Article Text

Original research
Multicenter investigation of technical and clinical outcomes after thrombectomy for distal vessel occlusion by frontline technique
  1. Ali M Alawieh1,
  2. Reda M Chalhoub2,
  3. Sami Al Kasab3,
  4. Pascal Jabbour4,
  5. Marios-Nikos Psychogios5,
  6. Robert M Starke6,
  7. Adam S Arthur7,8,
  8. Kyle M Fargen9,
  9. Reade De Leacy10,
  10. Peter Kan11,
  11. Travis M Dumont12,
  12. Ansaar Rai13,
  13. Roberto Javier Crosa14,
  14. Ilko Maier15,
  15. Nitin Goyal16,
  16. Stacey Q Wolfe17,
  17. C Michael Cawley1,
  18. J Mocco10,
  19. Stavropoula I Tjoumakaris18,
  20. Brian M Howard1,19,
  21. Laurie Dimisko20,
  22. Hassan Saad1,
  23. Christopher S Ogilvy21,
  24. R Webster Crowley22,
  25. Justin R Mascitelli23,
  26. Isabel Fragata24,
  27. Michael R Levitt25,
  28. Joon-tae Kim26,
  29. Min S Park27,
  30. Benjamin Gory28,
  31. Adam J Polifka29,
  32. Charles Matouk30,
  33. Jonathan A Grossberg1,
  34. Alejandro M Spiotta2
  35. on behalf of the STAR Collaborators
  1. 1 Department of Neurosurgery, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA
  2. 2 Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA
  3. 3 Neurology, Medical University of South Carolina, Charleston, South Carolina, USA
  4. 4 Neurological surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  5. 5 Department of Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland
  6. 6 Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
  7. 7 Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee, USA
  8. 8 Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
  9. 9 Neurosurgery, Wake Forest University, Winston-Salem, North Carolina, USA
  10. 10 Neurosurgery, Icahn School of Medicine at Mount Sinai, NEW YORK, New York, USA
  11. 11 Neurosurgery, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA
  12. 12 Department of Surgery, Division of Neurosurgery, University of Arizona/Arizona Health Science Center, Tucson, Arizona, USA
  13. 13 Radiology, West Virginia University Hospitals, Morgantown, West Virginia, USA
  14. 14 Endovascular Neurosurgery, Médica Uruguaya, Montevideo, Montevideo, Uruguay
  15. 15 Neurology, University Medicine Goettingen, Goettingen, NS, Germany
  16. 16 Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
  17. 17 Neurosurgery, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
  18. 18 Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
  19. 19 Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
  20. 20 Emory Healthcare, Atlanta, Georgia, USA
  21. 21 Neurosurgery, BIDMC, Boston, Massachusetts, USA
  22. 22 Neurosurgery, Rush University, Chicago, Illinois, USA
  23. 23 Department of Neurosurgery, University of Texas Health Science Center, San Antonio, Texas, USA
  24. 24 Neuroradiology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
  25. 25 Neurological Surgery, University of Washington School of Medicine, Seattle, Washington, USA
  26. 26 Neurology, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)
  27. 27 Neurosurgery, University of Virginia, Charlottesville, Virginia, USA
  28. 28 Department of Diagnostic and Interventional Neuroradiology, CHRU Nancy, Nancy, Lorraine, France
  29. 29 Department of Neurosurgery, University of Florida, Gainesville, Florida, USA
  30. 30 Neurosurgery, Yale University, New Haven, Connecticut, USA
  1. Correspondence to Dr Jonathan A Grossberg, Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA; jonathan.a.grossberg{at}emory.edu; Dr Alejandro M Spiotta; spiotta{at}musc.edu

Abstract

Background Endovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited.

Methods This was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retriever

Results We included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, p<0.05) irrespective of technique. Younger age, bridging therapy, and lower admission National Institutes of Health Stroke Scale (NIHSS) were also predictors of good outcome. Procedure time ≤1 hour or ≤3 thrombectomy attempts were independent predictors of good outcomes in DVOs irrespective of technique (aOR 4.5 and 2.3, respectively, p<0.05). There were no differences in outcomes in a DVO matched cohort of aspiration versus stent retriever. Rates of hemorrhage and good outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group and attempts in the stent retriever group.

Conclusions Outcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time.

  • Thrombectomy
  • Device
  • Stroke

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

  • Endovascular thrombectomy is standard of care for proximal large vessel occlusions, but data on disal occlusion is limited.

What this study adds

  • We show similar safety and efficacy profile of thrombectomy for distal compared to proximal occlusions.

  • No difference in clinical and technical outcomes between different thrombectomy techniques.

How this study might affect research, practice or policy

  • Distal occlusion stroke should be considered for thrombectomy in the real-world given safety profile.

Introduction

Several randomized controlled trials (RCTs) have supported the efficacy and safety of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke secondary to large vessel occlusion (LVO).1–3 Given the safety profile of EVT, endovascular interventions for acute ischemic stroke in the real-world have expanded these indications to include medium vessel occlusions (MeVO) and small distal vessel occlusions (DVOs), but the data on DVOs remain limited especially for outcomes and safety profiles of different techniques. Data from the ASTER and COMPASS trials established non-inferiority of direct aspiration (ADAPT: a direct aspiration first pass technique) and stent retriever thrombectomy (SRT) in LVO.4 5 However, the differential effect of frontline thrombectomy techniques on technical and clinical outcomes in DVO remains less characterized.

In this work, we evaluated the technical and clinical outcomes in isolated DVO including M3/4, A2/3, and P2/3 using a large cohort of patients from a prospectively maintained international multicenter registry. We specifically investigate the technical and clinical outcomes in DVO between different frontline thrombectomy techniques, and study whether similar procedural futility and safety metrics of thrombectomy in LVO also apply to the DVO population.

Methods

Patient cohort

Patients undergoing endovascular thrombectomy for acute ischemic stroke were included from the Stroke Thrombectomy and Aneurysm Registry (STAR) that includes prospectively maintained real-world data of consecutive patients undergoing endovascular thrombectomy for acute ischemic stroke at 32 centers in the USA and globally. Patients were included if they were treated with modern EVT devices used in the major RCTs regardless of location of occlusion, time from onset, and whether intravenous tissue plasminogen activator (IV-tPA) was administered. Each center collected local data that was eventually coded and shared with the central data analysis core for the registry. The study was approved by the individual institutional review boards at participating institutions, and informed consent was waived.

Endovascular thrombectomy

EVT was performed at each participating center based on institutional protocols and selection criteria at each participating site without influence from the study to reflect real-world practice. Participating sites performed EVT using operator-preferred frontline EVT technique that included aspiration thrombectomy (or ADAPT),6 stent retriever (SRT),7 or primary combined approach (PC)8 without influence from the study. All patients received non-contrast head CT before EVT. The decision to perform EVT in DVO was operator-dependent without a specific National Institutes of Health Stroke Scale (NIHSS) cut-off. However, patients undergoing EVT for DVO all demonstrated a perfusion deficit on pre-EVT CT perfusion which, at least in part, explained presenting deficits. For patients who received IV-tPA for DVO, EVT was still offered if symptoms persisted before groin puncture. Patients without evidence of occlusion on angiography were not included in this study.

Data collection

Patient charts were reviewed for patient demographics, comorbidities, treatment history, and admission deficits. Imaging was reviewed for Alberta Stroke Program Early CT Score (ASPECTS) post-procedural hemorrhage, and recanalization scores. Procedure notes were reviewed for devices, attempts, and complications.

Distal vessel occlusions

In this work, we defined MeVO to include the second major segment of the middle cerebral artery (MCA-M2), the first segment of the anterior cerebral artery (ACA-A1), and the first segment of the posterior cerebral artery (PCA-P1). We define DVO to include the third or fourth segments of the middle cerebral artery (MCA-M3/4), the second or third segment of the anterior cerebral artery (ACA-A2/3), and the second or third segment of the posterior cerebral artery (PCA-P2/3). Only patients with isolated distal occlusions without proximal intracranial occlusion were included in this definition, and rescue thrombectomy for distal embolization was excluded.

Technical outcomes

Procedure time was defined as the time from groin puncture to successful recanalization or last angiogram run in case of an aborted intervention. Successful recanalization was scored using the modified Thrombolysis In Cerebral Ischemia (mTICI), and defined as mTICI 2B or more. Procedural complications were noted to include intraoperative complications. Post-procedural hemorrhage was assessed using CT or MRI performed at 24 hours post-procedure and scored using European-Australasian Acute Stroke Study (ECASS) II criteria.9 Both mTICI scores and hemorrhage scores were performed by local sites and there was no central adjudication process across centers. Symptomatic intracranial hemorrhage (sICH) was defined as a parenchymal hematoma type 2 (PH2) hemorrhage on ECAS II or any type of hemorrhage with an associated 4-points decline in NIHSS.

Clinical outcomes

The primary clinical outcome was the modified Rankin Scale (mRS) at 90 days after procedure. This was recorded during routine neurology follow-up visits with stroke neurologists or a designated advance practice provider at 90±14 days post-intervention. Phone calls were used to confirm mortality or to contact patients discharged to nursing home, hospice or rehabilitation facilities. A good functional outcome was defined as mRS 0–2.

Statistical analysis

Data analysis was performed using SPSS Statistics v.28 (IBM Corp) and GraphPad Prism v.9.3 (GraphPad, San Diego, CA). Univariate analysis was performed using Student’s t-test or one-way analysis of variance (ANOVA) 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. All regression models were performed using the backward-conditional stepwise algorithm within SPSS to provide unbiased variable selection in models. Multiple imputations were used for handling missing variables in baseline characteristics (race, onset-to-groin, gender, other comorbidities) in order to avoid associated biases. Rubin’s rule was then used to approximate coefficients for regression analysis. For all models, a total of 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 was considered significant. Propensity score matching based on demographics, comorbidities and admission variables was performed using the Optmatch algorithm in R based on generalized linear models using 1:2 matching between ADAPT and SRT.10 Appropriate balance among covariates was confirmed using univariate testing on matched cohort. Statistical analyses were verified with the dedicated biostatistics team within the STAR collaboration.

Results

Patient population

A total of 8444 patients underwent mechanical thrombectomy for acute ischemic stroke at 32 stroke centers during the study period, of whom 7477 patients had complete technical and outcome variables and were included in the analysis. Among the included subset, 5977 (80%) patients had proximal LVO, 1287 (17%) had isolated MeVO, and 213 (3%) had DVO (online supplemental figure 1).

Supplemental material

Technical and clinical variables in proximal versus distal vessel occlusion EVT

Differences in procedural and clinical outcomes between LVO, MeVO and DVO are shown in online supplemental table 1). Patients with DVO were younger, had lower NIHSS on admission, higher rate of posterior circulation location, and higher rate of IV-tPA use compared with LVO and MeVO groups (online supplemental table 1). Rates of successful recanalization were significantly lower in DVO compared with MeVO and LVO (75% vs 85%, p<0.01). Rates of good outcome at 90 days were significantly higher in DVO and MeVO compared with LVO (44% and 44% vs 37%, p<0.01), and there were no significant differences in rates of sICH between the groups (online supplemental table 1).

Predictors of good outcome in DVOs

Using multivariate logistic regression with stepwise back propagation (see methods), we identified predictors of good outcome (mRS 0–2) in patients with DVO (figure 1A). These included lower age, absence of diabetes on admission, and lower NIHSS on admission. In addition, both use of IV-tPA and successful recanalization were predicted higher odds of good outcomes in this cohort (figure 1A). The distribution of 90-day mRS scores by different vascular territories or using different thrombectomy techniques is shown in figure 1B. In the full DVO cohort, patients treated with SRT had higher 90-day mRS scores compared with ADAPT and PC groups (figure 1B). We then evaluated the predictors of favorable shift in mRS scores using an ordinal regression of the 90-day mRS scores (figure 1C). Similar baseline predictors of favorable outcomes were noted as in figure 1B; however, use of SRT as the frontline thrombectomy technique was associated with lower mRS scores on 90 days when ADAPT was used as the reference technique (estimate for favorable mRS shift: −1.0, 95% CI −0.2 to −1.7, p<0.01) (figure 1C).

Figure 1

Predictors of 90-day mRS scores in patients with DVO. (A) Multivariate logistic regression results showing adjusted ORs for different predictors of 90-day functional independence (mRS 0–2). Model included thrombectomy technique and location (posterior vs anterior) in addition to variables selected based on backward-conditional selection as described in methods. (B) Distribution of 90-day mRS scores by vessel location and frontline thrombectomy technique. (C) Multivariate ordinal regression using Logit algorithm for prediction of favorable shift (decrease in 90-day mRS score). Model included same variables as in (A). Shown are adjusted estimates ±95% CI. Red highlights OR with p<0.05. Raw data for regression models are provided in online supplemental material. ADAPT, a direct aspiration first pass technique; ASPECT, Alberta Stroke Program Early CT; DM2, diabetes mellitus type 2; DVO, distal vessel occlusion; IV-tPA, intravenous tissue plasminogen activator; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; PC, primary combined approach; SR, stent retriever.

Outcomes and success of different thrombectomy techniques

We then investigated the impact of different thrombectomy techniques on secondary outcomes using logistic or linear regression models with stepwise back propagation for variable selection (figure 2). Frontline thrombectomy techniques were not independent predictors of rates of sICH or successful recanalization (figure 2A,B). Use of SRT or PC approaches independently predicted longer procedure times but lower number of required thrombectomy attempts compared with ADAPT as the reference group (figure 2C,D). Among the remaining variables, higher admission NIHSS was associated with higher odds of successful recanalization and use of IV-tPA predicted shorter procedure times (figure 2B,C).

Figure 2

(A) Multivariate logistic regression for predictors of sICH/PH2-type hemorrhage and (B) successful recanalization (TICI 2B or more). (C) Multivariate linear regression for predictors of procedure time and (D) number of thrombectomy attempts. Regression models were independently performed using backward-conditional stepwise selection as described in methods. Final model variables are included in the figures as OR or coefficient ±95% CI. Red highlight indicates p<0.05. Raw data for regression models are provided in online supplemental material. ADAPT, a direct aspiration first pass technique; AFIB, atrial fibrillation; ASPECT, Alberta Stroke Program Early CT; DM2, diabetes mellitus type 2; DVO, distal vessel occlusion; HLD, hyperlipidemia; HTN, hypertension; IV-tPA, intravenous tissue plasminogen activator; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; PC, primary combined approach; PH, parenchymal hematoma; sICH, symptomatic intracranial hemorrhage; SR, stent retriever; TICI, Thrombolysis In Cerebral Ischemia.

Outcomes in matched cohort of DVO patients by technique

We then identified, using propensity score matching, a matched cohort of ADAPT and SR/PC patients with DVO and balanced covariates as shown in table 1. In this group, there were no significant differences in the rates of good functional outcome, mortality, successful recanalization, procedure time, complications, or sICH between the two groups (table 1). Use of SR/PC, however, was associated with a lower number of thrombectomy attempts on average compared with ADAPT (1.9 vs 2.6, p=0.04) (table 1).

Table 1

Comparison of baseline, procedural and outcome variables in a matched cohort of DVO patients based on frontline thrombectomy technique

Impact of procedure time and thrombectomy on outcomes in DVO

The negative impact of procedure time and higher number of thrombectomy passes in LVO has been well-documented in real-world data and meta-analysis of RCTs.11 12 However, the impact of these metrics on DVO has not been evaluated, and was evaluated in this cohort of DVO patients. Within the full cohort, the cumulative rate of good outcome, successful recanalization and sICH were mapped over increased procedure time or number of thrombectomy attempts (figure 3). When studied over procedure time increment, these outcomes follow an exponential growth curve (R2 >0.95, p<0.001) (figure 3A,B), which all plateau after 60 min of procedure time. Using multivariate logistic regression with procedure time dichotomized at the 60 min cut-off, procedure time within 1 hour of groin puncture was an independent predictor of higher odds of good outcome (adjusted odds ratio (aOR) 17.8, p<0.05) (figure 3C). When the cohort was split based on frontline technique into ADAPT or SR/PC, procedure time within 1 hour predicted higher odds of good outcome in ADAPT but not SR/PC thrombectomy, despite the presence of a trend in the latter group (figure 3C). We then studied how technical and clinical metrics vary as a function of thrombectomy passes. The rate of good outcome and successful recanalization also followed an exponential growth curve (R2 >0.95, p<0.001) (figure 3D,E) that appears to plateau at two thrombectomy attempts whereas the curve for sICH/PH2 continues to rise. We then performed multivariate logistic regressions for predictors of good outcome with thrombectomy attempts dichotomized at more than two attempts (figure 3F). The aOR for good functional outcome at 90 days with a maximum of two attempts was 2.34 (p<0.01) (figure 3F) in the full cohort; however, a maximum of two attempts independently predicted 90-day good functional outcomes in the SR/PC subset (aOR 3.02, p<0.05) but not in the ADAPT group (p=0.2) (figure 3F). When the number of attempts was dichotomized at three attempts (3-pass rule), a maximum of three attempts did not independently predict good functional outcomes in the full cohort or the two subsets by technique (p>0.1).

Figure 3

(A, B) Cumulative rate of 90-day good outcome, sICH and successful recanalization rates as function of procedure time. Curve demonstrates a plateau in benefit (good outcome and TICI 2B) after 60 min of procedure time. Assessment of non-linear fit: R2 (good outcome)=0.99, R2 (successful recanalization)=0.99, R2 (sICH)=0.97. (C) Independent logistic regression models performed for effect of procedure time less than 1 hour on technical and clinical outcomes. Shown are aORs with 95% CI, red highlights significance. Raw data for regression models is provided in online supplemental material. (D, E) Cumulative rate of 90-day good outcome, sICH and successful recanalization rates as function of number of thrombectomy attempts. Curve demonstrates a plateau in benefit (good outcome and TICI 2B) after three attempts. Assessment of non-linear fit: R2 (good outcome)=0.99, R2 (successful recanalization)=0.99, R2 (sICH)=0.96. (F) Independent logistic regression models performed for effect of ≤3 attempts on technical and clinical outcomes. Shown are aORs with 95% CI, red highlights significance. Raw data for regression models are provided in online supplemental material. ADAPT, a direct aspiration first pass technique; AFIB, atrial fibrillation; aOR, adjusted OR; ASPECT, Alberta Stroke Program Early CT; DM2, diabetes mellitus type 2; DVO, distal vessel occlusion; HLD, hyperlipidemia; HTN, hypertension; IV-tPA, intravenous tissue plasminogen activator; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; PC, primary combined approach; PH, parenchymal hematoma; sICH, symptomatic intracranial hemorrhage; SR, stent retriever; TICI, Thrombolysis In Cerebral Ischemia.

We then proposed that outcomes in DVO treated with ADAPT were more sensitive to procedure time whereas those treated with SR/PC were more sensitive to the number of procedure attempts. To answer this question, we performed similar analysis to that shown in figure 3 while providing technique-based data measures. Cumulative rates of successful recanalization, good functional outcome and sICH as function of procedure time and thrombectomy attempts per technique is shown in figure 4, and it respects a similar exponential growth curve with R2 >0.92 (p<0.01) (figure 4A,B). We then computed the time constant (tau, τ) for the exponential growth curves. A higher relative time constant indicates procedural futility at a higher number of attempts or longer procedure time for the studied technique compared with the reference. For sICH/PH2 curves, a relatively lower time constant indicates a higher risk of hemorrhage at a given number of attempts or procedure time, or relatively smaller safety margin (figure 4C).

Figure 4

(A) Cumulative rate of 90-day good outcome, sICH and successful recanalization rates as function of procedure time dichotomized by frontline thrombectomy technique. Curves demonstrate an earlier plateau in the ADAPT group compared to SR/PC for good outcome and successful recanalization in contrast to a delayed plateau in sICH rate. (B) Cumulative rate of 90-day good outcome, sICH and successful recanalization rates as function of number of thrombectomy attempts dichotomized by frontline thrombectomy technique. Curve demonstrates a relatively earlier plateau of SR/PC compared with ADAPT for good outcome, successful recanalization and sICH. (C) Comparison of time constant (tau, τ) for exponential curves in (A) and (B) quantifying the differential susceptibility of ADAPT and SR curves to procedure time versus thrombectomy attempts. The time constant τ allows for comparison of either techniques with respect to their relative sensitivity of the dependent variable (good outcome, successful recanalization or hemorrhage) to either procedure time or number of attempts. Higher τ for ADAPT versus SR/PC was observed as function of procedure time whereas lower τ was observed in ADAPT versus SR/PC as function of number of attempts. *P<0.05. ADAPT, a direct aspiration first pass technique; mRS, modified Rankin Scale; PC, primary combined approach; PH, parenchymal hematoma; sICH, symptomatic intracranial hemorrhage; SR, stent retriever; TICI, Thrombolysis In Cerebral Ischemia.

When both techniques were evaluated against procedure time, ADAPT demonstrated a significantly higher time constant compared with SR/PC for 90-day functional independence rate. This indicates procedural futility for ADAPT at shorter procedure time compared with SR/PC (figure 4C). There was no difference in both curves in terms of rates of successful recanalization. However, when the number of attempts was studied, SR/PC demonstrated a significantly higher time constant compared with ADAPT when assessing 90-day good outcome and successful recanalization rate, indicating lower benefit from additional thrombectomy attempts with SR/PC compared with ADAPT (figure 4C). When rates of sICH/PH3 hemorrhage were evaluated, SR/PC showed a lower time constant compared with ADAPT as a function of procedure time and the number of attempts, indicating a higher risk of hemorrhage with prolonged procedures in SR/PC compared with ADAPT (figure 4C).

Discussion

This work presents the largest series to date to describe technical and clinical outcomes in patients with isolated distal small vessel occlusions (DVO). Findings of this work demonstrate that in a real-world setting and using various frontline thrombectomy techniques, a similar safety and efficacy profile can be achieved in DVO thrombectomy compared with LVO. We also demonstrate that there is no difference in clinical and technical outcomes between the different frontline thrombectomy techniques using propensity score matched analysis.

In the absence of RCT data on DVO, several small case series and a few multicenter studies have investigated outcomes in DVO.8 13–20 However, these studies have used variable definitions of DVO including combining the M2 division with DVO or including patients with distal emboli from proximal occlusions or those with concurrent proximal occlusion.8 13 15–21 In this work, we used the strict definition of isolated DVO thrombectomy to include patients with thrombectomy of the M3/4 segment of the MCA, A2/3 segment of the ACA or the P2/3 segments of the PCA in the absence of concurrent proximal occlusion or prior thrombectomy for proximal LVO. A recent study from the STAR collaboration on isolated DVO reported clinical outcomes in a cohort of 175 patients with distal occlusions that demonstrated similar profiles to existing studies, but did not investigate the impact of technical variables and technique-specific outcomes. This work further confirms these findings in a larger cohort of 213 patients with DVO showing a similar safety and efficacy profile of DVO thrombectomy compared with both MeVO and LVO. The hemorrhage rate in this group was 6% which is similar to the rate reported in LVO trials. As expected, the rates of good functional outcome in the DVO group (44%) was higher than that in the LVO group given lower admission deficits. However, it is still important to note that there is a paucity of data on the natural history of DVO and a significant proportion of these patients are expected to have a good outcome without intervention.22 In subsets of IV-tPA eligible DVO patients, up to a 50% good outcome rate has been reported with the limitation of significant inter-study heterogeneity.23 Notably, in our cohort, patients underwent EVT for DVO when perfusion imaging demonstrated a perfusion deficit that corresponded, at least in part, to the admission deficits on examination after IV-tPA administration in eligible patients.

Prior work from real-world data and RCTs has described the golden hour or 3-pass role for thrombectomy, demonstrating diminishing returns after 1 hour of procedure time or three thrombectomy attempts, specifically worse clinical outcomes and higher rates of hemorrhage.11 12 24 25 In the setting of DVO, we show that procedures extending >1 hour are also associated with lower odds of good outcomes at 90 days, but the 3-pass role was not applicable as in LVO. In fact, more than two attempts was an independent predictor of poor outcome at 90 days compared with three or more attempts, indicating that a lower number of thrombectomy attempts is tolerated in DVO compared with LVO. Notably, successful recanalization in this cohort was an independent predictor of good outcome in the DVO group; however, there was no correlation between the recanalization score (2B, 2C, vs 3) and clinical outcomes.26

Prior studies comparing different thrombectomy techniques have predominantly included LVO and less frequently the M2 segment, and showed similar overall outcomes between frontline aspiration or stent retriever thrombectomy.4 5 27 In this work, patients were enrolled from a prospectively maintained multicenter registry where the frontline thrombectomy technique is based on the preferred frontline technique for the operating physician, allowing representation of all major frontline approaches in our cohort. Therefore, findings relevant to specific techniques are unlikely to be related to the operator’s inexperience in a technique not commonly performed at his/her center. Our data do support findings in LVO and MeVO showing no difference in technical and clinical outcomes between the major thrombectomy techniques (aspiration, SR, PC). A recent single center series of 137 patients with DVO, comparing aspiration with 3MAX and SR using Trevo for distal occlusions, showed no difference in clinical outcomes, but higher rates of first pass success with Trevo.21 However, more than half of the cohort included the A1/P1/M2 segments in the distal definition and also included patients with concurrent proximal occlusion. In their work, Haussen et al reported that the rate of parenchymal hemorrhage was higher in Trevo compared with 3MAX (6% vs 2%).21 In fact, in our cohort, the rates of sICH/PH2 type post-procedural hemorrhage were significantly higher in the SR/PC group compared with ADAPT, and the use of SR was an independent predictor of sICH compared with aspiration. Several technical factors may contribute to the increased risk of sICH with SR use. The SR/PC approach requires the SR to be deployed across the thrombus to allow for full engagement; therefore, the microwire and microcatheter are navigated further distally into smaller branches of the target vessels. Deployment of the SR is expected to stretch the smaller caliber vessels, increasing the risk for bleeding. During the microcatheter advancement, the SR, in its constrained configuration within the microcatheter, adds further stiffness. During deployment, and as the SR is being pulled back across turns and bifurcations, the risk of vascular injury is higher. In contrast, a small aspiration catheter can be readily delivered over a microwire to the proximal end of the thrombus and then partially over the thrombus as the microwire is pulled back, thus reducing the risk of vascular injury.6

Finally, a novel aspect of this work is demonstrating that procedural futility measure is better assessed using procedure time with aspiration thrombectomy compared with the number of attempts with SR use. This provides insight to the interventionalist on what better metric to use to demonstrate procedural futility with each technique.

Limitations

Although our paper represents a large multicenter, prospectively maintained cohort of real-world patients undergoing thrombectomy for DVO, the lack of randomization to different interventional arms is a potential bias. In addition, the self-reported technical outcomes were not reviewed by a core lab, which also introduces potential bias to the paper. It is possible that a proportion of these patients with distal occlusions initially had an LVO that broke up and embolized distally by the time of imaging, which is difficult to rule out with our data. Collateral circulation is a significant factor that can contribute to outcome after stroke thrombectomy; however, there was no unified collateral circulation grading system used across centers in patient selection, and this variable was not reported in our analyses. Similarly, we included ASPECT score in our regression analysis given that it is uniformly used in patient selection for thrombectomy and in all major trials. However, it is important to note that the relevance of this score in distal occlusions is as yet undetermined, given that distal occlusions are likely to cover smaller territories than the full ASPECT score territories covered by the ICA/M1 in proximal occlusions. A smaller subset of this dataset was reported from institutions participating in our registry; however, this remains the largest cohort of DVO to date that allowed for sufficient power to study technique-based outcomes. Finally, our work specifically studies the impact of the frontline thrombectomy technique (first technique used to treat) and does not study the effect of switching techniques at the second or third attempts in patients who require multiple attempts to achieve recanalization.

Conclusion

There are comparable efficacy and safety outcomes of patients undergoing thrombectomy for DVO stroke as compared with LVO and MeVO stroke regardless of the frontline thrombectomy technique employed. Thrombectomy in DVO still follows the ‘golden hour’ role for procedural futility. With regard to the number of thrombectomy attempts in our DVO cohort, DVO thrombectomy follows a two-pass role where odds of poor outcome are higher at three or more attempts. Finally, different frontline techniques are differentially affected by the number of attempts or procedure time; SR thrombectomy was more influenced by more attempts whereas aspiration outcomes were more dependent on procedure time.

Supplemental material

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

Supplementary materials

  • Supplementary Data

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Footnotes

  • Twitter @ChalhoubReda, @PascalJabbourMD, @Starkeneurosurg, @AdamArthurMD, @rdeleacymd, @PeterKa80460001, @BrianHoward_MD, @jmascite, @DrMichaelLevitt

  • Collaborators Christian Mustroph, MD; Emory University School of Medicine, Atlanta, GA, USA

    Kareem E Naamani, MD; Thomas Jefferson University, Philadelphia, PA, USA

    Italo Linfante, MD; Florida International University; Miami, FL, USA

    Clemens Schirmer, MD; Geisinger Medical Group, Danville, PA, USA

    Toshiya Osanai, MD. PhD; Hokkaido University Hospita; Sapporo, Japan

    Shinichi Yoshimura, MD PhD; Hyogo College of Medicine; Nishinomiya, Japan

    Waleed Brinjikji, MD; Mayo Clinic, Rochester, MN, USA

    Richard Crowley, MD; Rush Univeristy; Chicago, IL, USA

    Adam Polifka, MD; University of Floride, Gainesville, FL, USA

  • Contributors All authors have: provided a substantial contribution to the conception and design of the studies and/or the acquisition and/or the analysis of the data and/or the interpretation of the data; drafted the work or revised it for significant intellectual content; approved the final version of the manuscript; and agree to be accountable for all aspects of the work, including its accuracy and integrity. JAG/AMS are guarantors of 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 AMA: None, RMC: None, SAK: Grant Funding-Stryker; PJ: Consultant-Balt, Cerus, Microvention, Medtronic. 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; RMS: None; 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; KMF: Editorial Board-JNIS; RDL: Consultant-Stryker, Imperative Care, Cerenovus, Asahi Intec, Research Funding-Hypervention, Kaneka, Siemens Healthineers, SNIS Foundation, Equity-Synchron, Endostream, Q’Apel, Spartan Micro, Editorial Board-JNIS; PK: Consultant- Stryker, Imperative Care, Microvention, Grant Support-NIH, Editorial-Board JNIS; TD: None; AR: None; RJC: None; IM: None; NG: None; SQW: Board of Directors-AANS, Associate Editor- S:VIN Journal; CMC: None; JM: PI on trials funded by- Stryker Neurovascular, Microvention, and Penumbra, Consultant-Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai, Perflow, CVAid, Stockholder-Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai, Synchron, Radical, and Truvic; Editorial Board-JNIS; SIT: Consultant- Microvention, Medtronic; BMH: None; LD: None; HS: None; CSO: Grant Support- Bee Foundation, Brain Aneurysm Foundation, DSMB- Medtronic; RWC: Consultant/Proctor: Medtronic, Microvention; JMa: consultant-Stryker; IF: None; 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; J-tK: None; MSP: DSMB-Medtronic; BG: None; AJP: Consultant-Depuy Synthes, Stryker, CM: Consultant-Silk Road, Penumbra, Microvention, Cerevasc, Stryker, Speaker-Silk Road, Penumbra; JAG: Grant Support- Georgia Research Alliance, Department of Defense, Emory Medical Care Foundation, Neurosurgery Catalyst, Stock- NTI, Cognition; AMS: Consultant- Stryker, Penumbra, Terumo, RapidAI; STAR: funded by Penumbra, Medtronic, Stryker.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.