Sudden Recanalization: A Game-Changing Factor in Endovascular Treatment of Large Vessel Occlusion Strokes
Abstract
Background and Purpose—
First pass (FP) recanalization has been shown to be a predictor of favorable outcome in endovascular treatment of stroke. The reasons why FP recanalization leads to better outcome as compared with multiple passes (MP) are unknown. We aim to investigate the recanalization pattern and its relationship with outcome.
Methods—
Six hundred nine consecutive patients underwent endovascular treatment. Recanalization was defined as modified Thrombolysis in Cerebral Infarction score 2B-3. Favorable outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Sudden recanalization (SR) was considered when modified Thrombolysis in Cerebral Infarction score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if modified Thrombolysis in Cerebral Infarction score 2A was achieved at an interim pass before achieving recanalization. Patients were also categorized as recanalizers at FP, MP, or nonrecanalizers.
Results—
Five hundred nine (83.9%) patients achieved recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR, and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of favorable outcome were similar between patients with FP-SR (57.5%) and MP-SR (57.1%; odds ratio [OR], 0.9 [CI, 0.53–1.54]; P=0.7) but lower in MP-PR (29.8%; OR, 3.33 [CI, 1.71–5.63]; P<0.01). Patients with MP-PR had better outcome than nonrecanalizer (17%; OR, 2.93 [CI, 1.42–6.15]; P<0.01). In univariate analysis, both FP recanalization (OR, 1.91 [CI, 1.31–2.72]; P<0.01) and SR (OR, 3.19 [CI, 2.12–4.95]; P<0.01) were associated with favorable outcome. However multivariate analysis adjusting for FP recanalization showed that the only procedural predictor of favorable outcome was SR (OR, 3.12 [CI, 1.91–5.16]; P<0.01). Higher number of passes were associated with worse outcome in patients with recanalization (OR, 0.75 [CI, 0.66–0.85]; P<0.01) but not in those with SR (OR, 0.94 [CI, 0.59–1.61]; P=0.937).
Conclusions—
SR strongly predicts favorable outcome in patients undergoing endovascular treatment, even after previous unsuccessful attempts. PR may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Prospective studies with independent assessment of recanalization pattern should validate these results.
The influence of the number of device passes on outcome in patients with acute ischemic stroke secondary to large vessel occlusion treated with endovascular therapy (EVT) has been an important issue in different studies published lately.1,2 The mechanisms by which a higher number of passes negatively influence outcome are uncertain.
Since the initial description of first pass effect,3 different studies have characterized the detrimental effect of accumulated device passes: each additional pass negatively impacts final outcome despite recanalization.1 Moreover, the rate of hemorrhagic transformation has been associated with higher number of passes.4 We hypothesized that clot fragmentation and circumstances leading to whole clot retrieval in one single pass (sudden recanalization [SR]), even after unsuccessful attempts, may be associated with better outcome. On the contrary, cases in which the same degree of recanalization was progressively achieved in several passes, reflecting a clot composition or techniques favoring fragmentation, may have a worse prognosis.
Methods
The data that support the findings of this study are available on reasonable request. Ethics approval was obtained from the local institutional review board, and written informed consent was obtained from patients.
Patient Selection
We performed a retrospective analysis that includes all patients undergoing EVT at our comprehensive stroke center since 2014. Patients were selected if they had an acute ischemic stroke secondary to an occlusion of terminal intracranial carotid artery or M1-M2 middle cerebral artery, an Alberta Stroke Program Early CT Score of ≥5, and were treated with EVT(n=679).
Clinical and Imaging Assessment
Clinical, imaging, and procedural data were prospectively collected. Intravenous tPA (tissue-type plasminogen activator) was administered according to center guidelines. Favorable outcome was defined as a modified Rankin Scale score of ≤2 at 90 days assessed by a blinded observer. Hemorrhagic transformation was assessed in a computed tomographic scan performed 48 to 72 hours following ECASS-II (European Cooperative Acute Stroke Study) criteria.
Degree of recanalization after each device pass was prospectively determined using modified Thrombolysis in Cerebral Infarction (mTICI) grading standards consensus. Patients with final mTICI2C were included in the mTICI3 group. Recanalization was considered when mTICI2B-3 degree was achieved.5
SR was considered when mTICI score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if mTICI2A was achieved at an interim pass before achieving recanalization (mTICI2B-3). Patients were also categorized as recanalizers at first pass and multiple passes (MP) or nonrecanalizers.
Seventy patients (10.3%) in the MP group were excluded from the final analysis because of missing data regarding recanalization status at interim passes. Table I in the Data Supplement shows demographic, clinical, procedural, and outcomes variables of excluded patients, Table II in the Data Supplement shows demographics of the study population, and Figure I in the Data Supplement shows a flowchart detailing recanalization pattern for each device pass attempted.
Statistical Analysis
Univariate comparisons were performed by Fisher exact test, Pearson χ2, Spearman correlation test, or Mann-Whitney U test, as appropriate to the type of variable and its distribution. Continuous variables are displayed as median and interquartile range. Categorical variables are displayed by number and frequencies. Multivariate regression models were performed to evaluate association of different variables with favorable outcome and SR. All analyses were performed using SPSS Statistics, version 25 (IBM, Armonk).
Results
A total of 609 patients were included in the study. Median National Institutes of Health Stroke Scale score was 17 (interquartile range, 11–20) and Alberta Stroke Program Early CT Score 9 (interquartile range, 8–10). Five hundred and nine patients (83.9%) achieved recanalization. At 3 months, 273 patients (44.8%) were functionally independent and 131 patients had died (21.5%).
The Table shows baseline characteristics, rates, and outcomes according to recanalization pattern. Figure 1 shows stacked bars with functional outcome depending on recanalization pattern.
| SR | No SR | SR vs No SR | MP-SR vs MP-PR | |||
|---|---|---|---|---|---|---|
| FP-SR | MP-SR | MP-PR | NR | |||
| n=280 (46%) | n=98 (16.1%) | n=131 (21.5%) | n=100 (16.4%) | OR (95% CI) | OR (95% CI) | |
| Clinical and imaging features | ||||||
| NIHSS, median (IQR) | 16 (11–20) | 17 (13–20) | 18 (15–21) | 17 (10–19) | 0.98 (0.93–1.02) | 0.99 (0.93–1.05) |
| Side (right), n (%) | 135 (48.2) | 44 (44.9) | 57 (43.5) | 39 (39) | 1.07 (0.70–1.65) | 1.61 (0.85–3.06) |
| ASPECTS, median (IQR) | 9 (8–10) | 9 (8–10) | 9 (8–10) | 9 (8–10) | 1.04 (0.88–1.23) | 0.94 (0.74–1.20) |
| Occlusion site, n (%) | ||||||
| TICA | 44 (15.7) | 28 (28.6) | 42 (32.1) | 20 (20) | 1.47 (1.05–2.06)* | 0.83 (0.43–1.60) |
| M1-MCA | 153 (54.6) | 56 (57.1) | 71 (54.2) | 51 (51) | ||
| M2-MCA | 83 (29.7) | 14 (14.3) | 18 (13.7) | 29 (29) | ||
| Tandem occlusion, n (%) | 59 (21.1) | 22 (22.4) | 27 (20.6) | 26 (26) | 0.92 (0.75–1.21) | 0.75 (0.36–1.58) |
| tPA, n (%) | 128 (45.7) | 50 (51) | 50 (38.2) | 5 (50) | 1.00 (0.65–1.55) | 0.81 (0.43–1.53) |
| Procedural features | ||||||
| Stent retriever, n (%) | 252 (90) | 88 (89.8) | 120 (91.6) | 93 (93) | 0.96 (0.47–1.97) | 0.80 (0.29–2.22) |
| Balloon-guided catheter, n (%) | 46 (16.4) | 23 (23.5) | 24 (18.3) | 15 (15) | 1.22 (0.71–2.09) | 0.87 (0.42–1.85) |
| Distal aspiration, n (%) | 172 (61.4) | 70 (71.4) | 91 (69.5) | 58 (58) | 0.95 (0.61–1.46) | 0.83 (0.43–1.60) |
| Final mTICI3, n (%) | 185 (66.1) | 50 (51) | 43 (32.8) | 0 (0) | 5.83 (3.70–9.09)* | 2.13 (1.24–3.65)* |
| TOR, min; median (IQR) | 266 (185–434) | 280 (188–420) | 325 (210–539) | 0.99 (0.97–0.99)* | 0.99 (0.99–1.01) | |
| Perforation/vasospasm, n (%) | 9 (3.2) | 5 (5.1) | 5 (3.9) | 13 (13) | 0.45 (0.22–0.93)* | 0.48 (0.10–2.15) |
| Outcomes | ||||||
| mRS ≤2 at 90 d, n (%) | 161 (57.5) | 56 (57.1) | 39 (29.8) | 17 (17) | 3.33 (2.12–5.23)* | 3.12 (1.89–5.12)* |
| HT, n (%) | 38 (13.6) | 25 (25.5) | 24 (18.3) | 35 (35) | 0.59 (0.39–0.87)* | 1.53 (0.81–2.88) |
| sICH, n (%) | 13 (4.6) | 5 (5.1) | 10 (7.6) | 18 (18) | 0.36 (0.19–0.67)* | 0.65 (0.22–1.97) |
| Mortality, n (%) | 41 (14.6) | 12 (12.2) | 41 (31.3) | 37 (37) | 0.32 (0.22–0.47)* | 0.31 (0.15–0.62)* |
ASPECTS indicates Alberta Stroke Program Early CT Score; FP, first pass; HT, hemorrhagic transformation; IQR, interquartile range; MCA, middle cerebral artery; MP, multiple passes; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; NR, nonrecanalizer; OR, odds ratio; PR, progressive recanalization; sICH, symptomatic hemorrhagic transformation; SR, sudden recanalization; TICA, terminal internal carotid artery; TOR, time onset-recanalization; and tPA, tissue-type plasminogen activator.
*
Statistically significant variables for a P value <0.05.
Among SR patients, the number of passes was not associated with functional outcome (odds ratio [OR], 0.94 [CI, 0.59–1.61]; P=0.937; Figure 1). There was a progressive decline in SR rate for each device pass attempted (OR, 0.43 [CI, 0.37–0.491]; P<0.01; Figure 2). The only variable associated with a higher proportion of SR was the presence of a more distal occlusion (terminal intracranial carotid artery, 54%, versus M1-middle cerebral artery, 63%, versus M2-middle cerebral artery, 67%; OR, 0.64 [CI, 0.44–0.95]; P=0.02; Table).
Multivariate analysis adjusted by confounding factors (Table III in the Data Supplement), including first pass recanalization, showed that SR was the strongest predictor of good functional outcome in patients with recanalization (OR, 3.1 [CI, 1.9–5.1]; P<0.01) and a predictor of absence of symptomatic and nonsymptomatic hemorrhage (OR, 0.4 [CI, 0.2–0.7]; P=0.002 and OR, 0.6 [CI, 0.4–0.9]; P=0.016, respectively).
Among patients with recanalization after MP (n=229; 37%), multivariate analysis showed that PR pattern, as compared with SR, had a negative impact in rate of good functional outcome (30% versus 57%, respectively; OR, 0.3 [CI, 0.2–0.6]; P<0.01) and worse final recanalization degree (final mTICI3: MP-PR, 33%, versus MP-SR, 51%; OR, 2.1 [CI, 1.2–3.6]; P<0.01). However, patients with MP-PR had significantly better functional outcome than patients with nonrecanalizer (30% versus 17%; OR, 2.9 [CI, 1.4–6.1]; P<0.01).
Discussion
Our study shows that patients who underwent EVT because of a large vessel occlusion stroke of the anterior circulation who achieved an SR pattern had better functional outcome. Patients who experienced an SR had similar rate of disability if recanalization was achieved in a single pass or in MP (Figure 1). On the other hand, the clinical benefits associated with recanalization were blunted if recanalization was progressively achieved in several passes. Finally, the inability to achieve recanalization was always associated to worse outcome, supporting the concept that recanalization should be the ultimate goal of EVT.2
Several mechanisms have been proposed to explain the negative impact of additional device passes in patients with stroke undergoing EVT. Repeated device/clot interactions may lead to changes in clot morphology and composition that increases its friction coefficient making retrieval progressively more difficult.6 Thrombus composition per-pass analysis shows a higher fibrin percentage in thrombus fragments after second device pass,7 expressing a dynamic evolution with each device pass. In addition, the device footprint on the vessel wall considered harmless in a single pass may induce a clinically relevant accumulated damage when successive passes are attempted.
We hypothesized that clot composition and its fragmentability may also explain at least to some extent the benefits of the first pass recanalization observed in previous studies.1,3 Theoretically friable clots might be more prone to fragmentation during the retrieval maneuvers, embolizing particles of different size.8 On the other hand, firm, solid clots may require several unsuccessful passes (unchanged mTICI) until a definitive attempt is able to retrieve the whole clot supporting our definition of SR.
The fragmentability of the clot may be due to its composition but also to the devices, combinations, and procedural techniques used. The present work is a hypothesis-generating study and did not address several relevant issues. Future studies should focus on the relationship between the device used and SR, to determine potential differences between them. Also, histological studies should determine whether SR is associated with a particular clot composition.
Our study has 2 major limitations. It is a single-center retrospective study, and recanalization degree was not assessed by a blinded core imaging laboratory. In 70 patients, detailed information about per-pass recanalization was missing and was excluded from the study.
Conclusions
SR is a strong predictor of good functional outcome in patients undergoing EVT, even if previous recanalization attempts failed. PR may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Prospective studies with independent assessment of recanalization pattern should validate these results.
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© 2020 American Heart Association, Inc.
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History
Received: 20 September 2019
Revision received: 13 January 2020
Accepted: 17 January 2020
Published online: 14 February 2020
Published in print: April 2020
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Dr Ribo is a cofounder and shareholder of Anaconda-Biomed and has served as an advisor for Stryker, Medtronic, Vesalio, Anaconda Biomed, and Apta Targets. The other authors report no conflicts.
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- Water content for clot composition prediction in acute ischemic stroke, PLOS ONE, 19, 5, (e0304520), (2024).https://doi.org/10.1371/journal.pone.0304520
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- Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study, Journal of NeuroInterventional Surgery, (jnis-2024-021654), (2024).https://doi.org/10.1136/jnis-2024-021654
- A prospective, multicentre, registry study of RECO in the endovascular treatment of acute ischaemic stroke, Scientific Reports, 14, 1, (2024).https://doi.org/10.1038/s41598-024-52207-z
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- Double stent-retriever as the first-line approach in mechanical thrombectomy: a randomized in vitro evaluation, Journal of NeuroInterventional Surgery, 15, 12, (1224-1228), (2023).https://doi.org/10.1136/jnis-2022-019887
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- Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry, Translational Stroke Research, (2023).https://doi.org/10.1007/s12975-023-01220-x
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