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REVIEW
Current status of mechanical thrombectomy for acute stroke treatment Vitor Mendes Pereira a,b,c,∗, Hasan Yilmaz c, Alain Pellaton c, Lee-Anne Slater a, Timo Krings a,b, Karl-Olof Lovblad c a
Division of Neuroradiology, Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada b Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada c Interventional Neuroradiology Unit, Service of Neuroradiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 4, 1211 Geneva, Switzerland
KEYWORDS Acute stroke; Endovascular treatment; Stent retriever; Thrombectomy
Summary Acute ischemic stroke is a morbid and disabling medical condition with a significant social and economic impact throughout the world. Intravenous thrombolysis (IVT) has been the first line treatment for patients presenting up to 4.5 hours after symptom onset for many years. Endovascular stroke treatment has been used successfully as rescue therapy after failed IVT; in patients with contraindications to rtPA or presenting outside the 4.5-hour window. The effectiveness of IVT is high for distal thrombi but significantly lower for proximal occlusions. Endovascular treatment has been revolutionized by the evolution from intra-arterial thrombolysis and first generation mechanical devices to the current generation of stent retrievers and aspiration systems with large bore catheters. These devices have been associated with excellent revascularization, improved clinical outcomes, shorter procedure times and reduced device and procedure related complications. We report the current literature, clinical standards and perspectives on mechanical thrombectomy in acute ischemic stroke. © 2015 Elsevier Masson SAS. All rights reserved.
Introduction ∗
Corresponding author. Division of Neuroradiology, Department of Medical Imaging and Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University Health Network, 3MCL-436, 399 Bathurst Street, M5T 2S8 Toronto, Ontario, Canada. Tel.: +416 603 5800x5564; fax: +416 603 4257. E-mail addresses: [email protected] (V.M. Pereira), [email protected] (H. Yilmaz), [email protected] (A. Pellaton), [email protected] (L.-A. Slater), [email protected] (T. Krings), [email protected] (K.-O. Lovblad).
Acute ischemic stroke (AIS) accounts for the highest morbidity and mortality in the aged population worldwide and is an important social and economic issue for the public health system [1,2]. AIS treatment has a potential to reverse presenting neurological deficits and improve patient’s outcome [1,3]. Its success is dependent on time and therefore requires a well-developed management strategy within local organizations [5—8].
http://dx.doi.org/10.1016/j.neurad.2014.11.002 0150-9861/© 2015 Elsevier Masson SAS. All rights reserved.
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Mechanical thrombectomy results with the new generation devices on recent multicenter studies.
n Age Male Baseline NIHSS, median % ICA occlusions % VBA occlusions Successful recanalization
mRS ≤ 2 at 3 months Mortality at 3 months Symptomatic ICH at 24 hours
Retrospective
SWIFT (Rand SFR group only)
TREVO
TREVO 2 (Rand Trevo group only)
ADAPT FAST
STAR
141 66.3 ± 13.1 56% (79/141) 18 28% 11% 85% (TICI ≥ 2b)
58 67.1 ± 12.0 48% (28)
60 65 (median) 45%
88 67.4 ± 13.9 45%
100 66 ± 15.7 54%
202 68.4 ± 12.5 40%
18 21% 1.7% 68.5% (TIMI ≥ 2) 75.9% (TICI ≥ 2b)
18 21.7% 8.3% 78.3% (TICI ≥ 2a)
19 16% 8% 86% (mTICI ≥ 2)
17.2 23% 5% 78% (TICI 2b/3)
36.4% (20/55) 17.2% (10/58) 1.7% (1/58)
55.0%
40%
40%
20%
33%
20
5% (3/60)
7%
0
17 18% N/A 84.2% (160/190) or 79.2% (160/202) (TICI ≥ 2b) 57.9% (117/202) 6.9% (14/202) 1.5% (3/202)
55% (77/141) 20% (20/141) 4% (5/141)
AIS treatment became widespread in the nineties with the introduction of IV thrombolysis (IVT) [1]. It was shown to be an intuitive and simple treatment option requiring an appropriately trained team but no exceedingly sophisticated medical infrastructure [1,9,10]. The efficacy of IVT has been shown to be greatest for distal occlusions and the approved time window is restricted to 4.5 hours [11]. Endovascular treatment for acute stroke commenced with intra-arterial thrombolysis that was shown to be superior compared to placebo up to 3 hours after stroke symptoms in the PROACT II study [12]. This approach consisted of navigation of a micro catheter to the occluded vessel and local injection of alteplase (rtPA) or urokinase. This method extended the therapeutic window but was still limited to patients with no contraindications to thrombolytics. This was followed by the introduction of mechanical thrombectomy devices as rescue therapy [13] and subsequent introduction of the Merci (Concentric Medical, Mountain View, California), Phenox (Phenox, Bochum, Germany) and Catch (Balt, Montgomery, France) devices as well as the Penumbra aspiration system [14—16]. These devices were reported to improve recanalization rates up to 80% in some of the latest studies from experienced centers, however failed to demonstrate significant improvement in clinical outcomes [14—16]. Mechanical thrombectomy was then revolutionized by the advent of a new generation of devices based on intracranial stenting (Table 1) [3,7,17—19]. The Solitaire stent was the pioneer of this technology, however subsequently companies engineered devices using a similar concept leading to the development stent retrievers. The stent retrievers led to improved classifications of cerebral revascularization and established high standards with regards to procedure times and clinical outcome [7,20—24]. The improved results meant that other systems used for mechanical thrombectomy such as the aspiration system, had to improve the technology, namely the large
bore catheters, to match the degrees of recanilization and reduced procedure times [25]. In this article, we review the current status of mechanical thrombectomy using the new generation devices.
Brief history of mechanical thrombectomy Mechanical thrombectomy started with use of a micro guidewire to macerate the thrombus inducing fragmentation and lysis. Although well recognized as a technique, there is no literature evaluating its efficacy as the sole method of treatment, however it is easy to imagine the degree of distal emboli and low recanalization rates related to this technique. Despite this, it was one of the main methods used on the Synthesis trial for thrombectomy [26]. The Merci (Concentric Medical, Mountain View, California) was the first device widely used [16]. It can be classified as a distal device since it cross the thrombus and recanalizes the vessels from distal to the occlusion. MERCI and MULTIMERCI studies reported recanalization results of 59 and 68% respectively in patients treated up to 8 h after the stroke onset harboring 7 and 5% complication rates and good clinical outcomes of 28 and 36% respectively [16,27]. Mortality rates were still quite high ranging from 34 to 44% probably related to poor patient selection and high rates of incomplete revascularization [28]. Other distal revascularisation technologies including Catch (Balt, Montgomery, France) and Phenox (Phenox, Bochum, Germany) devices followed and these demonstrated similar results to the MERCI device in single center series [13,14,29]. In parallel, techniques approaching the clot proximally started being used, becoming widespread with the introduction of the Penumbra aspiration system (Penumbra, Alameda, USA) [13,14,30]. Recanalization rates reached 80% with these aspiration techniques, however the clinical outcomes did not match. Good
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Figure 1 A 78-year-old woman, chronic atrial fibrillation that presented at the hospital 4 hours after stroke symptoms. NIHSS 14 at presentation. A. Initial non-contrasted CT. B. Right carotid injection showing an M1-M2 occlusion. C. Subtrated angiogram—intermediate control angiogram. D. Final control angiogram after aspiration using Penumbra aspiration system. E. Noncontrasted CT performed 24 h after procedure showing no infarction and no hemorrhages.
clinical outcomes, defined as modified Rankin Scale (mRS) from 0 to 2, varied from 20 to 45% in most of the published series [14,30]. Fig. 1 shows a patient with AIS, treated with the penumbra aspiration system. At this stage, using the described technology, randomized controlled trials comparing IV-rtPA to endovascular treatment were planned and executed. IMS-3 [31], Synthesis [26], MR-RESCUE [32], MR-CLEAN [33] and other studies were randomizing patients to treatment using these first generation devices against IV-rtPA. Despite of all criticisms to their protocols regarding selection and inclusion bias and imaging selection criteria, the performance of the endovascular arm with these devices were not superior to what have been published up to that time [12,14,16,20,27,30,34,35]. Reasons for that were multiple including incomplete recanalization, longer procedure times, technical inconsistencies and poor patient selection. Time to re-evaluate and discuss the field had come and a light at the end of the tunnel appeared from an intracranial stent, the Solitaire stent (Covidien, Irvine, USA) that was designed to be assisting aneurysm coiling and, serendipitously, was successfully used to remove thrombus
on AIS [3]. Fig. 2 demonstrates examples of patients with AIS treated with Solitaire stent.
Advent of stent retrievers: the revascularization breakthrough In 2008, mechanical thrombectomy with stent retrievers was initiated by the Solitaire stent [36]. It became the mechanical thrombectomy method of choice either adjunctive to IV-rTPA or as the primary treatment in the high-volume stroke centers in Europe and an initial but large multicenter study describing 141 patients treated with the Solitaire device for AIS was performed [3]. They reported revascularization rates of 85% and 55% good clinical outcomes (mRS ≤ 2). Mortality rate was 20% and symptomatic hemorrhagic complications rate was 4%. These results were far better than all those reported in the literature at that time with previous generation devices [3]. Furthermore, they used the modified Thrombolysis in Cerebral Infarction (mTICI) scores to describe the angiographic results making
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Figure 2 A 62-year-old, F, presented at the hospital 4 h after stroke symptoms. Baseline NIHSS—18. IV-rtPA 0.9 mg/kg while being transfer. A. Initial non-contrasted CT showing good ASPECT scores. B. Subtracted angiogram, lateral vie showing an intracranial carotid occlusion. C. Non-subtracted AP angiogram showing the stent retriever deployed over the thrombus. D. Lateral view showing a recovery procedure with a Balloon Guiding Catheter inflated. E and F. Subtracted angiogram, AP and Lateral views: complete revascularization.
a clear distinction between recanalization (using TIMI scores) and revascularization (using TICI and mTICI scores) [24]. This distinction between recanalization and revascularization was now given attention and the superiority of this method compared to past mechanical thrombectomy devices was definitively demonstrated. Other endovascular devices with a stent-like design appeared in the market and collectively were called stent retrievers [21,37,38]. With slight differences, the revascularization rates became more consistent and remained in the range of 80—85% with impressive decrease on the procedure times [21] among different studies. Two studies, SWIFT and TREVO 2, compared stent retrievers with first generation devices (MERCI device) and importantly demonstrated important superiority of the stent retrievers later compared to the former in with regards to recanalization, mortality and clinical outcomes [17,18]. They marked the clear boundary between the stent retrievers and the previous generation devices. The largest prospective multicenter study on stent retrievers for AIS is the STAR study [7]. This study selected high-volume centers with large experience with the technique and standardized the endovascular procedure with the obligatory use of balloon guiding catheters (BGC) and embedding minimal time required prior to device recovery. Study results were remarkable with a revascularization rate of 84%, good outcomes (mRS ≤ 2) rate of 58%, and mortality rate of 6.9% and intracranial hemorrhagic rate of 1.5% [7]. Procedural time (guiding catheter placement
to revascularization TICI ≥ 2b or end of the procedure) was 20 (mean, 29 ± 27) minutes demonstrating that, in highvolume centers, experienced interventionalists can really make significant difference in AIS treatment [39]. This landmark study settled ground minimum standards for the next generation devices: fast procedures time, effective revascularization and low morbidity and mortality. Other methods had to evolve and adjust to this new reality on the meet this new standard in the endovascular field of AIS. The aspiration approach integrated new catheter technology that permitted the use of large diameter aspiration directly to the thrombus. The name ADAPT was given to this technique and with the improved aspiration capabilities of the new catheters, the aspiration techniques of the past were revitalized [25]. Procedure and revascularization results comparable to stent retrievers were reported, however, this technique still presented suboptimal rates of good clinical outcomes (40% compared to 50—58% of stent retrievers) [25]. Regardless, these advances are undoubtedly beneficially for the field. New prospective randomized controlled trials now only include patients treated with this next generation devices to assure high standards in the endovascular arm [5].
Current mechanical thrombectomy technique After careful imaging and clinical selection, the management of a patient with AIS is a battle against the time. Most
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Figure 3 A and B. Subtracted and non-subtracted angiogram AP view showing left carotid access using an axial system with a selective catheter 125 cm with a VTK shape and a balloon guiding catheter 8F navigated through it contouring the accentuated curve. C and D. Non-subtracted angiogram AP views showing right carotid access using an axial system with a selective catheter 125 cm with a headhunter shape and a balloon guiding catheter 8F navigated through it. E. Subtracted angiogram AP view showing right vertebral access using an axial system with a selective catheter 125 cm with a vertebral shape and a guiding catheter 8F 80 cm length navigated through it until the subclavian. F. Subtracted angiogram showing a DAC into the right vertebral through a support catheter into the subclavian.
centers now accept that proximal occlusions will require treatment adjunct to intravenous rtPA [3,7,30,34,35,37,38]. As such, neurology and interventional teams should be activated in parallel to decrease the time to the endovascular procedure. The use of local or general anesthesia should follow local guidelines and preferences but should not delay the start of the procedure. These parallel actions seem to be key in gaining time [39]. Preparation for the endovascular procedure can commence with planning of the access based on the CTA evaluation. Most of the procedures can be performed using the femoral approach but in cases without femoral access, a radial or brachial approach can be used. Stroke patients have usually tortuous arterial anatomy and can require complex exchange maneuvers in order to navigate distal access
catheters (DAC) or BGC. We prefer to use a coaxial system with a long (125 cm) diagnostic selective catheters and the BGC in the carotid system [21]. For vertebrobasilar strokes, we use a long sheath in the subclavian artery and a DAC placed distally in one of the vertebral arteries. Alternatively, a radial approach can be performed using a 6F sheath and the DAC directly into the vertebral artery. Fig. 3 shows different access strategies for navigating BGC or DAC. Alternatively, radial approach can be used in case femoral cannot be used. Fig. 4 demonstrates different radial accesses. After placing the proximal access, the next step is to navigate the micro catheter across the clot using a 14-microguidewire with a ‘‘J’’ type of shape. The stent retriever is then delivered through the micro catheter and placed over the thrombus. The deployment is usually
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Figure 4 Radial approach for acute stroke treatment. A. Right Radial approach to the right ICA. B. Right radial approach to the left ICA. C. Left radial to the left vertebral artery. D. Right radial to the left vertebral artery. E. Configuration of the angiogram and tables for a radial procedure.
performed by unsheathing the microcatheter and keeping the device in position with slight forward tension on the pusher wire. Once the device is in place, it is recommend to wait at least 3 minutes for embedding time [21]. The device can be slightly recaptured into the micro catheter before the full recovery to facilitate navigation. Prior to the recovery, if a BGC is used, a temporary balloon occlusion is performed. A 60 cc syringe should be connected to the catheter connector to perform aspiration while the device is being pulled out. The catheters should be cleaned and balloon deflated before performing the control angiogram to access status of the occlusion. If the procedure is performed using one of the new large aspiration catheters, the 8F support system, is routed similarly to the BCG on the carotid circulation. Once the guiding catheter is in place, a coaxial system composed of an ACE catheter (Penumbra, Alameda, USA) and a 3F or Velocity microcatheter (Penumbra, Alameda, USA) will be navigated up to the thrombus and the ACE catheter placed proximal
to the clot. At this stage, there are two strategies: one is direct aspiration after stripping the 3F catheter or deploying a stent retriever over the thrombus and using the ACE as a DAC [21,25]. In case of a tandem occlusion, the carotid lesion can be treated first or after the intracranial thrombectomy. There are advantages and disadvantages to both approaches and has to be used according to center and interventionalist preference [21,25]. Fig. 5 shows a case of tandem occlusion treated with a stent retriever and a distal access catheter after carotid stent placement.
Future and perspectives of the mechanical thrombectomy 2013 was a challenging year for the endovascular treatment for acute stroke. The year started with the publication of three prospective randomized controlled trials comparing
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Figure 5 A 67-year-old, M, presented AIS symptoms corresponding to a baseline NIHSS 14. CT and CTA showed a right ICA tandem occlusion with ASPECTS score of 7. Endovascular procedure description. A and B. Subtracted angiogram right common carotid artery injection lateral views — Cervical ICA subocclusion associated with an intracranial occlusion. C and D. Non-subtracted angiogram lateral views showing the carotid stent after carotid angioplasty and a 5F distal access catheter (Navien, Covidien, Irvine, USA) crossing it to permit the mechanical thrombectomy with stent retriever distally. E. Subtracted angiogram (Roadmap view)—27-Microcatheter navigation through the intracranial circulation. F. Non-subtracted AP view — Solitare stent 6 mm deployed over the thrombus. G. Recovery procedure of the stent retriever. H. Subtracted angiogram AP view — Final control after complete recanalization.
intravenous thrombolysis and mechanical thrombectomy that turned out to be futile or negative [26,31,32]. Those studies, with different protocols and objectives, were not aligned with the current endovascular techniques and required many protocols adjustments to improve recruitment and equipoise issues [8,20,22]. Consequently, these trials incited some misunderstanding within the medical community concerning the utility of the mechanical thrombectomy in AIS treatment [16,20,31]. These trials used the old and first generation device technology or intra-arterial pharmacological thrombolysis and failed to consecutively recruit properly selected patients [6,32,36]. Many design, protocol or execution issues including poor patient selection proved responsible for a significant number of futile interventions, non-consecutive inclusions, and significant delay from stroke onset to recanalization. Furthermore, in some trials patients were included with no vascular occlusion and no recanalization results reported [26].
A potential benefit of these trials in the medical community was the overwhelming increased awareness regarding AIS treatment and the importance of generating good quality clinical evidence. Never before have we observed such a substantial mobilization to organize and produce welldesigned clinical studies to evaluate AIS treatment within committed and well-experienced centers [5,6,8,20,40]. There has been an exponential implementation of stroke networks, units and organizations worldwide. This organizational footstep has significantly improved the workflow and peri-operative management of AIS patients [39]. A focus on the treatment workflow and patient pathway inside the hospital gained attention and was also implemented in stroke trials [41]. The maxima ‘‘time is brain’’ rang true and demonstrated in each study dataset [42,43]. Time delays have been related to inferior clinical outcomes independent of the revascularization and collateral status [44,45]. A recent subgroup analysis of the Star study, demonstrated that even in high-volume and experienced
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centers, substantial time could be gained in various steps of the patients’ pathway to final revascularization [39]. Technically, the focus of the endovascular treatment of AIS will be continuous improvement of the stent retrievers and other mechanical methods. Procedural standards established are now very high: high revascularization rates, fast procedure times and good clinical outcomes. We believe that studies with the current generation devices and careful imaging selection criteria will be able to demonstrate when and how we should use mechanical thrombectomy to treat AIS.
Disclosure of interest V.M. Pereira - PI for STAR trial and co-PI for SWIFTPRIME study funded by Covidien. Other authors declare that they have no conflicts of interest concerning this article.
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[43] Khatri P, et al. Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial. Lancet Neurol 2014;13(6):567—74. [44] Goyal M, et al. Evaluation of interval times from onset to reperfusion in patients undergoing endovascular therapy in the Interventional Management of Stroke III trial. Circulation 2014;130(3):265—72. [45] Almekhlafi MA, et al. Impact of age and baseline NIHSS scores on clinical outcomes in the mechanical thrombectomy using solitaire FR in acute ischemic stroke study. AJNR Am J Neuroradiol 2014;35(7):1337—40.
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Available online at
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REVIEW
Current status of mechanical thrombectomy for acute stroke treatment Vitor Mendes Pereira a,b,c,∗, Hasan Yilmaz c, Alain Pellaton c, Lee-Anne Slater a, Timo Krings a,b, Karl-Olof Lovblad c a
Division of Neuroradiology, Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada b Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada c Interventional Neuroradiology Unit, Service of Neuroradiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 4, 1211 Geneva, Switzerland
KEYWORDS Acute stroke; Endovascular treatment; Stent retriever; Thrombectomy
Summary Acute ischemic stroke is a morbid and disabling medical condition with a significant social and economic impact throughout the world. Intravenous thrombolysis (IVT) has been the first line treatment for patients presenting up to 4.5 hours after symptom onset for many years. Endovascular stroke treatment has been used successfully as rescue therapy after failed IVT; in patients with contraindications to rtPA or presenting outside the 4.5-hour window. The effectiveness of IVT is high for distal thrombi but significantly lower for proximal occlusions. Endovascular treatment has been revolutionized by the evolution from intra-arterial thrombolysis and first generation mechanical devices to the current generation of stent retrievers and aspiration systems with large bore catheters. These devices have been associated with excellent revascularization, improved clinical outcomes, shorter procedure times and reduced device and procedure related complications. We report the current literature, clinical standards and perspectives on mechanical thrombectomy in acute ischemic stroke. © 2015 Elsevier Masson SAS. All rights reserved.
Introduction ∗
Corresponding author. Division of Neuroradiology, Department of Medical Imaging and Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University Health Network, 3MCL-436, 399 Bathurst Street, M5T 2S8 Toronto, Ontario, Canada. Tel.: +416 603 5800x5564; fax: +416 603 4257. E-mail addresses: [email protected] (V.M. Pereira), [email protected] (H. Yilmaz), [email protected] (A. Pellaton), [email protected] (L.-A. Slater), [email protected] (T. Krings), [email protected] (K.-O. Lovblad).
Acute ischemic stroke (AIS) accounts for the highest morbidity and mortality in the aged population worldwide and is an important social and economic issue for the public health system [1,2]. AIS treatment has a potential to reverse presenting neurological deficits and improve patient’s outcome [1,3]. Its success is dependent on time and therefore requires a well-developed management strategy within local organizations [5—8].
http://dx.doi.org/10.1016/j.neurad.2014.11.002 0150-9861/© 2015 Elsevier Masson SAS. All rights reserved.
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V.M. Pereira et al. Table 1
Mechanical thrombectomy results with the new generation devices on recent multicenter studies.
n Age Male Baseline NIHSS, median % ICA occlusions % VBA occlusions Successful recanalization
mRS ≤ 2 at 3 months Mortality at 3 months Symptomatic ICH at 24 hours
Retrospective
SWIFT (Rand SFR group only)
TREVO
TREVO 2 (Rand Trevo group only)
ADAPT FAST
STAR
141 66.3 ± 13.1 56% (79/141) 18 28% 11% 85% (TICI ≥ 2b)
58 67.1 ± 12.0 48% (28)
60 65 (median) 45%
88 67.4 ± 13.9 45%
100 66 ± 15.7 54%
202 68.4 ± 12.5 40%
18 21% 1.7% 68.5% (TIMI ≥ 2) 75.9% (TICI ≥ 2b)
18 21.7% 8.3% 78.3% (TICI ≥ 2a)
19 16% 8% 86% (mTICI ≥ 2)
17.2 23% 5% 78% (TICI 2b/3)
36.4% (20/55) 17.2% (10/58) 1.7% (1/58)
55.0%
40%
40%
20%
33%
20
5% (3/60)
7%
0
17 18% N/A 84.2% (160/190) or 79.2% (160/202) (TICI ≥ 2b) 57.9% (117/202) 6.9% (14/202) 1.5% (3/202)
55% (77/141) 20% (20/141) 4% (5/141)
AIS treatment became widespread in the nineties with the introduction of IV thrombolysis (IVT) [1]. It was shown to be an intuitive and simple treatment option requiring an appropriately trained team but no exceedingly sophisticated medical infrastructure [1,9,10]. The efficacy of IVT has been shown to be greatest for distal occlusions and the approved time window is restricted to 4.5 hours [11]. Endovascular treatment for acute stroke commenced with intra-arterial thrombolysis that was shown to be superior compared to placebo up to 3 hours after stroke symptoms in the PROACT II study [12]. This approach consisted of navigation of a micro catheter to the occluded vessel and local injection of alteplase (rtPA) or urokinase. This method extended the therapeutic window but was still limited to patients with no contraindications to thrombolytics. This was followed by the introduction of mechanical thrombectomy devices as rescue therapy [13] and subsequent introduction of the Merci (Concentric Medical, Mountain View, California), Phenox (Phenox, Bochum, Germany) and Catch (Balt, Montgomery, France) devices as well as the Penumbra aspiration system [14—16]. These devices were reported to improve recanalization rates up to 80% in some of the latest studies from experienced centers, however failed to demonstrate significant improvement in clinical outcomes [14—16]. Mechanical thrombectomy was then revolutionized by the advent of a new generation of devices based on intracranial stenting (Table 1) [3,7,17—19]. The Solitaire stent was the pioneer of this technology, however subsequently companies engineered devices using a similar concept leading to the development stent retrievers. The stent retrievers led to improved classifications of cerebral revascularization and established high standards with regards to procedure times and clinical outcome [7,20—24]. The improved results meant that other systems used for mechanical thrombectomy such as the aspiration system, had to improve the technology, namely the large
bore catheters, to match the degrees of recanilization and reduced procedure times [25]. In this article, we review the current status of mechanical thrombectomy using the new generation devices.
Brief history of mechanical thrombectomy Mechanical thrombectomy started with use of a micro guidewire to macerate the thrombus inducing fragmentation and lysis. Although well recognized as a technique, there is no literature evaluating its efficacy as the sole method of treatment, however it is easy to imagine the degree of distal emboli and low recanalization rates related to this technique. Despite this, it was one of the main methods used on the Synthesis trial for thrombectomy [26]. The Merci (Concentric Medical, Mountain View, California) was the first device widely used [16]. It can be classified as a distal device since it cross the thrombus and recanalizes the vessels from distal to the occlusion. MERCI and MULTIMERCI studies reported recanalization results of 59 and 68% respectively in patients treated up to 8 h after the stroke onset harboring 7 and 5% complication rates and good clinical outcomes of 28 and 36% respectively [16,27]. Mortality rates were still quite high ranging from 34 to 44% probably related to poor patient selection and high rates of incomplete revascularization [28]. Other distal revascularisation technologies including Catch (Balt, Montgomery, France) and Phenox (Phenox, Bochum, Germany) devices followed and these demonstrated similar results to the MERCI device in single center series [13,14,29]. In parallel, techniques approaching the clot proximally started being used, becoming widespread with the introduction of the Penumbra aspiration system (Penumbra, Alameda, USA) [13,14,30]. Recanalization rates reached 80% with these aspiration techniques, however the clinical outcomes did not match. Good
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Figure 1 A 78-year-old woman, chronic atrial fibrillation that presented at the hospital 4 hours after stroke symptoms. NIHSS 14 at presentation. A. Initial non-contrasted CT. B. Right carotid injection showing an M1-M2 occlusion. C. Subtrated angiogram—intermediate control angiogram. D. Final control angiogram after aspiration using Penumbra aspiration system. E. Noncontrasted CT performed 24 h after procedure showing no infarction and no hemorrhages.
clinical outcomes, defined as modified Rankin Scale (mRS) from 0 to 2, varied from 20 to 45% in most of the published series [14,30]. Fig. 1 shows a patient with AIS, treated with the penumbra aspiration system. At this stage, using the described technology, randomized controlled trials comparing IV-rtPA to endovascular treatment were planned and executed. IMS-3 [31], Synthesis [26], MR-RESCUE [32], MR-CLEAN [33] and other studies were randomizing patients to treatment using these first generation devices against IV-rtPA. Despite of all criticisms to their protocols regarding selection and inclusion bias and imaging selection criteria, the performance of the endovascular arm with these devices were not superior to what have been published up to that time [12,14,16,20,27,30,34,35]. Reasons for that were multiple including incomplete recanalization, longer procedure times, technical inconsistencies and poor patient selection. Time to re-evaluate and discuss the field had come and a light at the end of the tunnel appeared from an intracranial stent, the Solitaire stent (Covidien, Irvine, USA) that was designed to be assisting aneurysm coiling and, serendipitously, was successfully used to remove thrombus
on AIS [3]. Fig. 2 demonstrates examples of patients with AIS treated with Solitaire stent.
Advent of stent retrievers: the revascularization breakthrough In 2008, mechanical thrombectomy with stent retrievers was initiated by the Solitaire stent [36]. It became the mechanical thrombectomy method of choice either adjunctive to IV-rTPA or as the primary treatment in the high-volume stroke centers in Europe and an initial but large multicenter study describing 141 patients treated with the Solitaire device for AIS was performed [3]. They reported revascularization rates of 85% and 55% good clinical outcomes (mRS ≤ 2). Mortality rate was 20% and symptomatic hemorrhagic complications rate was 4%. These results were far better than all those reported in the literature at that time with previous generation devices [3]. Furthermore, they used the modified Thrombolysis in Cerebral Infarction (mTICI) scores to describe the angiographic results making
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Figure 2 A 62-year-old, F, presented at the hospital 4 h after stroke symptoms. Baseline NIHSS—18. IV-rtPA 0.9 mg/kg while being transfer. A. Initial non-contrasted CT showing good ASPECT scores. B. Subtracted angiogram, lateral vie showing an intracranial carotid occlusion. C. Non-subtracted AP angiogram showing the stent retriever deployed over the thrombus. D. Lateral view showing a recovery procedure with a Balloon Guiding Catheter inflated. E and F. Subtracted angiogram, AP and Lateral views: complete revascularization.
a clear distinction between recanalization (using TIMI scores) and revascularization (using TICI and mTICI scores) [24]. This distinction between recanalization and revascularization was now given attention and the superiority of this method compared to past mechanical thrombectomy devices was definitively demonstrated. Other endovascular devices with a stent-like design appeared in the market and collectively were called stent retrievers [21,37,38]. With slight differences, the revascularization rates became more consistent and remained in the range of 80—85% with impressive decrease on the procedure times [21] among different studies. Two studies, SWIFT and TREVO 2, compared stent retrievers with first generation devices (MERCI device) and importantly demonstrated important superiority of the stent retrievers later compared to the former in with regards to recanalization, mortality and clinical outcomes [17,18]. They marked the clear boundary between the stent retrievers and the previous generation devices. The largest prospective multicenter study on stent retrievers for AIS is the STAR study [7]. This study selected high-volume centers with large experience with the technique and standardized the endovascular procedure with the obligatory use of balloon guiding catheters (BGC) and embedding minimal time required prior to device recovery. Study results were remarkable with a revascularization rate of 84%, good outcomes (mRS ≤ 2) rate of 58%, and mortality rate of 6.9% and intracranial hemorrhagic rate of 1.5% [7]. Procedural time (guiding catheter placement
to revascularization TICI ≥ 2b or end of the procedure) was 20 (mean, 29 ± 27) minutes demonstrating that, in highvolume centers, experienced interventionalists can really make significant difference in AIS treatment [39]. This landmark study settled ground minimum standards for the next generation devices: fast procedures time, effective revascularization and low morbidity and mortality. Other methods had to evolve and adjust to this new reality on the meet this new standard in the endovascular field of AIS. The aspiration approach integrated new catheter technology that permitted the use of large diameter aspiration directly to the thrombus. The name ADAPT was given to this technique and with the improved aspiration capabilities of the new catheters, the aspiration techniques of the past were revitalized [25]. Procedure and revascularization results comparable to stent retrievers were reported, however, this technique still presented suboptimal rates of good clinical outcomes (40% compared to 50—58% of stent retrievers) [25]. Regardless, these advances are undoubtedly beneficially for the field. New prospective randomized controlled trials now only include patients treated with this next generation devices to assure high standards in the endovascular arm [5].
Current mechanical thrombectomy technique After careful imaging and clinical selection, the management of a patient with AIS is a battle against the time. Most
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Figure 3 A and B. Subtracted and non-subtracted angiogram AP view showing left carotid access using an axial system with a selective catheter 125 cm with a VTK shape and a balloon guiding catheter 8F navigated through it contouring the accentuated curve. C and D. Non-subtracted angiogram AP views showing right carotid access using an axial system with a selective catheter 125 cm with a headhunter shape and a balloon guiding catheter 8F navigated through it. E. Subtracted angiogram AP view showing right vertebral access using an axial system with a selective catheter 125 cm with a vertebral shape and a guiding catheter 8F 80 cm length navigated through it until the subclavian. F. Subtracted angiogram showing a DAC into the right vertebral through a support catheter into the subclavian.
centers now accept that proximal occlusions will require treatment adjunct to intravenous rtPA [3,7,30,34,35,37,38]. As such, neurology and interventional teams should be activated in parallel to decrease the time to the endovascular procedure. The use of local or general anesthesia should follow local guidelines and preferences but should not delay the start of the procedure. These parallel actions seem to be key in gaining time [39]. Preparation for the endovascular procedure can commence with planning of the access based on the CTA evaluation. Most of the procedures can be performed using the femoral approach but in cases without femoral access, a radial or brachial approach can be used. Stroke patients have usually tortuous arterial anatomy and can require complex exchange maneuvers in order to navigate distal access
catheters (DAC) or BGC. We prefer to use a coaxial system with a long (125 cm) diagnostic selective catheters and the BGC in the carotid system [21]. For vertebrobasilar strokes, we use a long sheath in the subclavian artery and a DAC placed distally in one of the vertebral arteries. Alternatively, a radial approach can be performed using a 6F sheath and the DAC directly into the vertebral artery. Fig. 3 shows different access strategies for navigating BGC or DAC. Alternatively, radial approach can be used in case femoral cannot be used. Fig. 4 demonstrates different radial accesses. After placing the proximal access, the next step is to navigate the micro catheter across the clot using a 14-microguidewire with a ‘‘J’’ type of shape. The stent retriever is then delivered through the micro catheter and placed over the thrombus. The deployment is usually
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Figure 4 Radial approach for acute stroke treatment. A. Right Radial approach to the right ICA. B. Right radial approach to the left ICA. C. Left radial to the left vertebral artery. D. Right radial to the left vertebral artery. E. Configuration of the angiogram and tables for a radial procedure.
performed by unsheathing the microcatheter and keeping the device in position with slight forward tension on the pusher wire. Once the device is in place, it is recommend to wait at least 3 minutes for embedding time [21]. The device can be slightly recaptured into the micro catheter before the full recovery to facilitate navigation. Prior to the recovery, if a BGC is used, a temporary balloon occlusion is performed. A 60 cc syringe should be connected to the catheter connector to perform aspiration while the device is being pulled out. The catheters should be cleaned and balloon deflated before performing the control angiogram to access status of the occlusion. If the procedure is performed using one of the new large aspiration catheters, the 8F support system, is routed similarly to the BCG on the carotid circulation. Once the guiding catheter is in place, a coaxial system composed of an ACE catheter (Penumbra, Alameda, USA) and a 3F or Velocity microcatheter (Penumbra, Alameda, USA) will be navigated up to the thrombus and the ACE catheter placed proximal
to the clot. At this stage, there are two strategies: one is direct aspiration after stripping the 3F catheter or deploying a stent retriever over the thrombus and using the ACE as a DAC [21,25]. In case of a tandem occlusion, the carotid lesion can be treated first or after the intracranial thrombectomy. There are advantages and disadvantages to both approaches and has to be used according to center and interventionalist preference [21,25]. Fig. 5 shows a case of tandem occlusion treated with a stent retriever and a distal access catheter after carotid stent placement.
Future and perspectives of the mechanical thrombectomy 2013 was a challenging year for the endovascular treatment for acute stroke. The year started with the publication of three prospective randomized controlled trials comparing
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Figure 5 A 67-year-old, M, presented AIS symptoms corresponding to a baseline NIHSS 14. CT and CTA showed a right ICA tandem occlusion with ASPECTS score of 7. Endovascular procedure description. A and B. Subtracted angiogram right common carotid artery injection lateral views — Cervical ICA subocclusion associated with an intracranial occlusion. C and D. Non-subtracted angiogram lateral views showing the carotid stent after carotid angioplasty and a 5F distal access catheter (Navien, Covidien, Irvine, USA) crossing it to permit the mechanical thrombectomy with stent retriever distally. E. Subtracted angiogram (Roadmap view)—27-Microcatheter navigation through the intracranial circulation. F. Non-subtracted AP view — Solitare stent 6 mm deployed over the thrombus. G. Recovery procedure of the stent retriever. H. Subtracted angiogram AP view — Final control after complete recanalization.
intravenous thrombolysis and mechanical thrombectomy that turned out to be futile or negative [26,31,32]. Those studies, with different protocols and objectives, were not aligned with the current endovascular techniques and required many protocols adjustments to improve recruitment and equipoise issues [8,20,22]. Consequently, these trials incited some misunderstanding within the medical community concerning the utility of the mechanical thrombectomy in AIS treatment [16,20,31]. These trials used the old and first generation device technology or intra-arterial pharmacological thrombolysis and failed to consecutively recruit properly selected patients [6,32,36]. Many design, protocol or execution issues including poor patient selection proved responsible for a significant number of futile interventions, non-consecutive inclusions, and significant delay from stroke onset to recanalization. Furthermore, in some trials patients were included with no vascular occlusion and no recanalization results reported [26].
A potential benefit of these trials in the medical community was the overwhelming increased awareness regarding AIS treatment and the importance of generating good quality clinical evidence. Never before have we observed such a substantial mobilization to organize and produce welldesigned clinical studies to evaluate AIS treatment within committed and well-experienced centers [5,6,8,20,40]. There has been an exponential implementation of stroke networks, units and organizations worldwide. This organizational footstep has significantly improved the workflow and peri-operative management of AIS patients [39]. A focus on the treatment workflow and patient pathway inside the hospital gained attention and was also implemented in stroke trials [41]. The maxima ‘‘time is brain’’ rang true and demonstrated in each study dataset [42,43]. Time delays have been related to inferior clinical outcomes independent of the revascularization and collateral status [44,45]. A recent subgroup analysis of the Star study, demonstrated that even in high-volume and experienced
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centers, substantial time could be gained in various steps of the patients’ pathway to final revascularization [39]. Technically, the focus of the endovascular treatment of AIS will be continuous improvement of the stent retrievers and other mechanical methods. Procedural standards established are now very high: high revascularization rates, fast procedure times and good clinical outcomes. We believe that studies with the current generation devices and careful imaging selection criteria will be able to demonstrate when and how we should use mechanical thrombectomy to treat AIS.
Disclosure of interest V.M. Pereira - PI for STAR trial and co-PI for SWIFTPRIME study funded by Covidien. Other authors declare that they have no conflicts of interest concerning this article.
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