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Abstract
Introduction For patients undergoing mechanical thrombectomy, numerous (>3) thrombectomy passes may be harmful. However, non-recanalization leads to poor outcomes. For patients requiring multiple thrombectomy passes to achieve reperfusion, it remains unclear if the risk/benefit ratio favors recanalization.
Objective To test the hypothesis that the benefits afforded by successful reperfusion outweigh the risk conveyed by the numerous passes required.
Methods We retrospectively reviewed prospectively collected data for patients presenting to a comprehensive stroke center with anterior circulation large vessel occlusion (ACLVO) and undergoing thrombectomy requiring more than one pass over 24 months. We stratified patients into three groups: group 1 (successful reperfusion in 2–3 passes), group 2 (successful reperfusion in ≥4 passes), and group 3 (unsuccessful reperfusion).
Results 250 patients with ACLVO constituted the study cohort. Despite similar demographics, group 2 patients had better clinical outcomes than those in group 3 at 24 hours (National Institutes of Health Stroke Scale (NIHSS) score 13.5 vs 19.1, p<0.001) and at 90 days (modified Rankin Scale score 0–2 rates of 31.1% vs 0.0%, p=0.006) On multivariate logistic regression analysis, age (p=0.034), Alberta Stroke Program Early CT Score (p<0.01), NIHSS score (p=0.02), and parenchymal hematoma type 2 (p=0.015) were significant predictors of functional independence among those who achieved successful reperfusion, but the number of passes required did not predict outcome for these patients (p=0.74).
Conclusion Patients who achieve successful reperfusion after many passes have better clinical outcomes than those who do not, despite the number of passes and procedural time required. The number of passes required to achieve successful reperfusion beyond the first pass is not a predictor of functional independence.
- acute ischemic stroke
- large vessel occlusion
- mechanical thrombectomy
- passes
- reperfusion
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Introduction
Patients undergoing mechanical thrombectomy for acute ischemic stroke secondary to large vessel occlusion who require a fewer number of passes to achieve successful reperfusion have better functional outcomes than patients who undergo a higher number of passes.1 2 First-pass effect has thus been used as a primary radiographic outcome measure in large studies.3–5 It has also been well established that successful reperfusion predicts outcome and is protective against symptomatic intracranial hemorrhage (sICH), which is associated with worse clinical outcomes after thrombectomy.6 7 For patients who are not recanalized in a single pass, it has been suggested by some that future studies should examine the question of whether the theoretical benefits of complete recanalization may be counterbalanced by possible detrimental effects of multiple passes.1 8
The aim of this study is to determine whether satisfactory final reperfusion (Thrombolysis in Cerebral Infarction (TICI) 2b or 3) obtained after many passes is associated with better clinical outcomes than thrombectomies which are aborted with unsatisfactory reperfusion (TICI 0–2a) in patients who require multiple thrombectomy passes. Our hypothesis is that the benefits afforded patients by obtaining successful reperfusion outweigh any additional risk conveyed by numerous passes required to achieve reperfusion.
Methods
A retrospective analysis of prospectively collected data was performed for all patients presenting to a tertiary care academic comprehensive stroke center with anterior circulation acute ischemic stroke between December 2015 and November 2017 using the Get-With-The-Guidelines database. Demographic characteristics, clinical and radiological data, treatment, and procedural information were extracted and analyzed. This study was approved by the local institutional review board.
Patient selection
Patients with acute ischemic stroke who presented to a single comprehensive stroke center and underwent thrombectomy for an anterior circulation large vessel occlusion during the study period were analyzed. Occlusion location was confirmed by CT angiography, magnetic resonance angiography, and/or cerebral angiography. The decision to offer endovascular therapy was based on the discretion of the vascular neurologist and treating neurointerventionalist, after detailed discussion with the patient and/or their family. Patients were included in this analysis if they required multiple passes of manual aspiration or stent retriever-assisted manual aspiration; we excluded patients with successful first-pass recanalization because this has been well established as a positive predictor of functional outcome2 and we aimed to examine the risk/benefit ratio of recanalization that necessitates multiple passes.
Baseline characteristics
Baseline demographic (age, sex), clinical (stroke severity, time from symptom onset, risk factor profile), radiographic (Alberta Stroke Program Early CT Score (ASPECTS), occlusion location) information, and procedural technique and efficiency (TICI score)9 were collected and analyzed by a vascular neurologist blinded to patient outcomes.
Patient stratification
Patients were stratified into groups based on their recanalization status and the number of thrombectomy passes attempted. Group 1 comprised patients undergoing successful (TICI 2b or higher) thrombectomy in two to three passes. Group 2 included patients undergoing thrombectomy in four or more passes with successful recanalization (TICI 2b or higher). Group 3 consisted of patients undergoing thrombectomy who did not achieve successful reperfusion (TICI 2a or lower) regardless of the number of passes required.
We directly compared patients in groups 1, 2, and 3. Separately, we performed an analysis directly comparing those patients with successful reperfusion (groups 1 and 2), stratified them by modified Rankin Scale (mRS) score at 90 days, and performed multivariate logistic regression analyses to identify whether or not good outcomes were predicted by demographic/stroke variables or the number of passes required for reperfusion.
Outcomes
The primary outcome was 90-day functional independence, defined as mRS score of 0–2. Other outcome measures included National Institutes of Health Stroke Scale (NIHSS) score at 24 hours and outcomes that may be associated with multiple passes: rates of parenchymal hematoma type 2 (PH2), sICH as defined by SITS-MOST criteria,10 and recanalization time. All post-treatment radiologic evaluation of intracranial hemorrhage was conducted by a vascular neurologist blinded to patient-specific data.
Statistical analyses
Continuous variables are reported as mean±SD or median with interquartile range (as appropriate) and categorical variables are reported as proportions. Between-groups comparison for continuous variables was performed using Student’s t-test, and categorical variables using Χ2 test or Fisher exact test, as appropriate. Significance was defined as p≤0.05. Statistical analysis was performed using IBM SPSS Statistics 23 (IBM-Armonk, New York, USA).
Results
Patient demographics
A total of 431 patients with acute ischemic stroke due to anterior circulation artery occlusion underwent thrombectomy at a single comprehensive stroke center during the study period. 181 patients (42%) had successful first-pass reperfusion and were thus excluded from this analysis. The remaining 250 patients constituted the study cohort. Mean age was 72.3 years and 57% were female (table 1). Median NIHSS score at hospital presentation was 17.7±5.8. Median ASPECTS score was 9% and 36% received IV tissue plasminogen activator (tPA).
Patient demographics
Internal carotid artery occlusion was found in 66 patients (26%), M1 occlusion in 144 (58%), and the remaining 40 patients (16%) harbored M2 occlusions. Successful recanalization (TICI ≥2b) was ultimately achieved in 230 patients (92%): TICI 2b in 178/250 (71%), TICI 2c in 40/250 (16%), and TICI 3 in 12 (5%). Recanalization rates of TICI 2a were achieved in 18 patients (7%), TICI 1 in two patients (1%) and no patients were TICI 0 at the conclusion of thrombectomy. No differences were noted in gender, age, presenting NIHSS score, comorbidities, site of occlusion, and use of IV tPA between the different groups. Compared with patients in group 2 (successful reperfusion in ≥4 passes), patients in group 1 (successful reperfusion in 2–3 passes) had higher ASPECTS (8.9 vs 8.4, p=0.02).
Clinical and radiographic outcomes
Patients were stratified into groups by final reperfusion and by number of passes taken (table 2). Group 2 (successful reperfusion achieved in ≥4 passes) was used as the reference group for statistical comparisons. The average number of passes for each group was 2.3 (IQR 2–3) for group 1, 5.0 (IQR 4–6) for group 2, and 5.5 (IQR 3–8) for group 3. Compared with group 2, patients in group 1 (successful reperfusion in 2–3 passes) had shorter time from groin puncture to recanalization (38.4 vs 65.1 min, p<0.001) with a lower NIHSS score at 24 hours after the procedure (10.6 vs 13.5, p=0.01), lower rates of sICH (1.3% vs 6.5%, p=0.04), and a higher rate of functional outcome at 90 days (45% vs 31.1%, p=0.04).
Outcomes stratified by group
Compared with group 2, patients in group 3 (unsuccessful reperfusion despite any number of passes) had longer procedures (84.4 vs 65.1 min, p=0.02) with a worse NIHSS score at 24 hours (19.1 vs 13.5, p<0.001) and worse rates of functional outcome at 90 days (0% vs 31.1%, p=0.006). Rates of PH2 and sICH were not statistically different between groups.
Patients with successful reperfusion (all patients in groups 1 and 2) were then analyzed separately for predictors of independent functional outcome at 90 days. On multivariate logistic regression analysis, age (OR=0.96, 95% CI 0.920 to 0.997, p=0.034), ASPECTS (OR=2.33, 95% CI 1.56 to 3.46, p<0.01), NIHSS score (OR=0.92, 95% CI 0.861 to 0.968, p=0.02), PH2 (OR=3.15, 95% CI 1.25 to 7.94, p=0.015), and diabetes mellitus (OR=3.16, 95% CI 1.15 to 8.67, p=0.026) were significant predictors of functional independence at 90 days among those who achieved successful reperfusion, but the number of passes required did not predict good outcome for these patients (OR=1.16, 95% CI 0.501 to 2.67, p=0.74).
Discussion
We aimed to test the hypothesis that a thrombectomy procedure should be halted at a given number of passes because the risk of detrimental injury to the patient outweighs the benefits of recanalization. In this analysis, we directly compared patients with successful reperfusion after four or more passes (group 2) with patients whose procedures were aborted with unsuccessful reperfusion (group 3) and with those with successful reperfusion after two or three attempts (group 1). We found that patients who achieve successful reperfusion after four or more passes have better rates of functional outcomes than those who do not achieve reperfusion (31.1% vs 0.0%, p=0.006). Furthermore, no patient in this study with TICI 2a or worse reperfusion achieved functional independence at 90 days.
Data obtained from retrospective registries has indicated that patients with anterior circulation large vessel occlusion who are recanalized with a single pass thrombectomy have better functional outcomes than those who do not.2 However, it is unclear if first-pass recanalization is a surrogate for good patient biology, good proceduralist technique, or some combination of both; the relationship between correlation and causation remains unknown. Despite the lack of clarity, data suggesting that patients who are successfully recanalized with a higher number of passes have a lower likelihood of functional independence at 90 days have been used to support the argument that additional attempts to achieve recanalization should be pursued until an optimal number of passes have been made, at which point the risks of further passes may outweigh the benefits of reperfusion.1
We also evaluated all patients with successful reperfusion (groups 1 and 2 combined) to identify predictors of independent functional outcome at 90 days. On multivariate logistic regression analyses, predictors of functional independence included age (p=0.034), ASPECTS (p<0.01), NIHSS score (p=0.02), PH2 (p=0.015), and the absence of diabetes mellitus (p=0.026); the number of passes required to achieve TICI 2b reperfusion beyond the first pass did not predict good outcome for these patients (p=0.74).
The results of this study suggest that successful recanalization should be pursued despite the number of attempts necessary. The number of passes required for reperfusion is a treatment effect modifier (as are age, infarct size, etc), but the data reported here suggest that the treatment effect still favors recanalization for these patients, despite a higher number of passes. Our findings are supported by the findings of Jindal et al, who retrospectively reviewed their institution’s experience with 205 cases of anterior circulation large vessel occlusion over 6 years in order to determine predictors of functional outcome; on multivariate analysis, the number of thrombectomy attempts alone was not an independent negative predictor of functional outcome.11 This is perhaps because some patients cannot be recanalized despite many attempts, therefore biasing the “higher passes” group to worse outcomes. In the study of Jindal et al, only age, presenting NIHSS score, and revascularization grade were predictors of functional outcome.11 This is consistent with prior literature12; revascularization remains the only modifiable factor. Notably, the study by Jindal et al included a substantial number of patients with successful first-pass recanalization, which has been shown to correlate with good clinical outcome in numerous other prior studies.2 In the cohort of patients reported here, we specifically excluded patients with successful first-pass recanalization because we aimed to examine what happens after the first pass, attempting to deal with the risk/benefit ratio of recanalization that necessitates multiple passes.
Nevertheless, the findings reported here strongly suggest that the goal of stroke thrombectomy should be revascularization, and we continue to advocate an aggressive approach that favors prompt uncomplicated revascularization. Despite longer procedure times associated with multiple passes, patients who achieved successful reperfusion had significantly better outcomes than those who did not both at 24 hours after the procedure (average NIHSS score 13.5 vs 19.1, p<0.001) and at 90 days (mRS score 0–2 in 31.1% vs 0%, p=0.006).
Study limitations
Limitations of this study include the retrospective nature of the data analysis and a modest number of patients with unsuccessful reperfusion. Reperfusion grades were determined at the end of each thrombectomy procedure and lack third-party validation. Future studies should attempt to study this question in a prospective manner to validate the findings reported here.
Conclusion
Patients who achieve successful reperfusion after many passes have better clinical outcomes than those who do not, despite the additional number of passes and procedural time required. The number of passes required to achieve successful reperfusion is not an independent predictor of functional independence in patients requiring more than one thrombectomy pass.
Footnotes
Twitter @shashvatdesaiMD
Contributors Study design: DAT, AJ; drafting the article: DAT; acquisition of data/data analysis: DAT/SMD; reviewed and revised article before submission: all authors. Study supervision: AJ.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests BTJ: consultant: Medtronic. MB: investor: Penumbra, Inc. BAG: consultant: Microvention. TGJ: consultant: Stryker Neurovascular (PI DAWN-unpaid); ownership Interest: Anaconda; advisory board/investor: FreeOx Biotech, Route92, Corindus, Viz. ai, Blockade Medical; honoraria: Cerenovus.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.