Purpose To compare rates of symptomatic intracranial hemorrhage (SICH) and good clinical outcome at 90 days in patients with ischemic strokes from anterior circulation emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy using either Solumbra or A Direct Aspiration first-Pass Thrombectomy (ADAPT) techniques.
Methods We compared clinical characteristics, procedural variables, and clinical outcomes in patients with anterior circulation ELVOs treated with mechanical thrombectomy using either a Solumbra or ADAPT technique at our institution over a 38-month period. SICH was defined using the SITS-MOST criteria. A good clinical outcome was defined as a modified Rankin Scale score of 0–2 at 90 days.
Results One hundred patients were included, 55 in the Solumbra group and 45 in the ADAPT group. Patients in the ADAPT group had higher National Institutes of Health Stroke Scale (NIHSS) (19.2 vs 16.8, p=0.02) and a higher proportion of internal carotid artery terminus thrombi (42.2% vs 20%, p=0.03) than patients in the Solumbra group. Patients in the ADAPT group had a trend toward a lower rate of SICH than patients in the Solumbra group (2.2% vs 12.7%, p=0.07). Patients in the ADAPT group had a significantly higher rate of good clinical outcome at 90 days than patients in the Solumbra group (55.6% vs 30.9%, p=0.015). Use of the ADAPT technique (OR 6 (95% CI 1.0 to 31.2), p=0.049) was an independent predictor of a good clinical outcome at 90 days in our cohort.
Conclusions In our cohort, the ADAPT technique was associated with significantly higher good clinical outcomes at 90 days in patients with acute ischemic stroke due to anterior circulation ELVOs treated with mechanical thrombectomy.
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Recent landmark randomized controlled trials have shown that, for patients with acute ischemic strokes due to anterior circulation emergent large vessel occlusions (ELVO), clinical outcomes are improved when best medical management including intravenous tissue plasminogen activator (IV-tPA) administration, if appropriate, is followed as soon as possible by mechanical thrombectomy.1–5 Hence, this strategy is now considered the standard of care in this patient population.6
However, debate still exists in the neurointerventional community regarding what constitutes the safest and most effective technique for performing mechanical thrombectomy.7 ,8 The two principal mechanical thrombectomy techniques involve the use of stent-retrievers such as the Solitaire FR device (Medtronic Neurovascular, Irvine, California, USA)9–11 or the Trevo device (Stryker Neurovascular, Fremont, California, USA),12 ,13 or direct aspiration at the face of the thrombus using A Direct Aspiration first-Pass Thrombectomy (ADAPT) technique with a large-bore aspiration catheter such as the 5 Max ACE or ACE 64 catheters (Penumbra, Alameda, California, USA).14–16 Furthermore, stent-retrievers can be used in conjunction with either proximal flow arrest in the cervical vasculature with a balloon guide catheter17 or direct aspiration at the face of the thrombus at the time of thrombectomy (Solumbra technique).18–20
The purpose of this study is to compare rates of successful recanalization, symptomatic intracranial hemorrhage (SICH), and clinical outcomes at 90 days in a consecutive cohort of patients with anterior circulation ELVOs who underwent mechanical thrombectomy using either the Solumbra or ADAPT techniques at a comprehensive stroke center.
Our study was approved by our hospital's institutional review board and conducted in compliance with the Health Insurance Portability and Accountability Act. We analyzed our prospectively maintained institutional neurointerventional database to examine the radiological and clinical outcomes in patients with anterior circulation ELVOs who were treated with mechanical thrombectomy using either the Solumbra or ADAPT techniques at our institution between 31 March 2012 and 11 June 2015.
Medical record review
We recorded baseline patient and radiological characteristics, procedural variables, periprocedural complications, and clinical outcomes at 90 days in a consecutive cohort of patients with ELVOs treated with mechanical thrombectomy at our institution during the study period.
The patient cohort was divided into two groups: (1) patients who underwent mechanical thrombectomy using the Solumbra technique (Solumbra group); and (2) patients who underwent mechanical thrombectomy using the ADAPT technique with Solumbra salvage if needed (ADAPT group).
Mechanical thrombectomy exclusion criteria
Institutional exclusion criteria for mechanical thrombectomy were: (1) mild stroke symptoms, defined as an admission National Institutes of Health Stroke Scale (NIHSS) score <6 without aphasia; (2) the presence of a large completed territorial infarction by non-contrast CT (NCCT), defined as an Alberta Stroke Program Early CT Score (ASPECTS) <6; (3) functional dependence prior to stroke onset, defined as a pre-stroke modified Rankin Scale (mRS) score of ≥3; or (4) any intracranial hemorrhage. There was no strict time from last known well (LKW) cut-off for exclusion as long as the NCCT ASPECTS at presentation was ≥6. CT angiography was generally performed in older patients to document an ELVO but was not required in younger patients with a high admission NIHSS score and LKW ≤6 h.
The mechanical thrombectomy procedure was performed in a biplane neuroangiography suite (Axiom Artis, Siemens, Munich, Germany) by one of four attending neurointerventional radiologists with 5–30 years of experience in neurointervention. The procedure was performed under monitored minimal to moderate conscious sedation with intravenous fentanyl administered by a sedation nurse. In patients requiring intubation prior to mechanical thrombectomy for airway protection, the procedure was performed under a propofol infusion which was started in the emergency department and titrated in the neuroangiography suite by a sedation nurse.
The type of mechanical thrombectomy technique employed was based on operator preference.
The Solumbra technique was performed using a long sheath positioned in the distal cervical vasculature (typically NeuronMax 088 sheath, Penumbra) using an exchange technique. A 0.025 inch microcatheter (typically Velocity, Penumbra) with a 0.016 inch microwire inside it (typically double-angled Headliner, Terumo Medical, Somerset, New Jersey, USA) was then introduced into a large-bore aspiration catheter (typically 5 Max ACE, Penumbra) and this construct was introduced into the long sheath as a unit. The 0.025 inch microcatheter was then advanced past the thrombus over the 0.016 inch microwire and the large-bore aspiration catheter was advanced as close to the proximal aspect of the thrombus as possible prior to stent-retriever deployment. The stent-retriever (typically either 4 mm×20 mm or 6 mm×30 mm Solitaire FR device) was then deployed across the thrombus via the 0.025 inch microcatheter and the microcatheter was subsequently removed completely from the patient. After a 3 min waiting period, the large-bore aspiration catheter was connected to continuous aspiration from the Penumbra pump and tension was applied on the stent-retriever delivery wire to pull it into the aspiration catheter while simultaneously advancing the aspiration catheter up to the face of the thrombus and past the origin of the anterior cerebral artery. If the thrombus was lodged between the stent-retriever and the tip of the aspiration catheter, then the system was carefully removed as a unit under continuous aspiration while also manually aspirating through the long sheath positioned in the cervical vasculature.20 This process was repeated until successful reperfusion (Thrombolysis In Cerebral Infarction (TICI) 2b/3) was achieved or the procedure was terminated. Online supplementary video 1 illustrates the Solumbra technique.
The ADAPT technique was performed using a short 8 F sheath through which a long sheath was positioned in the distal cervical vasculature (NeuronMax 088) using either an H1 or Simmons Select catheter (Penumbra). A 0.025 inch microcatheter (Velocity) with a 0.016 inch microwire inside it (double-angled Headliner) was introduced into a large-bore aspiration catheter (5 Max ACE or ACE 64) and this construct was introduced into the long sheath as a unit. The 0.025 inch microcatheter was then advanced past the thrombus over the 0.016 inch microwire and the large-bore aspiration catheter was advanced over it up to the thrombus. The 0.025 inch microcatheter and 0.016 inch microwire were then removed, the aspiration tubing was connected directly to the hub of the large-bore aspiration catheter, and the Penumbra aspiration pump was turned on. The aspiration tubing was then inspected to assess for passage of the thrombus. After a waiting period of 60–90 s, the large-bore aspiration catheter was gently advanced further into the thrombus and then slowly withdrawn under continuous aspiration until free blood flow was restored in the aspiration tubing. The aspiration tubing was then disconnected from the hub of the large-bore aspiration catheter and the catheter was manually aspirated with a syringe to remove any residual thrombus fragments. If free blood flow in the aspiration tubing was not restored upon withdrawing the large-bore aspiration catheter, then the catheter was slowly removed from the patient under continuous aspiration from the Penumbra pump and the NeuronMax 088 was manually aspirated with a syringe to remove any residual thrombus fragments.14 This process was repeated until successful reperfusion (TICI 2b/3) was achieved. However, if three ADAPT passes failed to achieve incremental reperfusion, then Solumbra salvage was employed using the Solumbra technique described above. Online supplementary video 2 illustrates the ADAPT technique.
Two experienced neurointerventionalists, unblinded to the mechanical thrombectomy technique employed, reviewed (1) the pretreatment NCCTs to determine the baseline ASPECTS; (2) treatment angiograms to determine thrombus location and post-thrombectomy TICI score; (3) follow-up NCCTs to determine the presence and type of intracranial hemorrhage; and (4) pretreatment CT angiograms, treatment angiograms, and/or post-treatment MR angiograms to determine the degree of cervical vascular tortuosity in the common and internal carotid arteries (CCA, ICA) proximal to the ELVO using the methodology described by Faggioli et al.21 Successful reperfusion was defined as a modified TICI score of 2b or 3 in the final post-thrombectomy angiogram. Severe vascular tortuosity proximal to the ELVO was defined as ≥360° in the combined common and internal carotid artery tortuosity score. Differences in image interpretation were resolved by consensus.
Determination of SICH
In cases where intracranial hemorrhage was present in the post-treatment NCCT, consensus with a vascular neurologist independent of the procedure was reached to determine if the hemorrhage was symptomatic according to the SITS-MOST criteria.22
An mRS score at 30 and 90 days post-thrombectomy was obtained during routine clinical follow-up visits performed by one of three nurse practitioners independent of the procedure and certified in the mRS. If the patient was unable to return to clinic for a follow-up visit, an mRS score was obtained using a validated telephone interview questionnaire.23 A good clinical outcome was defined as functional independence, mRS 0–2, at the time of the 90-day follow-up.
Statistical analysis was performed using the MedCalc V.11.1 software package (MedCalc Software, Mariakerke, Belgium). The Student t test was used to analyze continuous variables and the Fisher exact test was used to analyze categorical variables. Multiple logistic regression analysis was performed to identify the independent predictors of a good clinical outcome at 90 days in our patient cohort. A p value ≤0.05 was considered statistically significant.
From 31 March 2012 until 11 June 2015, 112 patients with acute ischemic strokes due to an ELVO underwent endovascular treatment with mechanical thrombectomy at our institution. Seven of these patients had a posterior circulation ELVO (6.3%) and five patients were enrolled in an investigational thrombectomy device clinical trial and were excluded from this study (4.5%). Hence, 100 patients with anterior circulation ELVOs comprised the study patient cohort, 55 in the Solumbra group and 45 in the ADAPT group.
Table 1 summarizes the baseline clinical and radiological patient characteristics. There was a significantly higher proportion of women in the Solumbra group than in the ADAPT group (58% vs 38%, p=0.05). Patients in the ADAPT group had a significantly higher admission NIHSS score than patients in the Solumbra group (mean 19.2 vs 16.8, p=0.02). Patients in the ADAPT group had significantly higher baseline NCCT ASPECTS than patients in the Solumbra group (mean 9.1 vs 8.2, p<0.01). Patients in the ADAPT group were significantly more likely to have thrombi in the ICA terminus than those in the Solumbra group (42.2% vs 20%, p=0.03). There was a significantly higher proportion of patients with severe cervical vascular tortuosity in the ADAPT group than in the Solumbra group (33% vs 15%, p=0.03). Of note, time from LKW to puncture was ≤6 h in 87 patients, >6 and ≤8 h in 9 patients, and >8 h in 4 patients.
Table 2 summarizes the procedural variables. There was no difference in the rates of successful reperfusion (TICI 2b/3) between the Solumbra (84%) and ADAPT (89%) groups. Similarly, there was no difference in the time from puncture to reperfusion between the Solumbra (51 min) and ADAPT (50 min) groups. However, there was a significant difference in the number of total thrombectomy device passes between the Solumbra and ADAPT groups (mean 2.2 vs 3.3, p=0.02). There were no significant differences in procedural complications between the two groups. Of note, in the Solumbra group there was one instance of an intra-procedural vascular perforation with contrast extravasation leading to a symptomatic subarachnoid hemorrhage (SAH) and death, and in the ADAPT group there was one instance of catheter rupture and retention leading to a large infarction and death.
In the Solumbra group the first stent-retriever used was a Solitaire FR in 50 patients (90.9%) and a Trevo in five patients (9.1%). Salvage was attempted with a second stent-retriever in five cases (9.1%, 4 with Trevo and 1 with Solitaire FR) and with a large-bore aspiration catheter in two cases (3.6%, both with 5 Max), achieving successful reperfusion (TICI 2b/3) in one case (14.3%). The mean number of stent-retriever passes in the Solumbra group was 2.1 (median 2, range 1–6).
In the ADAPT group the large-bore aspiration catheter used was a 5 Max ACE in 40 cases (88.9%), a 5 Max in 3 cases (6.7%) and an ACE 64 in 2 cases (4.4%). Solumbra salvage was attempted in 13 cases (28.9%, all with Solitaire FR), achieving successful reperfusion (TICI 2b/3) in 9 cases (69.2%). The mean number of ADAPT passes was 2.5 (median 2, range 1–7), while the mean number of stent-retriever passes in cases requiring Solumbra salvage was 2.8 (median 3, range 1–9). Of note, there was a statistically significant decrease in the Solumbra salvage rate between the first 20 ADAPT cases (45%) and the subsequent 25 ADAPT cases (16%, p=0.049).
Table 3 summarizes the clinical outcomes in our cohort. Patients in the Solumbra group had a significantly higher rate of any post-thrombectomy SAH compared with patients in the ADAPT group (23.6% vs 6.7%, p=0.03). Patients in the ADAPT group had a significantly shorter length of stay in the neurological intensive care unit (Neuro-ICU) than patients in the Solumbra group (2.4 days vs 3.7 days, p=0.04). Overall, 42 patients achieved a good clinical outcome at 90 days in our cohort, while 90-day mortality was 24%. Patients in the ADAPT group were more likely to achieve a good clinical outcome at 90 days than patients in the Solumbra group (55.6% vs 30.9%, p=0.015).
There were eight post-thrombectomy SICHs in our cohort, five subarachnoid and three intraparenchymal in location. There was a trend towards a higher rate of SICH in the Solumbra group than in the ADAPT group (12.7% vs 2.2%, p=0.07) and there was also a trend towards a higher rate of symptomatic SAH in the Solumbra group than in the ADAPT group (9.1% vs 0, p=0.06). Three of the symptomatic SAHs were associated with concurrent use of a stent-retriever and intra-procedural administration of either intra-arterial tissue plasminogen activator (IA-tPA) or a glycoprotein IIb/IIIa inhibitor, and the other two were associated with use of a stent-retriever in a distal vascular location (M3). Two of the three symptomatic intraparenchymal cerebral hemorrhages occurred in patients with LKW to reperfusion times of >300 min. All SICHs in our cohort led to the patient's death.
Independent predictors of a good clinical outcome at 90 days
Table 4 summarizes the independent predictors of a good clinical outcome in our cohort. In multivariate logistic regression analysis, patient age (p=0.002, OR 0.87, 95% CI 0.8 to 0.95), thrombus location (p=0.003, OR 5.6, 95% CI 1.8 to 17.3), NIHSS (p=0.034, OR 0.8, 95% CI 0.65 to 0.98), successful reperfusion (p=0.034, OR 36.3, 95% CI 1.3 to 1011.4), NCCT ASPECTS (p=0.041, OR 1.96, 95% CI 1 to 3.7), and use of the ADAPT technique (p=0.049, OR 6, 95% CI 1 to 36.2) were independent predictors of a good clinical outcome at 90 days (mRS 0–2) in our cohort. In addition to the aforementioned variables, the multivariate logistic regression model controlled for patient sex, atrial fibrillation, diabetes mellitus, hypertension, IV-tPA administration, tandem cervical ICA occlusion, cervical vascular tortuosity, presence of intra-procedural complications, performing neurointerventionalist, presence of post-thrombectomy SICH, presence of post-thrombectomy SAH, and LKW to reperfusion time.
Receiver operating characteristic analysis for the prediction of a good clinical outcome at 90 days showed an optimal age cut-off of ≤66 years (sensitivity 71.4%, specificity 75.9%, area under the curve (AUC) 0.77, 95% CI 0.67 to 0.85, p<0.0001), an optimal NIHSS cut-off of ≤21 (sensitivity 83.3%, specificity 36.2%, AUC 0.61, 95% CI 0.5 to 0.7, p=0.066), and an optimal NCCT ASPECT cut-off of 10 (sensitivity 40.5%, specificity 75.9%, AUC 0.56, 95% CI 0.46 to 0.66, p=0.3).
The overall rates of (1) successful reperfusion (TICI 2b/3) (86%), (2) SICH (8%), and (3) good clinical outcome at 90 days (42%) of our cohort are within the range of previously published mechanical thrombectomy studies7–18 as well as the more recent landmark randomized controlled trials.1–5
Overall, we achieved similar rates of successful reperfusion with both the Solumbra (84%) and ADAPT (89%) mechanical thrombectomy techniques. However, Solumbra salvage had to be employed in 29% of ADAPT cases, ultimately leading to successful reperfusion (TICI 2b/3) in 20% of ADAPT cases. Hence, if the ADAPT technique is to be adopted as the first-line thrombectomy technique, the treating neurointerventionalist should be prepared to employ potential salvage with a stent-retriever if several ADAPT passes fail to achieve incremental reperfusion or if the degree of proximal vascular tortuosity precludes navigation of the large-bore aspiration catheter to the thrombus. Nevertheless, we evidenced a significant decrease in our rate of Solumbra salvage between the first 20 ADAPT cases (45%) and the subsequent 25 ADAPT cases (16%), which is indicative of the presence of a learning curve for successful use of the ADAPT technique. Importantly, the operator should be cognizant that 2–3 ADAPT passes may be necessary in order to achieve successful reperfusion; hence, Solumbra salvage should not be employed immediately after the first ADAPT pass.
We found differences in the rates of SICH between the two patient groups in our cohort (12.7% vs 2.2%). The higher rate of SICH in the Solumbra group was primarily due to symptomatic SAHs associated with distal stent-retriever device use and concomitant intra-procedural use of a stent-retriever and potent antiplatelet/antithrombotic medications such as eptifibatide (Integrilin; Merck, Kenilworth, New Jersey, USA) or IA-tPA. These findings reflect the fact that stent-retriever deployment and retrieval during mechanical thrombectomy incites a certain degree of endothelial denudation and damage as the metal from the device comes into contact with the vessel's intima,24 which is potentiated when these devices are deployed in small distal vessels or when potent drugs that impede thrombosis are used in the periprocedural period. The treating neurointerventionalist should therefore exercise caution prior to deploying stent-retrievers in the distal cerebral vasculature or administering potent antiplatelet/antithrombotic medications intra-procedurally. Furthermore, some SAHs, albeit asymptomatic, were present in the ADAPT group. This finding serves as a reminder that manipulation of the intracranial vasculature during mechanical thrombectomy with any device incites some degree of intimal damage,24 particularly in older vessels, and these emergent procedures should only be undertaken in appropriately selected patients.
We found a statistically signicant difference in the rate of good clinical outcome at 90 days between the two patient groups in our cohort (30.9% Solumbra vs 55.6% ADAPT). Importantly, clinical outcomes were more favorable in the ADAPT group despite a higher proportion of patients with ICA terminus thrombi, higher presenting NIHSS, and more patients with severe cervical vascular tortuosity. In addition, patients in the ADAPT group had significantly shorter Neuro-ICU stays than patients in the Solumbra group. Furthermore, we found that use of the ADAPT technique was a statistically significant independent predictor of a good clinical outcome at 90 days independent of patient age, thrombus location, NIHSS, baseline NCCT ASPECTS, performing neurointerventionalist, intra-procedural complications, time from LKW to reperfusion, post-thrombectomy SAH and SICH. While patients in the ADAPT group had higher presenting NCCT ASPECTS which may be associated with a higher likelihood of a good clinical outcome, in multivariate logistic regression analysis use of the ADAPT technique was independently associated with improved clinical outcomes in our cohort. Given that the ADAPT technique may be simpler and more cost-effective than stent-retrievers,8 the finding that it may independently lead to improved clinical outcomes is encouraging. However, this finding will be investigated further in randomized controlled trials comparing the ADAPT and stent-retriever mechanical thrombectomy techniques, some of which are already underway.
Finally, it is important to highlight the additional independent predictors of a good clinical outcome in our cohort—namely, patient age ≤66 years, M1/M2 thrombus location, NIHSS ≤21, NCCT ASPECTS 10, and TICI 2b/3 reperfusion. Given that the degree of reperfusion may be controlled by the treating neurointerventionalist, it is important to strive to achieve successful reperfusion (preferably TICI 3) in order to maximize the likelihood of a good clinical outcome at 90 days, and this may be particularly important in younger patients who present with high NCCT ASPECTS and M1/M2 occlusions.
The limitations of our study are the modest sample size, retrospective design, lack of external adjudication of angiographic findings and clinical outcomes, and heterogeneous patient populations in the two groups (including a higher proportion of ICA terminus thrombi and higher NIHSS in the ADAPT group). Further, given that the type of mechanical thrombectomy technique used was dependent on the operator's preference, this could have introduced an inherent selection bias in the study. However, our patient cohort may reflect the application of these relatively new endovascular techniques for acute ischemic stroke treatment in a ‘real-world’ setting.
In our cohort, use of the ADAPT technique was associated with improved clinical outcomes at 90 days in patients with acute ischemic stroke due to anterior circulation ELVOs treated with mechanical thrombectomy. Future randomized controlled trials comparing the ADAPT and stent-retriever mechanical thrombectomy techniques are needed to determine the safest, most cost-effective, and efficacious mechanical thrombectomy technique.
The authors acknowledge Sandee K Verootis and Kira Tran, Department of Neurointerventional Radiology, Abbott Northwestern Hospital, for their contribution to the data collection for this manuscript.
Twitter Follow Yasha Kayan at @yashakayan
Contributors JEDA: Study design, data collection and analysis, statistical analysis, manuscript preparation, manuscript editing and guarantor of the whole study. YK: Study design, data collection and analysis, media editing, manuscript editing. MLY: Study design, data analysis, manuscript editing. JLF: Data collection and analysis, statistical analysis, media editing, manuscript editing. JMS and AMM: Data collection, manuscript editing. THH: Data collection and analysis. PR: Data collection and analysis, manuscript editing. MM and RMT: Data analysis, manuscript editing.
Competing interests JEDA and YK have consulting agreements with Medtronic Neurovascular and Penumbra.
Ethics approval Ethics approval was obtained from the Abbott Northwestern Hospital IRB.
Provenance and peer review Not commissioned; externally peer reviewed.