid requirement. Seven-day survival of 75% with no difference in NDS was observed in both groups. CONCLUSIONS: Our data show that the plasma expander in the CARL priming solution has a significant effect on the initial reperfusate and can potentially influence the course of resuscitation. However, seven-day survival and NDS did not differ between groups.

Cerebral Small Vessel Disease Burden and Futile Reperfusion after Endovascular Treatment for Patients with Acute Ischemic Stroke.

INTRODUCTION: Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). METHODS: Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b-3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3-6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. RESULTS: Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12 h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602-9.619; p = 0.003). CONCLUSIONS: We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD.