# Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome.

Gaultier Marnat, Benjamin Gory, Igor Sibon, Maéva Kyheng, Julien Labreuche, G. Boulouis, J. S. Liegey, J. Caroff, F. Eugène, O. Naggara, et al.

► To cite this version:

Gaultier Marnat, Benjamin Gory, Igor Sibon, Maéva Kyheng, Julien Labreuche, et al. Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome.. European Journal of Neurology, 2022, European Journal of Neurology, 29 (9), pp.2701-2707. 10.1111/ene.15429. hal-04575875

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ORIGINAL ARTICLE

european journal
of neurology

The official journal of the european academy of neurology

# Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome

Gaultier Marnat<fnref n="1" /> ID | Benjamin Gory<fnref n="2" />,<fnref n="3" /> | Igor Sibon<fnref n="4" /> ID | Maeva Kyheng<fnref n="5" /> |

Julien Labreuche<fnref n="5" /> | Grégoire Boulouis<fnref n="6" /> | Jean-Sebastien Liegey<fnref n="4" /> | Jildaz Caroff<fnref n="7" /> |

François Eugène<fnref n="8" /> | Olivier Naggara<fnref n="9" /> | Arturo Consoli<fnref n="10" /> | Mikael Mazighi<fnref n="11" /> |

Benjamin Maier<fnref n="11" /> | Sebastien Richard<fnref n="12" /> | Christian Denier<fnref n="13" /> | Guillaume Turc<fnref n="14" /> |

Bertrand Lapergue<fnref n="15" /> | Romain Bourcier<fnref n="16" /> | on behalf of Endovascular Treatment in Ischemic Stroke (ETIS) Investigators†

**Correspondence**

Gaultier Marnat, Department of
Neuroradiology, Hôpital Pellegrin, Place
Amélie Raba-Léon, 33000-Bordeaux,
France.

Email: gaultier.marnat@chu-bordeaux.fr

## Abstract

**Background and purpose:** Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure.

**Methods:** We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic

<footnote n="1">¹Neuroradiology Department, Bordeaux University Hospital, Bordeaux, France</footnote>

<footnote n="2">²Department of Diagnostic and Therapeutic Neuroradiology, CHRU-Nancy, Nancy, France</footnote>

<footnote n="3">³IADI, INSERM-U1254, Université de Lorraine, Nancy, France</footnote>

<footnote n="4">⁴Neurology Department, Bordeaux University Hospital, Bordeaux, France</footnote>

<footnote n="5">⁵CHU Lille, Department of Biostatistics, Lille, France</footnote>

<footnote n="6">⁶Neuroradiology Department, Tours University Hospital, Tours, France</footnote>

<footnote n="7">⁷Neuroradiology Department, CHU Kremlin Bicêtre, Paris, France</footnote>

<footnote n="8">⁸Department of Diagnostic and Interventional Neuroradiology, University Hospital of Rennes, Rennes, France</footnote>

<footnote n="9">⁹Department of Neuroradiology, GHU Paris, Centre Hospitalier Sainte-Anne, INSERM-UMR-894, Université de Paris, Paris, France</footnote>

<footnote n="10">¹⁰Department of Stroke Center and Diagnostic and Interventional Neuroradiology, University of Versailles and Saint Quentin-en-Yvelines, Foch Hospital, Suresnes, France</footnote>

<footnote n="11">¹¹Department of Interventional Neuroradiology, INSERM-1148, Fondation Rothschild Hospital, Paris, University of Paris, FHU-NeuroVASC, Paris, France</footnote>

<footnote n="12">¹²Department of Neurology, CHRU-Nancy, Nancy, France</footnote>

<footnote n="13">¹³Neurology Department, CHU Kremlin Bicêtre, Paris, France</footnote>

<footnote n="14">¹⁴Department of Neurology, GHU Paris, Centre Hospitalier Sainte-Anne, Paris, France</footnote>

<footnote n="15">¹⁵Department of Neurology, University of Versailles and Saint-Quentin-en-Yvelines, Foch Hospital, Suresnes, France</footnote>

<footnote n="16">¹⁶Department of Diagnostic and Interventional Neuroradiology, University Hospital of Nantes, Nantes, France</footnote>

<footnote n="1">¹See Appendix S1</footnote>

<footnote>This is an open access article under the terms of the [Creative Commons Attribution-NonCommercial-NoDerivs License](https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

© 2022 The Authors. *European Journal of Neurology* published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.</footnote>
ORIGINAL ARTICLE

european journal
of neurology

The official journal of the european academy of neurology

# Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome

Gaultier Marnat<fnref n="1" /> ID | Benjamin Gory<fnref n="2" />,<fnref n="3" /> | Igor Sibon<fnref n="4" /> ID | Maeva Kyheng<fnref n="5" /> |
Julien Labreuche<fnref n="5" /> | Grégoire Boulouis<fnref n="6" /> | Jean-Sebastien Liegey<fnref n="4" /> | Jildaz Caroff<fnref n="7" /> |
François Eugène<fnref n="8" /> | Olivier Naggara<fnref n="9" /> | Arturo Consoli<fnref n="10" /> | Mikael Mazighi<fnref n="11" /> |
Benjamin Maier<fnref n="11" /> | Sebastien Richard<fnref n="12" /> | Christian Denier<fnref n="13" /> | Guillaume Turc<fnref n="14" /> |
Bertrand Lapergue<fnref n="15" /> | Romain Bourcier<fnref n="16" /> | on behalf of Endovascular Treatment in
Ischemic Stroke (ETIS) Investigators†

**Correspondence**

Gaultier Marnat, Department of
Neuroradiology, Hôpital Pellegrin, Place
Amélie Raba-Léon, 33000-Bordeaux,
France.

Email: gaultier.marnat@chu-bordeaux.fr

Abstract

**Background and purpose:** Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure.

**Methods:** We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic

<footnote n="1">¹Neuroradiology Department, Bordeaux University Hospital, Bordeaux, France</footnote>

<footnote n="2">²Department of Diagnostic and Therapeutic Neuroradiology, CHRU-Nancy, Nancy, France</footnote>

<footnote n="3">³IADI, INSERM-U1254, Université de Lorraine, Nancy, France</footnote>

<footnote n="4">⁴Neurology Department, Bordeaux University Hospital, Bordeaux, France</footnote>

<footnote n="5">⁵CHU Lille, Department of Biostatistics, Lille, France</footnote>

<footnote n="6">⁶Neuroradiology Department, Tours University Hospital, Tours, France</footnote>

<footnote n="7">⁷Neuroradiology Department, CHU Kremlin Bicêtre, Paris, France</footnote>

<footnote n="8">⁸Department of Diagnostic and Interventional Neuroradiology, University Hospital of Rennes, Rennes, France</footnote>

<footnote n="9">⁹Department of Neuroradiology, GHU Paris, Centre Hospitalier Sainte-Anne, INSERM-UMR-894, Université de Paris, Paris, France</footnote>

<footnote n="10">¹⁰Department of Stroke Center and Diagnostic and Interventional Neuroradiology, University of Versailles and Saint Quentin-en-Yvelines, Foch Hospital, Suresnes, France</footnote>

<footnote n="11">¹¹Department of Interventional Neuroradiology, INSERM-1148, Fondation Rothschild Hospital, Paris, University of Paris, FHU-NeuroVASC, Paris, France</footnote>

<footnote n="12">¹²Department of Neurology, CHRU-Nancy, Nancy, France</footnote>

<footnote n="13">¹³Neurology Department, CHU Kremlin Bicêtre, Paris, France</footnote>

<footnote n="14">¹⁴Department of Neurology, GHU Paris, Centre Hospitalier Sainte-Anne, Paris, France</footnote>

<footnote n="15">¹⁵Department of Neurology, University of Versailles and Saint-Quentin-en-Yvelines, Foch Hospital, Suresnes, France</footnote>

<footnote n="16">¹⁶Department of Diagnostic and Interventional Neuroradiology, University Hospital of Nantes, Nantes, France</footnote>

<footnote n="1">¹See Appendix S1</footnote>

<footnote>This is an open access article under the terms of the [Creative Commons Attribution-NonCommercial-NoDerivs License](https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

© 2022 The Authors. *European Journal of Neurology* published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.</footnote>
Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome.

**Results:** The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12–21) and 7 (IQR 5–8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94–0.98, *p* < 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83–0.91, *p* < 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77–0.87, *p* < 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71–0.98, *p* = 0.026) and stroke etiology [significant difference among etiological subtypes (*p* = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71–5.67)] were significantly associated with a 90-day favorable outcome.

**Conclusions:** In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

### KEYWORDS

mechanical thrombectomy, prognosis, recanalization, reperfusion failure

## INTRODUCTION

Since the publication of several randomized trials demonstrating the benefit of mechanical thrombectomy (MT) in the treatment of large vessel occlusion stroke (LVOS) [1], indications are continuously broadening. MT allows satisfying intracranial recanalization in nearly 85% of cases at the end of the procedure with the remaining considered as failures since sufficient reperfusion is not reached [1–3].

The literature available about outcomes in this population experiencing unsuccessful revascularization is scarce [4–8]. In these patients with failed MT, the endovascular procedure itself might be the source of impaired outcome. Numerous factors can be hypothesized such as repeated endovascular MT maneuvers, in situ contrast media injections associated with multiple MT passes, anesthetic management, and blood pressure variability or multiple patient transfers. In cases of MT failure, rescue therapies such as intracranial stenting or angioplasty or pharmacological adjuvant therapies (in situ thrombolysis or intravenous antiplatelet agents such as GpIIb-IIIa inhibitors or cangrelor) are increasingly being considered with promising results [4, 5, 9–11]. Hence, recognizing factors associated with subsequent clinical outcome can improve decision making to tailor the rescue strategy in the context of MT failure. In addition, an improved knowledge of MT failure outcomes may also have an application in the development of neuroprotective or neuroreparative drugs [12, 13].

In the present study our aim was to assess the outcomes after MT failure in patients with anterior circulation LVOS as well as predictors of favorable functional outcome.

## METHODS

The data used in this study are available from the corresponding author upon reasonable request.

### Study population

We conducted a retrospective analysis of consecutive patients included in the prospective ongoing multicenter Endovascular Treatment in Ischemic Stroke registry (ETIS; ClinicalTrials.gov Identifier: NCT03776877). The study period was January 2015 to September 2020. At the time of the study, eight centers participated in the registry. Local ethical committees had approved data collection and analysis. Inclusion criteria were as follows: (i) LVOS of the anterior circulation (M1, M2 intracranial internal carotid artery [ICA] and tandem occlusions) and (ii) MT performed but ending with intracranial recanalization failure defined as a final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 or 2a. Exclusion criteria were favorable intracranial reperfusion defined as final mTICI ≥ 2b, posterior circulation stroke and isolated ICA occlusion without intracranial occlusion.
Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome.

**Results:** The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12–21) and 7 (IQR 5–8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94–0.98, *p* < 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83–0.91, *p* < 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77–0.87, *p* < 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71–0.98, *p* = 0.026) and stroke etiology [significant difference among etiological subtypes (*p* = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71–5.67)] were significantly associated with a 90-day favorable outcome.

**Conclusions:** In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

KEYWORDS

mechanical thrombectomy, prognosis, recanalization, reperfusion failure

INTRODUCTION

Since the publication of several randomized trials demonstrating the benefit of mechanical thrombectomy (MT) in the treatment of large vessel occlusion stroke (LVOS) [1], indications are continuously broadening. MT allows satisfying intracranial recanalization in nearly 85% of cases at the end of the procedure with the remaining considered as failures since sufficient reperfusion is not reached [1-3].

The literature available about outcomes in this population experiencing unsuccessful revascularization is scarce [4-8]. In these patients with failed MT, the endovascular procedure itself might be the source of impaired outcome. Numerous factors can be hypothesized such as repeated endovascular MT maneuvers, in situ contrast media injections associated with multiple MT passes, anesthetic management, and blood pressure variability or multiple patient transfers. In cases of MT failure, rescue therapies such as intracranial stenting or angioplasty or pharmacological adjuvant therapies (in situ thrombolysis or intravenous antiplatelet agents such as GpIIb-IIIa inhibitors or cangrelor) are increasingly being considered with promising results [4, 5, 9-11]. Hence, recognizing factors associated with subsequent clinical outcome can improve decision making to tailor the rescue strategy in the context of MT failure. In addition, an improved knowledge of MT failure outcomes may also have an application in the development of neuroprotective or neuroreparative drugs [12, 13].

In the present study our aim was to assess the outcomes after MT failure in patients with anterior circulation LVOS as well as predictors of favorable functional outcome.

METHODS

The data used in this study are available from the corresponding author upon reasonable request.

Study population

We conducted a retrospective analysis of consecutive patients included in the prospective ongoing multicenter Endovascular Treatment in Ischemic Stroke registry (ETIS; ClinicalTrials.gov Identifier: NCT03776877). The study period was January 2015 to September 2020. At the time of the study, eight centers participated in the registry. Local ethical committees had approved data collection and analysis. Inclusion criteria were as follows: (i) LVOS of the anterior circulation (M1, M2 intracranial internal carotid artery [ICA] and tandem occlusions) and (ii) MT performed but ending with intracranial recanalization failure defined as a final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 or 2a. Exclusion criteria were favorable intracranial reperfusion defined as final mTICI ≥ 2b, posterior circulation stroke and isolated ICA occlusion without intracranial occlusion.
## Treatment

The indications for MT were based on the timeframes, imaging data including perfusion imaging if available, global comorbidities and standard guidelines [14, 15]. MT procedure was performed in accordance with the patient's condition and local protocol. Prior intravenous thrombolysis (IVT) was administered according to international guidelines, using recombinant tissue plasminogen activator (0.9 mg/kg) in the absence of contraindications.

## Collected data

Clinical, imaging, timeline and angiographic data were recorded. Trained research nurses independently assessed the modified Rankin Scale (mRS) score at 90 days, during face-to-face interviews or via telephone conversations with the patients, their relatives or their general practitioners. Angiographic and imaging data were assessed locally by senior neuroradiologists. Collateral status was quantified when assessable using the ASITN classification: grades 3 and 4 were considered as favorable collateral scores. MT failure was defined as a final mTICI score of 0, 1 or 2a. The primary outcome was favorable outcome defined as a 90-day mRS score of 0-2 or equal to pre-stroke mRS. Preoperative adjuvant therapies were also recorded: pharmacological (aspirin, GpIIb/IIIa inhibitor, heparin and vasodilator) and/or mechanical (cervical or intracranial stenting or angioplasty). Procedural complications (dissection, embolism in a new territory and arterial perforation) and 90-day mortality rates were recorded. Intracranial hemorrhage (ICH) was assessed according to the ECASS II classification. Symptomatic intracranial hemorrhage (sICH) was defined as neurological deterioration (NIHSS worsening ≥ 4 points or death) together with ICH.

## Statistical analysis

See Appendix S2.

## RESULTS

### Study population

Among 5076 patients treated with MT and included in the ETIS registry, 533 patients finally met the inclusion exclusion criteria (see study flowchart, Figure 1). Baseline characteristics are presented in Table 1. Briefly, mean age was 68.8 ± 16 years and 48.0% were male. A history of high blood pressure and stroke or transient ischemic attack were observed in, respectively, 57.7% and 15.2%. Two hundred patients (38.9%) were under prior antithrombotic therapy: antiplatelet in 28.0% and anticoagulant in 15.8%. Median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were, respectively,

<figure><img src="image_1.png" /><figcaption>**FIGURE 1** Study flowchart. ETIS, endovascular treatment in ischemic stroke; mTICI, modified Thrombolysis In Cerebral Infarction</figcaption></figure>

17 (IQR 12-21) and 7 (IQR 5-8). The time of stroke onset was unclear in 33.9%. IVT was administered in 46.2%. Eighty-nine patients (17.0%) were treated under general anesthesia. Median time from stroke onset to arterial puncture was 261 min. Baseline characteristics of the study population in comparison with patients with favorable recanalization with MT are provided in 1.

### Clinical and radiological outcomes

Favorable outcome was achieved in 85 patients (18.2%) and 186 died (39.0%). Symptomatic ICH, Parenchymal hematoma (PH) and any ICH were observed in, respectively, 14.1%, 14.0% and 52.9%.

### Predictors of favorable outcome

In univariate analysis, younger age, the absence of history of high blood pressure, a lower initial NIHSS score, arterial site of occlusions, IVT prior to MT, a lower number of MT passes, a lower delta ASPECTS between initial and Day-1 imaging and stroke etiology were associated with favorable functional outcome (Table 2). In multivariable analysis, younger age (OR 0.96, 95% CI 0.94 to 0.94, *p* < 0.001), lower initial NIHSS score (OR 0.87, 95% CI 0.83 to 0.91, *p* < 0.001), lower number of MT passes (OR 0.77, 95% CI 0.77 to 0.87, *p* < 0.001), lower delta ASPECT score between initial and Day-1 imaging (OR = 0.83, 95% CI: 0.71 to 0.98, *p* = 0.026) and stroke etiology (significant difference according to etiology: using cardioembolic stroke as reference, OR = 0.70 [95% CI: 0.28 to 1.75] for large artery atherosclerosis, OR = 2.01 [95% CI: 0.71 to 5.67] for dissection, OR = 0.50 [95% CI: 0.24 to 1.05] for others or undetermined cause, *p* = 0.024) remained significantly associated with 90-day favorable outcome (Table 2).
## Treatment

The indications for MT were based on the timeframes, imaging data including perfusion imaging if available, global comorbidities and standard guidelines [14, 15]. MT procedure was performed in accordance with the patient's condition and local protocol. Prior intravenous thrombolysis (IVT) was administered according to international guidelines, using recombinant tissue plasminogen activator (0.9 mg/kg) in the absence of contraindications.

## Collected data

Clinical, imaging, timeline and angiographic data were recorded. Trained research nurses independently assessed the modified Rankin Scale (mRS) score at 90 days, during face-to-face interviews or via telephone conversations with the patients, their relatives or their general practitioners. Angiographic and imaging data were assessed locally by senior neuroradiologists. Collateral status was quantified when assessable using the ASITN classification: grades 3 and 4 were considered as favorable collateral scores. MT failure was defined as a final mTICI score of 0, 1 or 2a. The primary outcome was favorable outcome defined as a 90-day mRS score of 0-2 or equal to pre-stroke mRS. Preoperative adjuvant therapies were also recorded: pharmacological (aspirin, GpIIb/IIIa inhibitor, heparin and vasodilator) and/or mechanical (cervical or intracranial stenting or angioplasty). Procedural complications (dissection, embolism in a new territory and arterial perforation) and 90-day mortality rates were recorded. Intracranial hemorrhage (ICH) was assessed according to the ECASS II classification. Symptomatic intracranial hemorrhage (sICH) was defined as neurological deterioration (NIHSS worsening ≥ 4 points or death) together with ICH.

## Statistical analysis

See Appendix S2.

## RESULTS

### Study population

Among 5076 patients treated with MT and included in the ETIS registry, 533 patients finally met the inclusion exclusion criteria (see study flowchart, Figure 1). Baseline characteristics are presented in Table 1. Briefly, mean age was 68.8 ± 16 years and 48.0% were male. A history of high blood pressure and stroke or transient ischemic attack were observed in, respectively, 57.7% and 15.2%. Two hundred patients (38.9%) were under prior antithrombotic therapy: antiplatelet in 28.0% and anticoagulant in 15.8%. Median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were, respectively,

<figure><img src="image_2.png" /><figcaption>**FIGURE 1** Study flowchart. ETIS, endovascular treatment in ischemic stroke; mTICI, modified Thrombolysis In Cerebral Infarction</figcaption></figure>

17 (IQR 12-21) and 7 (IQR 5-8). The time of stroke onset was unclear in 33.9%. IVT was administered in 46.2%. Eighty-nine patients (17.0%) were treated under general anesthesia. Median time from stroke onset to arterial puncture was 261 min. Baseline characteristics of the study population in comparison with patients with favorable recanalization with MT are provided in 1.

### Clinical and radiological outcomes

Favorable outcome was achieved in 85 patients (18.2%) and 186 died (39.0%). Symptomatic ICH, Parenchymal hematoma (PH) and any ICH were observed in, respectively, 14.1%, 14.0% and 52.9%.

### Predictors of favorable outcome

In univariate analysis, younger age, the absence of history of high blood pressure, a lower initial NIHSS score, arterial site of occlusions, IVT prior to MT, a lower number of MT passes, a lower delta ASPECTS between initial and Day-1 imaging and stroke etiology were associated with favorable functional outcome (Table 2). In multivariable analysis, younger age (OR 0.96, 95% CI 0.94 to 0.94, *p* < 0.001), lower initial NIHSS score (OR 0.87, 95% CI 0.83 to 0.91, *p* < 0.001), lower number of MT passes (OR 0.77, 95% CI 0.77 to 0.87, *p* < 0.001), lower delta ASPECT score between initial and Day-1 imaging (OR = 0.83, 95% CI: 0.71 to 0.98, *p* = 0.026) and stroke etiology (significant difference according to etiology: using cardioembolic stroke as reference, OR = 0.70 [95% CI: 0.28 to 1.75] for large artery atherosclerosis, OR = 2.01 [95% CI: 0.71 to 5.67] for dissection, OR = 0.50 [95% CI: 0.24 to 1.05] for others or undetermined cause, *p* = 0.024) remained significantly associated with 90-day favorable outcome (Table 2).
<table><caption>TABLE 1 Baseline characteristics of study participants (N = 533)</caption><thead><tr><th>Characteristic</th><th>n</th><th>Value (%)</th></tr></thead><tbody><tr><td>Baseline demographics and medical history</td><td></td><td></td></tr><tr><td>Age, years, mean ± SD</td><td>533</td><td>68.8 ± 16.0</td></tr><tr><td>Men</td><td>531</td><td>255 (48.0)</td></tr><tr><td>Hypertension</td><td>520</td><td>300 (57.7)</td></tr><tr><td>Diabetes</td><td>519</td><td>80 (15.4)</td></tr><tr><td>Dyslipidemia</td><td>518</td><td>158 (30.5)</td></tr><tr><td>Current smoking</td><td>493</td><td>113 (22.9)</td></tr><tr><td>Previous stroke or TIA</td><td>415</td><td>63 (15.2)</td></tr><tr><td>Previous ischemic heart disease</td><td>409</td><td>63 (15.4)</td></tr><tr><td>Antithrombotic medications</td><td>514</td><td>200 (38.9)</td></tr><tr><td>Antiplatelet</td><td>514</td><td>144 (28.0)</td></tr><tr><td>Anticoagulant</td><td>514</td><td>81 (15.8)</td></tr><tr><td>Current stroke event</td><td></td><td></td></tr><tr><td>Systolic BP, mmHg, mean ± SD</td><td>446</td><td>148.8 ± 26.2</td></tr><tr><td>Diastolic BP, mmHg, mean ± SD</td><td>445</td><td>84.2 ± 18.1</td></tr><tr><td>Admission NIHSS score, median (IQR)</td><td>516</td><td>17 (12–21)</td></tr><tr><td>Admission ASPECTS, median (IQR)</td><td>506</td><td>7 (5–8)</td></tr><tr><td>Wake-up stroke or unknown onset</td><td>522</td><td>177 (33.9)</td></tr><tr><td>Pre-stroke mRS &lt; 2</td><td>515</td><td>454 (88.2)</td></tr><tr><td>Site of occlusion</td><td></td><td></td></tr><tr><td>M1-MCA</td><td>533</td><td>256 (48.0)</td></tr><tr><td>M2-MCA</td><td>533</td><td>70 (13.1)</td></tr><tr><td>Intracranial ICA</td><td>533</td><td>99 (18.6)</td></tr><tr><td>Tandem</td><td>533</td><td>108 (20.3)</td></tr><tr><td>Favorable cortical collateral score</td><td>371</td><td>202 (54.4)</td></tr><tr><td>Stroke etiology</td><td></td><td></td></tr><tr><td>Large artery atherosclerosis</td><td>485</td><td>83 (17.1)</td></tr><tr><td>Cardioembolic</td><td>485</td><td>200 (41.2)</td></tr><tr><td>Dissection</td><td>485</td><td>41 (8.5)</td></tr><tr><td>Others/undetermined</td><td>485</td><td>161 (33.2)</td></tr><tr><td>Intravenous thrombolysis</td><td>524</td><td>242 (46.2)</td></tr><tr><td>First-line strategy</td><td></td><td></td></tr><tr><td>Stent retriever</td><td>510</td><td>110 (21.6)</td></tr><tr><td>Contact aspiration</td><td>510</td><td>228 (44.7)</td></tr><tr><td>Combined</td><td>510</td><td>172 (33.7)</td></tr><tr><td>General anesthesia</td><td>523</td><td>89 (17.0)</td></tr><tr><td>Number of passes, median (IQR)</td><td>475</td><td>4 (2–5)</td></tr><tr><td>Adjuvant treatment</td><td></td><td></td></tr><tr><td>Pharmacological</td><td>498</td><td>151 (30.3)</td></tr><tr><td>Mechanical</td><td>151</td><td>76 (50.3)</td></tr><tr><td>Combined</td><td>151</td><td>49 (32.5)</td></tr><tr><td>Procedural times, min, median (IQR)</td><td></td><td></td></tr><tr><td>Onset to puncture</td><td>500</td><td>261 (193–339)</td></tr><tr><td>Outcomes</td><td></td><td></td></tr><tr><td>Favorable outcome (90-day mRS 0–2)</td><td>468</td><td>85 (18.2)</td></tr></tbody></table>
<table><caption>TABLE 1 Baseline characteristics of study participants (N = 533)</caption><thead><tr><th>Characteristic</th><th>n</th><th>Value (%)</th></tr></thead><tbody><tr><td>Baseline demographics and medical history</td><td></td><td></td></tr><tr><td>Age, years, mean ± SD</td><td>533</td><td>68.8 ± 16.0</td></tr><tr><td>Men</td><td>531</td><td>255 (48.0)</td></tr><tr><td>Hypertension</td><td>520</td><td>300 (57.7)</td></tr><tr><td>Diabetes</td><td>519</td><td>80 (15.4)</td></tr><tr><td>Dyslipidemia</td><td>518</td><td>158 (30.5)</td></tr><tr><td>Current smoking</td><td>493</td><td>113 (22.9)</td></tr><tr><td>Previous stroke or TIA</td><td>415</td><td>63 (15.2)</td></tr><tr><td>Previous ischemic heart disease</td><td>409</td><td>63 (15.4)</td></tr><tr><td>Antithrombotic medications</td><td>514</td><td>200 (38.9)</td></tr><tr><td>Antiplatelet</td><td>514</td><td>144 (28.0)</td></tr><tr><td>Anticoagulant</td><td>514</td><td>81 (15.8)</td></tr><tr><td>Current stroke event</td><td></td><td></td></tr><tr><td>Systolic BP, mmHg, mean ± SD</td><td>446</td><td>148.8 ± 26.2</td></tr><tr><td>Diastolic BP, mmHg, mean ± SD</td><td>445</td><td>84.2 ± 18.1</td></tr><tr><td>Admission NIHSS score, median (IQR)</td><td>516</td><td>17 (12–21)</td></tr><tr><td>Admission ASPECTS, median (IQR)</td><td>506</td><td>7 (5–8)</td></tr><tr><td>Wake-up stroke or unknown onset</td><td>522</td><td>177 (33.9)</td></tr><tr><td>Pre-stroke mRS &lt; 2</td><td>515</td><td>454 (88.2)</td></tr><tr><td>Site of occlusion</td><td></td><td></td></tr><tr><td>M1-MCA</td><td>533</td><td>256 (48.0)</td></tr><tr><td>M2-MCA</td><td>533</td><td>70 (13.1)</td></tr><tr><td>Intracranial ICA</td><td>533</td><td>99 (18.6)</td></tr><tr><td>Tandem</td><td>533</td><td>108 (20.3)</td></tr><tr><td>Favorable cortical collateral score</td><td>371</td><td>202 (54.4)</td></tr><tr><td>Stroke etiology</td><td></td><td></td></tr><tr><td>Large artery atherosclerosis</td><td>485</td><td>83 (17.1)</td></tr><tr><td>Cardioembolic</td><td>485</td><td>200 (41.2)</td></tr><tr><td>Dissection</td><td>485</td><td>41 (8.5)</td></tr><tr><td>Others/undetermined</td><td>485</td><td>161 (33.2)</td></tr><tr><td>Intravenous thrombolysis</td><td>524</td><td>242 (46.2)</td></tr><tr><td>First-line strategy</td><td></td><td></td></tr><tr><td>Stent retriever</td><td>510</td><td>110 (21.6)</td></tr><tr><td>Contact aspiration</td><td>510</td><td>228 (44.7)</td></tr><tr><td>Combined</td><td>510</td><td>172 (33.7)</td></tr><tr><td>General anesthesia</td><td>523</td><td>89 (17.0)</td></tr><tr><td>Number of passes, median (IQR)</td><td>475</td><td>4 (2–5)</td></tr><tr><td>Adjuvant treatment</td><td></td><td></td></tr><tr><td>Pharmacological</td><td>498</td><td>151 (30.3)</td></tr><tr><td>Mechanical</td><td>151</td><td>76 (50.3)</td></tr><tr><td>Combined</td><td>151</td><td>49 (32.5)</td></tr><tr><td>Procedural times, min, median (IQR)</td><td></td><td></td></tr><tr><td>Onset to puncture</td><td>500</td><td>261 (193–339)</td></tr><tr><td>Outcomes</td><td></td><td></td></tr><tr><td>Favorable outcome (90-day mRS 0–2)</td><td>468</td><td>85 (18.2)</td></tr></tbody></table>
<table><caption>TABLE 1 (Continued)</caption><thead><tr><td>Characteristic</td><td>n</td><td>Value (%)</td></tr></thead><tbody><tr><td>Poor outcome (90-day mRS 4-6)</td><td>477</td><td>344 (72.1)</td></tr><tr><td>90-day death</td><td>477</td><td>186 (39.0)</td></tr><tr><td>Procedural complication</td><td>470</td><td>101 (21.5)</td></tr><tr><td>Any ICH</td><td>454</td><td>240 (52.9)</td></tr><tr><td>sICH</td><td>454</td><td>64 (14.1)</td></tr><tr><td>PH 1-PH 2</td><td>449</td><td>63 (14.0)</td></tr><tr><td>Decompressive craniectomy</td><td>345</td><td>37 (10.7%)</td></tr></tbody></table>

Note: Values expressed as number (percentage) unless otherwise indicated.

Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; BP, blood pressure; CAD, coronary artery disease; ICA, internal carotid artery; ICH, intracranial hemorrhage; IQR, interquartile range; MCA, middle cerebral artery; mRS, modified Rankin Scale; mTICI, modified Thrombolysis In Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; sICH, symptomatic intracranial hemorrhage; TIA, transient ischemic attack.

<table><caption>TABLE 2 Multivariable regression analysis of predictors of favorable outcome at 90 days</caption><thead><tr><td>Predictor of favorable outcome</td><td>OR (95% CI)</td><td>p value*</td></tr></thead><tbody><tr><td>Age</td><td>0.96 (0.94 to 0.98)</td><td>&lt;0.001</td></tr><tr><td>Admission NIHSS</td><td>0.87 (0.83 to 0.91)</td><td>&lt;0.001</td></tr><tr><td>Number of passes</td><td>0.77 (0.67 to 0.87)</td><td>&lt;0.001</td></tr><tr><td>Delta ASPECTS Day 0-Day 1</td><td>0.83 (0.71 to 0.98)</td><td>0.026</td></tr><tr><td>Stroke etiology</td><td></td><td></td></tr><tr><td>Cardioembolic</td><td>1.00 (Ref.)</td><td>0.024</td></tr><tr><td>Large artery atherosclerosis</td><td>0.70 (0.28 to 1.75)</td><td></td></tr><tr><td>Dissection</td><td>2.01 (0.71 to 5.67)</td><td></td></tr><tr><td>Others or undetermined</td><td>0.50 (0.24 to 1.05)</td><td></td></tr></tbody></table>

Note: Values expressed as number (percentage) unless otherwise indicated.

Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; Ref., reference.

*p values calculated using backward multivariable mixed logistic regression model including center as random effect. Descriptive parameters, OR and p values were calculated after handling missing values using multiple imputation procedure (m = 10).

DISCUSSION

In the present study, we found that 18.2% of patients with MT failure (defined by final mTICI 0, 1 or 2a) had a favorable outcome at 90 days. We identified factors significantly associated with favorable outcome despite unsuccessful recanalization: younger age, lower initial NIHSS score, fewer MT passes, a limited infarct core extension at Day-1 and stroke etiology.

Unsurprisingly, if the MT procedure failed to recanalize the intracranial target artery, our results confirmed that patient prognosis was poor with a low likelihood of favorable outcome and a high mortality risk. At the time of expanding indications of rescue strategy after first-line standard MT failure, these findings are of interest as

they confirm the poor prognosis if sufficient intracranial reperfusion is not achieved. An improved knowledge of what is at stake if reperfusion fails is essential to clarify the role of rescue techniques such as intracranial stenting, intra-arterial thrombolysis or acute an tiplatelet therapies (GpIIb-IIIa inhibitors, cangrelor) [4, 5, 9-11].

We also observed that the rate of PH and sICH was quite high in this subgroup of patients with respective rates of 14.1% and 14.0%. This might seem higher than the usual published rates among overall MT patients (namely considering patients recanalized and those that were not) [1, 16]. This point probably has to be taken into account in postoperative antithrombotic and blood pressure management.

We have searched for factors associated with favorable outcome despite reperfusion failure. Younger age and lower initial NIHSS were associated with better functional outcome. Admission NIHSS is a well-established prognostic factor. Interestingly, younger age was also associated with more favorable outcomes despite the risk of malignant infarction in young patients [17]. This is in line with the identified significant prognosis of heterogeneity among stroke etiologies with a statistical tendency favoring dissection in comparison with cardioembolic and large artery atherosclerosis. This may also be explained by the singularly younger population involved in cervical dissection-related ischemic strokes.

Fewer MT passes was also found to be significantly associated with favorable outcome and an increased number of MT passes with mortality risk. The association between number of passes and poorer prognosis has already been reported [6, 18-20]. However, this point may be considered with caution. Indeed, the number of MT passes may actually be a reflection of important confounding factors such as more proximal occlusions sites, complex underlying occlusion etiology, operator's decision or more severe occlusion leading to more MT attempts [18]. Furthermore, the question of whether to stop MT after three or more passes could be a matter of debate [21]. Indeed, it has been reported that whatever the number of passes, recanalization has to be reached to ensure a better clinical outcome than without recanalization [18]. Therefore, based on our results, we cannot recommend interrupting the MT procedure for fear of worst outcome in case of final MT failure.
<table><caption>TABLE 1 (Continued)</caption><thead><tr><th>Characteristic</th><th>n</th><th>Value (%)</th></tr></thead><tbody><tr><td>Poor outcome (90-day mRS 4-6)</td><td>477</td><td>344 (72.1)</td></tr><tr><td>90-day death</td><td>477</td><td>186 (39.0)</td></tr><tr><td>Procedural complication</td><td>470</td><td>101 (21.5)</td></tr><tr><td>Any ICH</td><td>454</td><td>240 (52.9)</td></tr><tr><td>sICH</td><td>454</td><td>64 (14.1)</td></tr><tr><td>PH 1-PH 2</td><td>449</td><td>63 (14.0)</td></tr><tr><td>Decompressive craniectomy</td><td>345</td><td>37 (10.7%)</td></tr></tbody></table>

Note: Values expressed as number (percentage) unless otherwise indicated.

Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; BP, blood pressure; CAD, coronary artery disease; ICA, internal carotid artery; ICH, intracranial hemorrhage; IQR, interquartile range; MCA, middle cerebral artery; mRS, modified Rankin Scale; mTICI, modified Thrombolysis In Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; sICH, symptomatic intracranial hemorrhage; TIA, transient ischemic attack.

<table><caption>TABLE 2 Multivariable regression analysis of predictors of favorable outcome at 90 days</caption><thead><tr><th>Predictor of favorable outcome</th><th>OR (95% CI)</th><th>p value*</th></tr></thead><tbody><tr><td>Age</td><td>0.96 (0.94 to 0.98)</td><td>&lt;0.001</td></tr><tr><td>Admission NIHSS</td><td>0.87 (0.83 to 0.91)</td><td>&lt;0.001</td></tr><tr><td>Number of passes</td><td>0.77 (0.67 to 0.87)</td><td>&lt;0.001</td></tr><tr><td>Delta ASPECTS Day 0-Day 1</td><td>0.83 (0.71 to 0.98)</td><td>0.026</td></tr><tr><td>Stroke etiology</td><td></td><td></td></tr><tr><td>Cardioembolic</td><td>1.00 (Ref.)</td><td>0.024</td></tr><tr><td>Large artery atherosclerosis</td><td>0.70 (0.28 to 1.75)</td><td></td></tr><tr><td>Dissection</td><td>2.01 (0.71 to 5.67)</td><td></td></tr><tr><td>Others or undetermined</td><td>0.50 (0.24 to 1.05)</td><td></td></tr></tbody></table>

Note: Values expressed as number (percentage) unless otherwise indicated.

Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; Ref., reference.

*p values calculated using backward multivariable mixed logistic regression model including center as random effect. Descriptive parameters, OR and p values were calculated after handling missing values using multiple imputation procedure (m = 10).

DISCUSSION

In the present study, we found that 18.2% of patients with MT failure (defined by final mTICI 0, 1 or 2a) had a favorable outcome at 90 days. We identified factors significantly associated with favorable outcome despite unsuccessful recanalization: younger age, lower initial NIHSS score, fewer MT passes, a limited infarct core extension at Day-1 and stroke etiology.

Unsurprisingly, if the MT procedure failed to recanalize the intracranial target artery, our results confirmed that patient prognosis was poor with a low likelihood of favorable outcome and a high mortality risk. At the time of expanding indications of rescue strategy after first-line standard MT failure, these findings are of interest as

they confirm the poor prognosis if sufficient intracranial reperfusion is not achieved. An improved knowledge of what is at stake if reperfusion fails is essential to clarify the role of rescue techniques such as intracranial stenting, intra-arterial thrombolysis or acute an tiplatelet therapies (GpIIb-IIIa inhibitors, cangrelor) [4, 5, 9-11].

We also observed that the rate of PH and sICH was quite high in this subgroup of patients with respective rates of 14.1% and 14.0%. This might seem higher than the usual published rates among overall MT patients (namely considering patients recanalized and those that were not) [1, 16]. This point probably has to be taken into account in postoperative antithrombotic and blood pressure management.

We have searched for factors associated with favorable outcome despite reperfusion failure. Younger age and lower initial NIHSS were associated with better functional outcome. Admission NIHSS is a well-established prognostic factor. Interestingly, younger age was also associated with more favorable outcomes despite the risk of malignant infarction in young patients [17]. This is in line with the identified significant prognosis of heterogeneity among stroke etiologies with a statistical tendency favoring dissection in comparison with cardioembolic and large artery atherosclerosis. This may also be explained by the singularly younger population involved in cervical dissection-related ischemic strokes.

Fewer MT passes was also found to be significantly associated with favorable outcome and an increased number of MT passes with mortality risk. The association between number of passes and poorer prognosis has already been reported [6, 18-20]. However, this point may be considered with caution. Indeed, the number of MT passes may actually be a reflection of important confounding factors such as more proximal occlusions sites, complex underlying occlusion etiology, operator's decision or more severe occlusion leading to more MT attempts [18]. Furthermore, the question of whether to stop MT after three or more passes could be a matter of debate [21]. Indeed, it has been reported that whatever the number of passes, recanalization has to be reached to ensure a better clinical outcome than without recanalization [18]. Therefore, based on our results, we cannot recommend interrupting the MT procedure for fear of worst outcome in case of final MT failure.
We also observed that a lower delta ASPECT score between initial and Day-1 imaging was associated with a better outcome despite MT failure. In other words, the absence of infarct core extension or a limited progression of cerebral infarction between the acute phase and Day-1 imaging was associated with a favorable outcome among patients experiencing insufficient intracranial recanalization. Several potential mechanisms explaining such a finding can be discussed including persistency of efficient durable cortical collaterals, delayed spontaneous intracranial arterial recanalization or specific intracranial occlusion etiology and thrombus composition. Interestingly, an initial ASPECT score > 8 was not associated with an improved outcome in this specific population. Only a limited progression of cerebral infarction between initial and Day-1 imaging was associated with clinical prognosis.

Our study has some limitations. First, even though it was derived from our prospectively maintained and ongoing registry, our study was retrospective. The absence of comparison to a control group may be considered as a weakness. However, rather than analyzing the natural history of MT failure in patients with anterior circulation LVOS, here we aim to search for potential factors associated with favorable functional outcome within this population. We use self-adjudication of the final recanalization to include patients. Indeed, over-rating is a common ground in final TICI score by non-external core-laboratory evaluators and this could have led to selection bias [22]. However, we are focusing here on poor recanalization: it is very likely that poor final mTICI scores are reliably assessed. An over-rating phenomenon might be more frequent when declaring higher mTICI scores. Collateral status suffers from missing data limiting its interpretation. This was mostly explained by the impossibility in daily practice of exploring these cortical collaterals in many frequent angiographic presentations such as intracranial internal carotid artery, tandem occlusions or circle of Willis variations limiting its exploration during MT procedure. Contrast media used volumes were not available to explore their influence. However, the contrast media quantity is supposed to be closely related to endovascular procedure duration and repeated MT passes. Similarly, admission glucose level and postprocedural blood pressure values, which are previously identified factors influencing clinical prognosis, were not available. Lastly, we were unable to analyze the arterial patency at 24 or 48 h after MT. This would have been of interest in investigating a link between spontaneous delayed recanalization and clinical outcome [23, 24].

## CONCLUSIONS

Failed intracranial reperfusion after MT in anterior circulation LVOS was associated with a low rate of favorable outcome and a high mortality rate. Lower initial NIHSS, younger age, fewer MT passes, lower delta ASPECT score between initial and Day-1 imaging, and stroke etiology were associated with increased likelihood of favorable functional outcome.

## AUTHOR CONTRIBUTIONS

**Gaultier Marnat:** Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); supervision (lead); validation (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). **Benjamin Gory:** Conceptualization (equal); data curation (equal); methodology (equal); validation (equal); writing – review and editing (equal). **Igor Sibon:** Conceptualization (equal); investigation (equal); writing – review and editing (equal). **Maeva Kyheng:** Data curation (equal); formal analysis (lead); methodology (equal); software (lead); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). **Julien Labreuche:** Formal analysis (lead); software (equal); writing – review and editing (equal). **GrE:goire BOULLOUIS:** Data curation (equal); writing – review and editing (equal). **Jean-SE;bastien Liegey:** Writing – review and editing (equal). **Jildaz Caroff:** Data curation (equal); writing – review and editing (equal). **Francois Eugene:** Data curation (equal); writing – review and editing (equal). **Olivier Naggara:** Data curation (equal); writing – review and editing (equal). **Arturo Consoli:** Data curation (equal); writing – review and editing (equal). **Mikael Mazighi:** Writing – review and editing (equal). **Benjamin Maier:** Writing – review and editing (equal). **SE;bastien Richard:** Writing – review and editing (equal). **Christian Denier:** Writing – review and editing (equal). **Guillaume Turc:** Writing – review and editing (equal). **Bertrand Lapergue:** Conceptualization (equal); data curation (equal); investigation (equal); methodology (equal); validation (equal); writing – review and editing (equal). **Romain Bourcier:** Conceptualization (equal); data curation (equal); formal analysis (lead); investigation (equal); methodology (lead); supervision (equal); validation (equal); writing – original draft (supporting); writing – review and editing (lead).

## CONFLICT OF INTEREST

All the authors declare that they have no conflicts of interest related to this study.

## DATA AVAILABILITY STATEMENT

The data used in this study are available from the corresponding author upon reasonable request.

## ORCID

Gaultier Marnat https://orcid.org/0000-0002-7611-7753

Igor Sibon https://orcid.org/0000-0002-1171-4215

## REFERENCES

1. Goyal M, Menon BK, Van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. *Lancet*. 2016;387:1723-1731.

2. Lapergue B, Blanc R, Gory B, et al. Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel occlusion: the ASTER randomized clinical trial. *JAMA*. 2017;318:443-452.
We also observed that a lower delta ASPECT score between initial and Day-1 imaging was associated with a better outcome despite MT failure. In other words, the absence of infarct core extension or a limited progression of cerebral infarction between the acute phase and Day-1 imaging was associated with a favorable outcome among patients experiencing insufficient intracranial recanalization. Several potential mechanisms explaining such a finding can be discussed including persistency of efficient durable cortical collaterals, delayed spontaneous intracranial arterial recanalization or specific intracranial occlusion etiology and thrombus composition. Interestingly, an initial ASPECT score > 8 was not associated with an improved outcome in this specific population. Only a limited progression of cerebral infarction between initial and Day-1 imaging was associated with clinical prognosis.

Our study has some limitations. First, even though it was derived from our prospectively maintained and ongoing registry, our study was retrospective. The absence of comparison to a control group may be considered as a weakness. However, rather than analyzing the natural history of MT failure in patients with anterior circulation LVOS, here we aim to search for potential factors associated with favorable functional outcome within this population. We use self-adjudication of the final recanalization to include patients. Indeed, over-rating is a common ground in final TICI score by non-external core-laboratory evaluators and this could have led to selection bias [22]. However, we are focusing here on poor recanalization: it is very likely that poor final mTICI scores are reliably assessed. An over-rating phenomenon might be more frequent when declaring higher mTICI scores. Collateral status suffers from missing data limiting its interpretation. This was mostly explained by the impossibility in daily practice of exploring these cortical collaterals in many frequent angiographic presentations such as intracranial internal carotid artery, tandem occlusions or circle of Willis variations limiting its exploration during MT procedure. Contrast media used volumes were not available to explore their influence. However, the contrast media quantity is supposed to be closely related to endovascular procedure duration and repeated MT passes. Similarly, admission glucose level and postprocedural blood pressure values, which are previously identified factors influencing clinical prognosis, were not available. Lastly, we were unable to analyze the arterial patency at 24 or 48 h after MT. This would have been of interest in investigating a link between spontaneous delayed recanalization and clinical outcome [23, 24].

## CONCLUSIONS

Failed intracranial reperfusion after MT in anterior circulation LVOS was associated with a low rate of favorable outcome and a high mortality rate. Lower initial NIHSS, younger age, fewer MT passes, lower delta ASPECT score between initial and Day-1 imaging, and stroke etiology were associated with increased likelihood of favorable functional outcome.

## AUTHOR CONTRIBUTIONS

**Gaultier Marnat:** Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); supervision (lead); validation (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). **Benjamin Gory:** Conceptualization (equal); data curation (equal); methodology (equal); validation (equal); writing – review and editing (equal). **Igor Sibon:** Conceptualization (equal); investigation (equal); writing – review and editing (equal). **Maeva Kyheng:** Data curation (equal); formal analysis (lead); methodology (equal); software (lead); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). **Julien Labreuche:** Formal analysis (lead); software (equal); writing – review and editing (equal). **GrE:goire BOULLOUIS:** Data curation (equal); writing – review and editing (equal). **Jean-SE;bastien Liegey:** Writing – review and editing (equal). **Jildaz Caroff:** Data curation (equal); writing – review and editing (equal). **Francois Eugene:** Data curation (equal); writing – review and editing (equal). **Olivier Naggara:** Data curation (equal); writing – review and editing (equal). **Arturo Consoli:** Data curation (equal); writing – review and editing (equal). **Mikael Mazighi:** Writing – review and editing (equal). **Benjamin Maier:** Writing – review and editing (equal). **SE;bastien Richard:** Writing – review and editing (equal). **Christian Denier:** Writing – review and editing (equal). **Guillaume Turc:** Writing – review and editing (equal). **Bertrand Lapergue:** Conceptualization (equal); data curation (equal); investigation (equal); methodology (equal); validation (equal); writing – review and editing (equal). **Romain Bourcier:** Conceptualization (equal); data curation (equal); formal analysis (lead); investigation (equal); methodology (lead); supervision (equal); validation (equal); writing – original draft (supporting); writing – review and editing (lead).

## CONFLICT OF INTEREST

All the authors declare that they have no conflicts of interest related to this study.

## DATA AVAILABILITY STATEMENT

The data used in this study are available from the corresponding author upon reasonable request.

## ORCID

Gaultier Marnat https://orcid.org/0000-0002-7611-7753

Igor Sibon https://orcid.org/0000-0002-1171-4215

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6. García-Tornel Á, Requena M, Rubiera M, et al. When to stop. *Stroke*. 2019;50:1781-1788.

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11. Delvoye F, Loyau S, Labreuche J, et al. Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients. *Platelets*. 2021;1-6:285-290.

12. Venkat P, Shen Y, Chopp M, Chen J. Cell-based and pharmacological neurorestorative therapies for ischemic stroke. *Neuropharmacology*. 2018;134:310-322.

13. Chamorro Á, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. *Lancet Neurol*. 2016;15:869-881.

14. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the Early Management of Patients with Acute Ischemic Stroke Regarding Endovascular Treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. *Stroke*. 2015;46:3020-3035.

15. Turc G, Bhogal P, Fischer U, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological

Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke. *J Neurointerv Surg*. 2019; 1-30.

16. Boisseau W, Fahed R, Lapergue B, et al. Predictors of parenchymal hematoma after mechanical thrombectomy: a multicenter study. *Stroke*. 2020;2364-2370:2364-2370.

17. Bernsen MLE, Kauw F, Martens JM, et al. Malignant infarction after endovascular treatment: incidence and prediction. *Int. J. Stroke*. 2021;17:17474930211006290.

18. Mohammaden MH, Haussen DC, Pisani L, et al. Lack of reperfusion rather than number of passes defines futility in stroke thrombectomy: a matched case-control study. *Stroke*. 2021;52:2757-2763.

19. Flottmann F, Brekenfeld C, Broocks G, et al. Good clinical outcome decreases with number of retrieval attempts in stroke thrombectomy: beyond the first-pass effect. *Stroke*. 2021;52:482-490.

20. Baek J-H, Kim BM, Heo JH, et al. Number of stent retriever passes associated with futile recanalization in acute stroke. *Stroke*. 2018;49:2088-2095.

21. Bourcier R, Saleme S, Labreuche J, et al. More than three passes of stent retriever is an independent predictor of parenchymal hematoma in acute ischemic stroke. *J Neurointerv Surg*. 2019;11:625-629.

22. Fahed R, Ben Maacha M, Ducroux C, et al. Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial. *J Neurointerv Surg*. 2018;10:e30.

23. Camara R, Matei N, Zhang JH. Evolution of the stroke paradigm: a review of delayed recanalization. *J Cereb Blood Flow Metab*. 2021;41:945-957.

24. Molina CA, Montaner J, Abilleira S, et al. Timing of spontaneous recanalization and risk of hemorrhagic transformation in acute cardioembolic stroke. *Stroke*. 2001;32:1079-1084.

## SUPPORTING INFORMATION

Additional supporting information may be found in the online version of the article at the publisher's website.

**How to cite this article:** Marnat G, Gory B, Sibon I, et al. Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome. *Eur J Neurol*. 2022;29:2701-2707. doi: 10.1111/ene.15429
3. Turk AS, Siddiqui A, Fifi JT, et al. Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial. *Lancet*. 2019;393:998-1008.

4. Peng F, Wan J, Liu W, et al. Efficacy and safety of rescue stenting following failed mechanical thrombectomy for anterior circulation large vessel occlusion: propensity score analysis. *J Neurointerv Surg*. 2020;12:271-273.

5. Chang Y, Kim BM, Bang OY, et al. Rescue stenting for failed mechanical thrombectomy in acute ischemic stroke a multicenter experience. *Stroke*. 2018;49:958-964.

6. García-Tornel Á, Requena M, Rubiera M, et al. When to stop. *Stroke*. 2019;50:1781-1788.

7. Park H, Kim BM, Baek JH, et al. Predictors of good outcomes in patients with failed endovascular thrombectomy. *Korean J Radiol*. 2020;21:582-587.

8. Ospel JM, Hill MD, Demchuk A, et al. Clinical impact of EVT with failed reperfusion in patients with acute ischemic stroke: results from the ESCAPE and ESCAPE-NA1 trials. *Neuroradiology*. 2021;63:1883-1889.

9. Maingard J, Phan K, Lamanna A, et al. Rescue intracranial stenting after failed mechanical thrombectomy for acute ischemic stroke: a systematic review and meta-analysis. *World Neurosurg*. 2019;132:e235-e245. 10.1016/j.wneu.2019.08.192

10. Premat K, Dechartres A, Lenck S, et al. Rescue stenting versus medical care alone in refractory large vessel occlusions: a systematic review and meta-analysis. *Neuroradiology*. 2020;62:629-637.

11. Delvoye F, Loyau S, Labreuche J, et al. Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients. *Platelets*. 2021;1-6:285-290.

12. Venkat P, Shen Y, Chopp M, Chen J. Cell-based and pharmacological neurorestorative therapies for ischemic stroke. *Neuropharmacology*. 2018;134:310-322.

13. Chamorro Á, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. *Lancet Neurol*. 2016;15:869-881.

14. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the Early Management of Patients with Acute Ischemic Stroke Regarding Endovascular Treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. *Stroke*. 2015;46:3020-3035.

15. Turc G, Bhogal P, Fischer U, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological

Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke. *J Neurointerv Surg*. 2019; 1-30.

16. Boisseau W, Fahed R, Lapergue B, et al. Predictors of parenchymal hematoma after mechanical thrombectomy: a multicenter study. *Stroke*. 2020;2364-2370:2364-2370.

17. Bernsen MLE, Kauw F, Martens JM, et al. Malignant infarction after endovascular treatment: incidence and prediction. *Int. J. Stroke*. 2021;17:17474930211006290.

18. Mohammaden MH, Haussen DC, Pisani L, et al. Lack of reperfusion rather than number of passes defines futility in stroke thrombectomy: a matched case-control study. *Stroke*. 2021;52:2757-2763.

19. Flottmann F, Brekenfeld C, Broocks G, et al. Good clinical outcome decreases with number of retrieval attempts in stroke thrombectomy: beyond the first-pass effect. *Stroke*. 2021;52:482-490.

20. Baek J-H, Kim BM, Heo JH, et al. Number of stent retriever passes associated with futile recanalization in acute stroke. *Stroke*. 2018;49:2088-2095.

21. Bourcier R, Saleme S, Labreuche J, et al. More than three passes of stent retriever is an independent predictor of parenchymal hematoma in acute ischemic stroke. *J Neurointerv Surg*. 2019;11:625-629.

22. Fahed R, Ben Maacha M, Ducroux C, et al. Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial. *J Neurointerv Surg*. 2018;10:e30.

23. Camara R, Matei N, Zhang JH. Evolution of the stroke paradigm: a review of delayed recanalization. *J Cereb Blood Flow Metab*. 2021;41:945-957.

24. Molina CA, Montaner J, Abilleira S, et al. Timing of spontaneous recanalization and risk of hemorrhagic transformation in acute cardioembolic stroke. *Stroke*. 2001;32:1079-1084.

## SUPPORTING INFORMATION

Additional supporting information may be found in the online version of the article at the publisher's website.

**How to cite this article:** Marnat G, Gory B, Sibon I, et al. Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome. *Eur J Neurol*. 2022;29:2701-2707. doi: 10.1111/ene.15429