Field triage for endovascular stroke therapy: a population-based comparison.

BACKGROUND: Endovascular therapy (EVT) for stroke improves outcomes but is time sensitive. OBJECTIVE: To compare times to treatment and outcomes between patients taken to the closest primary stroke center (PSC) with those triaged in the field to a more distant comprehensive stroke center (CSC). METHODS: During the study, a portion of our region allowed field triage of patients who met severity criteria to a more distant CSC than the closest PSC. The remaining patients were transported to the closest PSC. We compared times to treatment and clinical outcomes between those two groups. Additionally, we performed a matched-pairs analysis of patients from both groups on stroke severity and distance to CSC. RESULTS: Over 2 years, 232 patients met inclusion criteria and were closest from the field to a PSC; 144 were taken to the closest PSC and 88 to the more distant CSC. The median additional transport time to the CSC was 7 min. Times from scene departure to alteplase and arterial puncture were faster in the direct group (50 vs 62 min; 93 vs 152 min; p<0.001 for both). Among patients who were independent before the stroke, the OR for less disability in the direct group was 1.47 (95% CI 1.13 to 1.93, p=0.003), and 2.06 (95% CI 1.10 to 3.89, p=0.01) for the matched pairs. CONCLUSIONS: In a densely populated setting, for patients with stroke who are EVT candidates and closest to a PSC from the field, triage to a slightly more distant CSC is associated with faster time to EVT, no delay to alteplase, and less disability at 90 days.

The left atrial appendage morphology is associated with embolic stroke subtypes using a simple classification system: A proof of concept study.

BACKGROUND AND PURPOSE: The current left atrial appendage (LAA) classification system (cLAA-CS) categorizes it into 4 morphologies: chicken wing (CW), windsock, cactus, and cauliflower, though there is limited data on either reliability or associations between different morphologies and stroke risk. We aimed to develop a simplified LAA classification system and to determine its relationship to embolic stroke subtypes. METHODS: Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology was classified using the traditional system (in which CW = low risk) and a new system (LAA-H/L, in which low risk morphology (LAA-L) was defined as an acute angle bend or fold from the proximal/middle portion of the LAA and high risk morphology (LAA-H) was defined as all others). As a proof of concept study, we determined reliability for the two classification systems, and we assessed the associations between both classification systems with stroke subtypes in our cohort and previous studies. RESULTS: We identified 329 ischemic stroke patients with a qualifying chest CT (126 cardioembolic subtype, 116 embolic stroke of undetermined source (ESUS), and 87 non-cardioembolic subtypes). Intra- and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85, respectively) vs. cLAA-CS (0.50 and 0.40). The LAA-H/L led to classifying 69 LAA morphologies that met criteria for CW as LAA-H. In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter- and intra-rater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes. CONCLUSION: The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk identify patients with cardioembolic stroke subtypes. Larger studies are needed to validate these findings.

Emergency medical systems education may improve knowledge of pre-hospital stroke triage protocols.

BACKGROUND: Following the results of randomized clinical trials supporting the use of mechanical thrombectomy (MT) with tissue plasminogen activator for emergent large vessel occlusion (ELVO), our state Stroke Task Force convened to: update legislation to recognize differences between Primary Stroke Centers (PSCs) and Comprehensive Stroke Centers (CSCs); and update Emergency Medical Services (EMS) protocols to triage direct transport of suspected ELVO patients to CSCs. PURPOSE: We developed a single-session training curriculum for EMS personnel focused on the Los Angeles Motor Scale (LAMS) score, its use to correctly triage patients as CSC-appropriate in the field, and our state-wide EMS stroke protocol. We assessed the effect of our training on EMS knowledge. METHODS: We assembled a focus group to develop a training curriculum and assessment questions that would mimic real-life conditions under which EMS personnel operate. Ten questions were formulated to assess content knowledge before and after training, and scores were compared using generalized mixed models. RESULTS: Training was provided for 179 EMS providers throughout the state.Average pre-test score was 52.4% (95% CI 49% to 56%). Average post-test score was 85.6% (83%-88%, P<0.0001). Each of the 10 questions was individually assessed and all showed significant gains in EMS knowledge after training (P<0.0001). CONCLUSIONS: A brief educational intervention results in substantial improvements in EMS knowledge of prehospital stroke severity scales and severity-based field triage protocols. Further study is needed to establish whether these gains in knowledge result in improved real-world performance.

Sex differences in 90-day outcomes after mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: It is largely unknown whether functional outcomes after mechanical thrombectomy for large vessel occlusion (LVO) ischemic strokes differ by sex in non-clinical trial populations. We investigated sex differences in 90-day outcomes among ischemic stroke patients receiving mechanical thrombectomy. METHODS: This was a prospective cohort of adults treated with mechanical thrombectomy for LVO at a single academic comprehensive stroke center from July 2015 to April 2017. Data on independence (mRS ≤2) at hospital discharge and 90 days were collected prospectively. Multiple logistic regression was used to determine the association between sex and 90-day independence, first adjusting for demographics, pre-stroke mRS, and NIHSS, then by co-morbidities and time to thrombectomy, and finally by vessel recanalization and use of intravenous thrombolysis. RESULTS: We included 279 patients, 52% of whom were female. Compared with males, females were older (median years (IQR) 81 (75-88) vs. 71.5 (60-81), P<0.001) and had higher baseline NIHSS (mean SD 18.2±7.5 vs . 16.0±7.1, P=0.02). Similar proportions of males and females had pre-stroke mRS ≤2 (73.3% vs.67.1%, P=0.27). In multivariate analyses, males and females had a similar likelihood of being independent at discharge (aOR 0.71 (95%CI 0.32 to 1.58)), but females were less likely to be independent at 90 days (aOR 0.37 95% CI 0.16 to 0.87). CONCLUSIONS: In patients treated with mechanical thrombectomy for LVOs at a large comprehensive stroke center, females were less likely to be independent at 90 days. Future research should investigate contributors to poor outcomes post-discharge in females with LVOs, along with potential interventions to improve outcomes.

Association between age and outcomes following thrombectomy for anterior circulation emergent large vessel occlusion is determined by degree of recanalisation.

BACKGROUND: Older patients undergoing thrombectomy for emergent large vessel occlusion have worse outcomes. However, complete or near-complete reperfusion (modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2 c/3) is associated with improved outcomes compared with partial recanalisation (mTICI 2b). OBJECTIVE: To examine the relationship between outcomes and age separately for the mTICI 2c/3, 2b and 0-2a groups in patients undergoing thrombectomy for anterior circulation emergent large vessel occlusion. METHODS: Retrospective review of 157 consecutive patients undergoing thrombectomy at a single centre with an occlusion of the internal carotid artery (ICA), M1 or proximal M2 segments of the middle cerebral artery (MCA). Angiograms were graded in a blinded fashion. Patients were divided into three groups: mTICI 0-2a, mTICI 2b, and mTICI 2c/3. Demographics and workflow parameters were compared. Outcomes at 90 days were compared as a function of age, using both the conventional modified Rankin scale (mRs) and utility weighted mRs (UWmRs). RESULTS: There were 72, 61 and 24 patients in the mTICI 2c/3, 2b and 0-2a groups, respectively. Outcomes were significantly worse with increasing age for the mTICI 2b group, but not for the mTICI 0-2a and 2c/3 groups (P=0.0002). With increasing age, outcomes of the mTICI 2b group approached those of the mTICI 0-2a group. However, outcomes of the mTICI 2c/3 groups were similar for all ages. This association was present for both the original mRs and UWmRs. CONCLUSION: Increasing age was associated with worse outcomes for those with partial (mTICI 2b) recanalisation, not in patients with complete (mTICI 2c/3) recanalisation.

Door-in-Door-Out Time at Primary Stroke Centers May Predict Outcome for Emergent Large Vessel Occlusion Patients.

Background and Purpose- Interfacility transfers for thrombectomy in stroke patients with emergent large vessel occlusion (ELVO) are associated with longer treatment times and worse outcomes. In this series, we examined the association between Primary Stroke Center (PSC) door-in to door-out (DIDO) times and outcomes for confirmed ELVO stroke transfers and factors that may modify the interaction. Methods- We retrospectively identified 160 patients transferred to a single Comprehensive Stroke Center (CSC) with anterior circulation ELVO between July 1, 2015 and May 30, 2017. We included patients with acute occlusions of the internal carotid artery or proximal middle cerebral artery (M1 or M2 segments), with a National Institutes of Health Stroke Scale score of ≥6. Workflow metrics included time from onset to recanalization, PSC DIDO, interfacility transfer time, CSC arrival to arterial puncture, and arterial puncture to recanalization. Primary outcome measure was National Institutes of Health Stroke Scale at discharge and modified Rankin Scale (mRS) score at 90 days. Results- The median (Q1-Q3) age and National Institutes of Health Stroke Scale of the 130 ELVO transfers analyzed was 75 (64-84) and 17 (11-22). Intravenous alteplase was administered to 64% of patients. Regarding specific workflow metrics, median (Q1-Q3) times (in minutes) were 241 (199-332) for onset to recanalization, 85 (68-111) for PSC DIDO, 26 (17-32) for interfacility transport, 21 (16-39) for CSC door to arterial puncture, and 24 (15-35) for puncture to recanalization. Median discharge National Institutes of Health Stroke Scale score was 5 (2-16), and 46 (35%) patients had a favorable outcome at 90 days. Complete reperfusion (modified Thrombolysis in Cerebral Ischemia 2c/3) modified the deleterious association of DIDO on outcome. Conclusions- For patients diagnosed with ELVO at a PSC who are being transferred to a CSC for thrombectomy, longer DIDO times may have a deleterious effect on outcomes and may represent the single biggest modifiable factor in onset to recanalization time. PSCs should make efforts to decrease DIDO and routine use of DIDO as a performance measure is encouraged.

Accuracy of smartphone-based evaluation of Emergent Large Vessel Occlusion on CTA.

OBJECTIVES: Mechanical thrombectomy is the standard of care for stroke caused by an emergent large vessel occlusion in the anterior circulation, and the ability to rapidly review CTA is one hurdle in minimizing the time from diagnosis to intervention. We evaluated the diagnostic accuracy and confidence in review of stroke CTA for ELVO via a smartphone-based application as compared to PACS workstation. PATIENTS AND METHODS: Seventy-six head and neck CTA studies performed for stroke from one comprehensive and seven primary stroke centers were independently reviewed remotely on smartphone by two blinded interventional neuroradiologists in actual-use circumstances. The presence and location of large vessel occlusion(s), diagnostic quality, and confidence in interpretation were recorded. Comparison was made to blinded PACS workstation review performed at a delayed interval. Weighted Kappa and Kendall's Tau statistics were calculated to evaluate intra- and inter-observer reliability. RESULTS: Of the 76 studies, 20 (26%) had a large vessel occlusion. 14 M1 segment occlusions (18%); 2 ICA terminus (3%); 2 tandem carotid and M1 (3%); and 2 basilar artery (3%). There was 100% diagnostic accuracy by both PACS workstation and smartphone review (p = .9999) with high inter- and intra-rater reliability for assessments of both image quality and diagnostic confidence. CONCLUSION: In actual-use circumstances, experienced neuroradiologists can diagnose ELVOs on CTA using a smartphone application as accurately as on PACS workstation without degradation of confidence. These findings support the use of mobile electronic devices by stroke centers to rapidly triage patients for mechanical thrombectomy.

Baseline NIH Stroke Scale is an inferior predictor of functional outcome in the era of acute stroke intervention.

Background and aims Baseline National Institutes of Health Stroke Scale (NIHSS) scores have frequently been used for prognostication after ischemic stroke. With the increasing utilization of acute stroke interventions, we aimed to determine whether baseline NIHSS scores are still able to reliably predict post-stroke functional outcome. Methods We retrospectively analyzed prospectively collected data from a high-volume tertiary-care center. We tested strength of association between NIHSS scores at baseline and 24 h with discharge NIHSS using Spearman correlation, and diagnostic accuracy of NIHSS scores in predicting favorable outcome at three months (defined as modified Rankin Scale 0-2) using receiver operating characteristic curve analysis with area under the curve. Results There were 1183 patients in our cohort, with median baseline NIHSS 8 (IQR 3-17), 24-h NIHSS 4 (IQR 1-11), and discharge NIHSS 2 (IQR 1-8). Correlation with discharge NIHSS was r = 0.60 for baseline NIHSS and r = 0.88 for 24-h NIHSS. Of all patients with follow-up data, 425/1037 (41%) had favorable functional outcome at three months. Receiver operating characteristic curve analysis for predicting favorable outcome showed area under the curve 0.698 (95% CI 0.664-0.732) for baseline NIHSS, 0.800 (95% CI 0.772-0.827) for 24-h NIHSS, and 0.819 (95% CI 0.793-0.845) for discharge NIHSS; 24 h and discharge NIHSS maintained robust predictive accuracy for patients receiving mechanical thrombectomy (AUC 0.846, 95% CI 0.798-0.895; AUC 0.873, 95% CI 0.832-0.914, respectively), while accuracy for baseline NIHSS decreased (AUC 0.635, 95% CI 0.566-0.704). Conclusion Baseline NIHSS scores are inferior to 24 h and discharge scores in predicting post-stroke functional outcomes, especially in patients receiving mechanical thrombectomy.

Level of consciousness at discharge and associations with outcome after ischemic stroke.

BACKGROUND: Many factors may potentially complicate the stroke recovery process, including persistently impaired level of consciousness (LOC)-whether from residual stroke effects or from superimposed delirium. We aimed to determine the degree to which impaired LOC at hospital discharge is associated with outcomes after ischemic stroke. METHODS: We conducted a single-center retrospective cohort study using prospectively-collected data from 2015 to 2017, collecting total NIHSS-LOC score at discharge as well as subscores for responsiveness (LOC-R), orientation questions (LOC-Q), and command-following (LOC-C). We determined associations between LOC scores and 3-month outcome using logistic regression, with discharge location (skilled nursing facility [SNF] vs. inpatient rehabilitation) representing a pre-specified secondary outcome. RESULTS: We identified 1003 consecutive patients with ischemic stroke who survived to discharge, of whom 32% had any LOC score > 0. Total LOC score at discharge was associated with unfavorable 3-month outcome (OR 4.9 [95% CI 2.4-9.8] for LOC = 1; OR 8.0 [2.7-23.9] for LOC = 2-3; OR 6.3 [2.1-18.5] for LOC = 4-5; all patients with LOC = 6-7 had poor outcomes), as were subscores for LOC-R (OR 5.3 [1.3-21.2] for LOC-R = 1; all patients with LOC-R = 2-3 had poor outcomes) and LOC-Q (OR 4.1 [2.1-8.3] for LOC-Q = 1; OR 4.9 [1.8-13.5] for LOC-Q = 2). Total LOC score (OR 2.6 [1.3-5.3] for LOC = 1; OR 3.1 [1.2-8.2] for LOC = 2-3) and LOC-Q (OR 3.3 [1.6-6.6] for LOC-Q = 1; OR 3.4 [1.3-9.0] for LOC-Q = 2) were also associated with discharge to SNF rather than to inpatient rehabilitation. CONCLUSIONS: The presence of impaired consciousness or disorientation at discharge is associated with markedly worse outcomes after ischemic stroke. Further studies are necessary to determine the separate effects of residual stroke-related LOC changes and those caused by superimposed delirium.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.

A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring after Embolic Stroke of Unknown Source.

BACKGROUND: Occult paroxysmal atrial fibrillation (AF) is detected in 16%-30% of patients with embolic stroke of unknown source (ESUS). The identification of AF predictors on outpatient cardiac monitoring can help guide clinicians decide on a duration or method of cardiac monitoring after ESUS. METHODS: We included all patients with ESUS who underwent an inpatient diagnostic evaluation and outpatient cardiac monitoring between January 1, 2013, and December 31, 2016. Patients were divided into 2 groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, and cardiac biomarkers between the 2 groups. Multivariable logistic regression was used to determine predictors of AF. RESULTS: We identified 296 consecutive patients during the study period; 38 (12.8%) patients had AF detected on outpatient cardiac monitoring. In a multivariable regression analysis, advanced age (ages 65-74: odds ratio [OR] 2.36, 95% confidence interval [CI] .85-6.52; ages 75 or older: OR 4.08, 95% CI 1.58-10.52) and moderate-to-severe left atrial enlargement (OR 4.66, 95% CI 1.79-12.12) were predictors of AF on outpatient monitoring. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, 75 years or older: 2 points) and left atrial enlargement (moderate or severe: 2 points) with good prediction of AF (area under the curve .725) and was internally validated using bootstrapping. The percentage of patients with AF detected in each score category were as follows: 0: 4.2%; 1: 14.8%; 2: 20.8%; 3: 22.2%; 4: 55.6%. CONCLUSIONS: The Brown ESUS-AF score predicts AF on prolonged outpatient monitoring after ESUS. More studies are needed to externally validate our findings.

Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion.

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume-infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30-47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.

Left Atrial Appendage Morphology and Embolic Stroke of Undetermined Source: A Cross-Sectional Multicenter Pilot Study.

BACKGROUND: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation, and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of NCW LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with noncardioembolic stroke (NCS). METHODS: This multicenter retrospective pilot study included consecutive patients with ischemic stroke from 3 comprehensive stroke centers who previously underwent a qualifying chest computed tomography (CT) to assess LAA morphology. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology was determined using clinically performed contrast enhanced thin-slice chest CT by investigators blinded to stroke subtype. The primary predictor was NCW LAA morphology and the outcome was stroke subtype (CE, ESUS, NCS). RESULTS: We identified 172 patients with ischemic stroke who had a clinical chest CT performed. Mean age was 70.1 ± 14.3 years and 51.7% were male. Compared with patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% versus 46.3%, P = .1) and ESUS (58.8% versus 46.3%, P = .2), but this difference did not achieve statistical significance. CONCLUSION: The prevalence of NCW LAA morphology may be similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm these associations.

Left Atrial Enlargement and Anticoagulation Status in Patients with Acute Ischemic Stroke and Atrial Fibrillation.

BACKGROUND: Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation. METHODS: We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe). RESULTS: We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16). CONCLUSION: LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies.

Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic Source.

BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002). CONCLUSIONS: We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Rethinking Thrombolysis in Cerebral Infarction 2b: Which Thrombolysis in Cerebral Infarction Scales Best Define Near Complete Recanalization in the Modern Thrombectomy Era?

BACKGROUND AND PURPOSE: Within the thrombolysis in cerebral infarction (TICI) classification, TICI 2b has been historically considered successful recanalization. Recent studies have suggested that TICI 3 and a proposed TICI 2c should be separately reported from TICI 2b, in both the original (>66% reperfusion) and modified (>50% reperfusion) definitions, because of differences in clinical outcomes with greater reperfusion. The purpose of this study was to evaluate differences in early neurological improvement and independence at 90 days using the original TICI, modified TICI, and modified TICI with 2c scales. METHODS: A retrospective review of 129 consecutive patients with middle cerebral artery, M1 segment or intracranial internal carotid artery occlusions. Patient angiograms were graded by 2 experienced readers by percentage recanalization. This was then categorized into original TICI, modified TICI (mTICI), and mTICI with TICI 2c (mTICI 2c) grading scales. Comparison of baseline demographics, early neurological improvement, and independence at 90 days was performed. RESULTS: A significant difference in early neurological improvement was observed between 2b and 3 (P=0.032), as well as between 2b and 2c (P=0.028) under the mTICI 2c grading scale. Similarly, a significant difference in functional independence was observed between 2b and 3 (P=0.037), as well as between 2b and 2c (P=0.047) under the mTICI 2c scale. The difference in early neurological improvement or functional independence between 2b and 3 for the original TICI and mTICI scales was not significant. When combining the 2c and 3 groups under the mTICI 2c scale, there were significant differences between 2b and 2c/3 in regards to both early neurological improvement (P=0.011) and independence (P=0.018). CONCLUSIONS: Using a TICI grading system that includes an additional category beyond TICI 2b allows for refined prediction of early neurological improvement and functional independence.

PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

BACKGROUND: Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. METHODS: We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (<200 milliseconds; ≥200 milliseconds) and other clinical and demographic factors between the 2 groups and used multivariate regression analyses to determine the association between PR interval prolongation and CS. RESULTS: We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). CONCLUSIONS: A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association.

Association of a Primary Stroke Center Protocol for Suspected Stroke by Large-Vessel Occlusion With Efficiency of Care and Patient Outcomes.

Importance: While prehospital triage to the closest comprehensive stroke center (CSC) may improve the delivery of care for patients with suspected emergent large-vessel occlusion (ELVO), efficient systems of care must also exist for patients with ELVO who first present to a primary stroke center (PSC). Objective: To describe the association of a PSC protocol focused on 3 key steps (early CSC notification based on clinical severity, vessel imaging at the PSC, and cloud-based image sharing) with the efficiency of care and the outcomes of patients with suspected ELVO who first present to a PSC. Design, Setting, and Participants: In this retrospective cohort study, 14 regional PSCs unfamiliar with the management of patients with ELVO were instructed on the use of the following protocol for patients presenting with a Los Angeles Motor Scale score 4 or higher: (1) notify the CSC on arrival, (2) perform computed tomographic angiography concurrently with noncontract computed tomography of the brain and within 30 minutes of arrival, and (3) share imaging data with the CSC using a cloud-based platform. A total of 101 patients were transferred from regional PSCs to the CSC between July 1, 2015, and May 31, 2016, and received mechanical thrombectomy for acute ischemic stroke. The CSC serves approximately 1.7 million people and partners with 14 PSCs located between 6.4 and 73.6 km away. All consecutive patients with internal carotid artery or middle cerebral artery occlusions transferred over an 11-month period were reviewed, and they were divided into 2 groups based on whether the PSC protocol was partially or fully executed. Main Outcomes and Measures: The primary outcomes were efficiency measures including time from PSC door in to PSC door out, time from PSC door to CSC groin puncture, and 90-day modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome). Results: Although 101 patients were transferred, only 70 patients met the inclusion criteria during the study period. The protocol was partially executed for 48 patients (68.6%) (mean age, 77 years [interquartile range, 65-84 years]; 22 of the 48 patients [45.0%] were women) and fully executed for 22 patients (31.4%) (mean age, 76 years [interquartile range, 59-86 years]; 13 of the 22 patients [59.1%] were women). When fully executed, the protocol was associated with a reduction in the median time for PSC arrival to CSC groin puncture (from 151 minutes [95% CI, 141-166 minutes] to 111 minutes [95% CI, 88-130 minutes]; P < .001). This was primarily related to an improvement in the time from PSC door in to door out that reduced from a median time of 104 minutes (95% CI, 82-112 minutes) to a median time of 64 minutes (95% CI, 51-71.0 minutes) (P < .001). When the protocol was fully executed, patients were twice as likely to have a favorable outcome (50% vs 25%, P < .04). Conclusions and Relevance: When fully implemented, a standardized protocol at PSCs for patients with suspected ELVO consisting of early CSC notification, computed tomographic angiography on arrival to the PSC, and cloud-based image sharing is associated with a reduction in time to groin puncture and improved outcomes.

Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging.

INTRODUCTION: There is very limited data on the use of MRI based perfusion imaging to select patients with acute ischemic stroke and large vessel occlusion (LVO) for intraarterial therapy beyond 6h from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6h from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. METHODS: This is a single institution (Rhode Island Hospital) retrospective study between December 1st, 2015, and July 30th, 2016 that included patients with acute ischemic stroke and proximal LVO with CT ASPECTS of 6 or more and 6-24h from symptom onset who were assessed for mechanical embolectomy using MRI based perfusion imaging. Favorable imaging profile was defined based on prior studies as 1) DWI lesion volume (as defined as apparent diffusion coefficient<620×10-6mm2/s) of 70ml or less; 2) Penumbra volume (as defined by volume of tissue with Tmax>6s) of 15ml or greater; 3) A mismatch ratio of 1.8 or more; and 4) Volume of tissue with perfusion lesion with Tmax>10s is <100ml. Good outcome was defined as a 90-day mRS≤2. RESULTS: 41 patients met the inclusion criteria; 22 (53.7%) had favorable imaging profile and underwent mechanical embolectomy. The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (63.6% vs. 46%, p=0.13). None of the patients in our cohort had symptomatic intracereberal hemorrhage. CONCLUSIONS: MRI perfusion based imaging may help select patients with acute ischemic stroke and proximal emergent LVO for embolectomy beyond the treatment window used in most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study endovascular treatment in this patient population.

Biomarkers of Atrial Cardiopathy and Atrial Fibrillation Detection on Mobile Outpatient Continuous Telemetry After Embolic Stroke of Undetermined Source.

BACKGROUND: Biomarkers of atrial dysfunction or "cardiopathy" are associated with embolic stroke risk. However, it is unclear if this risk is mediated by undiagnosed paroxysmal atrial fibrillation or flutter (AF). We aim to determine whether atrial cardiopathy biomarkers predict AF on continuous heart-rhythm monitoring after embolic stroke of undetermined source (ESUS). METHODS: This was a single-center retrospective study including all patients with ESUS undergoing 30 days of ambulatory heart-rhythm monitoring to look for AF between January 1, 2013 and December 31, 2015. We reviewed medical records for clinical, radiographic, and cardiac variables. The primary outcome was a new diagnosis of AF detected during heart-rhythm monitoring. The primary predictors were atrial biomarkers: left atrial diameter on echocardiography, P-wave terminal force in electrocardiogram (ECG) lead V1, and P wave - R wave (PR) interval on ECG. A multiple logistic regression model was used to assess the relationship between atrial biomarkers and AF detection. RESULTS: Among 196 eligible patients, 23 (11.7%) were diagnosed with AF. In unadjusted analyses, patients with AF were older (72.4 years versus 61.4 years, P < .001) and had larger left atrial diameter (39.2 mm versus 35.7 mm, P = .03). In a multivariable model, the only predictor of AF was age ≥ 60 years (odds ratio, 3.0; 95% CI, 1.06-8.5; P = .04). CONCLUSION: Atrial biomarkers were weakly associated with AF after ESUS. This suggests that previously reported associations between these markers and stroke may reflect independent cardiac pathways leading to stroke. Prospective studies are needed to investigate these mechanisms.