Poor Collaterals Research Articles

Abstract W MP18: NCCT ASPECTS Underestimates Infarct Core in Early Presenters with Poor Collateral Status

Background and Purpose: Noncontrast CT (NCCT) identifies early ischemic change that can predict irreversible ischemic injury. However DWI is more sensitive than NCCT in detection of early ischemic lesion. Our aim was to investigate the factors that influence discrepancy in early ischemic change detection between CT and DWI among good NCCT scan. Methods: We collected consecutive 167 ischemic stroke patients with occlusion of ICA and/or MCA M1 diagnosed by CTA and DWI within 6h of onset (last seen normal, LNT) between August 2004 and February 2013. Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was used to evaluate discrepancy between lesions on NCCT and DWI MR. We identified 109 patients with a good NCCT scan defined as ASPECTS 6-10. Discrepancy between NCCT and DWI was when DWI ASPECTS was 0-5 and no discrepancy was when DWI ASPECTS was 6-10. Regional leptomeningeal collateral (rLMC) score by CTA was used to evaluate collateral status. Results: We reviewed 109 patients (mean age 67.5 ± 12.5 years) with median baseline National Institutes of Health Stroke Scale (NIHSS) 14 (interquartile range, 10-19). Discrepancy group (N=40, 36.7%) had shorter time from LNT to CT (median 98 vs 132 min, p=0.013), higher score of initial NIHSS (median 17 vs 13, p=0.013), lower rLMC score (median 10.5 vs 14, p<0.001). There was no significant difference from CT to DWI time (median 41 vs 40 min) between both groups. In a multivariable logistic regression analysis, time from LNT to CT (OR 0.99; 95% CI 0.99-1.00; P=0.05), rLMC score (OR 0.21; 95% CI 0.08-0.56; P=0.002) were independently associated with the discrepancy group. Conclusion: Discrepancy between CT and DWI is common in patients with acute anterior circulation ischemic stroke. This discrepancy is more apparent when patients present early and have poor collaterals.

Extent of collateralization predicting symptomatic cerebral vasospasm among pediatric patients: correlations among angiography, transcranial Doppler ultrasonography, and clinical findings.

Although the development and prevalence of cerebral vasospasm (CV) has been extensively investigated in adults, little data exist on the development of CV in children. The authors hypothesized that even though children have highly vasoreactive arteries, because of a robust cerebral collateral blood flow, they rarely develop symptomatic CV. The authors retrospectively reviewed their university hospital's neurointerventional database for children (that is, patients ≤ 18 years) who were examined or treated for aneurysmal or traumatic subarachnoid hemorrhage (SAH) during the period 1990-2013. Images from digital subtraction angiography (DSA) were analyzed for the extent of CV and collateralization of the cerebral circulation. Results from transcranial Doppler (TCD) ultrasonography were correlated with those from DSA. Cerebral vasospasm on TCD ultrasonography was defined according to criteria developed for adults. Clinical outcomes of CV were assessed with the pediatric modified Rankin Scale (mRS). Among 37 children (21 boys and 16 girls ranging in age from 8 months to 18 years) showing symptoms of an aneurysmal SAH (comprising 32 aneurysms and 5 traumatic pseudoaneurysms), 17 (46%) had CV confirmed by DSA; CV was mild in 21% of these children, moderate in 50%, and severe in 29%. Only 3 children exhibited symptomatic CV, all of whom had poor collateralization of cerebral vessels. Among the 14 asymptomatic children, 10 (71%) showed some degree of vessel collateralization. Among 16 children for whom TCD data were available that could be correlated with the DSA findings, 13 (81%) had CV according to TCD criteria. The sensitivity and specificity of TCD ultrasonography for diagnosing CV were 95% and 59%, respectively. The time to CV onset detected by TCD ultrasonography was 5 ± 3 days (range 2-10 days). Twenty-five (68%) of the children had good long-term outcomes (that is, had mRS scores of 0-2). Children have a relatively high incidence of angiographically detectable, moderate-to-severe CV. Children rarely develop symptomatic CV and have good long-term outcomes, perhaps due to robust cerebral collateral blood flow. Criteria developed for detecting CV with TCD ultrasonography in adults overestimate the prevalence of CV in children. Larger studies are needed to define TCD ultrasonography-based CV criteria for children.

Influence of leptomeningeal collateral pattern on the prognostic value of mismatch in acute anterior circulation stroke.

This study aimed to investigate whether and to what degree leptomeningeal collateral flow as detected on angiography influences the prognostic value of computed tomography perfusion-estimated mismatch in interventional treatment of acute anterior circulation stroke. Thirty-eight consecutive patients with acute anterior circulation stroke who received interventional neuroradiologic treatment were assigned one of 2 groups depending on the patient's degree of collateral flow (18 patients with poor collaterals, 20 patients with high degree collaterals) according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system. In a multiregression model, we investigated a possible interaction between 2 independent variables mismatch ratio and degree of collateral flow using a "centered" variable approach. The mismatch ratio per se showed a significant correlation with final clinical outcome (β coefficient, -0.79; P = 0.02); whereas, there was no interaction shown between mismatch degree of collateral flow (β coefficient, 0.54; P = 0.1). This study suggests that the predictive value of computed tomography perfusion-estimated mismatch is not influenced by the degree of leptomeningeal collateral flow.

Impact of time-to-reperfusion on outcome in patients with poor collaterals.

The relationship between reperfusion and clinical outcome is time-dependent, and the effect of reperfusion on outcome can vary on the basis of the extent of collateral flow. We aimed to identify the impact of time-to-reperfusion on outcome relative to baseline angiographic collateral grade in patients successfully treated with endovascular revascularization for acute large-vessel anterior circulation stroke. Two hundred seven patients were selected for analysis from our prospectively maintained registry. Inclusion criteria were M1 MCA ± ICA occlusions, onset-to-puncture time within 8 hours, and successful endovascular reperfusion. Baseline angiographic collateral grades were independently evaluated and dichotomized into poor (0-1) versus good (2-4). Multivariable analyses were performed to identify the effect of collateral-flow adequacy on favorable outcome on the basis of onset-to-reperfusion time and puncture-to-reperfusion time. In the poor collateral group, the odds of favorable outcome significantly dropped for patients with onset-to-reperfusion time of >300 minutes or puncture-to-reperfusion time of >60 minutes (onset-to-puncture time: ≤300, 59% versus >300, 32%; OR, 0.24; P = .011; puncture-to-reperfusion time: ≤60, 73% versus >60, 32%; OR, 0.21, P = .011), whereas the probability of favorable outcome in the good collateral group was not significantly influenced by onset-to-reperfusion time or puncture-to-reperfusion time. In the subgroup lesion-volume growth analysis by using DWI, the effect of puncture-to-reperfusion time of >60 minutes was significantly greater compared with the effect of puncture-to-reperfusion time of <60 minutes in the poor collateral group (β = 41.6 cm(3), P = .001). Time-to-reperfusion including onset-to-reperfusion time and puncture-to-reperfusion time in patients with poor collaterals is an important limiting factor for favorable outcome in a time-dependent fashion. Future trials may benefit from a noninvasive imaging technique to detect poor collaterals along with a strategy for rapid reperfusion.

Anomalous origin of left coronary artery from pulmonary artery associated with pulmonary hypertension

This is a report on a 10-year-old child with anomalous origin of left coronary artery (LCA) from pulmonary artery (ALCAPA), severe pulmonary hypertension (PH), old myocardial infarction and poor intercoronary collateralization. It discusses the echocardiographic pitfalls in this particular setting and introduces a new echocardiographic view (posterior pulmonary cusp view) for visualization of the anomalous origin of LCA from the posterior pulmonary cusp (PC) in patients with ALCAPA from the PC of the pulmonary artery. We describe three echocardiographic pitfalls that can mislead the echocardiographer and two helpful hints that guide the clinician to the correct diagnosis.The survival of this child shows that limited size of left ventricular myocardial infarction and severe mitral regurgitation in early infancy can result in a life-saving pulmonary hypertension which preserves viability and function of left ventricle despite lack of intercoronary collateral arteries. After one year follow-up, she is doing well on medical treatment.

Assessment of intracranial collaterals on CT angiography in anterior circulation acute ischemic stroke.

Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010-2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0-1 and 5-6 points, respectively. Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079-1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560-20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203-5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113-6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075-6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156-6.237; P = .022) were independent predictors of extremely poor outcomes. Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.

Protocol for a prospective, multicentre registry study of stenting for symptomatic intracranial artery stenosis in China

IntroductionThe SAMMPRIS trial suggested that aggressive treatment was superior to endovascular stenting in patients with severe symptomatic intracranial atherosclerotic stenosis (ICAS) due to high complication rates in patients in the...

Collateral score complements clot location in predicting the outcome of intravenous thrombolysis.

Collateral circulation is an important determinant of stroke outcome. We studied the impact of leptomeningeal collateral circulation with respect to the location of the thrombus in predicting the clinical outcome of patients treated with intravenous thrombolytic therapy (<3 hours) in a retrospective cohort. Anterior circulation thrombus was detected with CT angiography in 105 patients. Baseline clinical and imaging information was collected, and the site of the occlusion was recorded. Collaterals were assessed by using a 5-grade collateral score and were entered into logistic regression analysis to predict favorable clinical outcome (3-month modified Rankin Scale score of 0-2). Two-thirds of patients with a proximal occlusion displayed poor collateral filling (collateral score 0-1), whereas in more distal clot locations, approximately one-third had poor collaterals. Only 36% of patients with a proximal occlusion and good collaterals experienced favorable clinical outcome. In multivariate analysis, both clot location and collateral score were highly significant (P = .003 and P = .001) and independent predictors of favorable clinical outcome. Good collateral status increased the odds of favorable clinical outcome about 9-fold (OR = 9.3; 95% CI, 2.4-35.8). After dichotomization, a distal clot location had a larger odds ratio (OR = 13.3; 95% CI, 3.0-60.0) compared with the odds ratio of good collaterals (OR = 5.9; 95% CI, 1.8-19.0). A proximal occlusion in the anterior circulation is associated with poorer collateral status compared with a more distal occlusion. Both the clot location and collateral score are important and independent predictors of favorable clinical outcome of hyperacute stroke treated with intravenous thrombolysis. The location of the clot is a stronger determinant of the outcome than the collateral score.

Leptomeningeal collateralization in acute ischemic stroke: Impact on prominent cortical veins in susceptibility-weighted imaging

BackgroundThe extent of hypoperfusion is an important prognostic factor in acute ischemic stroke. Previous studies have postulated that the extent of prominent cortical veins (PCV) on susceptibility-weighted imaging (SWI) reflects the extent of hypoperfusion. Our aim was to investigate, whether there is an association between PCV and the grade of leptomeningeal arterial collateralization in acute ischemic stroke. In addition, we analyzed the correlation between SWI and perfusion-MRI findings. Methods33 patients with acute ischemic stroke due to a thromboembolic M1-segment occlusion underwent MRI followed by digital subtraction angiography (DSA) and were subdivided into two groups with very good to good and moderate to no leptomeningeal collaterals according to the DSA. The extent of PCV on SWI, diffusion restriction (DR) on diffusion-weighted imaging (DWI) and prolonged mean transit time (MTT) on perfusion-imaging were graded according to the Alberta Stroke Program Early CT Score (ASPECTS). The National Institutes of Health Stroke Scale (NIHSS) scores at admission and the time between symptom onset and MRI were documented. Results20 patients showed very good to good and 13 patients poor to no collateralization. PCV-ASPECTS was significantly higher for cases with good leptomeningeal collaterals versus those with poor leptomeningeal collaterals (mean 4.1 versus 2.69; p=0.039). MTT-ASPECTS was significantly lower than PCV-ASPECTS in all 33 patients (mean 1.0 versus 3.5; p<0.00). ConclusionsIn our small study the grade of leptomeningeal collateralization correlates with the extent of PCV in SWI in acute ischemic stroke, due to the deoxyhemoglobin to oxyhemoglobin ratio. Consequently, extensive PCV correlate with poor leptomeningeal collateralization while less pronounced PCV correlate with good leptomeningeal collateralization. Further SWI is a very helpful tool in detecting tissue at risk but cannot replace PWI since MTT detects significantly more ill-perfused areas than SWI, especially in good collateralized subjects.

Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort

We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2). Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days. Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014. HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

The relationship between coronary collateral artery development and inflammatory markers.

This study aims to show the effect of myeloperoxidase (MPO), hsCRP, TNF-alpha values and leukocyte count on the development of coronary collateral arteries in patients with severely diseased coronary arteries. Current study is an observational cross-sectional study. In the study, 295 patients who had functional obstruction or total coronary occlusion at least 1 month on their angiograms were included. We divided the study population into two groups according to their collateral grade as good collateral (Group 1) (169 patients) and poor collateral (Group 2) (126 patients). Multiple logistic regression analysis was used for independent variables associated with the coronary collateral grade. History of stable angina pectoris was statistically more prevalent in good collateral group (61.5% and 48.4%, p=0.025). Furthermore, MPO activation was higher in good collateral group and the difference was statistically significant (3.7 U/mL and 3.0 U/mL p=0.001). In multiple logistic regression analysis, stable angina pectoris [OR 1.7, 95% CI (1.05-2.8), p=0.03] and high MPO levels [OR 2.7, 95% CI (1.7-4.3), p<0.001] were found to be independent predictors of good collateral development. We think that proinflammatory enzymes and cytokines released from these cells rather than inflammatory cells themselves may play an important role on the collateral development.

Effect of Collateral Blood Flow on Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke

Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke. Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90. Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06). Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score. http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

Abstract T P25: Poor Collaterals Necessitate Early Reperfusion: Relationship Between Time to Reperfusion, Collateral Flow, and Clinical Outcome

Background: Clinical outcome following reperfusion can be affected by the adequacy of baseline collaterals during endovascular therapy. We examined the relationship between onset-to-reperfusion time (ORT), collateral grade, and clinical outcome with the hypothesis that there is a narrow therapeutic time window for good clinical outcomes in patients having poor collaterals. Methods: Among 300 patients who underwent endovascular therapy for acute large vessel occlusion in the anterior circulation, we identified 220 patients having a final TICI score of 2 or more. Patients’ collateral grades, using the ASITN/SIR scale on baseline angiography, were dichotomized into poor (0-1) versus partial/complete (2-4). Favorable functional outcome was defined as a 3-month mRS of 0-2. Results: Angiographic data on collaterals were available for 207/220 patients, with 76 in the poor collateral group and 131 in the partial/complete group. The TICI 2b-3 reperfusion rates were similar between the two groups [51/76 (67%) vs. 89/131 (68%), p=0.902], though functional outcomes were significantly different [35/76 (46%) vs. 81/131 (63%), p=0.027]. In the poor collateral group, the odds of favorable outcome significantly dropped for patients reperfused beyond 6-hour from onset [28/53 (54%) vs. 7/24 (29%); odds ratio 0.35 (95% CI 0.13-0.99); p=0.045], whereas the probability of favorable outcome in partial/complete group was not as influenced by reperfusion beyond the 6-hour time window [56/85 (66%) vs. 25/46 (54%); odds ratio 0.62 (95% CI 0.30-1.29); p=0.195]. In subgroup analysis of the poor collateral group, each 30-minute increase in ORT was associated with a decreased chance of favorable outcome despite reperfusion after adjustment for age, baseline NIHSS score, and baseline ASPECTS score [odds ratio 0.77 (95% CI 0.64-0.93); p=0.006]. Conclusions: Onset-to-reperfusion time in patients with poor collaterals is an another important factor affecting favorable outcome, and future trials would benefit from a non-invasive imaging technique to detect poor collaterals along with a strategy for early reperfusion.

Abstract 7: Differential Effect of Baseline Cta Collateral Status on Clinical Outcomes in Patients Enrolled in the Ims-3 Trial

Introduction: In the IMS 3 trial, we test the hypothesis that a differential effect of endovascular therapy on clinical outcome will be most apparent in patients with severely ischemic but salvageable brain tissue (moderate collaterals on baseline CTA). Methods: Data is from patients in the IMS 3 study. Of 656 patients in the study, 306 patients had baseline CTA and 204 patients had M1 MCA +/_ intracranial ICA occlusion where baseline collaterals could be measured. Collateral status was assessed by consensus using 3 different scores and categorized as good, intermediate and poor. Details of the IMS 3 study protocol are described in the primary paper. Results: Of 204 patients, 138 received endovascular therapy (85.7% recanalized, 44.2% achieved 90-day mRS 0-2) and 66 received IV tPA only (57.1% recanalized, 36.4% achieved 90-day mRS 0-2). Proportion of patients with 90-day mRS 0-2 in good, intermediate and poor collateral categories between endovascular therapy and IV tPA across the 3 scores were: score 1(good: 56.5% vs. 41.7%, intermediate: 45.2% vs. 22.2%, poor: 18.4% vs. 23.5%); score 2 (good: 57.4% vs. 42.3%, intermediate: 40% vs. 23.1%, poor: 5.3% vs. 14.3%); score 3 (good: 51.6% vs. 42.3%, intermediate: 43.3% vs. 23.5%, poor: 20.6% vs. 18.8%). Using the van-Elteren test, a significant shift in 90-day mRS distribution in favor of endovascular therapy was noted only for subjects with intermediate collaterals. (p=0.01 for scores 1 and 2, Figure 1) Clinical outcome was poor with no differential effect of therapy in patients with poor collaterals. Conclusion: Patients with baseline intermediate collaterals have the highest likelihood of showing better clinical response to endovascular therapy. Future clinical trials testing IV tPA vs. endovascular therapy may have a higher likelihood of showing differential treatment effect if patients with baseline poor collaterals are excluded.

Abstract T P41: Determination of Collateral Supply Patterns Using MR or CT Perfusion Imaging

Introduction: In this study, we sought to develop a collateral flow mapping method based on MR or CT perfusion imaging and compare this method with the digital subtraction angiography (DSA) method. Methods: Ischemic tissue supplied by collateral flow is likely to have delayed tracer arrival but relatively normal flow. In this study, abnormal Tmax (&gt; 6 sec), MTT (4 sec or greater than unaffected hemisphere) and CBF (&lt;40% of unaffected hemisphere) were labeled with green, red and blue, respectively (Fig. A). Any perfusion patterns can then be represented by a combination of this integrated RGB maps (Integrated Collateral flow Maps, iCMaps). 24 patients were included in this study. DSA images were obtained from all patients, whereas MR and CT perfusion images were acquired from 15 and 9 patients, respectively, within 30 hours after MCA occlusion. iCMaps collateral flow was scored independently as follows. iCMaps without any perfusion abnormality was assigned “1”. iCMaps with white as the dominant perfusion pattern was assigned a “5”; while those with a dominant green and yellow pattern were assigned a “2” or a “3”, depending on the relative green and yellow volume. Finally, iCMaps with a white region surrounded with yellow and green was assigned a “4”. Examples of iCMaps scoring are shown in Fig. B. Using a DSA scoring method in the literature5, a score of 1-5 was given independently based on the degree of retrograde collateralization (5: poor collateralization). Results: Good correlation was found between the MR perfusion iCMaps and DSA (DSA=0.70*MR iCMaps+0.54, R=0.75). Moderate correlation was obtained between the CT perfusion iCMaps and DSA (DSA=0.51*CT iCMaps+1.9, R=0.56). Conclusions: Based on the different characteristics of Tmax, MTT and CBF maps, the proposed MR or CT perfusion based iCMaps method can provide DSA comparable collateral flow information.

Abstract W MP60: Atrial Fibrillation is Associated with Worse Collaterals in Acute Stroke: Angiography in the ENDOSTROKE Registry

Background: Risk factors for stroke may alter hemodynamics or invoke ischemic preconditioning, yet the impact of such factors on response to acute stroke treatment and the potential relationship with collateral circulation remains unknown. Methods: Consecutive cases enrolled in the International Multicenter Registry for Mechanical Recanalization Procedures in Acute Stroke (ENDOSTROKE) were analyzed with respect to collateral status on baseline angiography before endovascular therapy. ASITN/SIR collateral grade (0-1/2/3-4) was scored by the core lab, blind to all other data. Collateral grade was analyzed with respect to numerous baseline risk factors, demographics and outcomes after endovascular intervention. Results: 109 patients (median age 69 years (25 th , 75 th percentiles: 56, 77); 51% women; median baseline NIHSS 15 (13, 18)) with complete (TICI 0) anterior circulation occlusions (M1, n=71; ICA, n=28; M2, n=10) at baseline were evaluated based on collateral grade (0-1, n=12; 2, n=41; 3-4, n=56). Worse collaterals were noted in patients with atrial fibrillation (ASITN grades 0-1/2/3-4: 21%/30%/49%) as compared to patients without atrial fibrillation (5%/42%/53%, p=0.024), yet cardioembolic stroke etiology was unrelated. Other baseline features such as age, gender, time to presentation, other co-morbidities and labs were unrelated to collateral grade. Post-procedure reperfusion (TICI 2b-3) was significantly associated with better collaterals (OR 2.58 (1.343-4.957, p=0.004). Similarly, final infarct size was significantly smaller in those with better collaterals. Good clinical outcomes (mRS 0-2 at day 90) were less frequent in those with poorer collaterals (OR 0.403 (0.199-0.813, p=0.011). Conclusions: Atrial fibrillation, but not cardioembolic stroke etiology, is associated with worse collaterals. Hemodynamic implications, such as diminished cardiac output due to atrial fibrillation, may result in less favorable outcomes after endovascular therapy for acute stroke.

Abstract 3: Collaterals, Not Clots! CT Angiography Predictors of Recanalization, Reperfusion and Clinical Outcomes After Thrombectomy in Pooled Analyses of TREVO EU and TREVO2

Background: CTA is often used to define clot location prior to endovascular therapy yet systematic evaluation may reveal many details about underlying pathophysiology. We tested a battery of CTA measures to identify optimal predictors of response to thrombectomy. Methods: CTA datasets of anterior circulation strokes in TREVO EU and TREVO2 with available source images were reconstructed into 3D-curved and 2D-orthogonal maximum-intensity projections by the core lab. Occlusion site, clot length and volume, clot burden score (CBS) and regional leptomeningeal collateral score (rLMC) were scored on CTA. Hyperdense vessels, Hounsfield Unit (HU) indices and location of hyperdensity relative to CTA occlusion site were noted on noncontrast CT. Results: 111 cases (mean age 68.0 ± 13.8 years; 58.6% women; median baseline NIHSS 18 (8-28)) were analyzed. CTA occlusions were 68.5% M1, 22.5% M2, and 9.0% ICA. CTA clot volumes were mean 49.3 ± 36.3 mm 3 with mean CBS 6.7 ± 1.8 and mean rLMC 15.3 ± 4.2. Noncontrast hyperdensity was noted at M1 in 44.1%, M2 in 27.0%, and ICA 8.1%, with ipsilateral:contralateral HU indices of mean 1.3 ± 0.2. Noncontrast CT hyperdensity relative to CTA opacification revealed hyperdensity proximal to occlusions in 2.7%, just past occlusion in 55.0%, and distal to clot end in 6.2%. Only better collaterals on rLMC predicted AOL 2-3 recanalization (OR 1.26, p=0.058) in multivariate analyses and distal hyperdensity (OR 0.11, p=0.037) predicted worse recanalization. Similarly, only rLMC predicted TICI 2b-3 reperfusion (OR 1.27, p=0.004) and distal hyperdensity (OR 0.12, p=0.071) predicted worse reperfusion. Clots (CBS) and collaterals (rLMC) were moderately correlated with each other (0.44 Spearman) in multivariate models of good clinical outcome (mRS 0-2) at day 90, yet clots were significant only when removing collaterals. Conclusions: Collaterals, not clots, are the best CTA predictors of outcomes after thrombectomy. Worse outcomes with hyperdensity distal to clots on CTA likely reflect stasis due to poor retrograde collaterals.

Proximal Intracranial Arterial Occlusions

Over thepast2decades, the treatmentofacute ischemicstroke has undergone significant changes. The National Institute of Neurological Disorders andStroke tissueplasminogen activator study1 in 1995 followed by the third European Cooperative Acute Stroke Study (ECASS III)2 in 2008heralded major breakthroughs in the hyperacute management of patientswith ischemicstroke. Yet despite the promise of these landmark studies, the overall use of intravenous tissue plasminogen activator remained meager, reaching less than5%ofall strokepatients in theUnited States through 2006.3 Furthermore, for certain stroke subtypes, such as thosewith proximal intracranial arterial occlusions, therateof recanalizationremained low,4 resulting inpoor outcomes when early recanalization was not achieved.5 Over the ensuing years, major excitement was generated in the stroke community about endovascular therapy for ischemic stroke, which logically targeted this population. The Prolyse inAcuteCerebralThromboembolism(PROACT) study6 showed that intra-arterial prourokinase was superior to placebo in achieving recanalization and improving outcomes of stroke patients who were treated within 6 hours of symptom onset. The subsequent advances of new devices and techniques with high recanalization rates resulted in a tide of enthusiasmaseachnewendovascular technologybroughtgreater promise and a better chance of direct, early recanalization for patients with proximal intracranial arterial occlusions. The strokecommunityembracedtheconceptofendovascular treatment because the idea of direct revascularization just made somuch sense. Yet the recanalization rates, which continued to increase asdevices and techniques improved, began tooutstrip clinical outcomes in some studies, bringing into question the assumptions about what the recanalization was ultimately capable of achieving.7 Theexcitementoverdirect recanalizationwasquelled furtherby the results of 3 recent randomizedclinical trials8-10 that failed to show improvedclinical benefit for strokepatientsundergoing endovascular therapy. The Interventional Management of Stroke III (IMS-III) trial8 was an open-label study that randomly assigned 656 patients with a National Institutes of Health Stroke Scale (NIHSS) score of 10 or higher or an NIHSS score of 8 or 9 with vascular imaging evidence of large artery occlusion to thrombolytic therapy alone or thrombolytic therapy plus endovascular therapy. This study8 was stopped earlybecause therewasnodifference inoutcomebetween the 2 arms, and the investigators concluded that the addition of endovascular therapy to intravenous thrombolytic therapydid not improve stroke outcome. The Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) trial10 randomly assigned 118 patients with an anterior circulation large artery occlusionwithin 8hours of symptom onset to undergo mechanical thrombectomy (Merci Retriever or Penumbra System) or to receive the standard of care. This study10 showed no difference in reperfusion rates, and the outcomes between the 2 groups supported the nonsuperiorityofendovascular treatmentover thestandardofcare for acute ischemic stroke. The Endovascular Treatment for Acute Ischemic Stroke (SYNTHESIS) trial9 randomly assigned 362 patients within 4.5 hours of symptom onset to endovascular therapyvs intravenous thrombolytic therapy.This study9 showed that there was no difference in the 3-month outcomes between the 2 study arms, concluding also that endovascular therapy is not superior to intravenous thrombolytic therapy. The findings in these trials8-10 had a sobering effect on the field, limiting the use of endovascular treatment in the stroke community. Althoughallof those recent studieswerewelldesignedand well conducted, valid criticisms were brought to bear on the results.Most of the endovascular devicesusedwereolder and were associatedwith lower recanalization rates thanwere the newerdevices.11 Longer time to treatmentwaspresent in each of the studies compared with the standard treatment arms, with a post hoc analysis of the IMS III trial8 suggesting that thosewhogot earlier interventionshadgreater potential benefits. Could it be that these trialswere inadequate toprove the ultimate failure of endovascular interventions after all?Might there still be a rationale tomove aheadwith additional endovascular trials despite these compelling negative studies? In their article published in this issue of JAMANeurology, Lima et al12 retrospectively analyzed a prospective cohort of stroke patients with proximal intracranial arterial occlusions fromtheScreeningTechnologyandOutcomeProject inStroke (STOPStroke) study. The objective was to evaluate the natural history and outcome of this disease in patients who were not treatedwith intravenous thrombolysis or who did not receive endovascular therapy. In this study,12 the authors demonstrated that theoverallnaturalhistoryofpatientswithproximal intracranial arterial occlusions was poor, withmore than half (56%) not achieving functional independence and about a quarter (22%) dead at 6months. Furthermore, their study12 showed that older age, anNIHSS score of 10orhigher, andevidence of poor collaterals on computed tomography angioAuthor Audio Interview at jamaneurology.com

The Impact of Arterial Collateralization on Outcome after Intra-Arterial Therapy for Acute Ischemic Stroke

Although intra-arterial therapy for acute ischemic stroke is associated with superior recanalization rates, improved clinical outcomes are inconsistently observed following successful recanalization. There is emerging concern that unfavorable arterial collateralization, though unproven, predetermines poor outcome. We hypothesized that poor leptomeningeal collateralization, assessed by preprocedural CTA, is associated with poor outcome in patients with acute ischemic stroke undergoing intra-arterial therapy. We retrospectively analyzed patients with acute ischemic stroke with intracranial ICA and/or MCA occlusions who received intra-arterial therapy. The collaterals were graded on CTA. Univariate and multivariate analyses were used to investigate the association between the dichotomized leptomeningeal collateral score and functional outcomes at 3-months mRS ≤2, mortality, and intracranial hemorrhages. Eighty-seven patients were included. The median age was 66 years (interquartile range, 54-76 years) and the median NIHSS score at admission was 18 (interquartile range, 14-20). The leptomeningeal collateral score 3 was found to have significant association with the good functional outcome at 3 months: OR = 3.13; 95% CI, 1.25-7.825; P = .016. This association remained significant when adjusted for the use of IV tissue plasminogen activator: alone, OR = 2.998; 95% CI, 1.154-7.786; P = .024; and for IV tissue plasminogen activator and other confounders (age, baseline NIHSS score, and Thrombolysis in Cerebral Infarction grades), OR = 2.985; 95% CI, 1.027-8.673; P = .045. We found that poor arterial collateralization, defined as a collateral score of <3, was associated with poor outcome, after adjustment for recanalization success. We recommend that future studies include collateral scores as one of the predictors of functional outcome.

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

ObjectivesPatients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.MethodsWe evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.Results73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.ConclusionThe presence of CE was associated with poorer coronary collateral development in patients with SCAD.