Endovascular treatment for isolated posterior cerebral artery occlusion stroke in the MR CLEAN registry

Background Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) occlusions are limited, although PCA occlusions can cause severe neurological deficit. Objective To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions. Methods We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (?NIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications. Results Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median ?NIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred. Conclusions EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study

Prediction of Outcome and Endovascular Treatment Benefit

Background and purposeBenefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice.MethodsWe used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic.ResultsWe included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (<1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at www.mrpredicts.com.ConclusionsBecause of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center

Association between thrombus composition and stroke etiology in the MR CLEAN Registry biobank

Purpose: The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods: The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results: The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion: Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin

Association between thrombus composition and stroke etiology in the MR CLEAN Registry biobank

Purpose: The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods: The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results: The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion: Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin

Combined Effect of Age and Baseline Alberta Stroke Program Early Computed Tomography Score on Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry

Background and Purpose: Ischemic brain tissue damage in patients with acute ischemic stroke, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) may be more impactful in older than in younger patients, although this has not been studied. We aimed to investigate a possible interaction effect between age and ASPECTS on functional outcome in acute ischemic stroke patients undergoing endovascular treatment, and compared reperfusion benefit across age and ASPECTS subgroups. Methods: Patients with ischemic stroke from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; March 2014–November 2017) were included. Multivariable ordinal logistic regression was performed to obtain effect size estimates (adjusted common odds ratio) on functional outcome (modified Rankin Scale score) for continuous age and granular ASPECTS, with a 2-way multiplicative interaction term (age×ASPECTS). Outcomes in four patient subgroups based on age (&lt; versus ≥ median age [71.8 years]) and baseline ASPECTS (6–10 versus 0–5) were assessed. Results: We included 3279 patients. There was no interaction between age and ASPECTS on modified Rankin Scale ( P =0.925). The highest proportion of modified Rankin Scale 5 to 6 was observed in patients &gt;71.8 years with baseline ASPECTS 0 to 5 (68/107, 63.6%). There was benefit of reperfusion in all age-ASPECTS subgroups. Although the adjusted common odds ratio was lower in patients &gt;71.8 years with ASPECTS 0 to 5 (adjusted common odds ratio, 1.60 [95% CI, 0.66–3.88], n=110), there was no significant difference from the main effect ( P =0.299). Conclusions: Although the proportion of poor outcomes following endovascular treatment was highest in older patients with low baseline ASPECTS, outcomes did not significantly differ from the main effect. These results do not support withholding endovascular treatment based n a combination of high age and low ASPECTS. </jats:sec

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment.METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio &gt;1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes.RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.</p

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome

Effect of First‐Pass Reperfusion on Outcome After Endovascular Treatment for Ischemic Stroke

Background First‐pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C‐3) after multiple‐passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C‐3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01–1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06–1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03–1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01–1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24‐hour National Institutes of Health Stroke Scale (NIHSS) score (−37%; 95% CI, −43% to −31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83–2.54) compared with no FPR (multiple‐passes reperfusion+no excellent reperfusion), and compared with multiple‐passes reperfusion alone (24‐hour NIHSS score, (−23%; 95% CI, −31% to −14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19–1.78)). Conclusions FPR compared with multiple‐passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy. </jats:sec

Association between thrombus composition and stroke etiology in the MR CLEAN Registry biobank

Abstract Purpose The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice. Methods The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification. Results The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00–1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00–1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar. Conclusion Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin. </jats:sec

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

Background and Purpose— Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods— Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results— In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886–0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53–0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95–1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41–0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions— Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment. </jats:sec