Hrs Of Symptom Onset Research Articles

Abstract P638: Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Emergency Department Presentation Within a Population

Background: Hypertension is an important risk factor in the development of acute ischemic stroke (AIS). African American (AA) race is strongly associated with both hypertension and uncontrolled hypertension despite treatment, yet little is known about racial differences in presenting blood pressure (BP) in AIS. This study sought to describe differences in presenting BP and acute antihypertensive treatment between AA and white AIS patients who received and did not receive alteplase within a population. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) database for years 2005, 2010 and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥ 18 yrs of age presenting to a local ED within 4.5 hrs of symptom onset. Candidates were stratified by race and alteplase use. Socio-demographics, stroke risk factors, stroke severity, BP on arrival, and acute BP treatment were compared using chi-square, t-tests or Wilcoxon rank sum test, as appropriate. Results (Table 1): Of 1838 AIS patients included in the analysis, 392 (21%) received IV alteplase. AA patients were younger in both groups who received and did not receive alteplase. On presentation, AA stroke patients had higher diastolic BP. AA patients were more likely to receive 2 or more BP lowering medications compared to white patients in the alteplase treated group and the untreated group. Conclusion: AA patients presenting within 4.5 hours of AIS symptom onset are more likely to have elevated diastolic BP and to receive multiple BP lowering medications compared to white patients. These findings were significant regardless of alteplase treatment. To our knowledge, we report the first population-based distribution of BP, and medical treatment of BP, upon presentation to an ED in AIS. Further study is needed to determine if these racial differences in elevated BP and refractoriness of BP and/or aggressive treatment contribute to outcome differences.

Abstract P870: Disparities in Timelines of Hospital Presentation in Patients With Ischemic Stroke: Florida Stroke Registry

Introduction: Characterizing the population of ischemic stroke (IS) patients presenting in the delayed reperfusion window is important to ensure equitable implementation of recently updated acute IS treatment guidelines. Methods: Florida Stroke Registry (FSR) data from Jan 2010 - Jan 2020, provided a complete dataset of 98,372 IS cases presenting within 24 hrs of symptom onset. Generalized linear regression analysis was used to identify differences between delayed IS cases (>4.5 hours) versus those presenting within the early time window (≤ 4.5 hr). Results: A total of 60,311 presented with 4.5 hr (median age 74 (interquartile range (IQR) 62-83), 49% women, 67% white, 15% Black, 18% Hispanic), and 38,061 presented in the delayed window (median age 72 (IQR 61- 82), 49% women, 63% white, 18% Black, 19% Hispanic). As compared to early presenters, delayed window patients were younger (OR 1.23, 95% confidence interval (CI) 1.17-1.29); more Black vs. White (OR 1.12, 95% CI 1.06-1.18), have higher NIHSS (OR 1.05, 95% 1.01-1.10), insured (OR 1.18, 95% 1.11-1.25), presenting to an academic hospital (OR 1.24, 95% CI 1.09-1.40) in South Florida (OR 1.23, 95% CI (1.08, 1.41)); less likely to arrive by EMS (OR 0.59, 95% CI 0.56-0.62) and less likely to receive reperfusion therapies (OR 0.86, 95% CI 0.79-0.94). In multivariable analysis adjusting for age, race, NIHSS, EMS, reperfusion therapies, hospital academic status and region, delayed window presentation was negatively associated with discharge home (OR 0.82, 95% CI 0.76-0.89), and ambulatory status at discharge (OR 0.89, 95% CI 0.84-0.93). Conclusion: We found significant race, ethnic, socioeconomic and geographical disparities amongst those presenting in the delayed vs early reperfusion time windows with consequential effects on patient outcomes. Stroke education to younger minorities and adaptation of regional stroke systems of care are urgently needed.

Abstract WP346: Factors Associated With TPA Refusal via Telestroke

Introduction: tPA refusal occurs 4-8% when offered in-person for acute ischemic stroke (AIS). Telestroke (TS) has increased tPA use for AIS, but entails non-traditional patient-physician interaction. Refusal accounts for 16-18% of reasons patients do not receive tPA via TS. We report tPA refusal incidence and associated factors in our TS network. Methods: We identified patients in our TS registry (9/2015-12/2018) who were offered tPA for suspected AIS within 4.5 hrs of symptom onset. We compared demographics, clinical characteristics, and outcomes associated with tPA refusal. Results: Of 1242 patients offered tPA in our TS network, 101 (8%) refused. Of 1376 patients that did not receive tPA, refusal accounted for 7% (101/1376). Patients refusing tPA were younger than those that accepted (median age 61 vs 66, p=0.01) (Table 1). Male patients were less likely to decline tPA (OR 0.65, CI 0.43-0.98), and non-Hispanic black patients were more likely (OR 1.86, CI 1.18-2.93). tPA refusal was associated with mild stroke (median NIHSS 3 vs 7, p<0.0001) and prior ischemic stroke (OR 1.66, CI 1.06-2.60). Patients with final diagnosis of stroke vs stroke mimic were less likely to refuse tPA (OR 0.23, CI 0.15-0.36). Insurance status and baseline functional status were similar among patients who accepted and refused tPA. Patients who accepted tPA were more likely discharged to inpatient rehab. tPA was primarily refused for risk of adverse effects and mild/improving symptoms. Conclusion: Refusal contributes to lower utilization of tPA. Our incidence of refusal was comparable to historical data in non-TS settings. While some factors associated with tPA refusal via TS are consistent with historical data on tPA refusal in-person, differences in patient age, gender, and race/ethnicity still warrant further investigation. Specifically, studies are needed to understand if tPA refusal is related to care delivered via TS, or if patients are more reluctant due to perceived risks of tPA via TS.

Abstract WMP61: RNA Expression Signature to Diagnosis Stroke Etiology by Atrial Fibrillation versus Large Artery Atherosclerosis Cause: A BASE Clinical Trial Analysis

Background: Identifying atrial fibrillation in embolic stroke of ischemic stroke populations would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our goal was to determine if blood gene expression signatures accurately differentiated patients with atrial fibrillation from large artery stroke patients. Methods: The BASE trial enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAXgene tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, LLC, Dayton, OH) using Affymetrix HTA micro arrays. Approximately 38,000 genes on the HTA microarray were filtered to eliminate genes with low expression or high CV (> 10%) when run on replicate samples leaving 9,513 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 23 gene diagnostic signature. Results: There were 58 patients enrolled between 18 and 24 hours of symptom onset, with NIHSS>5, 27 (47%) with atrial fibrillation cause of stroke and 31 (53%) with large artery stroke; 64% were male, and median (IQR) age was 69.7 (62.8, 81.0). Median (IQR) time from symptoms to sample collection was 1323.5 (1208.8, 1381.3) minutes. Coexistent pathology at presentation was high blood pressure 49 (84%), hyperlipidemia 28 (48%), diabetes 9 (16%), and coronary artery disease 15 (26%). The panel was able to distinguish atrial fibrillation from large vessel stroke with a C-statistic 0.92 (0.55-1.0, 95% CI), sensitivity 0.90 (0.51-1.0, 95% CI) and specificity of 0.85. Conclusion: RNA expression differentiates strokes due to atrial fibrillation from large artery stroke and may have therapeutic and outcome implications in ischemic stroke populations.

Abstract WMP16: Radiographic Characteristics of Mild Ischemic Stroke Patients With Visible Intracranial Occlusion; Data From the INTERRSeCT Multi-Center Prospective Imaging Study

Background: Early neurological deterioration occurs in one third of mild ischemic strokes primarily due to the presence of a visible intracranial vessel occlusion. We studied the clinical and vascular occlusive patterns, thrombus characteristics and recanalization rates in patients with mild ischemic stroke and a visible intracranial vessel occlusion. Methods: We studied patients enrolled in the INTERRSeCT multi-center prospective study of acute ischemic strokes with visible intracranial occlusions. We compared the clinical, thrombus characteristics and recanalization rates between two groups, 1) mild ischemic NIHSS≤5 and 2) moderate/severe strokes NIHSS >5, with or without IV alteplase treatment. Vessel imaging with CT angiography (CTA) was initiated within 12 hrs of symptom onset followed by repeat imaging with CTA or cerebral angiogram (before endovascular therapy; EVT) within 4 +/- 2 hrs. Results: Among 575 patients with a visible intracranial occlusion, 12.9% had mild strokes with similar patient characteristics compared to the moderate/severe stroke group. Residual flow grades were similar between the two groups (residual flow grades I-II, 21% vs 19%). The mild stroke group had longer symptom-onset-to -CT (240 vs 167 min, p=0.02) and -CTA (246 vs 172 min, p=0.02) times, longer CT to needle time (35 vs 26 min, p<0.01), more distal occlusions (49% in M2 of the middle cerebral artery), lower clot burden scores 9 (6-9) vs 6 (4-9) (p<0.001), better collateral flow (9.1 vs 7.6, p=0.001) and no association between residual flow grade and recanalization. The mild stroke group was less likely to receive IV alteplase (62% vs 84%), but more likely to recanalize (rAOL2b and 3) with (46% vs 29%) and without (38% vs 26%) IV alteplase. Conclusion: Some thrombus characteristics that predict recanalization in more severe strokes do not predict recanalization in mild strokes, such as residual blood flow through intracranial occlusions, though they have similar cardiovascular risk factors. Less than half of patients with mild strokes recanalized with IV alteplase which was associated with longer decision-making times suggesting that more aggressive use of thrombolytics and/or EVT may be viable treatment options in this population.

Abstract TMP100: Biology of Stroke: Role of ELL2, GLIPR1, MAPKAPK3 Genes in Identifying Atrial Fibrillation Cause of Stroke

Background: An accurate test to identify atrial fibrillation in ischemic stroke populations would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our goal was to utilize a database of genes appearing in literature determine if gene expression accurately differentiate patients with atrial fibrillation from those with large artery stroke. Methods: BASE enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAXgene tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, LLC, Dayton, OH) using Affymetrix HTA micro arrays. Genes were filtered to those appearing in stroke literature resulting in 543 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 3 gene diagnostic signature with robust performance conserved across literature consisting of ELL2, GLIPR1, MAPKAPK3 genes. Results: Overall, 99 patients were enrolled with NIHSS>5, 68 (69%) with atrial fibrillation cause of stroke and 31 (31%) with large artery stroke; (48%) were male, and median (IQR) age was 74.4 (66.1,81.7). Median (IQR) time from symptoms to blood collection was 420 (322, 472) minutes. Coexistent pathology at presentation included high blood pressure 84 (85%), hyperlipidemia 45 (45%), diabetes 31 (31%), and coronary artery disease 38 (38%). Three genes were able to differentiate atrial fibrillation from large vessel stroke; C-statistic 0.86 (0.52-1.0, 95% CI), sensitivity 0.93 (0.56-1.0, 95% CI) and specificity of 0.58 (0.35-0.81, 95% CI ). Conclusion: RNA expression of ELL2, GLIPR1, MAPKAPK3 genes differentiates atrial fibrillation stroke patients from those with large artery stroke, and may have therapeutic and outcome implications.

Abstract 50: RNA Expression for Diagnosis of Stroke Etiology Differentiating Large Artery and Cardioembolic Stroke: Analytical Validation of Testing From the BASE Clinical Trial

Background: An accurate test to differentiate large artery stroke (LAS) patients from those with cardioembolic stroke (CES) would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our purpose was to utilize blood gene expression signatures for accurately differentiating LAS from CES acute stroke etiologies. Methods: The BASE trial enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAX tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, Dayton, OH) using Affymetrix HTA microarrays. Genes on the HTA microarray were filtered to eliminate genes with low expression or high CV (> 10%) when run on replicate samples leaving 9,513 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 45 gene diagnostic signature. Results: This is a planned interim cohort study of the 1700 patients enrolled in the BASE trial that does not include lacunar strokes, TIA, or stroke mimics. Overall, 222 patients were enrolled with NIHSS>5, 70 (32%) with LAS and 152 (68%) with CES; 59% were male, and median (IQR) age was 70.7 yrs (62.0, 80.2). Median (IQR) time from symptom onset to blood collection was 1200 (448, 1568) minutes. Coexistent pathology at presentation included atrial fibrillation 90 (48%), hypertension 153 (82%), hyperlipidemia 87 (47%), diabetes 60 (32%), and coronary artery disease 70 (37%). Patients were randomly divided into training (148), early symptom onset (<18hrs) validation (39) and a late symptom onset (>18 hrs) validation (35). The diagnostic gene signature results in the early validation cohort distinguished LAS from CES; C-statistic 0.78 (0.50-1.0, 95% CI), sensitivity 0.90 (0.55-1.0, 95% CI) and specificity of 0.70 (0.43-1.0, 95% CI). Conclusion: Early RNA expression differentiates large artery stroke patients from those with cardioembolic stroke, and may have therapeutic and secondary prevention implications.

<p>Reasons for delayed admission after stroke: results of a qualitative and quantitative survey</p>

Background: Acute stroke treatment shows time-dependent benefit to prevent disability. Public information campaigns and streamlining of emergency management have been performed, but still, only one-third of acute stroke patients are admitted >4.5 hrs after symptom onset.Patients and methods: We interviewed 15 patients, presenting >4.5 hrs after symptom onset, regarding symptom recognition, emotions and their first action after symptom onset. Recorded interviews were analyzed by standardized descriptive analysis. Based on the results, a quantitative survey was developed. One hundred consecutive stroke unit patients surveyed to compare patients presenting within 4.5 hrs and more than 4.5 hrs of symptom onset.Results: Patients predominantly noticed symptoms by themselves. The most commonly expressed feelings were uncertainty and shame. The most frequent action was waiting. Patients described moderate knowledge about stroke in general, but felt less informed regarding their stroke risk. Magazines (51%) were the most frequently indicated source of information, while general practitioners only accounted for 26%. Significantly better knowledge was shown in the answers on closed questions compared to open questions, although the same items were named.Conclusion: Shame, uncertainty and insufficient individual risk knowledge about stroke were the most important factors delaying admission after stroke. Individual risk counseling could be investigated to close the gap between general stroke knowledge and recognition of own stroke risk.

Assessment of Serum UCH-L1 and GFAP in Acute Stroke Patients.

A rapid and reliable diagnostic test to distinguish ischemic from hemorrhagic stroke in patients presenting with stroke-like symptoms is essential to optimize management and triage for thrombolytic therapy. The present study measured serum concentrations of ubiquitin C-terminal hydrolase (UCH-L1) and glial fibrillary astrocytic protein (GFAP) in acute stroke patients and healthy controls and investigated their relation to stroke severity and patient characteristics. We also assessed the diagnostic performance of these markers for the differentiation of intracerebral hemorrhage (ICH) from ischemic stroke (IS). Both UCH-L1 and GFAP concentrations were significantly greater in ICH patients than in controls (p < 0.0001). However, exclusively GFAP differed in ICH compared with IS (p < 0.0001). GFAP yielded an AUC of 0.86 for differentiating between ICH and IS within 4.5hrs of symptom onset with a sensitivity of 61% and a specificity of 96% using a cut-off of 0.34ng/ml. Higher GFAP levels were associated with stroke severity and history of prior stroke. Our results demonstrate that blood UCH-L1 and GFAP are increased early after stroke and distinct biomarker-specific release profiles are associated with stroke characteristics and type. We also confirmed the potential of GFAP as a tool for early rule-in of ICH, while UCH-L1 was not clinically useful.

Abstract 187: Magnetically-Enhanced Diffusion (MED™) of intravenous tPA in Acute Ischemic Stroke: A Pilot Safety and Feasibility Trial

Background: The MED device (Pulse Therapeutics, St. Louis, MO) uses an external magnet system and IV-administered magnetic particles to enhance delivery tPA within stagnant-flow vessels. We present the first human data from a safety feasibility study examining the utility of the technology for large-vessel intracranial occlusions. Methods: AIS patients (63-91y; median 82y) with acute M1 or M2 occlusions were treated within 4.5hrs of symptom onset. Magnetic particles were concurrently delivered to standard-dose IV-tPA. TICI Grade flow in the target vessel segment was assessed prior and post therapy via CTA and/or MRA. Results: Seven patients were enrolled with M1(6) and M2(1) arterial occlusion, with clot length &gt;6mm [2(6-8mm), 4(8-10mm), 1(&gt;25mm)]. Median baseline NIHSS was 16(3-24). All patients receiving post-therapy imaging demonstrated early recanalization (+3pnt median TICI improvement, FIGURE) accompanied with 24hr NIHSS improvement (3-15pnts; median 15pnts), sustained out to 90d. One delayed hemorrhage (9hrs post onset) was identified, however, immediate post-therapy imaging showed complete recanalization without hemorrhage. Reversible transient acute hypotension was observed in 5 patients during particle/tPA infusion. This response is associated with particle surface charge. Conclusion: These early data support the safety and efficacy of the MED system for enhancing the efficacy of IV tPA in an Emergency Department environment. Further studies will involve modifications of particle surface charge.

Abstract W MP35: The Re-examining Acute Eligibility for Thrombolysis Task Force Criteria for Defining Rapidly Improving Stroke Symptoms: A Pilot Prospective Study of tPA Treatment Decisions

Background: Rapidly Improving Stroke Symptoms (RISS) is a controversial exclusion criterion for tPA for acute ischemic stroke (AIS). Prior studies suggest 4-44% of AIS patients eligible are not given tPA solely because of RISS and their outcome is not invariably benign. In 2013 The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force published new criteria for defining RISS. Objectives: To estimate frequency and outcome of RISS based on TREAT criteria in a prospective cohort of consecutive AIS patients. Methods: Serial NIH Stroke Scales (NIHSS) for AIS patients admitted within 4.5 hrs of symptom onset were performed every 20 (±5) minutes until a treatment decision (tPA vs no tPA) was made, independent of the study. Improvement was calculated as the difference between baseline NIHSS (bNIHSS) and treatment decision NIHSS (tdNIHSS). Per TREAT criteria, RISS was defined as improvement to a non-disabling mild stroke and none of the following deficits present: complete hemianopsia; severe aphasia; visual or sensory extinction; any weakness limiting sustained effort against gravity; any total NIHSS &gt;5; any remaining deficit considered potentially disabling by the patient and the treater. We compared frequency and outcomes of TREAT-based RISS with the most commonly used RISS definition [≥4 point improvement (4PI) on NIHSS]. Good outcome was defined as modified Rankin Scale of 0-1 at 3 months. Results: Fifty AIS were enrolled: mean age 65 yrs; median bNIHSS=5 (IQR 2,11); median tdNIHSS=5 (IQR 2,9); tPA was given in 23 (46%). Five/50 (10%) were RISS according to TREAT criteria, all 5 had good outcome at 90 days without tPA. Five/50 (10%) were RISS according to 4PI, and only 2/5 (40%) had good outcome while 1/5 (20%) died. Conclusions: This is the first preliminary, prospective estimate of RISS frequency and outcome according to TREAT criteria vs. a commonly used RISS definition. Our pilot data suggest the TREAT RISS frequency is in the lower end of prior retrospective estimates and, as a more restrictive definition, may better predict good outcome of RISS in future, larger studies.

Abstract 146: Optimal Workflow and Process Based Performance Measures for Endovascular Therapy in Acute Ischemic Strokes From the Star Registry

Introduction: We report on workflow and process based performance measures and its impact on clinical outcome in STAR, a recent international, multi-center, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hrs of symptom onset. Methods: A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The following time intervals were measured: stroke onset to ED arrival; ED to baseline CT; CT to groin puncture; groin puncture to thrombus identification; thrombus identification to start of IA therapy and start of IA therapy to reperfusion. Effects of time of day, general anesthesia (GA) utilization and multi-modal imaging on workflow were evaluated. Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome (90-day mRS 0-2) were analyzed. Results: Distribution of all interval times are illustrated in Figure 1a. Median hospital arrival to final DSA run time was 150 mins (IQR=97 mins). Hospital arrival to final DSA run time was faster in women than men (158 vs. 139 mins). General anesthesia increased CT to groin puncture time by 22 mins and groin puncture to final DSA run by 13 minutes. Time of day or week did not effect interval times. CT based multi-modal imaging reduced time from CT to groin puncture by 24 mins. For each 60-minute increase in time from symptom onset to TICI 2b/3 (or final DSA run), a 33% decrease in odds of good clinical outcome (p&lt;0.01) was noted independent of the effect of increased age (p&lt;0.01), higher baseline NIHSS (p=0.02), and lower ASPECTS score (p=0.02). (Figure 1b) Conclusion: Interval times in the STAR study is a reflection of current IA therapy for patients with acute ischemic stroke. Improving workflow processes and reducing time to reperfusion could improve clinical outcomes further.

Abstract WP33: Reduced Cerebral Blood Flow on Acute Whole Brain CT Perfusion Best Predicts Hemorrhagic Transformation

Objective: Hemorrhagic transformation in ischemic stroke is a potentially life threatening complication of thrombolysis. Using perfusion MRI, very low cerebral blood volume (VLCBV) strongly predicts hemorrhagic transformation after reperfusion. CT perfusion (CTP) is currently more widely accessible than MRI and recent data have shown that CT relative cerebral blood flow (relCBF) provides a better estimate of infarct core than CBV. We aimed to determine the optimal parameter to predict hemorrhagic transformation using whole brain CTP. Methods: Patients with ischemic stroke were imaged with whole brain CTP within 6hrs of symptom onset. Hemorrhagic transformation was assessed on CT/MRI within 7 days of stroke using ECASS grade. CBF and CBV were analyzed within a relative time to peak &gt;4sec region of interest. Results were expressed as volumes below a given percentile relative to the contralateral hemisphere (relCBF and relCBV). Receiver operating characteristic (ROC) and logistic regression analysis were performed to determine the optimal parameter and percentile threshold correlating with parenchymal hemorrhage (PH). Results: 128 patients with acute CTP were analyzed, median age 76yr (IQR 66-83), median NIHSS 13 (IQR 9-16), 59% received IV thrombolysis. 11 patients had PH on follow-up. On ROC analysis, the optimal threshold for very low CBF (VLCBF) was at the &lt;0 th centile. VLCBF was significantly associated with PH in ROC analysis (AUC=0.760, p&lt;0.01) whereas VLCBV (AUC 0.638 at &lt;5 th centile, 0.618 at &lt;2.5 th centile, 0.440 at &lt;0 th centile) was not significant. Using VLCBF, the optimal lesion volume to predict PH was &gt;3mL with OR 12.0 (95%CI 2.4-58), sensitivity 0.82 (95%CI 0.48-0.98), specificity 0.73 (95%CI 0.64-0.80), negative predictive value 0.98 (95%CI 0.92-1.0) and positive predictive value 0.22 (95%CI 0.11-0.38). In logistic regression, PH was associated with increased VLCBF (p&lt;0.01) but not with VLCBV (p=0.08). The Bayesian information criterion for VLCBF compared to VLCBV was +5 indicating improved model fit. Conclusions: VLCBF appears to be more reliably associated with hemorrhagic transformation than VLCBV when CT perfusion is used. This may be due to reduced ability of VLCBV to distinguish regions of ischemia from normal white matter.

Abstract 194: Preliminary Results from the FIRST Trial: Natural History of Acute Stroke from Large Vessel Occlusion

Purpose: Current literature has limited information on the natural history of the stroke cohort eligible for mechanical thrombectomy. The placebo group from the PROACT II study is often used as a historical control, despite differences in entry criteria. Reported herein are data in a stroke cohort eligible for mechanical thrombectomy but untreated due to unavailability or inability to initiate endovascular treatment within the 8-hr window due to delayed presentation. The goal is to compare the functional independence rate with the PROACT placebo group. Methods: The FIRST Trial is a prospective, multicenter, natural history study of a stroke cohort eligible for but untreated by mechanical thrombectomy presenting within 8 hrs of symptom onset from a large vessel occlusion and a NIHSS of at least 10. The primary endpoint is functional outcome at 90 days as defined by a mRS 0-2. Results are reported from an interim analysis. Results: Fifty-nine (59) patients were enrolled and met study criteria for this interim analysis. The mean age was 68.2 ± 17 years; median NIHSS was 18 (5-34). Target vessel occlusions were in the ICA (35.7%), MCA (60.7%), and other (3.6%). At admission, the TIMI 0-1 rate was 89% (49/55), and the TICI 0-1 rate was 89% (48/54). Of these, only 10% (3/30) showed spontaneous recanalization (TIMI 2-3 or TICI 2a-3). Eleven of 55 (20%) patients achieved a good 90-day outcome, and 24 of 59 (40.7%) died. The serious adverse event rate was 52.6% (30/57), including respiratory failure (8 cases) and pneumonia (4 cases). A total of 6 (10%) patients suffered intracerebral hemorrhage (ICH). Below is a comparison of the MCA cohort vs. PROACT II placebo patients. Conclusion: Compared with PROACT II placebo patients, the stroke cohort eligible for mechanical thrombectomy who were untreated have a lower rate of recanalization and worse outcome. These results indicate it may not be appropriate to use the PROACT placebo patients as historical controls for mechanical thrombectomy trials.

Persistent Leukocytosis: A Persistent Problem for Stroke Patients (P06.229)

Objective: To determine the clinical significance of persistent versus transient leukocytosis in acute ischemic stroke (AIS). Background Transient but significant elevation in white cell counts have been described after status epilepticus, head trauma, and spinal cord injury, independent of steroid administration or infection.Leukocytosis may be secondary to alpha adrenergic stimuli, endogenous corticosteroid increase, or a combination of the two. Design/Methods: Patients who presented with AIS to our center within 48hrs of symptom onset between 7/2008 and 6/2010 were retrospectively identified by chart review. Patients were included if they had leukocytosis on admission (defined as WBC count >11,000/μl based on laboratory reference range). Demographics, NIHSS scores, leukocyte counts, length of stay (LOS), disposition, and good functional outcome (mRS 0-2) were compared in patients with persistent (still elevated 48hrs after admission) vs. transient (resolved Results: Of the 438 patients screened, 49 had leukocytosis on admission; (mean age 61.5, median admission NIHSS 9, mean LOS 8.5 days, and median discharge mRS 3). 24 (49%) had persistent leukocytosis. When compared to patients with transient leukocytosis, baseline NIHSS was significantly higher in the persistent leukocytosis group (p=0.0476), and the mean LOS was significantly longer (p=0.044). More people with transient leukocytosis had a good functional outcome (44% vs 16%, p=0.006). After adjusting for NIHSS, persistent leukocytosis was not an independent predictor of good functional outcome (OR=2.5, 95%CI 0.562-10.7, p=0.2322). NIHSS correlated significantly with persistence of leukocytosis (r=0.306, p=0.0044). Conclusions: Persistent leukocytosis, present in half of patients with AIS, is associated with higher baseline NIHSS scores, longer LOS, and poorer functional outcomes. Persistent leukocytosis is tightly linked with baseline stroke severity and may serve as a predictor of poor patient outcomes the setting of AIS. Disclosure: Dr. Boehme has nothing to disclose. Dr. Kumar has nothing to disclose. Dr. Gillette has received research support from the Infectious Disease Society of America. Dr. Siegler has nothing to disclose. Dr. Albright has nothing to disclose. Dr. Martin-Schild has nothing to disclose.

Abstract 2706: Patients with the Malignant Profile Within 3 Hours of Symptom Onset have Very Poor Outcomes Following IV tPA Therapy

Background: The “Malignant profile” is an MRI pattern that is associated with poor outcomes (mRS 5-6) following reperfusion in the 3-6 hr time window. The aim of this study was to estimate the incidence and prognostic implications of the Malignant profile, as identified by CT perfusion (CTP), in patients treated with tPA &lt;3 hrs from stroke onset. Methods: Consecutive patients treated with iv tPA at the Stanford Stroke Center from May 2009 to May 2011 who had CTP performed prior to tPA therapy, and within 3 hrs of symptom onset, were included. Perfusion data were acquired in cine mode on 16 and 64-row CT scanners; 2 separate scans were done yielding either 4 cm or 8 cm coverage depending on the scanner type. The incidence of the Malignant profile, based on the previously published definition of a Tmax &gt;8 sec perfusion lesion &gt; 85 mL, was assessed using a fully automated software program (RAPID). This program also estimates the infarct core based on cerebral blood flow (rCBF) and cerebral blood volume (rCBV) thresholds &lt;30% of the contralateral hemisphere. Poor outcome was defined as a mRS of 5-6 at 30 days. A receiver operating characteristic (ROC) curve analysis was done to identify Tmax and core volume thresholds that optimally define the Malignant profile (high specificity for poor outcome). Results: 121 patients were treated with iv tPA. Of these, 42 patients had an interpretable CTP performed within 3 hrs of symptom onset. Mean age was 75±14 years and median (IQR) NIHSS was 13 (6-19). Five patients (11%) met the pre-specified criteria for the Malignant profile and all 5 died during the acute hospitalization. ROC analysis determined that the optimized criteria were either a PWI Tmax &gt;8 sec lesion &gt;86 mL or an infarct core &gt;53 mL (both criteria had 100% specificity and 56% and 67% sensitivity respectively). The optimized criteria identified 6 patients as Malignant (14%). The poor outcome rate in these patients was 100% vs. 8.3% in the 36 patients non-malignant patients (p&lt;0.001). Conclusion: The incidence of the Malignant Profile is about 10-15% in tPA eligible patients imaged within 3 hrs of symptoms onset. The clinical outcome of these patients is very poor despite iv tPA therapy. This finding is consistent with data from patients treated with iv tPA in the 3-6 hr window. Further study is warranted to verify if CTP can reliably identify a subgroup of patients who do not benefit from iv tPA within 3 hours.

Abstract 2126: Twoaces (tia Work-up Asoutpatient: Assessment Of Clincal Efficacy And Safety)

Background: Much controversy exists as to which TIA patients need to be admitted to the hospital for evaluation and treatment and which can be sent home. One commonly used trigae tool is the ABCD 2 score (Age, presenting Blood Pressure, Clinical symptoms and Duration, and Diabetes). Although this tool gives good information for determining populations at low risk (score of 0-3) and high risk (score of 6-7) of stroke after TIA, it leaves a large moderate risk population (score of 4-5) for whom no clear triage guidance can be given. As previous studies have found large artery atherosclerosis to be a potent risk factor for stroke after TIA, we attempted to further delineate low and high risk TIA populations with the addition of non-invasive arterial imaging to the ABCD 2 score. Methods: All patients referred to the Stanford Stroke Service for possible TIA within 72 hrs of symptom onset between July 2007 and February 2010, and all patients referred to the Highland Park Stroke Service for possible TIA within 72 hrs of symptom onset after October 2009 were screened for enrollment in this observational study. Exclusion criteria included age &lt;18 years, use of TPA at initial presentation, and symptoms lasting &gt;24 hours. 352 patients were invited to enroll, 3 refused. Of the 349 enrolled, follow-up was obtained in 346 patients at 30 days. Patients were placed into two groups: 1) those with ABCD 2 scores of 0-3 or scores of 4-5 AND no sign of hemodynamically significant stenosis in an artery within the distribution of the TIA (Low Risk Group); and 2) those with ABCD 2 scores of 6-7 or scores of 4-5 AND a hemodynamically significant stenosis in an artery within the distribution of the TIA (High Risk Group). Non-invasive arterial imaging included CT angiogram, MR angiogram, and carotid ultrasound - all used at the discretion of the treating physician. 30 day stroke rates with 95% confidence intervals were recorded. Results: Of the 346 patients enrolled, 295 (85.3%) fell into the "Low Risk Group" based on ABCD 2 scoring and non-invasive arterial imaging. Within that group, the stroke rate at 30 days was 1.0% (3 strokes, 95% CI 0.2-3.1%). Within the "High Risk Group", the stroke rate at 30 days was 5.9% (3 strokes, 95% CI 1.4-16.5%). Within the "Low Risk Group", all 3 of the strokes occurred in patients with ABCD 2 scores of 4-5 (3/133 patients - 2.3% stroke rate with 95% CI 0.5-6.7%). The overall stroke rate was 6/346 (1.7%, 95% CI 0.7-3.8%). Conclusions: In our observational study we found that the overall 30 day stroke rate after TIA was quite low. The percentage of all TIA patients falling into the “Low Risk Group” was quite high, and these patients had a particularly low rate of stroke at 30 days. Given the high number of "Low Risk" patients and the low rate of stroke in that group at 30 days, the vast majority of TIA patients could likely be safely evaluated in an rapid outpatient setting provided that the treating physician is confident of the diagnosis.

Antihypertensive treatment of acute cerebral hemorrhage*

To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset. A traditional phase I, dose-escalation, multicenter prospective study. Emergency departments and intensive care units. Patients with intracerebral hemorrhage with elevated systolic blood pressure > or = 170 mm Hg who present to the emergency department within 6 hrs of symptom onset. Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort. Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs. Safety stopping rules based on neurologic deterioration and serious adverse events were prespecified and approved by an NIH-appointed Data and Safety Monitoring Board, which provided oversight on subject safety. Each subject was followed-up for 3 months to preliminarily assess mortality and the clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 months. The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage.

Abstract 569: NT-proBNP is an Important Independent Predictor of Clinical Events after Primary PCI for STEMI

Acute myocardial infarction with ST-segment elevation (STEMI) remains a major global public health issue. Despite advances in therapy, patients remain at risk for death, repeat myocardial infarction (MI) shock and heart failure (HF). Novel markers that predict those at risk are needed. We studied 903 STEMI patients in The Assessment of Pexelizumab in Acute Myocardial Infarction trial (which enrolled STEMI patients presenting &lt; 6 hrs of symptom onset who were to undergo primary PCI) in a case-control design (cases selected based on the trial’s primary composite outcome - death, shock or HF - and matched on age, gender and infarct location to controls). NT-proBNP (pg/ml) was measured at randomization and 24 hrs. Outcomes (individually and the composite) of death, shock, and HF at 90 days were examined by quartiles of NT-proBNP. A CART model was used to categorize adjusted risk. NT-proBNP was higher in patients who had events. Patients with higher NT-proBNP levels at baseline (median symptom onset to randomization 2.7 hrs) and 24 hrs had more events (composite p&lt;0.001; death p&lt;0.0001; HF p&lt;0.0001; shock p=0.05) - See figure . Using the CART model (adjusted for age, gender and infarct location), baseline Killip class and NT-proBNP could further subcategorize patients into 90 day mortality categories 4%, 10%, 30%, and 53%. In fact, only 4 patients (1%) with a 24 hour NT-proBNP &lt;999 pg/ml had any event in the next 90 days. Although the overall prognosis in STEMI patients undergoing primary PCI is good, NT-proBNP performed early and at 24 hrs provides important prognostic information for predicting negative outcomes i.e. shock, heart failure and death. Figure. Kaplan-Meier curve for the primary composite outcome stratified by baseline NT-proBNP (a), or 24 hour NT-proBNP (b).

Abstract 6178: Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) - Six Month Outcomes

Patients who present with ST-elevation myocardial infarction to hospitals without percutaneous coronary intervention (PCI) often cannot undergo primary PCI in a timely manner and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis, using contemporary stents and pharmacotherapy, has not been studied in a large adequately powered randomized trial. To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hrs after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI). Pts presenting to non-PCI centres with STEMI within 12 hrs of symptom onset and with high-risk features were randomized to a pharmacoinvasive strategy (transfer for PCI within 6 hrs of fibrinolysis) or to standard treatment after fibrinolysis (which included rescue PCI as required for ongoing chest pain and &lt; 50% resolution of ST-elevation at 60 –90 minutes). For standard treatment pts who did not require rescue PCI, cardiac catheterization was encouraged beyond 24 hrs. All pts received ASA and antithrombin therapy (unfractionated heparin or enoxaparin for age &lt;75 yrs); use of upfront clopidogrel was strongly encouraged; all other therapies were left to the discretion of the treating physician. The primary endpoint was the 30-day composite of death, reinfarction, recurrent ischemia, heart failure or shock. All patients were contacted at 6-months and 1-year for death and reinfarction, and all events were independently adjudicated. 1,059 pts were enrolled as of December 31, 2007. The preliminary 30-day results were recently presented, showing a 45% reduction in the primary endpoint with the pharmacoinvasive strategy (10.6% vs. 16.6%, p=0.01), with no difference in major bleeding complications. This study is the largest randomized trial to date comparing a pharmacoinvasive strategy with standard care after fibrinolysis. The 6-month outcomes will demonstrate whether the significantly lower rates of ischemic complications seen with the pharmacoinvasive strategy at 30-days are sustained and translate into lower rates of death or reinfarction at 6 months.