The overwhelming clinical benefit of intra-arterial stroke therapy owes to the major advance in revascularization brought on by the current generation of thrombectomy devices. Nevertheless, there remains a sizeable proportion of patients for whom substantial reperfusion cannot be achieved or is achieved too late. This article addresses the persistent challenges that face neurointerventionists and reviews technical refinements that may help to mitigate these obstacles to procedural success. Insights from in vitro modeling and clinical research are organized around a conceptual framework that examines the interaction between the device, the thrombus and the vessel wall.
In acute ischemic stroke (AIS), the overwhelming clinical benefit of intra-arterial treatment (IAT) seen in the recent randomized trials owes primarily to the effectiveness of stent retrievers [
The current benchmark for technical success of the endovascular procedure is a modified Treatment in Cerebral Ischemia (mTICI) 2b-3 score (reperfusion in greater than 50% of the target ischemic territory) [
The intra-procedural time to reperfusion is another critical measure of device effectiveness as well as ease of delivery, and has a direct impact on clinical outcomes. This can be reported in various ways, including the time from vessel access to reperfusion or from guide catheter placement to reperfusion, and the rate of first-pass success. The steady decline in the time to revascularization also accounts for the clinical success of the latest generation devices (
Despite the groundbreaking results of the recent trials, the variability in angiographic and clinical outcomes highlight the need to further improve neurointerventional tools and techniques (
Clearly, barriers to vessel access and to adequate guide catheter support will impede or prevent device delivery to the thrombus. Unfortunately, these obstacles are most common in high-risk stroke populations. Significant peripheral vascular disease can make traditional groin access either time consuming or impossible (e.g., aorto-iliac occlusion), necessitating alternative approaches or causing early termination of the thrombectomy procedure. Similarly, in patients with certain aortic arch configurations (e.g., type III) or with significant cervical vascular tortuosity, catheterization may be significantly delayed, and placement of large-bore guide catheters may be impossible [
In such situations, direct puncture of the common carotid artery may be the only viable option [
Another frequent obstacle to thrombectomy is significant stenosis or occlusion of the cervical ICA. In the recent trials, the rate of tandem occlusions ranged between 10–30% [
The primary challenge for neurointerventionists is the 20–30% of thrombi that are resistant to current retrieval approaches. In order to systematically address this challenge, it is useful to understand the interaction between the device, the thrombus, and the vessel wall, and how various factors and procedural techniques can influence this interaction (
There are two primary factors that determine how much force will be required to remove the thrombus. The first is the force of impaction, which is determined by the pressure gradient across the thrombus – in other words, systemic blood pressure acting on the proximal thrombus face minus the pressure from retrograde collateral blood flow at the distal thrombus face. This factor likely explains the decreased rate of successful revascularization among patients with worse collaterals [
Clearly, the ideal interaction is one in which the force of retrieval is greater than the overall inertial force (impaction force plus friction/adhesion force). There are several procedural techniques that can potentially shift this balance to favor success.
Optimizing stent retriever integration with thrombus. The amount of retrieval force that can be transmitted to the thrombus is directly related to the degree of thrombus integration with the stent retriever. The surest way to maximize device-thrombus interaction is to appropriately position the device so that the active element (i.e., segment with full stent diameter) is deployed within the thrombus. The proximal marker at the junction of the stent and the pusher wire should be proximal to the proximal thrombus face, recognizing that there is typically a short tapered segment between the marker and the active element in most stent retrievers.
For stents with a closed-cell design (e.g., Trevo), integration can be further enhanced by pushing the stent rather than unsheathing during deployment. This will result in an increase in stent diameter (along with foreshortening). An in-vitro study by van der Marel and colleagues demonstrated that pushing resulted in significantly greater integration of the stent retriever within hard thrombi [
Development of new devices. The most commonly used stent retrievers today are all based on the same principle, relying on the radial force to sufficiently penetrate the thrombus to achieve a grip firm enough to hold it while being removed. There are, however, new devices in different stages of development that incorporate new working principles (
Intermediate catheter and local aspiration. In cases with significant vessel tortuosity (e.g., S-shaped curve), placement of an intermediate catheter (IMC) in close proximity to the thrombus ensures that the greatest effective retrieval force is generated when removing the device (
The ability to deliver large-bore intermediate catheters to the thrombus also enables such a strong suction force that it is possible to remove a soft thrombus without a stent-retriever (ADAPT technique;
Balloon guide catheter. The traditional way to achieve flow arrest during thrombectomy is using a cervical BGC. This will reduce the impaction force on the thrombus allowing for more effective retrieval, as well as minimize the tendency for thrombus fragmentation and distal embolization compared to a traditional cervical guide catheter [
Combined stent-retriever and local aspiration. As mentioned above, another common approach is to perform stent-retriever thrombectomy through an IMC using added local aspiration (“pinning technique”) [
Procedural impact on friction-adhesion forces. It should be kept in mind that procedural manipulations can influence the interaction between the thrombus and the vessel wall. Because the coefficient of static friction is greater than that of kinetic friction, once the retrieval is begun, the pull should be steady until the thrombus is removed from the body. The retrieval should not be stopped and re-started because greater forces are required to get the thrombus moving again.
Also, with each thrombectomy attempt, there is the potential for compressing the thrombus (
Thromboemboli distal to the M2 segments. Even though none of the randomized controlled trials included clots distal to M2, there are stent retrievers available today with smaller diameter, typically 3 mm, which may be used in smaller arteries. Although distal thrombectomy in the anterior cerebral artery has been reported to have high revascularization rate with low complication profile [
Pharmacological augmentation of mechanical thrombectomy. Intra-arterial thrombolysis, mostly with recombinant tissue plasminogen activator (rt-PA), has been used for quite some time in combination with mechanical thrombectomy in order to initially “soften” the thrombus, or more commonly, to recanalize distal fragments, originally present or dislodged during the procedure. This may imply an increased risk for post-procedure hemorrhage, especially if the patient has been treated with intravenous thrombolysis, but seems in our experience to be safe if the dosage is limited (e.g., <10 mg rt-PA), particularly after intravenous rt-PA. Another option is to augment the mechanical thrombectomy with intra-arterial administration of GPIIb/IIIa inhibitors. Even though this strategy seems safe in small case-series [
Despite the recent success of intra-arterial stroke therapy, there remain numerous challenges for neurointerventionists. Difficult vascular anatomy may preclude access and introduce significant delays to reperfusion. Further work is needed to improve alternative access tools and techniques. Clinical and in-vitro data suggest that hypodense, fibrin-rich thrombi are more resistant to thrombectomy. However, it is unknown whether a thrombectomy strategy tailored to thrombus imaging characteristics improves angiographic and clinical outcomes. When using a stent-retriever alone, the use of a balloon guide catheter appears beneficial. This is based on nonrandomized clinical data, but is also supported by in-vitro modeling and theoretical considerations. With a closed-cell stent-retriever, deployment using a pushing technique may produce better thrombus integration and yield a greater force of retrieval. Based on recent randomized data from the ASTER trial, the use of aspiration thrombectomy as a first-line approach may be justified even though combined stent-retriever/aspiration approaches, particularly with partial capture of the stent-retriever (“pinning technique”), appear promising for refractory thrombi. Future studies, should examine whether this approach is superior as a first-line approach or if it should be reserved in case of difficulties with straight-forward stent retriever or aspiration techniques. It should be remembered that more complicated techniques may take longer and pose more problems, not least for relatively inexperienced operators; simple and fast is often preferable. With each thrombectomy attempt, there is potential for thrombus compression and increasing difficulty of subsequent retrieval. Therefore, it is essential to identify strategies that enhance first-pass revascularization, as well as rates of complete reperfusion.
Future areas of investigation and innovation: 1) Identify patient subgroups for whom alternative vascular access should be used initially; 2) Improve tools and techniques for direct carotid puncture; 3) Investigate reliable imaging predictors of refractory thrombi, and test whether a thrombectomy strategy tailored to thrombus imaging characteristics will improve outcomes; 4) Develop and evaluate thrombectomy approaches that maximize first-pass success and complete reperfusion; and 5) Evaluate the cost effectiveness of using a single- versus multi-device approach as frontline therapy.
The authors gratefully acknowledge David Vale and Michael Gilvarry of Neuravi Inc. for their valuable contributions to this review, including the use of figures and videos from their in vitro modeling.
AJY reports research grants from Penumbra Inc. and Neuravi/Codman Neurovascular Inc. TA is a consultant for Ablynx, Amnis Therapeutics, Medtronic, Neuravi (J&J), Rapid Medical and Stryker.
The authors have no financial conflicts of interest.
Friction versus thrombus composition (
Stent retriever thrombectomy versus thrombus composition (
Evolution of mTICI 2b-3 rates. First generation device = Merci. Second generation = initial smaller bore Penumbra catheters. Third generation = stent-retrievers and large-bore aspiration catheters (e.g., Penumbra 5 MAX ACE and larger). mTICI, modified Treatment in Cerebral Ischemia.
Evolution of procedural times. First generation device = Merci. Second generation = initial smaller bore Penumbra catheters. Third generation = stent-retrievers and large-bore aspiration catheters (e.g., Penumbra 5 MAX ACE and larger).
Variability in angiographic and clinical outcomes in the recent randomized trials of thrombectomy. TICI: Treatment In Cerebral Ischemia; mRS: modified Rankin Scale.
Device-thrombus-vessel interaction.
Line-of-force challenge. Top left image demonstrates a stent retriever deployed within a thrombus on the distal limb of an S-shaped curve. Top right image, taken during retraction of the stent retriever without an intermediate catheter, shows ineffective force transmission where some of the force deforms the original course of the vessel (depicted with the dotted lines). Bottom left image shows a stent retriever delivered through an intermediate catheter and deployed across a thrombus, again on the distal limb of an S-shaped curve. Bottom right image, taken during retraction of the stent retriever and with the intermediate catheter just proximal to the thrombus, demonstrates effective force transmission without deformation of the vessel.
ADAPT. Long thrombus retrieved from a cervical internal carotid artery occlusion using the ADAPT technique through a Penumbra ACE 68 catheter.
Combined stent-retriever/aspiration. (A) Baseline image of right MCA M1 segment occlusion. (B) Thrombus within the stent-retriever is partially captured within the aspiration catheter and removed as a single unit. (C and D) Final AP and lateral image demonstrating mTICI 2c reperfusion. Notice the S-shaped configuration of the supraclinoid ICA and M1 segment. MCA, middle cerebral artery; AP, FULL NAME; mTICI: modified Treatment In Cerebral Ischemia; ICA, internal carotid artery.
Risk of thrombus shearing when pulling the stent-retriever fully through the aspiration catheter (Courtesy of Neuravi Inc.). BG, balloon guide catheter.
Thrombus compression after stent-retriever attempt (Courtesy of Neuravi Inc.).
Relationship between thrombus compression and coefficient of friction (Courtesy of Neuravi Inc.).
Revascularization results with third-generation devices
Trial | Device | mTICI 2b-3 (%) | mTICI 3 (%) | Time from guide catheter to revasc/end (min) |
---|---|---|---|---|
SWIFT [ |
Solitaire | N/A | N/A | 36 (median) |
Merci | N/A | N/A | 52 (median) | |
Trevo 2 [ |
Trevo | 68 | 14 | 48 (mean) |
Merci | 44 | 6 | 47 (mean) | |
Trevo [ |
Trevo | 72 | 7 | N/A |
STAR [ |
Solitaire | 79 | 55 | 20 (mean) |
NASA registry |
Solitaire | 73 | 40 | N/A |
Humphries et al. |
Stent retriever+penumbra | 88 | 44 | N/A |
ADAPT FAST |
Penumbra 5MAX | 75 | 41 | 38 |
Penumbra 5MAX ACE | 82 | 61 | 36 |
mTICI, modified Treatment in Cerebral Ischemia; SWIFT, Solitaire With the Intention For Thrombectomy; N/A, not available; STAR, Solitaire flow restoration Thrombectomy for Acute Revascularization; NASA, North American Solitaire Acute stroke registry; ADAPT FAST, A Direct Aspiration first Pass Technique Fast.
Not core lab adjudicated;
Time from groin puncture to mTICI ≥2B or end.
New mechanical thrombectomy devices
Device | Company | Working principle |
---|---|---|
EMBOTRAP | Neuravi/Codman | Open outer cage, inner flow channel, closed distal end |
Neurovascular | ||
ERIC | Microvention | Interlinked cage technology with adjustable length; small (0.017) |
TIGER TRIEVER | Rapid Medical | Adjustable diameter; strong radial force |
GOLDEN RETRIEVER | Amnis Therapeutics | Cage formation expanding from a microwire; small (0.014) |
LAZARUS RE-COVER | Medtronic | Cover accessory device - combined with various stent retrievers |