Introduction ADAPT (a direct aspiration first pass technique) has been shown to be fast, cost-effective, and associated with excellent angiographic and clinical outcomes in the treatment of acute ischemic stroke (AIS).
Objective To identify any and all preoperative factors that are associated with successful revascularization using aspiration alone.
Methods A retrospective review of 76 patients with AIS treated with thrombectomy was carried out. Cohort 1 included cases in which aspiration alone was successful (Thrombolysis in Cerebral Infarction 2b or 3). Cohort 2 included cases in which aspiration was unsuccessful or could not be performed despite an attempt.
Results There was no difference between cohorts in gender, race, medications, National Institute of Health Stroke Scale score, IV tissue plasminogen activator, site or side of the occlusion, dense vessel sign, aortic arch type, severe stenosis, clot length, operator years of experience, and guide/aspiration catheters used. Patients in cohort 1 were on average younger (66.5 vs 74.1 years, p=0.025). There was a trend for more patients in cohort 2 to have atrial fibrillation/arrhythmias (62.5% vs 45.5%, p=0.168) and have a cardiogenic stroke etiology (78.1% vs 56.8%, p=0.086). There was also a trend for more reverse curves (2.3 vs 1.7, p=0.107), larger vessel diameter (3.26 mm vs 2.88 mm, p=0.184), larger vessel-to-catheter ratio (2.09 vs 1.87, p=0.192), and worse clot burden score (5.38 vs 6.68, p=0.104) in cohort 2.
Conclusions Aspiration success was associated with younger age. Our findings suggest that ADAPT can be used for the vast majority of patients but it may be beneficial to use a different method first in the elderly.
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The direct aspiration first pass (ADAPT) technique was recently introduced for the treatment of acute ischemic stroke (AIS).1 ,2 In this technique, direct aspiration is attempted first with a large-bore catheter and then devices used for subsequent thrombectomy attempts (if necessary) can be chosen at the discretion of the operator (eg, stent retrievers (SRs)). Aspiration alone has been shown to achieve successful revascularization in 78% of cases.2 Reported benefits of this technique include ease of use, time to recanalization, a reduction in distal embolic phenomenon, improved clinical outcomes, and cost-effectiveness.2–6
On the other hand, a number of recent randomized controlled trials have demonstrated excellent outcomes using SRs primarily,7–10 which has affected the specific recommendations in the 2015 American Heart Association guidelines.11 Given this clinical dilemma, it would be useful to know, before starting thrombectomy, which patients would be most likely to achieve a successful revascularization with aspiration alone. The purpose of our study is to identify any and all preoperative factors that are associated with successful revascularization using aspiration alone.
Institutional review board approval was given to perform this study. This is a retrospective review of 76 patients with AIS who were treated with thrombectomy in the Mount Sinai Health System between January 2014 and February 2016. Inclusion criteria included all patients treated with thrombectomy using the ADAPT technique (n=67) or with clear evidence of an initial intent to use this technique (n=9). Exclusion criteria included patients treated by other methods such as IA thrombolysis, angioplasty, or the primary use of a SR, usually with distal aspiration (also known as Solumbra).12
Clinical information was obtained by review of each patient's electronic medical record by a member of our research team in a non-blinded fashion. The primary source of information was the neurology admission and discharge notes. Information collected included age, gender, race, mode of arrival, past medical history (PMH), medication use, smoking status, likely stroke etiology, time last known well, hospital arrival time, initial National Institute of Health Stroke Scale (NIHSS) score, and IV tissue plasminogen activator status. Likely stroke etiology was either explicitly mentioned in the notes or was derived as the most likely etiology (eg, if a patient had atrial fibrillation and/or valvular disease but the neurology note did not explicitly say cardiogenic source). If no stroke source was mentioned and there was no obvious PMH or intraoperative finding to suggest a source, then the likely stroke etiology was recorded as cryptogenic.
The pre-intervention CT head (CTH) and CT angiograms (CTAs) were reviewed by one of the interventional radiologists on our team who was blinded to the study design. The CTHs were evaluated for a dense vessel sign. The CTAs were graded for arch difficulty (grade I, II, or III13), tortuosity on the path to the target vessel (defined by the number of reverse curves14), and presence of severe stenosis on the path to the target vessel (defined as >70%). If a CTA was not obtained or was inadequate for analysis, the angiogram was checked for the same factors. If an arch or common carotid artery run was not performed, then the factor was marked as ‘unknown’. The CTAs were also graded for target vessel diameter, thrombus length, and clot burden score.15
Procedural information was obtained by review of the brief operative note and official operative report by a member of our research team in a non-blinded fashion. Information collected included side and site of large vessel occlusion, puncture time, first-pass time, technique used, number of passes, degree of revascularization graded by the Thrombolysis in Cerebral Infarction (TICI) scale,16 and operator years of experience. In our overall practice, the method of thrombectomy is at the discretion of the operator. All of the interventions were performed by four neurosurgeons, one neurologist, and one radiologist with varying degrees of experience. Guide catheters used included the Neuron MAX (Penumbra, Alameda, California, USA), the 6 Fr Shuttle (Cook Medical, Bloomington, Indiana, USA), and the FlowGate balloon guide catheter (Stryker, Fremont, California, USA). Aspiration catheters included the 5 MAX ACE (Penumbra), ACE 64 (Penumbra), and Catalyst reperfusion catheter (Stryker). SRs included Trevo (Stryker) and Solitaire (Medtronic, Elizabeth, New Jersey, USA). Distal aspiration was performed by placing the aspiration catheter at the face of the thrombus, attaching it to the Penumbra aspiration pump (Penumbra), and applying 5 min of aspiration.
The study population was split into two cohorts: cohort 1 included cases in which successful revascularization was achieved with aspiration alone (n=44). To be included in cohort 1, the patient must have been treated with aspiration only and achieved a TICI 2b or 3 result. All other patients were included in cohort 2 (n=32), of which the majority were ADAPT cases in which a SR was used after aspiration failure (n=23). We also included patients in cohort 2 if there was intent to use ADAPT (n=9). To be included in the ‘intent to ADAPT’ group, there had to be a clear description in the operative report that there was difficulty navigating the aspiration catheter to the thrombus, in addition to evidence that only at that point was a SR obtained for use (eg, exchanging the XT-27 microcatheter (Stryker) for the Trevo microcatheter (Stryker)). Cases in which there was difficulty navigating the aspiration catheter but the SR microcatheter was already in use were excluded to account for the possibility that the operator intended to use the Solumbra technique primarily not the ADAPT technique. A failed ‘attempt to ADAPT’ counted as one pass.
Cohort 1 was compared with both cohort 2 as a whole and with cohort 2 without the ‘intent to ADAPT’ cases. Differences in variable distribution between cohorts were assessed using the Mann–Whitney or χ2 tests for continuous or categorical variables, respectively. All reported p values are two sided with a standard α set at 0.05. All ranges were reported as IQR, and plus–minus values are reported as mean±SD. All data management and analyses were conducted using SPSS V.20.0 (IBM, Inc, Armonk, New York, USA).
The entire study population included 76 patients, with 44 patients in cohort 1 and 32 in cohort 2. There was no difference in gender, race, mode of arrival, percentage of patients with a wake-up cerebral vascular accident, admission NIHSS score, and percentage of patients receiving IV tissue plasminogen activator between cohorts (table 1). Patients in cohort 1 were on average younger (66.5 vs 74.1 years, p=0.025). There was no difference in PMH, medication use, and overall likely stroke etiology between cohorts (table 2). There was a trend for more patients in cohort 2 to have atrial fibrillation/arrhythmias (62.5% vs 45.5%, p=0.168). Additionally, if evaluating cardiogenic etiology specifically, there was a trend for more patients in cohort 2 to have a cardiogenic etiology (78.1% vs 56.8%, p=0.086).
There was no difference in the side or location of the stroke between groups (table 3).
The M1 segment of the middle cerebral artery was the most common location in both cohorts. There was also no difference between groups in dense vessel sign, aortic arch type, presence of severe stenosis on the path to the target vessel, and clot length. There was a trend for more reverse curves on the path to the target vessel on average in cohort 2 (2.3 vs 1.7, p=0.107). A trend for larger vessel diameter (3.26 mm vs 2.88 mm, p=0.184) and a larger vessel to catheter ratio (2.09 vs 1.87, p=0.192) in cohort 2 was also seen. Additionally, there was a trend for worse clot burden score in cohort 2 (5.38 vs 6.68, p=0.104).
All the patients in cohort 1, by definition, underwent successful thrombectomy by aspiration (table 4). In cohort 2, 68.8% of patients underwent thrombectomy with a SR following attempted aspiration, and 28.1% of patients underwent thrombectomy with a SR following unsuccessful attempts to navigate the aspiration catheter to the thrombus (ie, ‘intent to ADAPT’). One patient treated by aspiration alone with a TICI 2a was included in cohort 2. There was no difference in operator experience and no difference in symptom to puncture or arrival to punctures times. The puncture to first-pass time was shorter in cohort 1 (27.4 vs 40.0 min, p=0.005). There were fewer passes, on average, in cohort 1 (1.34 vs 3.25, p<0.001).
There was no difference between cohorts in the materials used. The Neuron MAX (Penumbra) was the most common guide catheter, the 5 MAX ACE (Penumbra) was the most common aspiration catheter, and the Trevo SR (Stryker) was the most common SR in cohort 2. Overall, the aspiration component of the ADAPT technique alone was successful in achieving TICI 2b or 3 revascularization in 65.7% of ADAPT cases and the additional use of SRs improved the TICI 2b/3 revascularization rate to 94% (excluding the ‘intent to ADAPT’ cases). All patients in cohort 1, by definition, had a TICI 2b or 3 revascularization. In cohort 2, 81.3% of patients had a TICI 2b or 3 revascularization.
After removing the nine ‘intent to ADAPT’ patients from cohort 2 and repeating the analysis (table 5), there was still a trend for younger patients in cohort 1 (66.5 vs 72.7 years, p=0.095). There were new trends for more patients in cohort 2 with cardiac valvular disease (30.4% vs 13.6%, p=0.115) and taking anticoagulation (47.8% vs 29.5%, p=0.182) as well as more patients in cohort 1 with cancer (13.6% vs 0.0%, p=0.087). The puncture to first-pass time remained shorter in cohort 1 (27.4 vs 42.0 min, p=0.007). The number of passes remained fewer in cohort 1 (1.34 vs 3.39, p<0.001).
Our study demonstrates that younger age was associated with successful aspiration. Additionally, there were trends for aspiration failure to be associated with cardiogenic etiology, more difficult vascular anatomy (as defined by more reverse curves), larger vessel size and vessel to catheter ratio, and worse clot burden score. These findings are important because they show that ADAPT is a suitable thrombectomy method for many patients with AIS. Our findings may also be useful when deciding between ADAPT and other thrombectomy methods. The ADAPT technique is advantageous because thrombectomy is performed quickly and certainly at a lower cost. If aspiration does not provide revascularization, however, and a SR is needed, then there is potentially a delay in brain reperfusion that might have been avoided by using a SR primarily. Perhaps older patients with significant heart disease and difficult vascular anatomy would benefit from an initial approach with a different technique.
A number of studies have validated the ADAPT technique. In the ADAPT FAST study,2 the authors achieved a TICI 2b/3 rate of 78% using aspiration alone and 95% including patients who needed SRs. The average puncture time to TICI 2b recanalization was 37 min. Forty per cent of patients had a modified Rankin Scale score of 0–2 at 90 days. Moreover, the same authors compared this cohort of ADAPT patients with those who received other methods of thrombectomy using either the traditional Penumbra system or SR with local aspiration and found better reperfusion rates, lower cost, faster puncture to reperfusion times, and similar clinical outcomes.3 The technique has been validated in Europe as being fast, effective, and safe.17 Additionally, it has even been shown in another population of patients that ADAPT was associated with improved clinical outcomes in comparison with Solumbra (SR with distal aspiration).4 Despite the overwhelming success of SRs in recent clinical trials7–10 and American Heart Association recommendations,11 the ADAPT technique is, at the very least, a viable alternative to the primary use of SRs.
Difficult vascular anatomy
Difficult vascular anatomy has a significant impact on the technical success of endovascular procedures, and thus may directly affect the clinical outcomes of stroke intervention. There has been limited discussion of difficult anatomy in association with stroke intervention specifically. In one study assessing the technical challenges of intracranial stenting, the authors observed that tortuous vascular anatomy, defined as two or more reverse curves in the vascular access path, led to a 100% initial procedural failure rate.14 Several other features have been identified in carotid artery stenting, including distance between target artery and origin of the descending aorta, tortuosity of the common or internal carotid arteries, aortic arch calcification, and carotid or innominate artery stenosis.13 ,18 ,19
Our findings both directly (number of reverse curves) and indirectly (age, puncture to first-pass time) suggest that more difficult vascular anatomy is associated with aspiration failure. The most likely explanation for this finding is that it is difficult to navigate the large-bore catheter to the thrombus. It is interesting, however, that a number of these factors remained similar even after removing the ‘intent to ADAPT’ group. Possibly, there is another explanation, such as thrombus composition, that accounts for these findings. For stroke intervention, time is of the essence; shorter times to reperfusion have been shown to significantly improve neurologic outcomes.20 In contrast, difficult catheter access, as defined by a time of >30 min from groin puncture to carotid catheterization, has been shown to have lower recanalization rates and, consequently, poorer clinical outcomes.21 Given the findings in our study, it may be reasonable to use a SR primarily for older patients with more difficult vascular anatomy.
Cardiogenic stroke etiology
These data suggest that the efficacy of ADAPT correlates to non-cardiogenic thrombus source. Previous reports have linked overall mechanical thrombectomy success with clot composition and have suggested that preoperative information about clot composition could guide interventional treatment strategies.22 ,23 Boeckh-Behrens et al24 compared histological clot composition with angiographic outcome, clinical outcome, and stroke etiology. Consistent with the findings in our study, they found that clots with a higher percentage of white blood cells were associated with a cardioembolic source, longer recanalization times, lower TICI score, and worse clinical outcome.
The study of clot histology and etiology in stroke is fairly new given the recent and rapid development of mechanical thrombectomy devices. A trend in the literature, however, is that emboli originating in the heart are generally more complex with a higher fibrin content, whereas emboli found to originate from large artery atherosclerosis have a higher percentage of red blood cells and a lower percentage of fibrin.25 In an animal model of mechanical thrombectomy in acute stroke using the Merci device, researchers found that clots high in fibrin were more difficult to remove.22 The authors hypothesize that fibrin clots are more difficult to remove for three reasons: they are firmer and therefore more difficult to manipulate, they are more cohesive and therefore more difficult to extract piecemeal, and they are less compliant and therefore more difficult to pull into the guide catheter. To summarize, clots of cardioembolic origin appear to be higher in fibrin, higher in white blood cell content, lower in red blood cell content, and more difficult to extract by all means of mechanical thrombectomy, including the ADAPT technique.
To our knowledge, the technical success of ADAPT has not been linked to vessel diameter or vessel to catheter ratio. One possible explanation, is that larger diameter clots will lodge into large vessels and have a poorer response to aspiration. The clot burden score has been linked to functional outcome, final infarct size, and parenchymal hematoma risk.15 Although a worse score may portend a worse response to ADAPT aspiration, it is also possible that a worse score simply identifies clots that must be removed with multiple passes and operators will naturally move from aspiration to SRs as the procedure goes on.
Intent to ADAPT
The ‘intent to ADAPT’ cases were included in cohort 2 because, although aspiration was not ultimately attempted, they still represent a group of patients in whom aspiration ‘fails’, usually owing to difficult vascular anatomy. By performing the analysis a second time with these cases removed, we attempted to focus more on the thrombus characteristics that would hinder aspiration, rather than the vascular anatomy. Interestingly, there were still trends for older patients to have a cardiogenic etiology and more reverse curves in cohort 2, suggesting that these factors may also influence the thrombus composition and are not just surrogate markers of difficult vascular anatomy.
Our study has some limitations. The retrospective nature has inherent bias and the small numbers limit the significance of our findings. Because thrombectomy type was at the discretion of the operator, it is possible there is a selection bias in this cohort of patients and the results/conclusions are not representative of all patients with AIS who may be eligible for ADAPT. The nine patients who were included in the ‘intent to ADAPT’ group were identified based on the operative report and the operator might not have had an intent to use an ADAPT technique but an intent to use Solumbra instead. We attempted to minimize this limitation by including only cases in which the report clearly showed that there was difficulty navigating the aspiration catheter to the thrombus and only at that point was the SR obtained for use. Finally, we did not use the Sofia Plus aspiration catheter (Microvention; 0.070 in), which may improve aspiration success given its larger size.
Within the ADAPT technique for AIS, aspiration success is associated with younger age and there is a trend for aspiration failure to be associated with cardiogenic etiology, more difficult vascular anatomy, larger vessel size, and worse clot burden score. Our findings suggest that the ADAPT technique can be used for the vast majority of patients but it may be beneficial to use another technique when performing thrombectomy in the elderly. Further research validating these findings and analyzing thrombus characteristics is needed.
Twitter Follow Christopher Kellner at @chriskellner
Contributors JRM, CPK, and CSO collected the clinical and procedural data. RADL performed the blinded radiographic review. EKO performed the statistical analysis. JRM, CPK, and KY prepared the manuscript. All authors reviewed the manuscript. JRM, JTF, SP, and RADL performed the interventions. JRM and JTF supervised the study.
Competing interests SP is a consultant to Microvention. JTF is a consultant to Microvention and Penumbra and is an investor in Lazarus Effect. JRM has the following conflicts of interest: National/International PI/Co-PI for the following trials: THERAPY (PI), FEAT (PI), INVEST (Co-PI), COMPASS (Co-PI), LARGE (Co-PI), COAST (Co-PI), POSITIVE (Co-PI). He is on the steering committee for the MAPS trial. Consultant: Rebound Therapeutics, TSP Inc, Cerebrotech, Lazarus Effect, Pulsar, Medina; Investor: Blockade Medical, TSP Inc., Lazarus Effect, Medina.
Ethics approval Institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.
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