Article Text
Abstract
Background Endovascular thrombectomy (EVT) has become the mainstay treatment for large vessel occlusion, with favorable safety and efficacy profile. However, the safety and efficacy of EVT in concurrent multi-territory occlusions (MTVOs) remains unclear.
Objective To investigate the prevalence, clinical and technical outcomes of concurrent EVT for MTVOs.
Methods Data were included from the Stroke Thrombectomy and Aneurysm Registry (STAR) with 32 stroke centers for EVT performed to treat bilateral anterior or concurrent anterior and posterior circulation occlusions between 2017 and 2021. Patients with MTVO were identified, and propensity score matching was used to compare this group with patients with occlusion in a single arterial territory.
Results Of a total of 7723 patients who underwent EVT for acute ischemic stroke, 54 (0.7%) underwent EVT for MTVOs (mean age 69±12.5; female 50%). 28% had bilateral and 72% had anterior and posterior circulations occlusions. The rate of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3), complications, modified Rankin score at 90 days, and mortality was not significantly different between the matched cohorts. Multivariate analysis confirmed that MTVOs were not associated with poor functional outcome, symptomatic intracranial hemorrhage, or longer procedure time.
Conclusion Compared with EVT for single vessel occlusions, EVT in appropriately selected patients with MTVOs has a similar efficacy and safety profile.
- intervention
- stroke
- thrombectomy
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
To date, only anecdotal evidence from small case series exists regarding endovascular thrombectomy (EVT) in concurrent multivessel occlusions (MTVOs). Prior work reported poor functional outcomes with high mortality rates despite high recanalization rate, and the question remains whether patients with MTVO should be offered EVT.
WHAT THIS STUDY ADDS
Our current study is the largest study to date showing that there is no difference in safety profile, successful recanalization, or functional independence at 90 days between patients with MTVO and those with single vessel occlusion who undergo EVT.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY
In appropriately selected patients with MTVO, EVT should be considered as it does not confer additional safety risk compared with single vessel occlusion.
Introduction
Acute ischemic stroke (AIS) secondary to concurrent multivessel occlusions (MTVOs) represents a small proportion of large vessel occlusions, with potentially devastating functional outcomes and mortality.1 2 Although endovascular thrombectomy (EVT) has become the mainstay treatment for large vessel occlusions,3 its role in the treatment of MTVOs has not been well established. Only a handful of studies, most of which contain anecdotal evidence combined with small case series, have explored the utility of EVT in achieving recanalization and improving outcomes in patients with MTVOs.2 4–15 The incidence of endovascularly treated MTVOs in specialized centers is still not clear and ranges between 0.34% and 2%.5 16 The overall functional outcomes in patients with MTVOs treated with EVT are poor, with high mortality rates, despite relatively high recanalization rates.2 4 This has raised the question of whether this subset of patients should be excluded from consideration for EVT.4
In this work, we queried a large prospectively maintained multicenter patient registry to explore the prevalence of MTVO, technical and clinical outcomes as well predictors of favorable outcomes, compared with patients undergoing EVT for single vessel occlusion (SVO) AIS.
Methods
Patient population
We reviewed patient data from the Stroke Thrombectomy and Aneurysm Registry (STAR), a prospectively maintained real-world registry of patients with AIS undergoing EVT.17 Among the STAR collaborators, 32 comprehensive stroke centers from around the world participated in this study. We included patients who were aged 18 years and older presenting with AIS who were treated with modern frontline thrombectomy techniques irrespective of clot location, time of onset, and whether intravascular tissue plasminogen activator (IV tPA) was administered. Data were collected independently by each center, and coded data were shared through the STAR collaboration. The study was approved by the institutional review board at the University of South Carolina (ID: Pro00090704) along with individual institutional review boards at the participating institutions. The requirement for a written consent was waived.
Endovascular thrombectomy
All patients underwent a non-contrast head CT scan and vascular imaging (CT or magnetic resonance angiography) prior to EVT. Patients then underwent EVT based on the selection criteria followed at each institution. There was no standardized cut-off point for symptom onset to EVT across all participating centers. The frontline thrombectomy technique was performed based on the interventionalist’s discretion and included contact aspiration,18 stent retriever,19 or a combined approach.20
Data collection
Data collected included patient demographics, comorbidities, procedural details, imaging findings, postprocedure intracranial hemorrhage (ICH), procedural complications (including, but not limited to, vessel dissections, perforations, perioperative myocardial ischemia, access site hematoma), recanalization scores, and 90-day functional outcome scores via the modified Rankin Scale (mRS).
Multivessel occlusions
For the purpose of this work, we define MTVOs as concurrent occlusions that affect at least two distinct unrelated intracranial vessels, including the bilateral anterior circulations or anterior and posterior circulations, each of which was targeted for EVT during the same procedure. Patients with chronic vessel occlusion documented on previous vascular imaging or ipsilateral tandem vessel occlusion were excluded. We also excluded patients with ipsilateral anterior and posterior circulation occlusions in the context of ipsilateral fetal posterior communicating artery; and patients who had an initial single territory occlusion that then broke and became a multi-territory occlusion.
Technical outcomes
Procedure time was defined as the time from arterial puncture to successful recanalization. Recanalization was scored using the modified Thrombolysis in Cerebral Infarction (mTICI) score, and successful recanalization was defined as mTICI ≥2b. Procedural complications were also recorded. Postprocedural ICH was diagnosed using CT or MRI within 24 hours of the procedure and was scored using European Collaborative Acute Stroke Study (ECASS) criteria.21
Clinical outcomes
The primary clinical outcome was the modified Rankin score (mRS) at 90 days after the procedure. Telephone calls were used to confirm mortality or to contact patients discharged to a nursing home, hospice, or rehabilitation facility. A good functional outcome was defined as mRS score ≤2.
Propensity score matching
We used propensity score matching to account for covariates when comparing the MTVO and SVO groups. Matching was performed based on the following variables: age, gender, race, admission National Institutes of Health Stroke Scale (NIHSS) score, baseline mRS score, onset to puncture, and use of IV tPA. Propensity score analysis was performed in IBM SPSS Statistics, version 25 (IBM Corp.) using the Fuzzy algorithm. We used 1:1 matching paradigm, and univariate analysis was used to confirm balanced groups.
Statistical analysis
Data analysis was performed using IBM SPSS Statistics, version 25 (IBM Corp.) and GraphPad Prism, version 8 (GraphPad, California, USA). Univariate analysis was performed using Student’s t-test or one-way analysis of variance with Bonferroni for parametric variables, Mann-Whitney test or Kruskal-Wallis test for non-parametric variables, and χ2 test with likelihood ratios for categorical variables. Multivariate analysis was then performed for predictors of technical and clinical outcomes using logistic, linear, or ordinal regressions, as appropriate. Variables included in the model include predetermined variables (age, gender, race, admission NIHSS score, pre-stroke mRS score, comorbidities) in addition to variables with P<0.1 on univariate testing. Multiple imputations were used for handling missing variables in baseline characteristics (race, onset-to-puncture time, gender, other comorbidities) to avoid associated biases. Rubin’s rule was used to approximate coefficients for regression analysis. For all models, 10 imputations were performed. Exponential and linear curve fitting was performed in GraphPad prism and assessed for best fit using R2 coefficient. For determining significance, a two-tailed P value <0.05 is considered significant, and a trend is defined as P<0.1.
Results
Patient population
A total of 7745 patients underwent EVT for AIS at 32 stroke centers during the study period, of whom 7723 patients had detailed description of the vessels treated and were included in the analysis. Among the included subset, 7669 (99.3%) patients had AIS secondary to SVO and 54 (0.7%) had MTVOs as defined in the methods and were included in the MTVO group. In patients with MTVOs, stroke etiology was available for 31 patients and was thought to be secondary to cardioembolism in 51% (atrial fibrillation, left ventricular thrombus, aortic thrombus), large vessel atherosclerosis in 29%, hypercoagulability in 10%, and unclear etiology in 10%.
Technical and clinical variables in SVO versus MTVO EVT
Table 1 summarizes the difference in baseline, procedural, and clinical variables between patients with AIS secondary to MTVOs versus the unmatched SVO cohort. Patients with MTVOs presented with a higher NIHSS score (18.3±8 vs 15.5±7, P=0.004) but had comparable age, race, Alberta Stroke Program Early CT (ASPECT) score, and rates of IV tPA use compared with SVOs (table 1). Both groups had comparable rates of internal carotid artery angioplasty, distribution of frontline thrombectomy technique used, procedure time, and rates of intra-arterial tPA use (P>0.05). The rates of successful recanalization were comparable between the two groups, however patients with MTVOs required a higher number of procedural attempts (3±2.5 vs 2±1.5, P=0.007). Functional outcome at 90 days, mortality rate, and postprocedural ICH were similar between the two groups (table 1). The rate of complications (other than ICH) was higher in the MTVO group (13% vs 6%, P=0.022). These complications include intraoperative cardiac events (ST elevation myocardial infarction), vessel dissection, groin hematoma, immediate reocclusion, seizures, and vasospasm.
Although functional outcome at 90 days was not significantly different between the two groups, there was a trend towards better functional outcome at 90 days in patients with AIS due to SVO (38% vs 28%, P=0.118). Patients with MTVOs affecting the bilateral anterior circulations had comparable functional outcome at 90 days compared with patients with MTVOs involving anterior and posterior circulations (33% vs 26%, p>0.1) (figure 1). In patients with concurrent anterior and posterior circulation (n=39), the anterior circulation was reperfused first in the majority of cases (66%) without difference in overall outcomes between the posterior-first and anterior-first approach.
Predictors of good outcome
Predictors of good outcome (mRS score 0–2) were assessed using multivariate analysis in the full cohort of patients with AIS (table 2). Younger age, male gender, white race, lower admission NIHSS score, high ASPECT score (≥6), earlier onset-to-puncture time, use of IV tPA, successful reperfusion, lower number of thrombectomy attempts, and contact aspiration were independently associated with higher odds of good outcome at 90 days. The presence of MTVO was not associated with a worse outcome using multivariate analysis in the full cohort (OR=1.08, P=0.838). The same result also held when mTICI scores and number of attempts were not included in the models (table 2).
MTVO was not associated with longer procedure or postprocedural symptomatic ICH
Logistic regression was used to determine predictors of symptomatic ICH in AIS after EVT (table 3). MTVO was not independently associated with symptomatic ICH (OR=1.00, P=0.998), though the use of contact aspiration, successful recanalization, fewer thrombectomy attempts, and higher ASPECT score at presentation were associated with lower rates of symptomatic ICH. Secondary outcomes in this study included technical outcomes such as procedure time (table 4). On multivariate logistic regression, MTVO was not associated with longer procedure time (P=0.572).
Matched cohort of patients with SVOs versus MTVOs: technical and clinical outcomes
Propensity score matching was used to match our MTVO patients with corresponding SVO patients (table 5), with no significant differences between the groups on univariate analysis based on matched variables. There was no difference in the successful recanalization rate, functional outcome at 90 days, mortality, or complication rate between the matched cohorts (p>0.05).
Discussion
In the absence of randomized controlled trials and few limited case series evaluating EVT in MTVOs,2 4 this work is the largest multicenter study to date that reports prevalence, technical and clinical outcomes of patients with MTVOs treated with EVT. The prevalence of patients with AIS secondary to MTVOs who were treated with EVT was 0.7%, which falls within the range reported in the literature (0.35–2%).2 4 5 16 Our data demonstrate that EVT in MTVOs has a similar safety profile, successful recanalization, and rate of functional independence at 90 days compared with patients with SVO on both unadjusted and propensity-matched analyses.
As expected, patients with AIS secondary to MTVOs had higher admission NIHSS score; however, there were no significant differences in rates of favorable ASPECT scores (≥6) which suggests similar EVT selection criteria in the MTVO group. The higher admission NIHSS score probably reflects a larger territory at risk in the MTVO group than in those with SVO. Concerns about safety and complications in the MTVO setting may affect patient selection for MTVO EVT.
Prior studies have shown that patients with MTVO undergoing EVT have poor functional outcome at 90 days and higher mortality despite successful reperfusion compared with patients with SVO.2 4 16 These studies suggested that EVT in patients with MTVOs might have limited efficacy. In contrast, patients with MTVOs in our cohort had comparable functional outcomes at 90 days and mortality rates on both unadjusted and adjusted analysis. The difference might be due to a lower rate of IV tPA administration (18.2–38.1%2 4) in other studies compared with our cohort (55%). Similarly, admission NIHSS score was higher in the previously published series and one4 had lower rates of successful recanalization (36.4% vs 86%). Direct comparison is somewhat limited due to the small sample sizes of other series.2 4
In our cohort, recanalization rates and postoperative hemorrhagic complications in patients with MTVOs were similar to those in patients with SVOs, in keeping with previous publications.2 4 16 The rate of non-ICH complications in the MTVO group in unadjusted analysis was 13% vs 6%, respectively (P=0.022). Nevertheless, EVT for MTVO increases procedural complexity, and the risk of additional complications cannot be ruled out given the relative rarity of these incidents and the small, matched sample size.
Limitations
Although our study represents the largest multicenter cohort of patients with MTVOs treated with EVT, results are limited by its retrospective nature and the small sample size in the MTVO group. There is also no consensus among neurointerventionalists regarding indications for EVT in patients with MTVOs. Treatment in our study population was based on expert opinion and technical experience, which contributes to selection bias, and patients with AIS secondary to MTVOs who were not treated with EVT were not available for comparison analysis. Predictors of good outcome in patients with MTVO were not assessed owing to the relatively small sample size.
Conclusion
Patients with MVOs undergoing EVT had comparable procedural and functional outcomes compared with patients with AIS and SVO. There was also a trend towards higher complications in the MTVO group compared with SVO. In appropriately selected patients with MTVO, concurrent multivessel EVT should be considered in surgical decision-making and patient counseling.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
References
Footnotes
Twitter @BrianHoward_MD, @PascalJabbourMD, @Starke_neurosurgery, @AdamArthurMD, @DrMichaelLevitt
Contributors Conception or design of the work: HS, SE, AA, CMC, BMH, AS, JAG. Data collection: all authors. Data analysis and interpretation: HS, SE, AA, JAG. Drafting the article: HS, SE, AA, JAG. Critical revision of the article: all authors. Final approval of the version to be published: all authors. JAG: Guarantor for the work and the conduct of the study.
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 SAK: Grant funding-Stryker. PJ: Consultant - Balt, Cerus, Microvention, Medtronic. SQW: Board of directors - AANS; associate editor - S:VIN journal. M-NP: Honoraria - Stryker, Medtronic, Penumbra, Acandis, Phenox, Siemens Healthineers; research support - Swiss National Science Foundation, Bangerter-Rhyner Stiftung, Stryker, Phenox, Medtronic, Rapid, Penumbra, Siemens Healthineers. ASA: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker; research support from Balt, Medtronic, Microvention, Penumbra, and Siemens; shareholder - Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Neuros, Scientia, Serenity, Synchron, Tulavi, Vastrax, VizAI. AJP: Consultant - Depuy Synthes, Stryker. JM: consultant - Stryker. CM: Consultant-Silk Road, Penumbra, Microvention, Cerevasc, Stryker; speaker-Silk Road, Penumbra. MSP: DSMB-Medtronic. MRL: Educational grant - Stryker, Medtronic; consultant - Medtronic, Aeaean Advisers; travel Support - Penumbra; editorial board, JNIS; stock - Hyperion Surgical, Proprio, Synchron, Cerebrotech, Fluid Biomed, Stereotaxis; advisor - Metis Innovative. AMS: Consultant - Stryker, Penumbra, Terumo, RapidAI. JAG: Grant support- Georgia Research Alliance, Department of Defense, Emory Medical Care Foundation, Neurosurgery Catalyst; Stock - NTI, Cognition. STAR: funded by Penumbra, Medtronic, Stryker.
Provenance and peer review Not commissioned; externally peer reviewed.