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.

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.

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.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

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.

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.

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.

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.

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.

Accuracy of a Smartwatch to Assess Heart Rate Monitoring and Atrial Fibrillation in Stroke Patients.

(1) Background: Consumer smartwatches may be a helpful tool to screen for atrial fibrillation (AF). However, validation studies on older stroke patients remain scarce. The aim of this pilot study from RCT NCT05565781 was to validate the resting heart rate (HR) measurement and the irregular rhythm notification (IRN) feature in stroke patients in sinus rhythm (SR) and AF. (2) Methods: Resting clinical HR measurements (every 5 min) were assessed using continuous bedside ECG monitoring (CEM) and the Fitbit Charge 5 (FC5). IRNs were gathered after at least 4 h of CEM. Lin's concordance correlation coefficient (CCC), Bland-Altman analysis, and mean absolute percentage error (MAPE) were used for agreement and accuracy assessment. (3) Results: In all, 526 individual pairs of measurements were obtained from 70 stroke patients-age 79.4 years (SD ± 10.2), 63% females, BMI 26.3 (IQ 22.2-30.5), and NIHSS score 8 (IQR 1.5-20). The agreement between the FC5 and CEM was good (CCC 0.791) when evaluating paired HR measurements in SR. Meanwhile, the FC5 provided weak agreement (CCC 0.211) and low accuracy (MAPE 16.48%) when compared to CEM recordings in AF. Regarding the accuracy of the IRN feature, analysis found a low sensitivity (34%) and high specificity (100%) for detecting AF. (4) Conclusion: The FC5 was accurate at assessing the HR during SR, but the accuracy during AF was poor. In contrast, the IRN feature was acceptable for guiding decisions regarding AF screening in stroke patients.

Defining a Target Population to Effectively Test a Neuroprotective Drug.

BACKGROUND AND PURPOSE: We aim to identify the subgroup of acute ischemic stroke patients with higher probabilities of benefiting from a potential neuroprotective drug using baseline outcome predictors and test whether different selection criteria strategies can improve detected treatment effect. METHODS: We analyzed the association between final infarct volume (FIV), measured on 24- to 72-hour computed tomography, and National Institutes of Health Stroke Scale at discharge/day 5 of acute stroke patients who underwent endovascular treatment. Models were adjusted for age, sex, and affected hemisphere. We analyzed the impact of absolute (5-15 mL) and relative (33%) FIV reductions in the National Institutes of Health Stroke Scale in the whole population and in different subsets of patients selected according to baseline imaging criteria using computed tomography perfusion. RESULTS: We analyzed 627 patients; association between FIV and 5-day National Institutes of Health Stroke Scale was best described with a quadratic function, with a regression coefficient ß=1.56 ([95% CI, 1.45-1.67] P<0.001) in the adjusted analysis. In the models considering a fixed absolute (5/15 mL) FIV reduction, treatment effect was highest when patients with predicted larger FIV were excluded, whereas in a 33% FIV reduction model, treatment effect increased with the exclusion of patients with expected excellent outcomes. CONCLUSIONS: Patients either with excellent outcomes after endovascular thrombectomy or with large infarcts may dilute the treatment effect in stroke neuroprotective drug trials. Computed tomography perfusion on admission may help selecting adequate patients according to expected drug effect profile.

Ischemic Core Overestimation on Computed Tomography Perfusion.

Background and Purpose: Different studies have pointed that CT perfusion (CTP) could overestimate ischemic core in early time window. We aim to evaluate the influence of time and collateral status on ischemic core overestimation. Methods: Retrospective single-center study including patients with anterior circulation large-vessel stroke that achieved reperfusion after endovascular treatment. Ischemic core and collateral status were automatically estimated on baseline CTP using commercially available software. CTP-derived core was considered as tissue with a relative reduction of cerebral blood flow <30%, as compared with contralateral hemisphere. Collateral status was assessed using the hypoperfusion intensity ratio (defined by the proportion of the time to maximum of tissue residue function >6 seconds with time to maximum of tissue residue function >10 seconds). Final infarct volume was measured on 24 to 48 hours noncontrast CT. Ischemic core overestimation was considered when CTP-derived core was larger than final infarct. Results: Four hundred and seven patients were included in the analysis. Median CTP-derived core and final infarct volume were 7 mL (interquartile range, 0­27) and 20 mL (interquartile range, 5­55), respectively. Median hypoperfusion intensity ratio was 0.46 (interquartile range, 0.23­0.59). Eighty-three patients (20%) presented ischemic core overestimation (median overestimation, 12 mL [interquartile range, 41­5]). Multivariable logistic regression analysis adjusted by CTP-derived core and confounding variables showed that poor collateral status (per 0.1 hypoperfusion intensity ratio increase; adjusted odds ratio, 1.41 [95% CI, 1.20­1.65]) and earlier onset to imaging time (per 60 minutes earlier; adjusted odds ratio, 1.14 [CI, 1.04­1.25]) were independently associated with core overestimation. No significant association was found with imaging to reperfusion time (per 30 minutes earlier; adjusted odds ratio, 1.17 [CI, 0.96­1.44]). Poor collateral status influence on core overestimation differed according to onset to imaging time, with a stronger size of effect on early imaging patients(Pinteraction <0.01). Conclusions: In patients with large-vessel stroke that achieve reperfusion after endovascular therapy, poor collateral status might induce higher rates of ischemic core overestimation on CTP, especially in patients in earlier window time. CTP reflects a hemodynamic state rather than tissue fate; collateral status and onset to imaging time are important factors to consider when estimating core on CTP.

Leptomeningeal Collateral Flow Modifies Endovascular Treatment Efficacy on Large-Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: We aim to evaluate if good collateral flow (CF) modifies endovascular therapy (EVT) efficacy on large-vessel stroke. To do that, we used final degree of reperfusion and number of device-passes performed, factors previously associated with better functional outcome, as main outcome measures. METHODS: Single-center retrospective study including consecutive stroke patients receiving EVT for anterior circulation large-vessel stroke. CF degree was assessed on CT angiography before EVT using a previously validated 4-grade score. Final degree of reperfusion, using modified Thrombolysis in Cerebral Ischemia (mTICI), and number of device-passes performed were prospectively collected. Multivariable analysis was performed to evaluate the influence of collateral flow degree on final degree of reperfusion and number of device-passes performed. RESULTS: Six hundred twenty-six patients were included in the study; 369 patients (59%) presented good collateral flow on CT angiography. Five hundred twenty-two patients (84%) achieved successful reperfusion (mTICI 2B-3) after EVT, 304 (48%) of them with a final mTICI 2C-3. Median number of device-passes was 2 (interquartile range, 1-3). Good CF was independently associated with better final degree of reperfusion (shift analysis for mTICI0-2A/2B/2C-3%, poor CF 19/38/43 versus good CF 15/32/53, adjusted odds ratio, 1.51 [95% CI, 1.08-2.11]). Poor CF was independently associated with higher number of device-passes performed to achieve successful reperfusion (mTICI2B-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.59, [95% CI, 1.09-2.31]) and complete reperfusion (mTICI2C-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.70 [95% CI, 1.04-2.90]). CONCLUSIONS: Patients with good CF treated with EVT experience higher rates of successful reperfusion with lower number of device-passes. CF may facilitate thrombus retrieval and prevent distal embolization of clot fragments, improving device-passes efficacy.

Time Matters: Adjusted Analysis of the Influence of Direct Transfer to Angiography-Suite Protocol in Functional Outcome.

Background and Purpose- Direct transfer to angiography-suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The magnitude of the improvement of good outcome rates in function of time depends of several factors. We aim to analyze the benefit of DTAS according to time from symptom onset. Methods- Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to computed tomography (directly transferred to computed tomography) from February 2016 to June 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline National Institutes of Health Stroke Scale score (±2 points), and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (modified Rankin Scale score, 0-2) and safety variables stratified in less or more than 3 hours from onset to arrive. Results- There were no significant differences regarding age, sex, or baseline National Institutes of Health Stroke Scale score. Median door-to-groin time was shorter in the DTAS patients (16 [3-21] minutes versus 70 [41.5-98.5]; P<0.01). DTAS patients presented lower National Institutes of Health Stroke Scale score at 24 hours (9 [3.5-17] versus 14 [5-19]; P=0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, P<0.03). At 90 days, DTAS patients had a higher rate of good functional outcome (43% versus 29%; odds ratio, 1.81 [95% CI, 1.14-2.87]; P=0.01). Better outcome in DTAS was observed in patients admitted in the 0 to 3 hours form onset window (n=156, odds ratio 2.63 [95% CI, 1.31-5.28]; P<0.01), but not in patients admitted in the 3 to 6 hours window (n=193, odds ratio, 1.37 [95% CI, 0.72-2.60]; P=0.2). Conclusions- DTAS seems a feasible and safe strategy to improve functional outcome in patients who undergo endovascular treatment mainly within 3 hours from symptoms onset.

Computed Tomography Perfusion After Thrombectomy: An Immediate Surrogate Marker of Outcome After Recanalization in Acute Stroke.

Background and Purpose- Despite recanalization, almost 50% of patients undergoing endovascular treatment (EVT) experience poor outcome. We aim to evaluate the value of computed tomography perfusion as immediate outcome predictor postendovascular treatment. Methods- Consecutive patients receiving endovascular treatment who achieved recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] 2a-3) underwent computed tomography perfusion within 30 minutes from recanalization (CTPpost). Hypoperfusion was defined as the Tmax>6 second volume; hyperperfusion as visually increased cerebral blood flow/cerebral blood volume with reduced Tmax compared with unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. Delayed recovery was defined as no-DCR with favorable outcome (modified Rankin Scale score 0-2) at 3 months. Results- We included 151 patients: median National Institutes of Health Stroke Scale score 16 (interquartile range, 10-21), median admission ASPECTS 9 (interquartile range, 8-10). Final recanalization was the following: mTICI2a 11 (7.3%), mTICI2b 46 (30.5%), and mTICI3 94 (62.3%). On CTPpost, 80 (52.9%) patients showed hypoperfusion (median Tmax>6 seconds: 4 cc [0-25]) and 32 (21.2%) hyperperfusion. There was an association between final TICI and CTPpost hypoperfusion(median Tmax>6: 91 [56-117], 15 [0-37.5], and 0 [0-7] cc, for mTICI 2a, 2b, and 3, respectively, P<0.01). Smaller hypoperfusion volumes on CTPpost were observed in patients with DCR (0 cc [0-13] versus non-DCR 8 cc [0-56]; P<0.01) or favorable outcome (modified Rankin Scale score 0-2: 0 cc [0-13] versus 7 [0-56] cc; P<0.01). No associations were detected with hyperperfusion pattern. An hypoperfusion volume <3.5 cc emerged as independent predictor of DCR (OR, 4.1 [95% CI, 2.0-8.3]; P<0.01) and 3 months favorable outcome (OR, 3.5 [95% CI, 1.6-7.8]; P<0.01). Conclusions- Hypoperfusion on CTPpost constitutes an immediate accurate surrogate marker of success after endovascular treatment and identifies those patients with delayed recovery and favorable outcome.

Sudden Recanalization: A Game-Changing Factor in Endovascular Treatment of Large Vessel Occlusion Strokes.

Background and Purpose- First pass (FP) recanalization has been shown to be a predictor of favorable outcome in endovascular treatment of stroke. The reasons why FP recanalization leads to better outcome as compared with multiple passes (MP) are unknown. We aim to investigate the recanalization pattern and its relationship with outcome. Methods- Six hundred nine consecutive patients underwent endovascular treatment. Recanalization was defined as modified Thrombolysis in Cerebral Infarction score 2B-3. Favorable outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Sudden recanalization (SR) was considered when modified Thrombolysis in Cerebral Infarction score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if modified Thrombolysis in Cerebral Infarction score 2A was achieved at an interim pass before achieving recanalization. Patients were also categorized as recanalizers at FP, MP, or nonrecanalizers. Results- Five hundred nine (83.9%) patients achieved recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR, and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of favorable outcome were similar between patients with FP-SR (57.5%) and MP-SR (57.1%; odds ratio [OR], 0.9 [CI, 0.53-1.54]; P=0.7) but lower in MP-PR (29.8%; OR, 3.33 [CI, 1.71-5.63]; P<0.01). Patients with MP-PR had better outcome than nonrecanalizer (17%; OR, 2.93 [CI, 1.42-6.15]; P<0.01). In univariate analysis, both FP recanalization (OR, 1.91 [CI, 1.31-2.72]; P<0.01) and SR (OR, 3.19 [CI, 2.12-4.95]; P<0.01) were associated with favorable outcome. However multivariate analysis adjusting for FP recanalization showed that the only procedural predictor of favorable outcome was SR (OR, 3.12 [CI, 1.91-5.16]; P<0.01). Higher number of passes were associated with worse outcome in patients with recanalization (OR, 0.75 [CI, 0.66-0.85]; P<0.01) but not in those with SR (OR, 0.94 [CI, 0.59-1.61]; P=0.937). Conclusions- SR strongly predicts favorable outcome in patients undergoing endovascular treatment, even after previous unsuccessful attempts. PR may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Prospective studies with independent assessment of recanalization pattern should validate these results.

Stroke Risk Analysis, a System With a High Detection Rate of Atrial Fibrillation in Stroke and Transient Ischemic Attack.

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P<0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.

COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center.

BACKGROUND: An increased rate of thrombotic events has been associated to Coronavirus Disease 19 (COVID-19) with a variable rate of acute stroke. Our aim is to uncover the rate of acute stroke in COVID-19 patients and identify those cases in which a possible causative relationship could exist. METHODS: We performed a single-center analysis of a prospective mandatory database. We studied all patients with confirmed COVID-19 and stroke diagnoses from March 2nd to April 30th. Demographic, clinical, and imaging data were prospectively collected. Final diagnosis was determined after full diagnostic work-up unless impossible due to death. RESULTS: Of 2050 patients with confirmed SARS-CoV-2 infection, 21 (1.02%) presented an acute ischemic stroke 21 and 4 (0.2%) suffered an intracranial hemorrhage. After the diagnostic work-up, in 60.0% ischemic and all hemorrhagic strokes patients an etiology non-related with COVID-19 was identified. Only in 6 patients the stroke cause was considered possibly related to COVID-19, all of them required mechanical ventilation before stroke onset. Ten patients underwent endovascular treatment; compared with patients who underwent EVT in the same period, COVID-19 was an independent predictor of in-hospital mortality (50% versus 15%; Odds Ratio, 6.67; 95% CI, 1.1-40.4; p 0.04). CONCLUSIONS: The presence of acute stroke in patients with COVID-19 was below 2% and most of them previously presented established stroke risk factors. Without other potential cause, stroke was an uncommon complication and exclusive of patients with a severe pulmonary injury. The presence of COVID-19 in patients who underwent EVT was an independent predictor of in-hospital mortality.

Farmalarm.

Background and Purpose- Risk factor control and treatment compliance in the following months after stroke are poor. We aim to validate a digital platform for smartphones to raise awareness among patients about the need to adopt healthy lifestyle, improve communication with medical staff, and treatment compliance. Methods- Farmalarm is an application (app) for smartphones designed to increase stroke awareness by medication alerts and compliance control, chat communication with medical staff, didactic video files, exercise monitoring. Patients with stroke discharged home were screened for participation and divided into groups: to follow the FARMALARM program for 3 to 4 weeks or standard of care follow-up. We determined achievement of risk factor control goals at 90 days. Results- From August 2015 to December 2016, from the 457 patients discharged home, 159 (34.8%) were included: Farmalarm (n=107); age 57±12, Control (n=52), age 59±10; without significant differences in baseline characteristics between groups. At 90 days, knowledge of vascular risk factors was higher in FARMALARM group (86.0% versus 69.2%, P<0.01). The rate of patients with diabetes mellitus (83.2% versus 63.5%, P<0.01) and hypercholesterolemia (80.3% versus 63.5%, P=0.03) under control and the rate of patients with 4 out of 4 risk factors under control was higher in FARMALARM group (50.4% versus 30.7%, P=0.02). A regression model showed that the use of Farmalarm was independently associated with all risk factors under control at 90 days (odds ratio, 2.3; 95% CI, 1.14-4.6; P=0.02). Conclusions- In patients with stroke discharged home, the use of mobile apps to monitor medication compliance and increase stroke awareness is feasible and seems to improve the control of vascular risk factors.

When to Stop.

Background and Purpose- Substantial proportion of patients who achieve successful recanalization of acute ischemic stroke due to large vessel occlusion do not achieve good functional outcome. We aim to analyze the effect of number of thrombectomy device passes and degree of the recanalization (by modified Thrombolysis in Cerebral Infarction) on the clinical and functional outcome. Methods- Five hundred forty-two consecutive patients underwent mechanical thrombectomy for large vessel occlusion in the anterior circulation at a single tertiary stroke center. Baseline characteristics, number of passes, recanalization degree, clinical outcome at 24 hours (measured by National Institutes of Health Scale score), and functional outcome (measured by modified Rankin Scale at 90 days) were registered. Multivariate analysis was performed to determine the association of number of passes and degree of recanalization with dramatical clinical recovery (final National Institutes of Health Scale score ≤2 or decrease in 8 or more National Institutes of Health Scale score points in 24 hours) and good functional outcome (modified Rankin Scale score ≤2 at 90 days). Results- Four hundred fifty-nine patients (84%) achieved successful recanalization (modified Thrombolysis in Cerebral Infarction 2B-3), 213 (39%) of them after first device pass. In the multivariate analysis, first-pass recanalization and modified Thrombolysis in Cerebral Infarction 3 were independent predictors of good functional outcome (odds ratio, 2.5; 95% CI, 1.4-4.5; P=0.002 and odds ratio, 2.6 CI; 1.5-4.7; P=0.001, respectively) and dramatical clinical recovery (odds ratio, 1.8; 95% CI, 1.1-3; P=0.032 and odds ratio, 2.9; 95% CI, 1.7-5.1; P<0.001, respectively). Rate of recanalization declined after each pass 39% (213/542), 35% (113/310), 33% (63/190), and 24% (26/154) for passes 1 to 4, respectively and 28% (45/158) for every attempt above 4 passes ( P<0.001). In patients who achieved recanalization, a linear association between number of passes and good functional outcome was observed: 1 pass (58.6%), 2 passes (50.5%), 3 passes (48.4%), 4 passes (38.5%), or 5 or more passes (25.6%; P<0.001) as compared with patients who did not achieve recanalization (16.9%). Conclusions- High number of device passes and less degree of recanalization are associated with worse outcome in patients with acute ischemic stroke secondary to large vessel occlusion. Future studies should investigate the optimal number of passes that should be attempted in patients without substantial recanalization.