Abstract
This study aimed to investigate the safety and efficacy of endovascular treatment (EVT) in acute ischemic stroke (AIS) patients caused by large-vessel occlusion (LVO) with different etiologies of stroke. A total of 928 AIS patients were assigned into intracranial atherosclerotic stenosis (ICAS)-LVO, cardioembolic (CE)-LVO, and artery to artery embolism (ATA)-LVO groups. The safety and efficacy endpoints were symptomatic intracranial hemorrhage (SICH) at 24 h after EVT, 90-day favorable outcomes (modified Rankin Scale (mRS) of 0–2), successful recanalization (modified thrombolysis in cerebral infarct (mTICI) 2b/3), and complete recanalization (mTICI 3). The logistic regression analysis was used to determine the associations between the safety and efficacy endpoints. There were 305 (32.9%), 535 (57.6%), and 88 (9.5%) patients in ICAS-LVO, CE-LVO, and ATA-LVO groups, respectively. No significant difference was found in the 90-day mRS and successful recanalization among the three groups. However, compared with the ICAS-LVO group, complete recanalization rate was higher in the CE-LVO (adjusted odds ratio, 4.50; 95% confidence interval (CI), 2.37–8.56) and ATA-LVO groups (aOR, 2.43; 95% CI, 1.16–5.10). The results of subgroup analysis showed a significant association between CE-LVO stroke etiology and complete recanalization in the age population < 65 years old (aOR, 14.33; 95% CI, 4.39–46.79, P = 0.019). Functional outcomes were similar among different etiologies of stroke. CE-LVO and ATA-LVO could be related to a higher rate of complete recanalization, and there was a trend of the increased risk of parenchymal hemorrhage in the CE-LVO group.
Supplementary Information
The online version contains supplementary material available at 10.1007/s13311-022-01189-9.
Keywords: Endovascular treatment, Etiologies of stroke, Safety, Efficacy, Outcomes
Introduction
Endovascular treatment (EVT) has become the standard therapy to treat acute ischemic stroke (AIS) patients with large-vessel occlusion (LVO) [1–7]. Little is known regarding the safety and efficacy of EVT for stroke from different etiologies, as most studies only included patients with isolated intracranial occlusion from either cardioembolic (CE) or intracranial atherosclerotic stenosis (ICAS) [8–13]. However, those studies mainly excluded tandem lesions or artery to artery (ATA) embolism.
To date, studies evaluating the safety and efficacy of EVT among these etiologies of stroke were scarce and scattered. Moreover, those studies rarely included all these three etiologies of stroke [8, 11, 14–17]. Prior to starting the EVT, the etiology of the occlusion may not be clear. The early signs from initial reperfusion manipulation can provide hits for the etiology of the occlusion. Knowing the different complication and outcome profiles from different etiologies of stroke can assist clinicians to more reliably select the subsequent strategies/techniques or remedy therapy for recanalization.
Several studies reported that different clinical and lesion characteristics among etiologies of stroke might influence outcomes. In contrast, a recent study showed similar functional outcomes of ICAS-LVO, CE-LVO, and ATA-LVO, despite different clinical characteristics [18]. Although the sample size was relatively large, their results might be biased, as that study was limited to a single center, and the results might not be sufficient to be generalized to the real-world setting.
Therefore, a study involving multiple centers is needed to validate the efficacy and safety of EVT in AIS patients with different etiologies of stroke. In the present study, we evaluated the efficacy and safety in 928 AIS patients caused by LVO with different etiologies of stroke.
Methods
Study Population
We enrolled patients with AIS caused by LVO from ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke). ANGEL-ACT is a prospective nationwide registry of 1793 consecutive patients with AIS caused by LVO undergoing EVT in 111 hospitals in China between November 2017 and March 2019. The inclusion criteria were considered according to a previous study [19]. Of the 1793 patients, we excluded 345 patients due to no EVT record (n = 25), and no ICAS/TOAST/ATA assessment (n = 320). We further excluded a total of 520 patients due to stroke of undetermined etiology (SUE)/stroke of other determined etiology (SOE) (n = 162), LAA without ICAS/ATA, as well as patients with two possible causes of stroke identified, such as ICAS and ATA (n = 90), ICAS and CE (n = 32), and undistinguishable (n = 20).
The ethics committees of all participating centers or their legal representatives approved this study. We obtained informed consent forms from patients or their legally authorized representatives before commencing the study.
Classification of the Stroke Mechanism
All types of stroke, including anterior and posterior circulation, were classified into three groups according to the pathogenic mechanism (Fig. 1) [18, 20–22], based on imaging and angiographic findings. We used site-reported data for patients whose images could not be obtained. The imaging review criteria of local investigators were fully consistent with those of core laboratory. Reconstructed images acquired from preprocedural computed tomography angiography (CTA) or magnetic resonance angiography (MRA), which were confirmed with intraprocedural digital subtraction angiography (DSA), were used to determine the classification as follows:
CE-LVO group, defined as a lesion with mere embolism in one of any arteries without concomitant ICA or vertebral artery (VA) steno-occlusion.
ICAS-LVO group, defined as a lesion with in situ atherosclerotic thromboses in an intracranial artery. In this group, the target arterial site was characterized by moderate-to-severe fixed stenosis (> 50% or > 70%) with distal blood flow impairment or evidence of repeated occlusion.
ATA-LVO group, defined as those patients with ipsilateral extracranial steno-occlusion (internal carotid artery, common carotid artery [up to the levels of C1], vertebral artery [V1–3 segment]) ≥ 90% of the proximal internal carotid artery or vertebral artery, evident on angiography with the impaired distal flow or partial filling of these arteries from collaterals associated with relevant, distal artery occlusion.
Fig. 1.
Illustration of the three etiologies of stroke in anterior and posterior circulation. (A and D) cardioembolic, (B and E) intracranial atherosclerotic stenosis, and (C and F) artery to artery embolism
We categorized patients whose stroke etiology could not be determined even after extensive evaluation as the SUE [23]. Moreover, patients with two or more potential causes of stroke, disabling physicians to make final diagnoses, were also included in this group. Meanwhile, we categorized patients with rare causes of stroke as the SOE, such as non-atherosclerotic vasculopathy, hypercoagulable states, or hematologic disorders [23]. These diagnoses should be confirmed by diagnostic studies, including angiography or blood tests. In addition, we excluded patients with two possible causes of stroke identified in the present analysis (e.g., ICAS and ATA, ICAS, and CE).
Baseline Data Collection
The baseline characteristics were patient demographics, risk factors, medical history, National Institutes of Health Stroke Scale (NIHSS) score on admission, location of the infarcted cerebral tissue (anterior vs. posterior circulation), procedural details (general anesthesia, GPIIb/IIIa receptor inhibitor, stent retriever, intraarterial thrombolysis, balloon angioplasty, and stenting), number of mechanical thrombectomies, and the time points of working flow, including onset to door (OTD), door to puncture (DTP), and puncture to recanalization (PTR). We sent the collected data to the central core laboratory in digital forms. All the pre-treatment imaging data, including non-contrast CT, MRI, and digital subtraction angiography (DSA) images during EVT and follow-up head CT or MRI, were anonymized and reviewed centrally by two independent physicians. A consensus between the physicians was obtained to resolve any disagreements; if no agreement was achieved, a third physician blinded to this study was introduced for a final consensus.
EVT
Intravenous thrombolysis (IVT) was introduced to AIS patients who were admitted within 4.5 h from stroke onset, according to the guidelines. On the other hand, direct mechanical thrombectomy (MT) was performed if IVT was contraindicated. We performed advanced imaging in cases with unknown or prolonged (> 6 h) time window from the stroke onset to evaluate mismatch between diffusion-weighted imaging/perfusion-weighted imaging (DWI/PWI) or cerebral blood volume/cerebral blood flow (CBV/CBF) to select eligible patients with salvageable tissue for MT. Intraoperatively, additional thrombectomy attempts and any alternative rescue therapies, such as administration of tirofiban, balloon angioplasty, thrombolysis, and rescuing stent, were adopted at the operator’s discretion. Post-operatively, patients were admitted to the intensive care unit for a standard therapy. The blood pressure parameters were set and adjusted by the operator according to the modified thrombolysis in cerebral infarct (mTICI) grade of antegrade blood flow.
The antiplatelet therapy was given 24 h after EVT after excluding intracranial hemorrhage. If patients with ICAS-LVO or ATA-LVO had undergone balloon/stenting angioplasty, antiplatelet therapy was first given using tirofiban for 24–48 h, then overlapping 4 ~ 6 h for oral antiplatelet therapy.
Safety and Efficacy Outcomes
At 90-day after endovascular therapy, the outcomes of all patients were assessed through telephone follow-up. The follow-up was based on a shared standardized interview protocol and centrally conducted by a third-party Clinical Research Organization (CRO). We defined functional outcomes at 90 days as the primary efficacy endpoints, including modified Rankin Scale (mRS) of shift analysis, mRS of 0–1, mRS of 0–2, and mRS of 0–3. Meanwhile, we considered successful recanalization of mTICI 2b/3 and complete recanalization (mTICI 3) on the final angiogram as the secondary efficacy outcomes. The safety endpoints were any symptomatic intracranial hemorrhage (SICH) according to the Heidelberg Bleeding Classification and parenchymal hematoma (PH) according to the European Co-operative Acute Stroke Study II (ECASS II) within 24 h post-EVT, and death within 90 days.
Statistical Analysis
Data were displayed as proportions for categorical variables and median, interquartile range (IQR) for continuous variables. We performed the Pearson χ2 test or Kruskal–Wallis test to compare the baseline characteristics among the groups. We calculated the odds ratios (OR) or common OR using logistic regression analysis with their 95% confidence intervals (CI). We selected variables with a p-value of < 0.05 in the univariable analysis (age, sex, current smoking history, SBP, ASPECTS, admission NIHSS, hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, prior use of anticoagulant, occlusion location (anterior/posterior circulation), general anesthesia, GPIIb/IIIa receptor inhibitor, stent retriever as first-line, direct aspiration as the first-line, direct aspiration + stent retriever as the first-line, rescue balloon/stenting angioplasty, MT times, time-metric parameters (OTD, DTP, and PTR)) as potential predictors in the multivariable logistic regression analysis. Subgroup analysis defined by prognostic variables was performed to discriminate the relationship between the three different stroke etiologies and efficacy and safety outcomes. Significance level was set to α = 0.05 (2-sided). We conducted the statistical analyses using SAS software version 9.4 (SAS Institute Inc, Cary, NC).
Results
Baseline Characteristics
We enrolled 1793 AIS patients who underwent EVT, of whom 865 patients were excluded based on the exclusion criteria (Fig. 2). We assigned the remaining patients into the CE-LVO group (n = 535), ICAS-LVO group (n = 305), and ATA-LVO group (n = 88). Patients in the CE-LVO group were older and had higher National Institutes of Health Stroke Scale (NIHSS) scores on admission than those in the ICAS-LVO and ATA-LVO groups. The patients’ baseline characteristics are shown in Table 1. The frequency of current smoking habits, hypertension, systolic blood pressure (SBP) on admission, diabetes mellitus, hyperlipidemia, and history of stroke was higher in the ICAS-LVO group than that in the CE-LVO and ATA-LVO groups. Besides, the presence of atrial fibrillation was the highest in the CE-LVO group. CE-LVO was frequent in the anterior circulation, while ICAS-LVO was frequent in the posterior circulation. We identified that the use of anticoagulants was the highest in the CE-LVO group, and the use of glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitors was the highest in the ICAS-LVO group. However, no significant difference was found among groups on the prior use of antiplatelet drugs.
Fig. 2.
Flow chart of patient selection. EVT endovascular treatment, TOAST The Trial of ORG 10,172 in Acute Stroke Treatment classification, LAA large-artery atherosclerosis, ICAS intracranial arterial stenosis, CE cardioembolism, SUE/SOE stroke of unknown etiology/stroke of other determined etiology
Table 1.
Baseline characteristics and outcome of different etiologies of stroke
| Variables | Total (n = 928) | ICAS-LVO (n = 305) | CE-LVO (n = 535) | ATA-LVO (n = 88) | P |
|---|---|---|---|---|---|
| Baseline clinical parameters | |||||
| Age, median (IQR) | 66 (57–74) | 61 (54–68) | 69 (61–77) | 66 (59–73) | < 0.001 |
| Male, n (%) | 575 (62.0) | 249 (81.6) | 257 (48.0) | 69 (78.4) | < 0.001 |
| Current smoking, n (%) | 264 (28.5) | 141 (46.2) | 87 (16.3) | 36 (40.9) | < 0.001 |
| SBP, median (IQR) | 147 (131–162) | 150 (134–167) | 145 (130–160) | 148 (135–168) | 0.002 |
| ASPECTSd, median (IQR) | 9 (7–10) | 8 (7–10) | 10 (7–10) | 9 (7–10) | < 0.001 |
| Admission NIHSSd, median (IQR) | 17 (12–22) | 15 (10–22) | 18 (13–22) | 16 (11–21) | 0.002 |
| Comorbidities | |||||
| Hypertension, n (%) | 562 (60.6) | 216 (70.8) | 290 (54.2) | 56 (63.6) | < 0.001 |
| Diabetes mellitus, n (%) | 162 (17.5) | 67 (22.0) | 81 (15.1) | 14 (15.9) | 0.040 |
| Hyperlipidemia, n (%) | 92 (9.9) | 41 (13.4) | 42 (7.9) | 9 (10.2) | 0.033 |
| Atrial fibrillation, n (%) | 404 (43.5) | 8 (2.6) | 390 (72.9) | 6 (6.8) | < 0.001 |
| Prior stroke, n (%) | 217 (23.4) | 84 (27.5) | 113 (21.1) | 20 (22.7) | 0.106 |
| Pretreatment | |||||
| Prior use of antiplatelet agents, n (%) | 133 (14.3) | 51 (16.7) | 73 (13.6) | 9 (10.2) | 0.243 |
| Prior use of anticoagulants, n (%) | 56 (6.0) | 5 (1.6) | 50 (9.4) | 1 (1.1) | < 0.001 |
| Bridging IVT, n (%) | 258 (27.8) | 73 (23.9) | 159 (29.7) | 26 (29.6) | 0.184 |
| Procedural parameters | |||||
| Occlusion location, n (%) | < 0.001 | ||||
| Anterior circulation | 741 (79.9) | 195 (63.9) | 474 (88.6) | 72 (81.8) | |
| Posterior circulation | 187 (20.2) | 110 (36.1) | 61 (11.4) | 16 (18.2) | |
| General anesthesia, n (%) | 361 (38.9) | 121 (39.7) | 193 (36.1) | 47 (53.4) | 0.008 |
| GP IIb/IIIa receptor inhibitor, n (%) | 489 (52.7) | 242 (79.3) | 189 (35.3) | 58 (65.9) | < 0.001 |
| Stent retriever as first-line, n (%) | 641 (69.1) | 221 (72.5) | 384 (71.8) | 36 (40.9) | < 0.001 |
| Direct aspiration as first-line, n (%) | 59 (6.4) | 8 (2.6) | 47 (8.8) | 4 (4.6) | 0.002 |
| Direct aspiration + stent retriever as first-line | 106 (11.4) | 29 (9.5) | 74 (13.8) | 3 (3.4) | 0.008 |
| IAT, n (%) | 51 (5.5) | 17 (5.6) | 30 (5.6) | 4 (4.6) | 0.919 |
| Rescue balloon/stenting angioplasty, n (%) | 162 (17.5) | 147 (48.2) | 15 (2.8) | 0 (0) | < 0.001 |
| MT times, median (IQR) | 2 (1–3) | 1 (1–2) | 2 (1–3) | 1 (1–2) | < 0.001 |
| MT ≤ 3 times, n (%) | 782 (84.3) | 267 (87.5) | 440 (82.2) | 75 (85.2) | 0.124 |
| FPR, n (%) | 434 (46.8) | 139 (45.6) | 259 (48.4) | 36 (40.9) | 0.374 |
| Time-metric parameters | |||||
| OTDb, median (IQR), min | 150 (60–280) | 177 (75–342) | 126 (60–254) | 145 (66–300) | 0.009 |
| DTPc, median (IQR), min | 120 (80–170) | 130 (94–203) | 116 (76–160) | 117 (83–170) | 0.001 |
| Procedure duration, median (IQR), min | 86 (53–126.5) | 96 (60–139) | 76 (50–115) | 102 (64.5–132.5) | < 0.001 |
| Primary outcome | |||||
| 90-day mRSa, median (IQR) | 3 (0–5) | 3 (0–4) | 3 (1–5) | 4 (0–5) | 0.007 |
| Secondary outcomes | |||||
| 90-day mRS 0–1a, n (%) | 362 (39.5) | 143 (47.2) | 185 (35.2) | 34 (39.1) | 0.003 |
| 90-day mRS 0–2a, n (%) | 401 (43.8) | 150 (49.5) | 213 (40.5) | 38 (43.7) | 0.042 |
| 90-day mRS 0–3a, n (%) | 494 (53.9) | 178 (58.7) | 273 (51.9) | 43 (49.4) | 0.110 |
| mTICI, n (%) | < 0.001 | ||||
| mTICI 0–1 | 41 (4.4) | 8 (2.6) | 30 (5.6) | 3 (3.4) | |
| mTICI 2a | 38 (4.1) | 7 (2.3) | 28 (5.2) | 3 (3.4) | |
| mTICI 2b | 213 (23.0) | 105 (34.4) | 91 (17.0) | 17 (19.3) | |
| mTICI 3 | 636 (68.5) | 185 (60.7) | 386 (72.2) | 65 (73.9) | |
| Successful recanalization, n (%) | 849 (91.5) | 290 (95.1) | 477 (89.2) | 82 (93.2) | 0.011 |
| Complete recanalization, n (%) | 636 (68.5) | 185 (60.7) | 386 (72.2) | 65 (73.9) | 0.001 |
| Safety outcomes | |||||
| Death within 90 daysa, n (%) | 120 (13.1) | 30 (9.9) | 77 (14.6) | 13 (14.9) | 0.130 |
| PHe, n (%) | 88 (9.7) | 10 (3.4) | 72 (13.8) | 6 (7.1) | < 0.001 |
| SICHf, n (%) | 65 (7.3) | 9 (3.0) | 48 (9.40) | 8 (9.4) | 0.003 |
ICAS intracranial atherosclerotic stenosis; CE cardioembolic; ATA arterial to arterial embolism; LVO large-vessel occlusion; SD standard deviation; SBP systolic blood pressure; IQR interquartile range; NIHSS National Institutes of Health Stroke Scale score; ASPECTS Alberta Stroke Program Early CT score; OTD onset-to-door, DTP door-to-puncture; PTR puncture-to-recanalization; IVT intravenous thrombolysis; IAT intraarterial thrombolysis; MT mechanical thrombectomy; FPR first-pass recanalization; SICH symptomatic intracranial hemorrhage; PH parenchymal hemorrhage; mRS modified Rankin Scale
a12 missing data
b19 missing data/
c72 missing data/
d5 missing data
e23 missing data/
f32 missing data/
The time for symptom onset-to-door (OTD) was the longest in the ICAS-LVO group (177 min; interquartile range [IQR], 75–342), followed by the ATA-LVO (145 min; IQR, 66–300) and CE-LVO (126 min; IQR, 60–254) groups (P < 0.009). Consistently, the time for door-to-puncture (DTP) was the longest in the ICAS-O group (130 min; IQR, 94–203), followed by the ATA-LVO (117 min; IQR, 83–170) and CE-LVO (116 min; IQR, 76–160) groups (P = 0.001). On the other hand, the time for puncture-to-recanalization (PTR) was significantly shorter in the CE-LVO group than that in the ICAS-LVO and ATA-LVO groups (P < 0.001). The use of general anesthesia was greater in the ATA-LVO group than that in the other two groups. We found that the prevalence of stent retriever as the first-line therapy was higher in the ICAS-LVO group than that in the CE-LVO and ATA-LVO groups (72.5% vs. 71.8% vs. 40.9%, P < 0.001). In comparison, the prevalence of direct aspiration as the first-line therapy was greater in the CE-LVO group than that in the ICAS-LVO and ATA-LVO groups (8.8% vs. 2.6% vs. 4.6%, P = 0.002). At the same time, we also noted a higher frequency of direct aspiration + stent retriever as the first-line therapy in the CE-LVO group than that in the ICAS-LVO and ATA-LVO groups (13.8% vs. 9.5% vs. 3.4%, P = 0.008). We also found that the number of passes was the highest in the CE-LVO group than that in the other two groups (P < 0.001). We observed that the prevalence of rescue balloon/stenting angioplasty was higher in the ICAS-LVO group (48.2% vs. 2.8% vs. 0%, P < 0.001). There was no significant difference in intraarterial thrombolysis among the groups.
Efficacy and Safety Outcomes and Subgroup Analysis
The safety and efficacy outcomes of EVT in different pathogenic types of stroke and the subgroup analysis are shown in Tables 2, 3, and 4 and supplementary Table 1. The distribution of the 90-day mRS scores after stroke was higher in the ATA-LVO group (P = 0.007). Meanwhile, the proportion of patients with mRS 0–1 and mRS 0–2 at 90 days was higher in the ICAS-LVO group than that in the CE-LVO and ATA-LVO groups (P = 0.003 and P = 0.042; Fig. 3). However, we did not find statistical significant among groups regarding the 90-day mRS after adjusting for potential confounders. Further analysis did not find reveal interactions between different etiologies of stroke, age, gender, NIHSS score on admission, use of general anesthesia, the circulation system, time workflow, and successful recanalization on 90-day mRS.
Table 2.
Adjusted OR of safety and efficacy outcome according to different etiologies of stroke
| Outcomes | Groups | Unadjusted OR/HR (95% CI) | P value | Adjusted OR/HR (95% CI) | P value |
|---|---|---|---|---|---|
| 90-day mRSa, median (IQR) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 1.50 (1.17–1.93) | 0.002 | 1.09 (0.70–1.71) | 0.705 | |
| ATA-LVO | 1.35 (0.89–2.06) | 0.164 | 1.19 (0.69–2.06) | 0.540 | |
| 90-day mRS 0–1a, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 0.61 (0.46–0.81) | 0.001 | 0.83 (0.47–1.46) | 0.517 | |
| ATA-LVO | 0.72 (0.44–1.17) | 0.181 | 0.72 (0.36–1.44) | 0.352 | |
| 90-day mRS 0–2a, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 0.69 (0.52–0.92) | 0.012 | 1.08 (0.62–1.87) | 0.793 | |
| ATA-LVO | 0.79 (0.49–1.28) | 0.338 | 0.86 (0.44–1.71) | 0.674 | |
| 90-day mRS 0–3a, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 0.76 (0.57–1.01) | 0.057 | 1.07 (0.62–1.85) | 0.819 | |
| ATA-LVO | 0.69 (0.43–1.11) | 0.123 | 0.75 (0.38–1.46) | 0.392 | |
| Successful recanalization, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 0.43 (0.24–0.76) | 0.004 | 0.46 (0.18–1.22) | 0.119 | |
| ATA-LVO | 0.71 (0.27–1.88) | 0.487 | 0.84 (0.24–2.94) | 0.783 | |
| Complete recanalization, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 1.68 (1.25–2.26) | 0.001 | 4.50 (2.37–8.56) | < 0.001 | |
| ATA-LVO | 1.83 (1.08–3.11) | 0.025 | 2.43 (1.16–5.10) | 0.019 | |
| Death within 90 days, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 1.56 (0.99–2.44) | 0.051 | 1.06 (0.47–2.37) | 0.893 | |
| ATA-LVO | 1.60 (0.79–3.22) | 0.189 | 1.49 (0.55–4.00) | 0.430 | |
| SICHc, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 3.32 (1.60–6.86) | 0.001 | 2.82 (0.83–9.60) | 0.097 | |
| ATA-LVO | 3.34 (1.25–8.93) | 0.017 | 3.90 (0.96–15.88) | 0.058 | |
| PHb, n (%) | ICAS-LVO | Ref | Ref | ||
| CE-LVO | 4.61 (2.34–9.08) | < 0.001 | 6.71 (2.19–20.56) | 0.001 | |
| ATA-LVO | 2.19 (0.77–6.20) | 0.141 | 2.37 (0.56–9.93) | 0.240 |
ICAS intracranial atherosclerotic stenosis; CE cardioembolic; ATA arterial to arterial embolism; LVO large-vessel occlusion; SICH symptomatic intracranial hemorrhage; PH parenchymal hemorrhage; mRS modified Rankin Scale
a12 missing data
b23 missing data
c32 missing data
Table 3.
Subgroup analysis regarding 90-day mRSa of different etiologies of stroke
| Variables | Numbers | Adjusted OR and 95% CI |
P for interaction ICAS vs. CE |
P for interaction ICAS vs. ATA |
||
|---|---|---|---|---|---|---|
| ICAS-LVO (reference) | CE-LVO | ATA-LVO | ||||
| Age | ||||||
| Age < 65 | 397 | 1 | 1.04 (0.52–2.09) | 1.28 (0.56–2.90) | 0.571 | 0.970 |
| Age ≥ 65 | 519 | 1 | 1.21 (0.66–2.23) | 1.14 (0.53–2.45) | ||
| Gender | ||||||
| Male | 567 | 1 | 1.02 (0.59–1.76) | 1.37 (0.73–2.55) | 0.096 | 0.543 |
| Female | 349 | 1 | 0.81 (0.33–1.99) | 0.57 (0.16–2.03) | ||
| NIHSS | ||||||
| NIHSS ≤ 15 | 412 | 1 | 1.07 (0.53–2.18) | 1.30 (0.56–3.03) | 0.794 | 0.416 |
| NIHSS > 15 | 504 | 1 | 0.96 (0.53–1.72) | 1.09 (0.52–2.30) | ||
| Anesthesia | ||||||
| GA | 354 | 1 | 1.02 (0.47–2.20) | 1.08 (0.48–2.46) | 0.187 | 0.627 |
| LA | 562 | 1 | 1.11 (0.63–1.96) | 1.37 (0.62–3.02) | ||
| Occlusion location | ||||||
| Anterior circulation | 731 | 1 | 1.20 (0.73–1.97) | 1.38 (0.74–2.59) | 0.114 | 0.585 |
| Posterior circulation | 185 | 1 | 1.89 (0.54–6.65) | 0.80 (0.21–3.09) | ||
| OTD (min) | ||||||
| OTD ≤ 270 | 686 | 1 | 1.10 (0.65–1.86) | 1.17 (0.60–2.27) | 0.877 | 0.387 |
| OTD > 270 | 230 | 1 | 0.97 (0.40–2.35) | 0.81 (0.28–2.38) | ||
| DTP (min) | ||||||
| DTP ≤ 90 | 328 | 1 | 0.81 (0.40–1.68) | 1.10 (0.47–2.64) | 0.738 | 0.659 |
| DTP > 90 | 588 | 1 | 1.38 (0.79–2.42) | 1.08 (0.55–2.10) | ||
| Procedure duration (min) | ||||||
| Procedure duration ≤ 90 | 499 | 1 | 0.67 (0.37–1.23) | 1.04 (0.45–2.45) | 0.111 | 0.438 |
| Procedure duration > 90 | 417 | 1 | 2.01 (1.00–4.04) | 1.56 (0.74–3.30) | ||
| Successful recanalization | ||||||
| Yes | 840 | 1 | 1.00 (0.62–1.59) | 1.25 (0.71–2.20) | 0.245 | 0.672 |
| No | 76 | 1 | 0.87 (0.14–5.38) | 0.08 (0.002–3.28) | ||
ICAS intracranial atherosclerotic stenosis; CE cardioembolic; ATA arterial to arterial embolism; LVO large-vessel occlusion; NIHSS National Institutes of Health Stroke Scale score; GA general anesthesia; LA local anesthesia; OTD onset to door; DTP door to puncture; PTR puncture to recanalization
a12 missing data
Table 4.
Subgroup analysis regarding complete recanalization (mTICI 3) after EVT of different etiologies of stroke
| Variables | Numbers | Adjusted OR and 95% CI |
P for interaction ICAS vs. CE |
P for interaction ICAS vs. ATA |
||
|---|---|---|---|---|---|---|
| ICAS-LVO (reference) | CE-LVO | ATA-LVO | ||||
| Age | ||||||
| Age < 65 | 401 | 1 | 14.33 (4.39–46.79) | 2.69 (0.83–8.75) | 0.019 | 0.724 |
| Age ≥ 65 | 527 | 1 | 2.45 (1.04–5.77) | 2.58 (0.88–7.56) | ||
| Gender | ||||||
| Male | 575 | 1 | 4.92 (2.14–11.28) | 2.79 (1.15–6.73) | 0.967 | 0.406 |
| Female | 353 | 1 | 5.91 (1.59–21.93) | 1.46 (0.26–8.12) | ||
| NIHSS | ||||||
| NIHSS ≤ 15 | 417 | 1 | 2.45 (0.92–6.55) | 3.61 (1.10–11.88) | 0.926 | 0.742 |
| NIHSS > 15 | 511 | 1 | 9.04 (3.56–22.95) | 1.62 (0.59–4.44) | ||
| Anesthesia | ||||||
| GA | 361 | 1 | 4.03 (1.33–12.23) | 3.45 (1.03–11.51) | 0.768 | 0.575 |
| LA | 567 | 1 | 5.12 (2.22–11.83) | 2.06 (0.72–5.86) | ||
| Occlusion location | ||||||
| Anterior circulation | 741 | 1 | 3.87 (1.87–8.01) | 1.80 (0.75–4.28) | 0.262 | 0.392 |
| Posterior circulation | 187 | 1 | 4.97 (0.90–27.51) | 5.80 (0.97–37.68) | ||
| OTD (min) | ||||||
| OTD ≤ 270 | 692 | 1 | 5.47 (2.55–11.74) | 2.38 (0.99–5.72) | 0.806 | 0.918 |
| OTD > 270 | 236 | 1 | 2.02 (0.53–7.72) | 1.88 (0.36–9.79) | ||
| DTP (min) | ||||||
| DTP ≤ 90 | 335 | 1 | 5.30 (1.97–14.24) | 2.24 (0.74–6.79) | 0.285 | 0.451 |
| DTP > 90 | 593 | 1 | 5.40 (2.25–12.95) | 3.35 (1.24–9.04) | ||
| Procedure duration (min) | ||||||
| Procedure duration ≤ 90 | 503 | 1 | 6.09 (2.55–14.54) | 2.22 (0.71–6.97) | 0.996 | 0.649 |
| Procedure duration > 90 | 425 | 1 | 2.90 (1.06–7.95) | 2.27 (0.82–6.28) | ||
ICAS intracranial atherosclerotic stenosis; CE cardioembolic; ATA arterial to arterial embolism; LVO large-vessel occlusion; NIHSS National Institutes of Health Stroke Scale score; GA general anesthesia; LA local anesthesia; OTD onset to door; DTP door to puncture; PTR puncture to recanalization
Fig. 3.
Shift on 90-day mRS score stratified by different etiologies of stroke. LVO large-vessel occlusion, ATA artery to artery, ICAS intracranial atherosclerotic stenosis, CE cardioembolic, mRS modified Rankin Scale
The rate of successful recanalization was higher in the ICAS-LVO and ATA-LVO groups (P = 0.011), while the rate of complete recanalization was higher in the ATA-LVO and CE-LVO groups than that in the ICAS-LVO group (P = 0.001). Logistic regression analysis showed that the CE-LVO (adjusted odds ratio (aOR), 4.50; 95% confidence interval (CI), 2.37–8.56; P < 0.001) and ATA-LVO group (aOR, 2.43; 95% CI, 1.16–5.10; P = 0.019) were the predictors for complete recanalization. Further subgroup analysis showed a significant association between CE-LVO stroke etiology and complete recanalization in the age population < 65 years old (aOR, 14.33; 95% CI, 4.39–46.79; P = 0.019).
The rate of parenchymal hemorrhage was significantly higher in the CE-LVO group (P = 0.001). Logistic regression analysis showed that the CE-LVO group was the predictor for parenchymal hemorrhage (aOR, 6.71; 95% CI, 2.19–20.56; P = 0.001) after adjusting for some potential confounders. There was no statistically significant evidence for association of the stroke etiologies and SICH when some possible confounding factors, including age, gender, use of general anesthesia, occlusion location, time workflow (OTD, DTP, and PTR), and successful recanalization, were stratified.
Discussion
In this subgroup analysis of the ANGEL-ACT registry, we found that favorable outcomes were similar among different etiologies of stroke. Complete recanalization was higher in the CE-LVO and ATA-LVO groups, while CE-LVO may increase the risk of PH. Recanalization is essential to achieve favorable outcomes despite the different etiologies of stroke. However, EVT should be individualized in different etiologies of stroke to balance the functional outcome and potential risk of bleeding.
The outcome of EVT may depend on the etiology of stroke. The Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification is the most widely used when the influence of stroke etiologies on the stroke treatment outcome are evaluated [24–28]. However, several patients with different subcategories of TOAST classification, such as small-vessel disease and unknown etiologies, do not have LVO. They are not appropriate patient population to evaluate the outcome of EVT. The etiologies of ICAS and CE and ATA stroke were the common stroke etiologies with LVO. Thus, they are appropriate patient population for evaluating the outcome of EVT based on the stroke etiology. CE-LVO and ICAS-LVO are well-known mechanisms of stroke. However, ATA-LVO was poorly represented and often excluded from the EVT trial [1, 4, 5, 7]. As the feature of ATA-LVO is the embolic occlusion resulting from atherosclerosis at a different location, the pathological process at the occlusion site is similar to CE-LVO. Thus, numerous studies included them in the embolism group [8–10, 13, 29, 30].
We found that CE-LVO was more frequent in the anterior circulation, while ICAS-LVO was more frequent in the posterior circulation. This finding was in agreement with a previous study, which reported that the unique and distinct characteristics of AC and PC anatomical structure might lead to different pathogeneses of stroke [31, 32]. Furthermore, the anatomical structure of the carotid artery may provide a better access for the thrombus to enter the anterior circulation. This might partly explain the higher frequency of CE-LVO in the anterior circulation.
Significant differences in the time workflow among the groups could be attributable to the different characteristics of stroke patients among the three groups. In concordance with a previous study [18], the duration of OTD and DTP was longer in the ICAS-LVO group, followed by ATA-LVO and CE-LVO groups. A plausible explanation for this result might be that patients with ICAS-LVO often presented with milder symptoms due to a better collateral circulation, leading to more observation of the fluctuating symptoms rather than selecting for more aggressive treatment. On the other hand, the lack of collateral circulation in CE-LVO mainly causes sudden arterial occlusion symptoms. Importantly, the PTR time was the longest in patients with ATA-LVO. A longer time for recanalization in this group might be due to the necessity to overcome the proximal lesion, which often needs to additional stent placement to access the distal occluded vessel.
To date, only few studies have compared the efficacy of EVT according to its etiologies, and the results were controversial. One study reported that ICAS-LVO stroke has better outcomes than CE-LVO stroke [10]. In contrast, another study demonstrated that CE-LVO has relatively better functional outcomes than ICAS-LVO [8]. On the other hand, a research reported that ATA-LVO independently predicts poor outcomes [33]. Importantly, we found that the recanalization status determines whether the outcomes were favorable or unfavorable in these studies [22]. Patients with ICAS had more favorable outcomes than those without ICAS in Yoon et al.’s study [10], in which the successful recanalization rate in the ICAS group was higher (95% vs. 81.8%). Lee et al. [8] demonstrated that patients in the embolic group had better outcomes than those in the ICAS group, and a higher final recanalization grade (89.1% vs. 15.2%) was observed in the embolic group versus ICAS group. Consistently, successful recanalization after MT is also essential for a favorable outcome in tandem lesions [14, 15, 34].
Recent studies have confirmed that the recanalization status might be a relevant factor influencing patients’ functional outcomes. Baek et al. [11] reported that the clinical outcome did not differ as the recanalization rate was comparable between ICAS and non-ICAS groups. Consistently, another study performed by Lee et al. [18] revealed that the functional outcomes among different stroke etiologies were similar, because their successful recanalization rates were comparable. Our results were consistent with these findings. We also noted that etiologies of stroke were not associated with a favorable outcome at 90-day follow-up. We confirmed that etiologies of stroke were not associated with successful recanalization after adjusting for potential confounders. Thus, we assumed that different characteristics in different etiologies of stroke did not prevent successful recanalization in AIS-LVO patients. This conclusion was also verified by further analysis in the present study. Nevertheless, different etiologies of stroke demonstrated different characteristics, which were important in determining the EVT clinical and procedural characteristics, such as ICAS-LVO and ATA-LVO that were characterized by delay and more extended time workflow. However, they had a better collateral circulation than CE-LVO [16, 18].
Atherosclerotic lesions in ICAS-LVO and ATA-LVO groups were mainly related to a more complex procedure, and sometimes rescue therapy might be necessary to achieve successful recanalization [8, 12]. Recanalization of an atherosclerotic lesion has been a main challenge in EVT. According to our multicenter experience, when ICAS was confirmed by the appearance of residual stenosis after stent retriever, we mainly switched the procedure into angioplasty to reduce the possibility of endothelial injury. Previous studies also reported multimodal approaches, such as balloon angioplasty, stenting, and Tirofiban infusion to open atherosclerosis lesions. Consistently, we noted that the frequency of balloon angioplasty and stenting was higher in the ICAS-LVO group than that in the other two groups.
The subgroup analysis did not show any association between etiologies of stroke, favorable outcomes, and successful recanalization. However, in patients who aged < 65 years old, CE-LVO showed an association with complete recanalization. It seems that MT was performed with a more aggressive procedural approach in this population compared with less aggressive procedural approaches in older patients. This result might be due to the concern of a higher surgical risk in the elderly. Moreover, atherosclerotic lesions mainly present in older patients, and the complexity of the atherosclerotic lesions often limits the MT to achieve complete recanalization.
There is an important consideration when analyzing the results of the current study, raising the question of how aggressive we should be in achieving complete recanalization in different etiologies of stroke. We noted an association between CE-LVO and PH in the present study. We assumed that this might be due to over manipulation during procedures, as we found that patients with CE-LVO had a higher retrieval times. This result might also explain the association between CE-LVO and complete recanalization in the present study. However, a conclusion could not be drawn regarding why retrieval time was higher in this group, as histopathological results were not provided. Nevertheless, the operator should consider whether it is necessary to achieve complete recanalization if successful recanalization is sufficient to achieve a favorable outcome after EVT. We therefore recommended more aggressive procedures [35] or the use of rescue therapies to achieve successful recanalization, rather than to achieve complete recanalization.
In summary, it is essential to individualize EVT treatment in different etiologies of stroke to balance the functional outcome and bleeding risk, as the clinical and lesion characteristics were significantly different among etiologies of stroke. Our study has several limitations. First, it is challenging to standardize practice in this multicenter study, including surgical technique, anesthesia, and post-procedure care. Therefore, bias in results is probable. Second, the retrospective nature of this study and lack of control arm population are noteworthy. Third, our study population was limited to the Chinese population, leading to a selection bias, hindering the generalization of our findings. Fourth, we did not analyze the collateral vasculature status and thrombus characteristics, which are essential factors in determining the outcomes in different etiologies of stroke. Fifth, the present study did not provide information regarding the hyper-perfusion after stenting of a chronically stenotic lesion. Sixth, the exclusion criteria for a patient with two possible causes of stroke might result in selection bias. However, this exclusion might reduce the ambiguity and increase the influence of different etiologies of stroke on the outcomes. Despite these limitations, the strength of the present study lies in a large number of patients involved in multiple centers, which could provide a closer representation of real-world situations.
Conclusions
The current subgroup analysis of the ANGEL-ACT registry study showed that a favorable outcome after EVT was similar in different etiologies of stroke. Complete recanalization was more prevalent in the CE-LVO and ATA-LVO groups. There is an increased risk of PH in the CE-LVO group. Further large-scale multiethnic clinical trials are needed to confirm our finding.
Supplementary Information
Below is the link to the electronic supplementary material.
Required Author Forms
Disclosure forms provided by the authors are available with the online version of this article.
Funding
This work was supported by the National Key Research and Development Program of China (grant number 2016YFC1301500) and China Postdoctoral Science Foundation (grant number 2020-YJ-008).
Declarations
Ethics Approval
This study was reviewed and approved by our Institutional Review Board and procedures followed were in accordance with institutional guidelines and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committees of Beijing Tiantan Hospital, Capital Medical University, and all participating centers. Subjects or their legally authorized representatives provided written informed consent (http://www.clinicaltrials.gov; unique identifier: NCT03370939).
Conflict of Interest
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Raynald and Dapeng Sun contributed equally.
Contributor Information
Xiaochuan Huo, Email: huoxiaochuan@126.com.
Zhongrong Miao, Email: doctorzhongrongm@126.com, Email: zhongrongm@163.com.
References
- 1.Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R, Investigators SP. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285–2295. 10.1056/NEJMoa1415061 [DOI] [PubMed]
- 2.Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG, Investigators D. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708–718. doi: 10.1056/NEJMoa1713973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A, Investigators RT. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296–2306. doi: 10.1056/NEJMoa1503780. [DOI] [PubMed] [Google Scholar]
- 4.Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW, Investigators MC. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20. 10.1056/NEJMoa1411587
- 5.Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM, Investigators E-I. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–1018. doi: 10.1056/NEJMoa1414792. [DOI] [PubMed] [Google Scholar]
- 6.Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD, Investigators ET. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019–1030. doi: 10.1056/NEJMoa1414905. [DOI] [PubMed] [Google Scholar]
- 7.Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG, collaborators H. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–1731. 10.1016/S0140-6736(16)00163-X [DOI] [PubMed]
- 8.Lee JS, Lee SJ, Yoo JS, Hong JH, Kim CH, Kim YW, Kang DH, Kim YS, Hong JM, Choi JW, Ovbiagele B, Demchuk AM, Sohn SI, Hwang YH. Prognosis of acute intracranial atherosclerosis-related occlusion after endovascular treatment. J Stroke. 2018;20(3):394–403. doi: 10.5853/jos.2018.01627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Lee JS, Hong JM, Lee KS, Suh HI, Demchuk AM, Hwang YH, Kim BM, Kim JS. Endovascular therapy of cerebral arterial occlusions: intracranial atherosclerosis versus embolism. J Stroke Cerebrovasc Dis. 2015;24(9):2074–2080. doi: 10.1016/j.jstrokecerebrovasdis.2015.05.003. [DOI] [PubMed] [Google Scholar]
- 10.Yoon W, Kim SK, Park MS, Kim BC, Kang HK. Endovascular treatment and the outcomes of atherosclerotic intracranial stenosis in patients with hyperacute stroke. Neurosurgery. 2015;76(6):680–686. Discussion 686. 10.1227/NEU.0000000000000694 [DOI] [PubMed]
- 11.Baek JH, Kim BM, Heo JH, Kim DJ, Nam HS, Kim YD. Outcomes of endovascular treatment for acute intracranial atherosclerosis-related large vessel occlusion. Stroke. 2018;49(11):2699–2705. doi: 10.1161/STROKEAHA.118.022327. [DOI] [PubMed] [Google Scholar]
- 12.Jia B, Feng L, Liebeskind DS, Huo X, Gao F, Ma N, Mo D, Liao X, Wang C, Zhao X, Pan Y, Li H, Liu L, Wang Y, Wang Y, Miao ZR, Group ES Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis. J Neurointerv Surg. 2018;10(8):746–750. doi: 10.1136/neurintsurg-2017-013489. [DOI] [PubMed] [Google Scholar]
- 13.Lee JS, Lee SJ, Hong JM, Choi JW, Yoo J, Hong JH, Kim CH, Kim YW, Kang DH, Kim YS, Hwang YH, Sohn SI. Solitaire thrombectomy for acute stroke due to intracranial atherosclerosis-related occlusion: ROSE ASSIST study. Front Neurol. 2018;9:1064. doi: 10.3389/fneur.2018.01064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Gory B, Haussen DC, Piotin M, Steglich-Arnholm H, Holtmannspotter M, Labreuche J, Kyheng M, Taschner C, Eiden S, Nogueira RG, Papanagiotou P, Boutchakova M, Siddiqui AH, Lapergue B, Dorn F, Cognard C, Killer M, Mangiafico S, Ribo M, Psychogios MN, Spiotta AM, Labeyrie MA, Biondi A, Mazighi M, Turjman F. Thrombectomy In Tli. Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion and clinical outcomes in patients with acute stroke with tandem lesion treated with thrombectomy: a collaborative pooled analysis. Eur J Neurol. 2018;25(9):1115–1120. 10.1111/ene.13633 [DOI] [PubMed]
- 15.Zhu F, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Mione G, Humbertjean L, Lacour JC, Hossu G, Anadani M, Richard S, Gory B. Impact of emergent cervical carotid stenting in tandem occlusion strokes treated by thrombectomy: a review of the TITAN collaboration. Front Neurol. 2019;10:206. doi: 10.3389/fneur.2019.00206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Guglielmi V, LeCouffe NE, Zinkstok SM, Compagne KCJ, Eker R, Treurniet KM, Tolhuisen ML, van der Worp HB, Jansen IGH, van Oostenbrugge RJ, Marquering HA, Dippel DWJ, Emmer BJ, Majoie C, Roos Y, Coutinho JM, Investigators M-CR. Collateral circulation and outcome in atherosclerotic versus cardioembolic cerebral large vessel occlusion. Stroke. 2019;50(12):3360–3368. 10.1161/STROKEAHA.119.026299 [DOI] [PMC free article] [PubMed]
- 17.Rebello LC, Bouslama M, Haussen DC, Grossberg JA, Dehkharghani S, Anderson A, Belagaje SR, Bianchi NA, Grigoryan M, Frankel MR, Nogueira RG. Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes. Eur J Neurol. 2017;24(6):762–767. doi: 10.1111/ene.13287. [DOI] [PubMed] [Google Scholar]
- 18.Lee D, Lee DH, Suh DC, Kim BJ, Kwon SU, Kwon HS, Lee JS, Kim JS. Endovascular treatment in patients with cerebral artery occlusion of three different etiologies. J Stroke. 2020;22(2):234–244. doi: 10.5853/jos.2019.02404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jia B, Ren Z, Mokin M, Burgin WS, Bauer CT, Fiehler J, Mo D, Ma N, Gao F, Huo X, Luo G, Wang A, Pan Y, Song L, Sun X, Zhang X, Gui L, Song C, Peng Y, Wu J, Zhao S, Zhao J, Zhou Z, Li Y, Jing P, Yang L, Liu Y, Zhao Q, Liu Y, Peng X, Gao Q, Guo Z, Chen W, Li W, Cheng X, Xu Y, Zhang Y, Zhang G, Lu Y, Lu X, Wang D, Wang Y, Li H, Ling L, Peng G, Zhang J, Zhang K, Li S, Qi Z, Xu H, Tong X, Ma G, Liu R, Guo X, Deng Y, Leng X, Leung TW, Liebeskind DS, Wang Y, Wang Y, Miao Z, Groupdagger A-AS. Current status of endovascular treatment for acute large vessel occlusion in China: a real-world nationwide registry. Stroke. 2021;52(4):1203–1212. 10.1161/STROKEAHA.120.031869 [DOI] [PubMed]
- 20.Anadani M, Spiotta A, Alawieh A, Turjman F, Piotin M, Steglich-Arnholm H, Holtmannspotter M, Taschner C, Eiden S, Haussen DC, Nogueira R, Papanagiotou P, Boutchakova M, Siddiqui AH, Lapergue B, Dorn F, Cognard C, Killer-Oberpfalzer M, Mangiafico S, Ribo M, Psychogios MN, Labeyrie MA, Mazighi M, Biondi A, Anxionnat R, Bracard S, Richard S, Gory B, Investigators T. Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry. J Neurointerv Surg. 2019;11(10):970–974. doi: 10.1136/neurintsurg-2018-014629. [DOI] [PubMed] [Google Scholar]
- 21.Anadani M, Spiotta AM, Alawieh A, Turjman F, Piotin M, Haussen DC, Nogueira RG, Papanagiotou P, Siddiqui AH, Lapergue B, Dorn F, Cognard C, Ribo M, Psychogios MN, Labeyrie MA, Mazighi M, Biondi A, Anxionnat R, Bracard S, Richard S, Gory B, Investigators T. Emergent carotid stenting plus thrombectomy after thrombolysis in tandem strokes: analysis of the TITAN registry. Stroke. 2019;50(8):2250–2252. doi: 10.1161/STROKEAHA.118.024733. [DOI] [PubMed] [Google Scholar]
- 22.Baik SH, Park HJ, Kim JH, Jang CK, Kim BM, Kim DJ. Mechanical thrombectomy in subtypes of basilar artery occlusion: relationship to recanalization rate and clinical outcome. Radiology. 2019;291(3):730–737. doi: 10.1148/radiol.2019181924. [DOI] [PubMed] [Google Scholar]
- 23.Adams HP, Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. 10.1161/01.str.24.1.35 [DOI] [PubMed]
- 24.Tiedt S, Wollenweber FA. Response by Tiedt and Wollenweber to letter regarding article, "Stroke etiology modifies the effect of endovascular treatment in acute stroke". Stroke. 2020;51(8):e159–e160. doi: 10.1161/STROKEAHA.120.030266. [DOI] [PubMed] [Google Scholar]
- 25.Grau AJ, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S, Glahn J, Brandt T, Hacke W, Diener HC. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke. 2001;32(11):2559–2566. doi: 10.1161/hs1101.098524. [DOI] [PubMed] [Google Scholar]
- 26.Mustanoja S, Meretoja A, Putaala J, Viitanen V, Curtze S, Atula S, Artto V, Happola O, Kaste M. Helsinki Stroke Thrombolysis Registry G. Outcome by stroke etiology in patients receiving thrombolytic treatment: descriptive subtype analysis. Stroke. 2011;42(1):102–106. 10.1161/STROKEAHA.110.597534 [DOI] [PubMed]
- 27.Lang Q, Zhou M, Feng H, Guo J, Chen N, He L. Research on the relationship between fibrinogen level and subtypes of the TOAST criteria in the acute ischemic stroke. BMC Neurol. 2013;13:207. doi: 10.1186/1471-2377-13-207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Ois A, Cuadrado-Godia E, Rodriguez-Campello A, Giralt-Steinhauer E, Jimenez-Conde J, Lopez-Cuina M, Ley M, Soriano C, Roquer J. Relevance of stroke subtype in vascular risk prediction. Neurology. 2013;81(6):575–580. doi: 10.1212/WNL.0b013e31829e6f37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Al Kasab S, Almadidy Z, Spiotta AM, Turk AS, Chaudry MI, Hungerford JP, Turner RDt. Endovascular treatment for AIS with underlying ICAD. J Neurointerv Surg. 2017;9(10):948–951. 10.1136/neurintsurg-2016-012529 [DOI] [PubMed]
- 30.Hwang YH, Kim YW, Kang DH, Kim YS, Liebeskind DS. Impact of target arterial residual stenosis on outcome after endovascular revascularization. Stroke. 2016;47(7):1850–1857. doi: 10.1161/STROKEAHA.116.013046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Caplan LR, Wityk RJ, Glass TA, Tapia J, Pazdera L, Chang HM, Teal P, Dashe JF, Chaves CJ, Breen JC, Vemmos K, Amarenco P, Tettenborn B, Leary M, Estol C, Dewitt LD, Pessin MS. New England Medical Center Posterior Circulation registry. Ann Neurol. 2004;56(3):389–398. doi: 10.1002/ana.20204. [DOI] [PubMed] [Google Scholar]
- 32.Zurcher E, Richoz B, Faouzi M, Michel P. Differences in ischemic anterior and posterior circulation strokes: a clinico-radiological and outcome analysis. J Stroke Cerebrovasc Dis. 2019;28(3):710–718. doi: 10.1016/j.jstrokecerebrovasdis.2018.11.016. [DOI] [PubMed] [Google Scholar]
- 33.Rubiera M, Ribo M, Delgado-Mederos R, Santamarina E, Delgado P, Montaner J, Alvarez-Sabin J, Molina CA. Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis. Stroke. 2006;37(9):2301–2305. doi: 10.1161/01.STR.0000237070.80133.1d. [DOI] [PubMed] [Google Scholar]
- 34.Sadeh-Gonik U, Tau N, Friehmann T, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Richard S, Armoiry X, Gory B. Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions: a clinical registry and an update of a systematic review with meta-analysis. Eur J Neurol. 2018;25(4):693–700. doi: 10.1111/ene.13577. [DOI] [PubMed] [Google Scholar]
- 35.Gao F, Lo WT, Sun X, Mo DP, Ma N, Miao ZR. Combined use of mechanical thrombectomy with angioplasty and stenting for acute basilar occlusions with underlying severe intracranial vertebrobasilar stenosis: preliminary experience from a single Chinese center. AJNR Am J Neuroradiol. 2015;36(10):1947–1952. doi: 10.3174/ajnr.A4364. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.