Stent retriever AssIsted Lysis (SAIL) Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting.

BACKGROUND AND PURPOSE: Angioplasty and stenting (A&S) have been described as bailout technique in individuals with failed thrombectomy. We aim to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban prior to A&S. MATERIALS AND METHODS: Patients from 2 comprehensive stroke centers were reviewed (2020-2023). We included patients with failed thrombectomy and/or underlying intracranial stenosis who received SAIL with tirofiban prior to intended A&S.SAIL consisted in deploying a SR through the occluding lesion to create a by-pass channel and infuse 10ml of tirofiban over 10 minutes either intraarterially (IA) or intravenously (IV). The SR was re-sheathed before retrieval. Primary endpoints were successful reperfusion (eTICI 2b-3) and sICH. Additional endpoints included 90-day mRS 0-2 and mortality. RESULTS: After a median of 3 (IQR 2-4) passes, 44 patients received the SAIL bridging protocol with tirofiban and later they were considered potential candidates for A&S bailout (43.2% IA-SAIL). Post-SAIL successful reperfusion was obtained in 79.5%. A significant residual stenosis (>50%) after successful SAIL was observed in 45.7%.No significant differences were detected according to post-SAIL successful reperfusion (IA-SAIL 80.0% vs IV-SAIL 78.9%; p=0.932), post-SAIL significant stenosis (33.3% vs 55.0%; p=0.203), early symptomatic reocclusion (0% vs 8.0%; p=0.207), or sICH (5.3% vs 8.0%; p=0.721). Rescue A&S was finally performed in 15 (34.1%) patients (IA-SAIL 21.0% vs IV-SAIL 44%; p=0.112).At 90 days, mRS 0-2 (IA-SAIL 50.0% vs IV-SAIL 43.5%; p=0.086) and mortality (26.3% vs 12.0%; p=0.223) were also similar. CONCLUSIONS: In stroke patients in which A&S bailout is considered, SAIL with tirofiban, either intraarterial or intravenous, seems to safely induce sustained recanalization, offering a potential alternative to definitive A&S. ABBREVIATIONS: A&S = Angioplasty and stenting, ICAD = Intracranial Atherosclerotic Disease, ICAS-LVO = Intracranial atherosclerosis related large vessel occlusion, EVT = Endovascular Treatment, LVO = Large Vessel Occlusion; MT = Mechanical Thrombectomy; SR = SR Stent Retriever; SAIL = Stent retriever AssIsted Lysis, sICH = Symptomatic Intracranial Hemorrhage.

Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC. METHODS: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients. RESULTS: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16). DISCUSSION: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03956485.

Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study.

BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.

Radial Versus Femoral Access for Mechanical Thrombectomy in Patients With Stroke: A Noninferiority Randomized Clinical Trial.

BACKGROUND: Transfemoral access is predominantly used for mechanical thrombectomy in patients with stroke with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the noninferiority of radial access in terms of final recanalization. METHODS: The study was an investigator-initiated, single-center, evaluator-blinded, noninferiority randomized clinical trial. Patients with stroke undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5 mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (expanded Treatment in Cerebral Ischemia score, 2b-3) assigned by blinded evaluators. We established a noninferiority margin of -13.2%, considering an acceptable reduction of 15% in the expected recanalization rates. RESULTS: From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access and 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted 1 side risk difference [RD], -5.0% [95% CI, -6.61% to +13.1%]) showing noninferiority of transradial access. Median time from angiosuite arrival to first pass (femoral, 30 [interquartile range, 25-37] minutes versus radial: 41 [interquartile range, 33-62] minutes; P<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR, 28-74) versus radial: 59.5 (IQR, 44-81) minutes; P<0.050) were longer in the transradial access group. Both groups presented 1 severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (P=0.751). CONCLUSIONS: Among patients who underwent mechanical thrombectomy, transradial access was noninferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default first-line approach. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05225636.

Acute management of cerebral venous thrombosis: Indications, technique, and outcome of endovascular treatment in two high-volume centers.

INTRODUCTION: After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT. METHODS: We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients. RESULTS: We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25-28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2-17) vs 0 (0-2.7), p = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2-17) vs 1(0-3.75); p < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73-2.8, p = 0.307)]. CONCLUSIONS: EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment.

PRERISK: A Personalized, Artificial Intelligence-Based and Statistically-Based Stroke Recurrence Predictor for Recurrent Stroke.

BACKGROUND: Predicting stroke recurrence for individual patients is difficult, but individualized prediction may improve stroke survivors' engagement in self-care. We developed PRERISK: a statistical and machine learning classifier to predict individual risk of stroke recurrence. METHODS: We analyzed clinical and socioeconomic data from a prospectively collected public health care-based data set of 41 975 patients admitted with stroke diagnosis in 88 public health centers over 6 years (2014-2020) in Catalonia-Spain. A new stroke diagnosis at least 24 hours after the index event was considered as a recurrent stroke, which was considered as our outcome of interest. We trained several supervised machine learning models to provide individualized risk over time and compared them with a Cox regression model. Models were trained to predict early, late, and long-term recurrence risk, within 90, 91 to 365, and >365 days, respectively. C statistics and area under the receiver operating characteristic curve were used to assess the accuracy of the models. RESULTS: Overall, 16.21% (5932 of 36 114) of patients had stroke recurrence during a median follow-up of 2.69 years. The most powerful predictors of stroke recurrence were time from previous stroke, Barthel Index, atrial fibrillation, dyslipidemia, age, diabetes, and sex, which were used to create a simplified model with similar performance, together with modifiable vascular risk factors (glycemia, body mass index, high blood pressure, cholesterol, tobacco dependence, and alcohol abuse). The areas under the receiver operating characteristic curve were 0.76 (95% CI, 0.74-0.77), 0.60 (95% CI, 0.58-0.61), and 0.71 (95% CI, 0.69-0.72) for early, late, and long-term recurrence risk, respectively. The areas under the receiver operating characteristic curve of the Cox risk class probability were 0.73 (95% CI, 0.72-0.75), 0.59 (95% CI, 0.57-0.61), and 0.67 (95% CI, 0.66-0.70); machine learning approaches (random forest and AdaBoost) showed statistically significant improvement (P<0.05) over the Cox model for the 3 recurrence time periods. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors. CONCLUSIONS: PRERISK is a novel approach that provides a personalized and fairly accurate risk prediction of stroke recurrence over time. The model has the potential to incorporate dynamic control of risk factors.

Enhancing blood pressure management protocol implementation in patients with acute intracerebral haemorrhage through a nursing-led approach: A retrospective cohort study.

AIM: To evaluate the impact of nurse care changes in implementing a blood pressure management protocol on achieving rapid, intensive and sustained blood pressure reduction in acute intracerebral haemorrhage patients. DESIGN: Retrospective cohort study of prospectively collected data over 6 years. METHODS: Intracerebral haemorrhage patients within 6 h and systolic blood pressure ≥ 150 mmHg followed a rapid (starting treatment at computed tomography suite with a target achievement goal of ≤60 min), intensive (target systolic blood pressure < 140 mmHg) and sustained (maintaining target stability for 24 h) blood pressure management plan. We differentiated six periods: P1, stroke nurse at computed tomography suite (baseline period); P2, antihypertensive titration by stroke nurse; P3, retraining by neurologists; P4, integration of a stroke advanced practice nurse; P5, after COVID-19 impact; and P6, retraining by stroke advanced practice nurse. Outcomes included first-hour target achievement (primary outcome), tomography-to-treatment and treatment-to-target times, first-hour maximum dose of antihypertensive treatment and 6-h and 24-h systolic blood pressure variability. RESULTS: Compared to P1, antihypertensive titration by stroke nurses (P2) reduced treatment-to-target time and increased the rate of first-hour target achievement, retraining of stroke nurses by neurologists (P3) maintained a higher rate of first-hour target achievement and the integration of a stroke advanced practice nurse (P4) reduced both 6-h and 24-h systolic blood pressure variability. However, 6-h systolic blood pressure variability increased from P4 to P5 following the impact of the COVID-19 pandemic. Finally, compared to P1, retraining of stroke nurses by stroke advanced practice nurse (P6) reduced tomography-to-treatment time and increased the first-hour maximum dose of antihypertensive treatment. CONCLUSION: Changes in nursing care and continuous education can significantly enhance the time metrics and blood pressure outcomes in acute intracerebral haemorrhage patients. REPORTING METHOD: STROBE guidelines. PATIENT AND PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Clinico-radiological features of intracranial atherosclerosis-related large vessel occlusion prior to endovascular treatment.

The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11-78.42; p = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50-0.95; p = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64-26.42, p = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23-13.03; p = 0.021), and smoking (OR 2.91, 95% CI 1.08-7.90; p = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83-0.94; p < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.

Radial Versus Femoral Access for Mechanical Thrombectomy in Patients With Stroke: A Noninferiority Randomized Clinical Trial.

BACKGROUND: Transfemoral access is predominantly used for mechanical thrombectomy in patients with stroke with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the noninferiority of radial access in terms of final recanalization. METHODS: The study was an investigator-initiated, single-center, evaluator-blinded, noninferiority randomized clinical trial. Patients with stroke undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5 mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (expanded Treatment in Cerebral Ischemia score, 2b-3) assigned by blinded evaluators. We established a noninferiority margin of -13.2%, considering an acceptable reduction of 15% in the expected recanalization rates. RESULTS: From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access and 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted 1 side risk difference [RD], -5.0% [95% CI, -6.61% to +13.1%]) showing noninferiority of transradial access. Median time from angiosuite arrival to first pass (femoral, 30 [interquartile range, 25-37] minutes versus radial: 41 [interquartile range, 33-62] minutes; P<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR, 28-74) versus radial: 59.5 (IQR, 44-81) minutes; P<0.050) were longer in the transradial access group. Both groups presented 1 severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (P=0.751). CONCLUSIONS: Among patients who underwent mechanical thrombectomy, transradial access was noninferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default first-line approach. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05225636.

Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry.

Occult atrial fibrillation (AF) is a common cause of cryptogenic stroke. This study aimed to investigate the utility of surrogate markers within the clot (clot markers), in combination with serum biomarkers, to identify AF-associated clots in patients who underwent mechanical thrombectomy. Each retrieved thrombus was analyzed to identify fibrin, red blood cells, platelets - CD61 staining (PLT) and T-CD4 lymphocyte/macrophage/monocyte (CD4) profile. Serum biomarkers such as D-dimer, lipoprotein (A), and brain natriuretic peptide (BNP) were also assessed in the acute phase of the stroke. Patients with stroke-related AF and large artery atherosclerosis (LAA) stroke were compared by matched case-control design to identify markers associated with AF clot profile. The predictive abilities of clot markers and serum biomarkers to detect AF clot were tested in patients with cryptogenic stroke. In patients with AF clot, the PLT percentage was higher (66.64% vs. 55.43%, OR = 1.03); CD4 percentage was lower (3.84% vs. 7.95%, OR = 0.95); and BNP marker was higher (2114 pg/ml vs. 276 pg/ml, OR = 1.04) compared to LAA clot. PLT was independently associated to AF-clot (OR, 1.04) but demonstrated moderate ability to identify AF-clot cases (C-test 0.668, p = 0.018). The combination of PLT with BNP significantly improved AF-clot prediction (C-test 0.847, p < 0.001). The clot composition of patients with cryptogenic stroke and AF detection showed four-fold higher PLT and BNP pattern of risk than patients with cryptogenic stroke without AF detection (38.5% vs. 8.7%) (OR = 1.40). Integrating intra-thrombus platelet with serum BNP offers a promising approach for detecting AF-associated clots in patients with cryptogenic stroke.

Effect of Bypassing the Closest Stroke Center in Patients with Intracerebral Hemorrhage: A Secondary Analysis of the RACECAT Randomized Clinical Trial.

Importance: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final diagnosis of intracerebral hemorrhage (ICH) is unknown. Objective: To determine the effect of direct transport to an endovascular treatment (EVT)-capable stroke center vs transport to the nearest local stroke center. Design, Setting, and Participants: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale [RACE] score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022. Intervention: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165). Main Outcomes and Measures: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5. Results: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 [67.5%] men; mean [SD] age 71.7 [12.8] years; and median [IQR] RACE score, 7 [6-8]). For the primary outcome, direct transfer to an EVT-capable stroke center (mean [SD] mRS score, 4.93 [1.38]) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean [SD] mRS score, 4.66 [1.39]; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 [48.9%] vs 62 of 165 [37.6%]; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 [22.6%] vs 9 of 165 patients [5.6%]; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients [35.8%] vs 29 of 165 patients [17.6%]; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group. Conclusions and Relevance: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes.

We aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.

Derivation and validation of three intracerebral hemorrhage expansion scores using different CT modalities.

OBJECTIVES: To derivate and validate three scores for the prediction of intracerebral hemorrhage (ICH) expansion depending on the use of non-contrast CT (NCCT), single-phase CTA, or multiphase CTA markers of hematoma expansion, and to evaluate the added value of single-phase and multiphase CTA over NCCT. METHODS: After prospectively deriving NCCT, single-phase CTA, and multiphase CTA hematoma expansion scores in 156 patients with ICH < 6 h, we validated them in 120 different patients. Discrimination and calibration of the three scores was assessed. Primary outcome was substantial hematoma expansion > 6 mL or > 33% at 24 h. RESULTS: The evaluation of single-phase and multiphase CTA markers gave a steadily increase in discrimination for substantial hematoma expansion over NCCT markers. The C-index (95% confidence interval) in derivation and validation cohorts was 0.69 (0.58-0.80) and 0.59 (0.46-0.72) for NCCT score, significantly lower than 0.75 ([0.64-0.87], p = 0.038) and 0.72 ([0.59-0.84], p = 0.016) for single-phase CTA score, and than 0.79 ([0.68-0.89], p = 0.033) and 0.73 ([0.62-0.85], p = 0.031) for multiphase CTA score, respectively. The three scores showed good calibration in both derivation and validation cohorts: NCCT (χ2 statistic 0.389, p = 0.533; and χ2 statistic 0.352, p = 0.553), single-phase CTA (χ2 statistic 2.052, p = 0.359; and χ2 statistic 2.230, p = 0.328), and multiphase CTA (χ2 statistic 0.559, p = 0.455; and χ2 statistic 0.020, p = 0.887) scores, respectively. CONCLUSION: This study shows the added prognostic value of more advanced CT modalities in acute ICH evaluation. NCCT, single-phase CTA, and multiphase CTA scores may help to refine the selection of patients at risk of expansion in different decision-making scenarios. KEY POINTS: • This study shows the added prognostic value of more advanced CT modalities in acute intracerebral hemorrhage evaluation. • The evaluation of single-phase and multiphase CTA markers provides a steadily increase in discrimination for intracerebral hemorrhage expansion over non-contrast CT markers. • Non-contrast CT, single-phase CTA, and multiphase CTA scores may help clinicians and researchers to refine the selection of patients at risk of intracerebral hemorrhage expansion in different decision-making scenarios.

Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia.

BACKGROUND: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. METHODS: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. RESULTS: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction=0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction<0.01); no heterogeneity was observed for other stroke subtypes (P interaction>0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. CONCLUSIONS: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

Intracranial Artery Calcifications Profile as a Predictor of Recanalization Failure in Endovascular Stroke Treatment.

BACKGROUND: Acute ischemic stroke with large or medium-vessel occlusion associated with intracranial artery calcification (IAC) is an infrequent phenomenon presumably associated with intracranial atherosclerotic disease. We aimed to characterize IAC and its impact on endovascular treatment outcomes. METHODS: We performed a retrospective cross-sectional study of consecutive patients with stroke treated with thrombectomy from January 2020 to July 2021 in our institution. We described IAC findings (length, density, and location pattern) on baseline noncontrast computed tomography. Patients were divided into 3 groups: IAC related to the occlusion location (symptomatic-IAC group), unrelated to the occlusion (asymptomatic-IAC group), and absence of any IAC (non-IAC group). We analyzed the association between the IAC profile and outcomes using logistic regression models. Intracranial angioplasty and stenting were considered rescue treatments. RESULTS: Of the 393 patients included, 26 (6.6%) patients presented a symptomatic-IAC, 77 (19.6%) patients an asymptomatic-IAC, and in 290 (73.8%) patients no IAC was observed. The rate of failed recanalization (expanded Thrombolysis in Cerebral Infarction 0-2a) before rescue treatment was higher in symptomatic-IAC (65.4%) than in asymptomatic-IAC (15.6%; P<0.001) or non-IAC (13.4%; P<0.001). Rescue procedures were more frequently performed in symptomatic-IAC (26.9%) than in asymptomatic-IAC (1.3%; P<0.001) and non-IAC (4.1%; P<0.001). After adjusting for identifiable clinical and radiological confounders, symptomatic-IAC emerged as an independent predictor of failed recanalization (odds ratio, 11.89 [95% CI, 3.94-35.91]; P<0.001), adoption of rescue procedures (odds ratio, 12.38 [95% CI, 2.22-69.09]; P=0.004), and poor functional outcome (90-day modified Rankin Scale score ≥3; odds ratio, 3.51 [95% CI, 1.02-12.00]; P=0.046). CONCLUSIONS: The presence of IAC related to the occlusion location is associated with worse angiographic and functional outcomes. Therefore, identification of symptomatic-IAC on baseline imaging may guide optimal endovascular treatment strategy, predicting the need for intracranial stenting and angioplasty.

Intensive 90-day textile wearable Holter monitoring: an alternative to detect paroxysmal atrial fibrillation in selected patients with cryptogenic stroke.

We aimed to demonstrate the feasibility of 90-day cardiac monitoring with an external Holter device and to find a target population able to benefit from such a technique. Cryptogenic stroke patients were continuously monitored for 90 days with a textile wearable Holter (TWH). Compliance and quality of the monitoring were assessed by the number of hours of ECG stored per month. Mean predictors of pAF, including age, gender, stroke severity, and atrial size (LAVI), were evaluated. One-year follow-up assessed pAF detection outside per protocol monitoring. Out of 224 patients included in 5 stroke centers, 163 patients (72.76%) fulfilled the criteria for the protocol. Median monitoring time was similar among the three months. Per protocol pAF detection reached 35.37% at 90 days. The age (OR 1.095; 95% CI 1.03-1.14) and the LAVI (OR 1.055; 95% CI 1.01-1.09) independently predicted pAF. The cut-off point of 70 years (AUC 0.68) (95% CI 0.60-0.76) predicted pAF with a sensitivity of 75.8% and specificity of 50.5%. The LAVI cut-off point of 28.5 (AUC 0.67) (95% CI 0.56-0.77) had a sensitivity of 63.6% and a specificity of 61.8% to detect pAF. The combination of both markers enhanced the validity of pAF detection sensitivity to 89.6%, with a specificity of 27.59%. These patients had increased risk of pAF during the 90-day monitoring HR 3.23 (χ2 7.15) and beyond 90 days (χ2 5.37). Intensive 90-days TWH monitoring detected a high percentage of pAF. However, a significant number of patients did not complete the monitoring. Patients older than 70 years and with enlarged left atria benefitted more from the protocol.

Multiparametric Neuroimaging and Its Association with Non-Contrast Computed Tomography in Late-Window Large Vessel Occlusion Acute Stroke.

INTRODUCTION: Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 and 24 h is established as a standard of care among patients selected by multiparametric neuroimaging. We aimed to explore neuroimaging parameters in late-window large vessel occlusion (LVO) patients and its association with non-contrast computed tomography (NCCT) findings. METHODS: We included consecutive AIS patients within 6-24 h from the symptoms onset with LVO. We described multiparametric imaging findings, the rate of patients who fulfilled imaging perfusion criteria according to the DAWN and DEFUSE-3 trials that define the computed tomography perfusion mismatch (CTP-MM) group and its association with NCCT focused on Alberta Stroke Program Early CT Score (ASPECTS). We also analyzed the association between neuroimaging parameters and the clinical outcome determined by the 90-day modified Rankin scale (mRS). RESULTS: We included 206 patients, of them, 176 (85.4%) presented CTP-MM and 184 (89.3%) presented an ASPECTS ≥6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥6, compared with 40.9% in those with low ASPECTS. ASPECTS was moderately correlated with ischemic core determined by cerebral blood flow <30% volume (rS = -0.557, p < 0.001). In EVT-treated patients (185, 89.8%), after adjusting for identifiable confounders, the presence of CTP-MM was a predictor of 90-day functional independence (OR: 3.38; 95% CI: 1.01-11.29; p = 0.048). We did not find an association between CTP-MM and 90-day functional disability (ordinal mRS shift, aOR: 1.39; 95% CI: 0.58-3.34; p = 0.459). CONCLUSIONS: A great majority of patients who presented a LVO in the late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥6). Our data suggest that NCCT with CT angiography could be a reasonable approach for AIS treatment selection also in the late window.

Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology.

The aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion treatment data to obtain FC predictors for HRCE. Multilevel decision tree with boosting random forest classifiers was performed with each feature importance for HRCE diagnosis among CS. We tested the validity of the best FC predictor in a cohort of CS that underwent extensive diagnostic workup. Among 211 patients, 178 cases underwent per-protocol workup. The percentage of monocytes (OR 1.06, 95% CI 1.01-1.11) and MLr (OR 1.83, 95% CI 1.12-2.98) independently predicted HRCE diagnosis when LAA clots (n = 28) were matched with HRCE clots (n = 28). Among CS (n = 82), MLr was the feature with the highest weighted importance in the multilevel decision tree as a predictor for HRCE. MLr cutoff point of 1.59 yield sensitivity of 91.23%, specificity of 44%, positive predictive value of 78.79%, and negative predictive value of 68.75 for HRCE diagnosis among CS. MLr ≥ 1.6 in clot analysis predicted HRCE diagnosis (OR, 6.63, 95% CI 1.85-23.71) in a multivariate model adjusted for age. Clot analysis by FC revealed high levels of monocyte-to-lymphocyte ratio as an independent marker of cardioembolic etiology in cryptogenic strokes.

Systematic CT perfusion acquisition in acute stroke increases vascular occlusion detection and thrombectomy rates.

BACKGROUND: In patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols. METHODS: From April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO). RESULTS: Of the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29-127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63-160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46-99.5) mL). CONCLUSION: Systematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.

Direct to Angiography Suite Without Stopping for Computed Tomography Imaging for Patients With Acute Stroke: A Randomized Clinical Trial.

Importance: Direct transfer to angiography suite (DTAS) for patients with suspected large vessel occlusion (LVO) stroke has been described as an effective and safe measure to reduce workflow time in endovascular treatment (EVT). However, it is unknown whether DTAS improves long-term functional outcomes. Objective: To explore the effect of DTAS on clinical outcomes among patients with LVO stroke in a randomized clinical trial. Design, Setting, and Participants: The study was an investigator-initiated, single-center, evaluator-blinded randomized clinical trial. Of 466 consecutive patients with acute stroke screened, 174 with suspected LVO acute stroke within 6 hours of symptom onset were included. Enrollment took place from September 2018 to November 2020 and was stopped after a preplanned interim analysis. Final follow-up was in February 2021. Interventions: Patients were randomly assigned (1:1) to follow either DTAS (89 patients) or conventional workflow (85 patients received direct transfer to computed tomographic imaging, with usual imaging performed and EVT indication decided) to assess the indication of EVT. Patients were stratified according to their having been transferred from a primary center vs having a direct admission. Main Outcomes and Measures: The primary outcome was a shift analysis assessing the distribution of the 90-day 7-category (from 0 [no symptoms] to 6 [death]) modified Rankin Scale (mRS) score among patients with LVO whether or not they received EVT (modified intention-to-treat population) assessed by blinded external evaluators. Secondary outcomes included rate of EVT and door-to-arterial puncture time. Safety outcomes included 90-day mortality and rates of symptomatic intracranial hemorrhage. Results: In total, 174 patients were included, with a mean (SD) age of 73.4 (12.6) years (range, 19-95 years), and 78 patients (44.8%) were women. Their mean (SD) onset-to-door time was 228.0 (117.9) minutes, and their median admission National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). In the modified intention-to-treat population, EVT was performed for all 74 patients in the DTAS group and for 64 patients (87.7%) in the conventional workflow group (P = .002). The DTAS protocol decreased the median door-to-arterial puncture time (18 minutes [IQR, 15-24 minutes] vs 42 minutes [IQR, 35-51 minutes]; P < .001) and door-to-reperfusion time (57 minutes [IQR, 43-77 minutes] vs 84 minutes [IQR, 63-117 minutes]; P < .001). The DTAS protocol decreased the severity of disability across the range of the mRS (adjusted common odds ratio, 2.2; 95% CI, 1.2-4.1; P = .009). Safety variables were comparable between groups. Conclusions and Relevance: For patients with LVO admitted within 6 hours after symptom onset, this randomized clinical trial found that, compared with conventional workflow, the use of DTAS increased the odds of patients undergoing EVT, decreased hospital workflow time, and improved clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04001738.