Direct aspiration for thrombectomy in ischemic stroke: Impact of dwell time

Abstract

Objective

To evaluate the impact of dwell time on the efficacy of the direct aspiration thrombectomy in ischemic stroke.

Methods

The study is a review of our prospective cerebral thrombectomy database of subjects admitted from January to December 2017. We performed direct aspiration with 2 min dwell time as recommended by the manufacturer (group 1) and 5 min dwell time (group 2) between January–June and July–December, respectively. The primary outcome was successful reperfusion after the first pass defined as modified Thrombolysis in Cerebral Infarction scores 2 b/3.

Results

Eighty-five patients had a cerebral thrombectomy by direct aspiration, 45 in group 1 and 40 in group 2. There was no statistically significant difference between the two groups but a trend toward a better modified Thrombolysis in Cerebral Infarction first pass 2 b/3 rate in group 2 (70% versus 48.8%, p = 0.06). Although not statistically significant (p = 0.07), the ratio of rescue therapy with stent retriever was higher in group 1 (40%) than in group 2 (22.5%). After all passes, modified Thrombolysis in Cerebral Infarction 2 b-3 was obtained in 82.2% (37/45) of cases in group 1 and in 90% (36/40) of cases in group 2. Among 76 patients (89.5%) with modified Rankin Scale assessment at three months, no significant difference (p = 0.3) was found in the proportion of functionally independent individuals between groups 1 and 2 (51.8% versus 55.6%, respectively).

Conclusion

Although statistical significance was not reached, our retrospective analysis exhibited a strong trend toward modified Thrombolysis in Cerebral Infarction first pass improvement when dwell time was increased from 2 to 5 min.

Introduction

In combination with intravenous tissue type plasminogen activator, mechanical thrombectomy has become the standard of care in ischemic stroke consecutive to large vessel occlusion.^1–5

The main technique evaluated in the controlled studies was the stent retriever but, more recently, a direct aspiration first pass technique (ADAPT) was reported to be as effective as the stent retriever method.^6,7 The ADAPT technique consists in direct aspiration of the thrombus with large bore aspiration catheter and, in case of failure of aspiration alone, the adjunction of stent retriever. Recent studies reported a good reperfusion rate after ADAPT ranging from 53 to 78% after aspiration alone and 75 to 94% after adjunctive technique.^6,8–12

However, several technical questions about ADAPT persist, for instance the location of the tip catheter (close but not touching, touching, attempted corking), the dwell time duration, the retrieval rate (slow versus fast), etc. We aimed at assessing the impact of dwell time on our ADAPT technique efficacy.

Material and methods

We performed a review of our prospective cerebral thrombectomy database of subjects admitted from January to December 2017. Eligible patients were admitted for mechanical thrombectomy performed with ADAPT technic as frontline therapy. We performed direct aspiration with 2 min dwell time as recommended by the manufacturer (group 1) and 5 min dwell time (group 2) between January–June and July–December, respectively. This retrospective, single-institution study was approved by the institutional review board. Informed consent was waived.

Patient’s selection

Inclusion criteria were anterior circulation acute cerebral occlusion, age ≥18 years, with National Institutes of Health Stroke Scale (NIHSS) score ≥4. When not contraindicated, in stroke <4.5 h from symptom onset, all patients received intravenous thrombolysis before intervention. Exclusion criteria included the presence of intracranial hemorrhage or the Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 on diffusion-weighted imaging-ASPECTS. Patients referred for acute ischemic stroke consecutive to vertebro-basilar occlusion, tandem occlusion, or treated with stent retriever alone or combined with aspiration as frontline therapy were excluded.

Endovascular procedure

All procedures were performed under conscious sedation. After femoral puncture made by a 8 F introducer sheath, a Neuron Max 088 catheter (Penumbra, Alameda, California, USA) was placed in the common carotid artery to confirm the location of arterial occlusion. Through this long sheath, an ACE 060 or 068 catheter (Penumbra, Alameda, California, USA) was advanced over a 3.8 F reperfusion catheter 3MAX (Penumbra, Alameda, California, USA) and positioned in order to touch the proximal part of the clot. Then, the microwire was removed and the ACE catheter was connected to the Penumbra aspiration pump for 2 min (group 1) or 5 min (group 2). Afterward, the reperfusion catheter was slowly removed under aspiration. The ACE 068 and ACE 060 catheters were used for terminal carotid artery occlusion and M1 or M1/M2 occlusion, respectively. Two direct aspiration attempts were performed before the second-line option using a stent retriever was considered.

Outcome

The primary outcome was a successful reperfusion after the first pass defined as modified Thrombolysis in Cerebral Infarction (mTICI) scores 2 b/3 evaluated by an interventional neuroradiologist (>20 years of experience) who did not perform these thrombectomy procedures. Secondary outcomes were the proportion of rescue therapy with stent and 90-day functional outcome assessed with the modified Rankin Scale (mRS) score during routine follow-up by a neurologist. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage.

Statistical analysis

Variables are expressed as absolute value, percentage, or mean/median value. Statistical analysis was performed using the R computing environment.

Comparisons between groups for continuous/ordinal variables were made using the Student’s t test or Mann–Whitney U test. Categorical variables were compared using χ² or Fisher’s exact test. A p-value <0.05 was considered statistically significant.

Results

Between January and December 2017, 121 patients with acute ischemic stroke due to an ELVO underwent a mechanical thrombectomy at our institution. Among these patients, 85 were treated using ADAPT technique as frontline therapy: 45 with 2 min dwell time (group 1) and 40 with 5 min dwell time (group 2). The baseline clinical and radiological patient characteristics are summarized in Table 1.

Table 1.

Baseline characteristics.

	Group 1	Group 2
No. of patients	45	40
Age (mean)	67.8 ± 15.4	69.5 ± 14.4
Female	23 (51%)	21 (52.5%)
Hypertension	25 (55.5%)	22 (55%)
Diabetes mellitus	17 (37.7%)	5 (12.5%)
Dyslipidemia	18 (40%)	9 (22.5%)
Current smoking	19 (42.2%)	11 (27.5%)
Antithrombotic medications	13 (28.8%)	8 (20%)
Previous use of IV thrombolysis	29 (64.4%)	25 (62.5%)
Admission NIHSS (median)	17.3 ± 7	16.6 ± 6.8
Site of occlusion
T carotid artery	9 (22.5%)	8 (20%)
MCA M1, M1/M2	34 (75.5%)	32 (80%)

IV: intravenous; MCA: middle cerebral artery; NIHSS: National Institutes of Health Stroke Scale.

The two groups were similar regarding the population characteristics. Mean age of groups 1 and 2 was 67.8 year old (range 36–88 y.o.) and 69.5 year old (range 43–90 y.o), respectively. There were 51% (23/45) and 52.5% (21/40) of female subjects in groups 1 and 2, respectively. Patients presented with a median NIHSS score of 17.3 (range 4–34) in group 1 and 16.6 (range 4–27) in group 2.

In the first group, the target vessel occlusion was terminus carotid artery treated with ACE 068 in 22.5% of cases (9/45) and M1 or M1/M2 treated with ACE 060 in 80% of cases (36/45). In the second group, target vessel occlusion was carotid artery terminus treated with ACE 068 in 20% (8/40) of cases and M1 or M1/M2 treated with ACE 060 in 80% (32/40) of cases. IV rt-PA was administered in 64.4% (29/45) and 62.5% (25/40) of cases in groups 1 and 2, respectively.

Efficacy of ADAPT technique in each group and procedure variables are summarized in Table 2. We did not observe any significant difference between groups, but a trend toward a better TICI 2b/3 first pass in group 2 was observed (70% versus 48.8%, p = 0.06). Though statistical significance was not reached, the ratio of rescue therapy with stent retriever was higher in group 1 (40 versus 22.5%, p = 0.07).

Table 2.

Procedure characteristics.

	Group 1	Group 2	p
Number of patients	45	40
Time delay from symptom onset to groin puncture (min) (median (range))	282.4 (188–360)	377.4 (154–1868)	0.08
Time from puncture to recanalization (min) (median (range))	52.8 (10–200)	45.5 (12–99)	0.32
mTICI 2 b-3 (n (%))	37 (82.2%)	36 (90%)	0.3
mTICI 2 b-3 first pass (n (%))	22 (48.8%)	28 (70%)	0.06
mTICI 3 first pass (n (%))	15 (33%)	14 (35%)	0.3
Use of rescue therapy (n (%))	18 (40%)	9 (22.5%)	0.07

mTICI: modified Thrombolysis in Cerebral Infarction.

In each group, the stent retriever was used to perform an anchor technique in four patients. The stent retriever was used due to aspiration failure in 14 cases in groups 1 and 3 cases in group 2 and for distal complementary thrombectomy in 2 cases in group 2. Mean time delay from groin puncture to reperfusion time was shorter in group 2 (45.5 versus 52.8 min, p = 0.2). After the first ADAPT pass, mTICI 3 was achieved in 15 out of 45 patients (33%) and in 14 out of 40 patients (35%) in groups 1 and 2, respectively.

After all passes, mTICI 2b/3 was achieved in 82.2% (37/45) of cases in group 1 and in 90% (36/40) of cases in group 2. We did not observe any significant difference regarding the total number of revascularization attempts, with a median value of 2 in group 1 (range 1–5) and 2 (range 1–6) in group 2 (p = 0.6). For terminus carotid artery occlusion for which ACE 068 was used, a favorable mTICI first pass was obtained in 12.5% of cases (1/9) and 37.5% of cases (3/8) in groups 1 and 2, respectively. For M1 or M1/M2 occlusion for which ACE 060 was used, a favorable mTICI first pass was obtained in 61.7% of cases (21/34) in group 1 and in 78.1% of cases (25/32) in group 2.

Table 3 summarizes the complications in both groups and their outcomes. The rates of embolus to new territory were similar and only one traumatic carotid artery dissection was observed in each group. Symptomatic ICH was observed in 8.8% (4/45) and 5% (2/40) of patients in groups 1 and 2, respectively. Early improvement in neurological outcomes was not significantly different between groups, with a mean change in NIHSS score at 24 h of −4.5 points in group 1 and −5.1 points in group 2 (p = 0.8). Among 76 patients (89.5%) with mRS assessment at three months, no significant difference (p = 0.3) was observed in the proportion of functionally independent individuals between groups 1 and 2 (51.8 versus 55.6%, respectively). The mortality rate was 22.2% (10/45) in group 1 and 17.5% (7/40) in group 2.

Table 3.

Outcomes and complications.

	Group 1	Group 2	(p = )
No. of patients	45	40
ENT (n (%))	1 (2.2%)	2 (5%)	0.51
Vessel perforation	0	0
Vessel dissection (n (%))	1 (2.2%)	1 (2.5%)
Symptomatic ICH (n (%))	4 (8.8%)	2 (5%)	0.82
Δ NIHSS at 24 h	−4.5	−5.1	0.82
90-d mRS score ≤ 2 (n/N (%))	20/39 (51.8%)	20/36 (55.6%)	0.3

ENT: emboli in a new territory; ICH: intracranial hemorrhage; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; Δ NIHSS: improvement 24 h after admission.

Discussion

In our study, we showed a strong trend toward an improvement in mTICI first pass when the dwell time was increased (48.8 versus 70%). This longer dwell time also permitted a reduction of the rescue therapy by stent retriever ratio (40 versus 22.5%).

These results were compared to the results described in the other studies using the ADAPT technique with ACE 068 catheter^7,13,14 judged more efficient than ACE 060 that we mainly used in our study. In the Compass trial,⁷ a randomized study comparing ADAPT and stent retriever techniques, favorable mTICI first pass was obtained in 57% of cases. In this study, the authors mainly used ACE 068 (62.8%) or ACE 064 (29.8%) aspiration catheters, whereas ACE 060 catheter was mainly used in the present study (80%). Similarly, the rate of favorable mTICI first pass in the Promise trial¹³ which aimed at evaluating the safety and efficacy of ADAPT technique using ACE 068 and ACE 064 catheters was 60.2%. Finally, Delgado et al.¹⁴ compared ACE 060, ACE 064, and ACE 068 and showed that the mTICI first pass was 33, 37, and 53% for the three catheters, respectively (p = 0.04).

Mechanically, the suction force is known to be proportional to the square of the catheter’s diameter. As the distal internal diameters of ACE 060 and 068 catheters are different (1.8 and 2 mm, respectively), the ACE 068 generates nearly 25% more aspiration force than the ACE 060 do.^14,15 This mechanical effect associated with the results of the previously cited studies therefore suggests that a larger bore aspiration catheter is more efficient. However, as our results could suggest, dwell time is also important as it could allow to probably compensate for this size difference. Indeed, we obtained 70% favorable mTICI first pass with the ACE 060 catheter which has a lower diameter than the ACE 068. As the aspiration force is less powerful using ACE 060, we can suppose that it takes more time to “unlock” and trap the thrombus inside the catheter. Moreover, a small-bore catheter is sometimes an advantage as a larger bore may cause damages to the vessel wall as described in Delgado et al.’s¹⁴ study, where 1.8, 5.7, and 5% of intracranial vascular injuries were observed with ACE 060, ACE 064, and ACE 068, respectively. In addition, it is not always possible to set up a large bore aspiration catheter as it requires sufficient vessel diameter to safely perform the intervention; anatomic variations may require a smaller-bore catheter.

Up to now, no study evaluating the ADAPT technique has specified the dwell time probably because it could be variable according to the center or the operator in a single center. This study is therefore the first to focus on the impact of dwell time in ADAPT procedure. An increase in dwell time allowed us to decrease the use of rescue therapy with stent retriever which ratios were 40 and 22.5% in groups 1 and 2, respectively. These results are also consistent with the results of earlier studies: in Compass and Promise trials,^7,13 the rescue therapy was used in 21 and 20.9% of cases, respectively. The results in our first group are similar to the observations of Blanc et al.¹⁶ using ACE 060 and ACE 064 (40%). In our second group, the longer dwell time compensated for the catheter size difference so that our results were comparable to Promise and Compass trials’ observations.

The use of rescue therapy after direct aspiration thrombectomy has three main causes: the first is the impossibility to reach the thrombus (impossibility to cross the ophthalmic artery with the catheter, substantial tortuosity, etc.) and requires an anchor technique with stent; the second cause is an aspiration failure where thrombus extrication is not achievable; the last cause is a distal thrombus preventing to bring a large bore aspiration catheter in contact with the thrombus requiring a stent retriever.

To our knowledge, only the Promise trial¹³ specified the cause of failure: aspiration failure was observed in 13.4% of cases, need of distal thrombectomy in 9% of cases, and apparently no case of anchor technique reported. In our cohort, stent retriever was used for distal complementary thrombectomy in 5% of cases; for anchor technique in 8.8 and 10% in groups 1 and 2, respectively; and for failure of aspiration in 31.1 and 7.5% in groups 1 and 2, respectively. The discrepancies observed might be explained by the change of design when comparing the two catheters: while ACE 060 has 12 transition zones, ACE 068 has 16 transition zones and a new coil winding geometry which is designed to optimize the pushability and trackability of the device.

In our opinion, the best strategy is to adjust the size of the aspiration catheter to the vessel caliber in order to obtain an optimal vessel size to catheter diameter ratio and to adapt the dwell time to the size of the catheter. It is also likely that increasing the dwell time with the ACE 068 catheter may generate better results as observed in terminal carotid artery occlusions in our cohort. A randomized study is warranted to confirm this finding. Future studies using ADAPT technique require to clearly specify the dwell times associated with the procedures for proper comparison purpose.

Limitations

Our study has several limitations mainly related to the retrospective design, the small sample size which is responsible for the lack of statistic power, and lack of external adjudication of angiographic findings and clinical outcomes.

Conclusion

Though our study did not highlight a statistical difference between the two groups with specific dwell times, our retrospective analysis exhibited a strong trend toward TICI first pass improvement when the dwell time was increased from 2 to 5 min (48.8 versus 70%, p = 0.06). A randomized study is clearly warranted in order to confirm these findings.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.