Thrombectomy in Stroke Patients With Low Alberta Stroke Program Early Computed Tomography Score: Is Modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 Superior to mTICI 2b?

Article information

J Stroke. 2024;26(1):95-103

Publication date (electronic) : 2024 January 30

doi : https://doi.org/10.5853/jos.2023.02292

Sameh Samir Elawady¹, Brian Fabian Saway¹, Hidetoshi Matsukawa^1,2, Kazutaka Uchida^1,2, Steven Lin¹, Ilko Maier³, Pascal Jabbour⁴, Joon-Tae Kim⁵, Stacey Quintero Wolfe⁶, Ansaar Rai⁷, Robert M. Starke⁸, Marios-Nikos Psychogios⁹, Edgar A Samaniego¹⁰, Adam Arthur¹¹, Shinichi Yoshimura², Hugo Cuellar¹², Jonathan A. Grossberg¹³, Ali Alawieh¹³, Daniele G. Romano¹⁴, Omar Tanweer¹⁵, Justin Mascitelli¹⁶, Isabel Fragata¹⁷, Adam Polifka¹⁸, Joshua Osbun¹⁹, Roberto Crosa²⁰, Charles Matouk²¹, Min S. Park²², Michael R. Levitt²³, Waleed Brinjikji²⁴, Mark Moss²⁵, Travis Dumont²⁶, Richard Williamson²⁷, Pedro Navia²⁸, Peter Kan²⁹, Reade De Leacy³⁰, Shakeel Chowdhry³¹, Mohamad Ezzeldin³², Alejandro M. Spiotta¹, Sami Al Kasab^,1, on behalf of the STAR Collaborators

¹Department of Neurosurgery, Division of Neuroendovascular Surgery, Medical University of South Carolina, Charleston, SC, USA

²Department of Neurosurgery, Hyogo Medical University, Nishinomiya, Japan

³Department of Neurology, University Medical Center Göttingen, Göttingen, Germany

⁴Department of Neurosurgery, Thomas Jefferson University Hospitals, Philadelphia, PA, USA

⁵Department of Neurology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea

⁶Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA

⁷Department of Radiology, West Virginia School of Medicine, Morgantown, WV, USA

⁸Department of Neurosurgery, University of Miami Health System, Miami, FL, USA

⁹Department of Interventional and Diagnostical Neuroradiology, University of Basel, Basel, Switzerland

¹⁰Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

¹¹Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

¹²Department of Neurosurgery and Neurointerventional Radiology, Louisiana State University, Shreveport, LA, USA

¹³Department of Neurosurgery, Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA

¹⁴Department of Neuroradiology, University Hospital San Giovanni di Dio e Ruggi d’Aragona, University of Salerno, Salerno, Italy

¹⁵Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

¹⁶Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

¹⁷Department of Neuroradiology, Hospital São José Centro Hospitalar, Lisboa, Portugal

¹⁸Department of Neurosurgery, University of Florida, Gainesville, FL, USA

¹⁹Department of Neurological Surgery, Washington University, St. Louis, MO, USA

²⁰Department of Neurosurgery, Endovascular Neurological Center, Montevideo, Uruguay

²¹Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA

²²Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA

²³Department of Neurosurgery, University of Washington, Seattle, WA, USA

²⁴Department of Radiology, Mayo Clinic, Rochester, MN, USA; Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA

²⁵Department of Neuroradiology, Washington Regional J.B. Hunt Transport Services Neuroscience Institute, Fayetteville, AZ, USA

²⁶Department of Neurosurgery, University of Arizona, Tucson, AZ, USA

²⁷Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA, USA

²⁸Department of Neuroradiology, Hospital Universitario La Paz, Madrid, Spain

²⁹Department of Neurological Surgery, University of Texas Medical Branch - Galveston, TX, USA

³⁰Department of Neurosurgery, Mount Sinai Health System, New York, NY, USA

³¹Department of Neurosurgery, NorthShore University Health System, Evanston, IL, USA

³²University of Houston, Department of Clinical Neuroscience, HCA Houston Healthcare Kingwood, Houston, TX, USA

Correspondence: Sami Al Kasab Medical University of South Carolina, Department of Neurosurgery, Division of Neuroendovascular Surgery, 96 Jonathan Lucas St Charleston, SC 29425 Tel: +4042139556 E-mail: alkasab@musc.edu

Received 2023 July 15; Revised 2023 September 13; Accepted 2023 October 4.

Abstract

Introduction

The current endpoint for successful endovascular treatment of large vessel occlusion (LVO) of the anterior circulation is achievement of a modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2b or greater as multiple studies have demonstrated a strong association with this angiographic, recanalization outcome and subsequent neurologic and clinical recovery [1-3]. Furthermore, recent reports have assessed the outcomes of angiographic mTICI scores greater than 2b and have demonstrated a continuous relationship between recanalization grade and functional outcome [4]. As the number of mechanical thrombectomy (MT) attempts has been revealed to have a negative correlation with patient outcomes, operators are faced with balancing maximizing angiographic recanalization grade with thrombectomy retrieval attempts [5-9].

Patients with LVO of the anterior circulation with a low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of less than 6 were previously thought to not be ideal candidates for MT due to relatively smaller volume of salvageable penumbra and risk of cerebral hemorrhage. Recent randomized clinical trials have demonstrated that this patient population may attain long term functional independence after MT if they achieve successful recanalization defined as a recanalization grade of 2b or greater [10,11]. However, the presence of a similar continuous relationship between recanalization grade and functional outcome, as previously demonstrated for patients with ASPECTS 6–10, has yet to be demonstrated among low ASPECTS patients. Among a large, real-world population of patients undergoing MT with low ASPECTS (2–5) on presentation, we investigated whether achieving mTICI 2c/3 recanalization confers additional benefit for outcome compared to mTICI 2b.

Methods

Results

Of the 10,229 consecutive patients who underwent thrombectomy, 234 met the inclusion criteria. Among the included subset, 136 (58.1%) achieved an mTICI of 2c/3 and 98 (41.9%) achieved an mTICI of 2b (Figure 1).

Figure 1.

Patient selection flow chart. STAR, Stroke Thrombectomy and Aneurysm Registry; ASPECTS, Alberta Stroke Program Early Computed Tomography Score; M1, M1 segment of the middle cerebral artery; ICA, internal carotid artery; mTICI, modified Thrombolysis in Cerebral Infarction; mRS, modified Rankin Scale.

Patient characteristics

Table 1 summarizes the baseline, clinical, and procedural characteristics of patients in the mTICI 2b and mTICI 2c/3 groups. There were no significant differences in age, sex, comorbidities, admission NIHSS, ASPECTS, and use of intravenous thrombolysis between the two groups (P>0.05). However, the distribution of occluded vessels differed significantly between the mTICI 2b and mTICI 2c/3 groups (P<0.01). M1 occlusion was observed in 37.8% of cases in the mTICI 2b group compared to 58.1% in the mTICI 2c/3 group. ICA occlusion was present in 37.8% of cases in the mTICI 2b group compared to 27.9% in the mTICI 2c/3 group. Both M1 and ICA occlusion were observed in 24.5% of cases in the mTICI 2b group compared to 14.0% in the mTICI 2c/3 group.

Table 1.

Characteristics of low ASPECTS patients who underwent mechanical thrombectomy for ICA or M1 occlusion with achievement of recanalization grade of mTICI 2b or 2c/3

Patients who achieved mTICI 2b required a higher number of procedural attempts, with a median of 3 attempts (IQR 2–4), compared to a median of 2 attempts (IQR 1–3) in the mTICI 2c/3 group (P<0.01). The procedure duration was longer for patients in the mTICI 2b group, with a median of 53 minutes (IQR 28–80), compared to a median of 29 minutes (IQR 15–59) in the mTICI 2c/3 group (P<0.01).

Outcomes

The mTICI 2c/3 group demonstrated a significantly higher rate of favorable outcomes at 90 days, defined as mRS score of 0–3, compared to the mTICI 2b group (adjusted odds ratio [aOR]=2.35; 95% confidence interval [CI]=1.18–4.81; P=0.02). There was no significant difference between the two groups in achieving functional independence (mRS 0–2) (aOR=1.78; 95% CI=0.77–4.31; P=0.20). The proportion of patients with an mRS score of 0–3 at 90 days was significantly higher in the mTICI 2c/3 group, with 60 patients (44.1%), compared to 24 patients (24.5%) in the mTICI 2b group (P<0.01). The distribution of mRS scores among the mTICI 2b and mTICI 2c/3 groups is depicted in Figure 2. mTICI 2c/3 group showed significantly higher neurological improvement at 24 hours post-procedure and at discharge (aOR 2.01, 95% CI=1.04–4.28; P=0.04; aOR=2.76; 95% CI=1.31–6.01; P<0.01, respectively).

Figure 2.

Scores on the mRS at 90 days for low ASPECTS patients who underwent mechanical thrombectomy for internal carotid artery or M1 occlusion with achievement of recanalization grade of mTICI 2b versus 2c/3. mRS, modified Rankin Scale; ASPECTS, Alberta Stroke Program Early Computed Tomography Score; M1, middle cerebral artery; mTICI, modified Thrombolysis in Cerebral Infarction.

Both sICH and mortality rates were no different between the mTICI 2c/3 and mTICI 2b groups (sICH: aOR=1.30, 95% CI=0.58–3.04, P=0.60; mortality: aOR=0.68, 95% CI=0.38–1.24, P=0.20, respectively). However, distal embolization was significantly higher in the mTICI 2b group (aOR=0.16; 95% CI=0.07–0.34; P<0.01) (Table 2).

Table 2.

Outcomes of low ASPECTS patients who underwent mechanical thrombectomy for ICA or M1 occlusion with achievement of recanalization grade of mTICI 2b versus 2c/3

Subgroup analysis of mTICI 3 versus mTICI 2c

Further comparison of mTICI 2c (n=33) recanalization with mTICI 3 (n=103) showed no significant difference between the two groups in terms of clinical outcomes and complications (Table 3).

Table 3.

Outcomes of low ASPECTS patients who underwent mechanical thrombectomy for ICA or M1 occlusion with achievement of recanalization grade of mTICI 2c versus 3

Multivariate analysis

A binary logistic regression analysis was conducted to identify predictors of 90-day outcome in low ASPECTS stroke patients who underwent MT for ICA or M1 occlusion. The analysis revealed that younger age (OR, 0.95; 95% CI, 0.92–0.97; P<0.01), lower admission NIHSS score (OR, 0.91; 95% CI, 0.86–0.96; P<0.01), and mTICI score of 2c/3 (OR, 2.14; 95% CI, 1.07–4.41; P=0.04) were significantly associated with favorable 90-day outcomes (mRS 0–3). However, no significant associations were found for procedure duration, time from symptom onset to groin puncture, female sex, intravenous thrombolysis, ICA occlusion, and ASPECTS (Table 4).

Table 4.

Multivariate regression analysis for predictors of 90-day mRS 0–3

Discussion

This large, multicenter, real-world experience series investigates the clinical outcomes of patients with acute LVO and low ASPECTS on presentation treated with MT and achieving a post-thrombectomy recanalization grade of mTICI 2b versus 2c/3. We found that a recanalization grade of mTICI 2c/3 was associated with a significantly higher rate of achieving a good functional outcome of mRS of 0–3 at 90 days compared to mTICI 2b. Moreover, despite the theoretical increased risk of recanalization-associated hemorrhagic transformation occurring in patients with large core infarcts undergoing successful thrombectomy, the rates of hemorrhage were not observed to be different between the two cohorts.

Recently published randomized controlled trials [18-20] and large multicenter registry data [10,11,21-25] have provided definitive evidence for beneficial effect of MT in LVO patients with low ASPECTS. In a large, multicenter, retrospective series, Almallouhi et al. [10] demonstrated that more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT, and a favorable outcome was nearly five times more likely for patients with low ASPECTS who had successful recanalization. This functional recovery was similarly found in patients presenting in both the early and extended windows. Altogether, current evidence demonstrates that patients with low ASPECTS can have a good functional recovery following successful thrombectomy.

Beyond mTICI 2b, the additional positive impact on outcome for achieving mTICI 2c/3 among small core patients has been emphasized in the literature and has led practitioners to strive to maximize the post-thrombectomy recanalization grade. Early recommendations considered achieving mTICI of 2b or higher to be a successful recanalization and did not necessarily recommend increasing the number of thrombectomy attempts to achieve an mTICI 2c/3 if a grade of 2b had already been achieved [1,3]. However, a recently published meta-analysis identified an incremental association between mTICI score and clinical outcome, emphasizing the importance of maximizing recanalization grade to greater than 2b if possible [26]. More recent data from a large multicenter registry further confirmed this notion and reported a positive, continuous relationship between recanalization grade and functional outcomes, with an extended thrombolysis in cerebral infarction of 3 leading to the best outcome [4]. In our study, we found similar degree of benefit of mTICI 2c/3 compared to mTICI 2b in patients with low ASPECTS. Whether additional passes or adjunct therapy such as intra-arterial thrombolysis should be considered to achieve complete recanalization is yet to be answered.

The role of thrombectomy attempts on procedural complications and outcome has been thoroughly assessed and reported in the literature. Several studies have demonstrated a negative impact on outcomes following multiple thrombectomy attempts with best outcomes occurring in patients requiring only one attempt [5-8,22,27,28]. Even among patients with failed recanalization (mTICI 0), more than two attempts were associated with a worse clinical outcome, demonstrating the harmful effect of multiple thrombectomy attempts [8]. Ultimately, neurointerventionalists are left with the goal of optimizing post-thrombectomy recanalization grade with as minimal amount of attempts as possible, with the knowledge that greater than two attempts has a potentially harmful effect on patient outcomes, but also knowing that successful recanalization is the only chance the patient has to restore neurologic function.

In the setting of patients with LVO and low ASPECT that undergo thrombectomy, the clinical significance of an mTICI grade of 2b versus 2c/3 is not well defined, and the role of balancing thrombectomy attempts to achieve a maximal recanalization grade as demonstrated by previous data in cohorts of patients with high mTICI grades, may not apply to patients with low ASPECT. This study demonstrates that patients with an ASPECT of 2–5 that achieved a recanalization grade of mTICI 2c/3 had a significantly higher rate of achieving a good functional outcome of mRS of 0–3 at 90 days compared to the mTICI 2b cohort. Furthermore, a subgroup analysis demonstrated that this clinical significance was not maintained when comparing the mTICI 2c cohort to mTICI 3.

While these two cohorts were well matched, as shown by the comparable baseline characteristics, there were interesting periprocedural differences that are worth noting. Primarily, the median number of thrombectomy attempts seen on the mTICI 2b cohort of 3 was significantly higher than the mTICI 2c/3 cohort of 2. Additionally, the procedural duration was significantly higher in the mTICI 2b. This increase in attempts observed could be a consequence of a more complex pathology or anatomy present in the mTICI 2b group that was not accounted for in this analysis that is impacting the difference in number of thrombectomy attempts and functional outcome. This undefined variable could also be the driver of the difference seen in procedural duration time. Nonetheless, even after adjusting for age and location of occlusion, the mTICI 2c/3 group still demonstrated better functional outcomes.

Importantly, the rates of both any intracerebral hemorrhage and sICH were similar between the two cohorts. Given the higher rates of post-thrombectomy intracerebral hemorrhage associated with successful recanalization in patients with low ASPECTS compared to patients with high ASPECTS, it was important to determine whether a higher mTICI grade similarly was associated with a higher rate of hemorrhage in patients with low ASPECTS. This study provides evidence that an mTICI of 2c/3 is associated with improved functional outcome at 90 days without any associated difference in post-thrombectomy intracerebral hemorrhage.

There are several limitations in this study that must be noted. Primarily, as this is a retrospective, observational study, causality cannot be concluded, and further randomized control trials must be performed to further assess the role of mTICI score on patient outcomes. Additionally, as this is a multicenter study, there is likely heterogeneity in the periprocedural management of the patients in this study. Moreover, as the ASPECTS and mTICI scores were calculated by the investigators at the sites included in this study, there may be interrater variance. Lastly, this study did not include data regarding diffusion imaging. Future studies will benefit from both interrater reliability protocols and incorporation of perfusion and diffusion imaging data.

Conclusions

This large multicenter study provides evidence that the degree of successful recanalization in patients with low ASPECTS on presentation that undergo thrombectomy for LVO of the anterior circulation correlates with 90-day good functional outcome. A recanalization grade of mTICI 2c/3 resulted in greater likelihood of good outcome compared to mTICI 2b, without a trade-off of higher rates post-procedure hemorrhage. While further studies are necessary to validate these findings, it is recommended that a post-thrombectomy recanalization grade mTICI grade of 2c/3 is recommended in patients with low ASPECTS.

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