Random expert sampling for deep learning segmentation of acute ischemic stroke on non-contrast CT.

BACKGROUND: Outlining acutely infarcted tissue on non-contrast CT is a challenging task for which human inter-reader agreement is limited. We explored two different methods for training a supervised deep learning algorithm: one that used a segmentation defined by majority vote among experts and another that trained randomly on separate individual expert segmentations. METHODS: The data set consisted of 260 non-contrast CT studies in 233 patients with acute ischemic stroke recruited from the multicenter DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. Additional external validation was performed using 33 patients with matched stroke onset times from the University Hospital Lausanne. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. The median of volume, overlap, and distance segmentation metrics were determined for agreement in lesion segmentations between (1) three experts, (2) the majority model and each expert, and (3) the random model and each expert. The two sided Wilcoxon signed rank test was used to compare performances (1) to 2) and (1) to (3). We further compared volumes with the 24 hour follow-up diffusion weighted imaging (DWI, final infarct core) and correlations with clinical outcome (modified Rankin Scale (mRS) at 90 days) with the Spearman method. RESULTS: The random model outperformed the inter-expert agreement ((1) to (2)) and the majority model ((1) to (3)) (dice 0.51±0.04 vs 0.36±0.05 (P<0.0001) vs 0.45±0.05 (P<0.0001)). The random model predicted volume correlated with clinical outcome (0.19, P<0.05), whereas the median expert volume and majority model volume did not. There was no significant difference when comparing the volume correlations between random model, median expert volume, and majority model to 24 hour follow-up DWI volume (P>0.05, n=51). CONCLUSION: The random model for ischemic injury delineation on non-contrast CT surpassed the inter-expert agreement ((1) to (2)) and the performance of the majority model ((1) to (3)). We showed that the random model volumetric measures of the model were consistent with 24 hour follow-up DWI.

Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow.

BACKGROUND: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy. METHODS: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes. RESULTS: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (ß 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (ß 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence. CONCLUSION: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters.

BACKGROUND: Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters. METHODS: We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass. RESULTS: The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min). CONCLUSION: BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

CT perfusion to measure venous outflow in acute ischemic stroke in patients with a large vessel occlusion.

BACKGROUND: Robust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute ischemic stroke treated by thrombectomy. However, VO measurements are laborious and require neuroimaging expertise. OBJECTIVE: To develop a semi-automated method to measure VO using CTA and CT perfusion imaging studies. METHODS: We developed a graphical interface using The Visualization Toolkit, allowing for voxel selection at the confluence and bilateral internal cerebral veins on CTA along with arterial input functions (AIFs) from both internal carotid arteries. We extracted concentration-time curves from the CT perfusion study at the corresponding locations associated with AIF and venous output function (VOF). Outcome analyses were primarily conducted by the Mann-Whitney U and Jonckheere-Terpstra tests. RESULTS: Segmentation at the pre-selected AIF and VOF locations was performed on a sample of 97 patients. 65 patients had favorable VO (VO+) and 32 patients had unfavorable VO (VO-). VO+ patients were found to have a significantly shorter VOF time to peak (8.26; 95% CI 7.07 to 10.34) than VO- patients (9.44; 95% CI 8.61 to 10.91), P=0.007. No significant difference was found in VOF curve width and the difference in time between AIF and VOF peaks. CONCLUSIONS: Time to peak of VOF at the confluence of sinuses was significantly associated with manually scored venous outflow. Further studies should aim to understand better the association between arterial inflow and venous outflow, and capture quantitative metrics of venous outflow at other locations.

Favourable arterial, tissue-level and venous collaterals correlate with early neurological improvement after successful thrombectomy treatment of acute ischaemic stroke.

BACKGROUND AND PURPOSE: Early neurological improvement (ENI) after thrombectomy is associated with better long-term outcomes in patients with acute ischaemic stroke due to large vessel occlusion (AIS-LVO). Whether cerebral collaterals influence the likelihood of ENI is poorly described. We hypothesised that favourable collateral perfusion at the arterial, tissue-level and venous outflow (VO) levels is associated with ENI after thrombectomy. MATERIALS AND METHODS: Multicentre retrospective study of patients with AIS-LVO treated by thrombectomy. Tissue-level collaterals (TLC) were measured on cerebral perfusion studies by the hypoperfusion intensity ratio. VO and pial arterial collaterals (PAC) were determined by the Cortical Vein Opacification Score and the modified Tan scale on CT angiography, respectively. ENI was defined as improvement of ≥8 points or a National Institutes of Health Stroke Scale score of 0 hour or 1 24 hours after treatment. Multivariable regression analyses were used to determine the association of collateral biomarkers with ENI and good functional outcomes (modified Rankin Scale 0-2). RESULTS: 646 patients met inclusion criteria. Favourable PAC (OR: 1.9, CI 1.2 to 3.1; p=0.01), favourable VO (OR: 3.3, CI 2.1 to 5.1; p<0.001) and successful reperfusion (OR: 3.1, CI 1.7 to 5.8; p<0.001) were associated with ENI, but favourable TLC were not (p=0.431). Good functional outcomes at 90-days were associated with favourable TLC (OR: 2.2, CI 1.4 to 3.6; p=0.001), VO (OR: 5.7, CI 3.5 to 9.3; p<0.001) and ENI (OR: 5.7, CI 3.3 to 9.8; p<0.001), but not PAC status (p=0.647). CONCLUSION: Favourable PAC and VO were associated with ENI after thrombectomy. Favourable TLC predicted longer term functional recovery after thrombectomy, but the impact of TLC on ENI is strongly dependent on vessel reperfusion.

Cerebral venous outflow profiles are associated with the first pass effect in endovascular thrombectomy.

BACKGROUND: Recent studies found that favorable venous outflow (VO) profiles are associated with higher reperfusion rates after mechanical thrombectomy (MT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Fewer retrieval attempts and first-pass revascularization during MT lead to better functional outcomes. OBJECTIVE: To examine the hypothesis that favorable VO profiles assessed on baseline CT angiography (CTA) images correlate with successful vessel reperfusion after the first retrieval attempt and fewer retrieval attempts. METHODS: A multicenter retrospective cohort study of patients with AIS-LVO treated by MT. Baseline CTA was used to determine the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcomes were successful with excellent vessel reperfusion status, defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 and 2c/3 after first retrieval attempt. RESULTS: 617 patients were included in this study, of whom 205 (33.2%) had first pass reperfusion. In univariate analysis, ordinal COVES (p=0.011) values were significantly higher in patients with first pass than in those with non-first pass reperfusion, while the number of patients exhibiting favorable pial arterial collaterals using the Maas scale on CTA did not differ (p=0.243). In multivariable logistic regression analysis, higher COVES were independently associated with TICI 2b/3 (OR=1.25, 95% CI 1.1 to 1.42; p=0.001) and TICI 2c/3 (OR=1.2, 95% CI 1.04 to 1.36; p=0.011) reperfusion after one retrieval attempt, controlling for penumbra volume and time from symptom onset to vessel reperfusion. CONCLUSIONS: Favorable VO, classified as higher COVES, is independently associated with successful and excellent first pass reperfusion in patients with AIS-LVO treated by endovascular thrombectomy.

What predicts poor outcome after successful thrombectomy in late time windows?

BACKGROUND: Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors. METHODS: Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6). RESULTS: 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes. CONCLUSIONS: In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02586415.

Hypoperfusion Intensity Ratio Predicts Malignant Edema and Functional Outcome in Large-Vessel Occlusive Stroke with Poor Revascularization.

BACKGROUND AND OBJECTIVE: Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a < 80 mL ischemic core who do not achieve complete reperfusion. METHODS: We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct < 80 mL, a Tmax > 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6-48 h after the pre-ET perfusion scan. RESULTS: Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p < 0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was ≥ 0.54 (OR 14.7, 95% CI 2.4-78.0, p = 0.003). HIR was also associated with 3-month mRS (HIR ≥ 0.54 for mRS of 3-6: OR 10.8, 95% CI 1.9-44.0, p = 0.02). CONCLUSIONS: Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02446587.

A Relative Noncontrast CT Map to Detect Early Ischemic Changes in Acute Stroke.

BACKGROUND AND PURPOSE: Early ischemic changes on noncontrast computed tomography (NCCT) are often subtle. We developed a novel postprocessing technique that aids in detecting such changes. METHODS: NCCT maps were generated that display the relative density difference between corresponding voxels in contralateral hemispheres (ratio maps of the NCCT [rNCCT]). Voxels with a relative density difference below .95 were designated as infarct. We pilot tested the rNCCT for infarct segmentation on 6 consecutive subjects enrolled in the CT Perfusion to predict Response in Ischemic Stroke Project (CRISP) study and applied the inclusion criteria of an adequate quality NCCT and successful endovascular reperfusion. rNCCT infarct segmentation was compared to baseline NCCT, baseline CTP, and day-5 follow-up fluid-attenuated inversion recovery (FLAIR). RESULTS: Five of the six selected cases met the inclusion criteria. Their median time from symptom onset to CT was 4.95 hours (standard deviation [SD], ±3.5; range, 1.05-10.45), and median NIHSS was 13. Early ischemic changes were identified on the rNCCT in all five cases and on the standard NCCT in three of the five cases. Lesions outlined by the rNCCT maps trended toward a better estimation of the day-5 FLAIR volume (median difference = 6.2 mL) than the ischemic core volumes assessed on baseline CTP (median difference = 51.7 mL) in the four cases with a day-5 FLAIR (P = .1). CONCLUSION: In this proof-of-concept study, the rNCCT appears promising for detecting and quantifying early ischemic changes. These findings should be confirmed in a larger cohort.

Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke.

BACKGROUND AND PURPOSE: This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. METHODS: We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5. RESULTS: Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001). CONCLUSIONS: Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy?

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET). MATERIALS AND METHODS: This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location. RESULTS: Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529). CONCLUSION: AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion.

BACKGROUND: The degree of variability in the rate of early diffusion-weighted imaging expansion in acute stroke has not been well characterized. AIM: We hypothesized that patients with slowly expanding diffusion-weighted imaging lesions would have more penumbral salvage and better clinical outcomes following endovascular reperfusion than patients with rapidly expanding diffusion-weighted imaging lesions. METHODS: In the first part of this substudy of DEFUSE 2, growth curves were constructed for patients with >90% reperfusion and <10% reperfusion. Next, the initial growth rate was determined in all patients with a clearly established time of symptom onset, assuming a lesion volume of 0 ml just prior to symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion-weighted imaging after endovascular therapy) were categorized into tertiles according to their initial diffusion-weighted imaging growth rates. For each tertile, penumbral salvage [comparison of final volume to the volume of perfusion-weighted imaging (Tmax > 6 s)/diffusion-weighted imaging mismatch prior to endovascular therapy], favorable clinical response (National Institutes of Health Stroke Scale improvement of ≥8 points or 0-1 at 30 days), and good functional outcome (90-day modified Rankin score of ≤2) were calculated. A multivariate model assessed whether infarct growth rates were an independent predictor of clinical outcomes. RESULTS: Sixty-five patients were eligible for this study; the median initial growth rate was 3·1 ml/h (interquartile range 0·7-10·7). Target mismatch patients (n = 42) had initial growth rates that were significantly slower than the growth rates in malignant profile (n = 9 patients, P < 0·001). In patients who achieved reperfusion (n = 38), slower early diffusion-weighted imaging growth rates were associated with better clinical outcomes (P < 0·05) and a trend toward more penumbral salvage (n = 31, P = 0·103). A multivariate model demonstrated that initial diffusion-weighted imaging growth rate was an independent predictor of achieving a 90-day modified Rankin score of ≤2. CONCLUSIONS: The growth rate of early diffusion-weighted imaging lesions in acute stroke patients is highly variable; malignant profile patients have higher growth rates than patients with target mismatch. A slower rate of early diffusion-weighted imaging growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.

Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke.

BACKGROUND: Patients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion. METHODS: Nine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion. RESULTS: 36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ(2) p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05). CONCLUSIONS: Reperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.

Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome.

OBJECTIVE: To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth. METHODS: Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12 h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2. RESULTS: Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3. CONCLUSIONS: TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

Patients with the malignant profile within 3 hours of symptom onset have very poor outcomes after intravenous tissue-type plasminogen activator therapy.

BACKGROUND AND PURPOSE: The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset. METHODS: The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6). RESULTS: Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74±14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001). CONCLUSIONS: The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.

Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.

Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD). METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B). CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization.