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Abstract
Introduction The use of retrievable stents for acute ischemic stroke (AIS) may result in the release of distal emboli in 12–22% of cases. The Lazarus Funnel is a novel CE-marked thrombectomy assist device designed to capture the stentriever and thrombus to minimize the likelihood of distal embolization. To study this technology, we performed a randomized blinded in vitro evaluation of this device.
Methods A cerebral flow model was used as an in vitro simulator for cerebral arterial thrombectomy procedures. Stratified block randomization was performed following embolus injection into one of three cohorts: Solitaire stentriever plus guide catheter (control); control plus proximal Funnel placement; or control plus distal Funnel placement. Time to embolectomy, recanalization, and incidence of distal emboli were determined by a blinded observer.
Results Forty-five thrombectomy trials were performed (15 in each group). The average time required for thrombectomy in each group was 8 min 26 s, 11 min 0 s and 9 min 24 s, respectively (p=NS). Use of the Funnel was associated with significantly improved recanalization compared with stentriever alone (p<0.01). Use of the proximal Funnel resulted in a 25% increase in successful recanalization and a 20% reduction in distal emboli. Use of the distal Funnel resulted in a 200% increase in successful recanalization and a 60% reduction in emboli.
Conclusions In this AIS embolism flow model with Solitaire thrombectomy, the Lazarus Funnel resulted in a significant increase in recanalization and significant reduction in distal emboli without increase in time to recanalization.
- Device
- Embolic
- Intervention
- Stroke
- Thrombectomy
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Introduction
Retrievable stents or ‘stentrievers’ have gained considerable notoriety in the acute ischemic stroke community recently due to reports of excellent recanalization rates in multiple studies.1–4 However, the use of stentrievers may cause fragmentation of thrombus with the release of distal emboli in about 12–22% of cases while the construct is being pulled from the vasculature into the guide catheter.5–7 Distal emboli of clot fragments may occlude small arteries (or previously unoccluded vessels) that may not be recanalized with current thrombolytic technology and may negatively affect patient outcomes.
The Lazarus Funnel (Lazarus Effect, Campbell, California, USA) is a novel CE-marked thrombectomy assist device designed to smoothly capture the stentriever and thrombus to minimize the likelihood of clot fragmentation and distal embolization. The Funnel fits through a distal access or guide catheter of ≥5.2 F and can assist with the delivery and removal of thrombectomy devices of ≤0.027 inch. The cranial end of the Funnel has a 30 mm fine-woven, double-layered mesh funnel that expands to encompass the vessel lumen without occluding flow, covering the stentriever and thrombus and allowing its safe return into the guide catheter as it is withdrawn without distal embolization of fragments.
There is an increasing body of literature reporting on the efficacy of mechanical thrombectomy devices and techniques in both in vitro and in vivo experimental settings.8–11 To study the Funnel device, we performed a randomized blinded in vitro evaluation of this technology.
Methods
Device
The Lazarus 4F Funnel is a single-lumen catheter with an atraumatic funnel-shaped nitinol mesh distal end. The flexible funnel segment facilitates the insertion and guidance of smaller interventional and/or diagnostic devices (microcatheters) into the guide catheter. The proximal end of the Funnel Guide Catheter has a standard luer hub that may be attached to a short Tuohy-Borst Adaptor or rotating hemostasis valve and pressurized perfusion line. The Funnel is delivered to the target anatomy through a 6 F guide catheter or 5.2 F distal access catheter. The Lazarus 4F Funnel has an inner diameter of 0.041 inch (3.1 F) and accepts interventional or diagnostic devices within its lumen that have an outer diameter of 2.8 F (0.036 inch) or less.
The Funnel is deployed by first positioning the guide catheter or intermediate guide catheter in the anatomy where the position of the Funnel will be desired. The Funnel is then advanced to the distal region of the guide catheter. The guide catheter is then retracted proximally about 4 cm to expose the funnel portion of the device and allow it to self-expand to the vessel.
Model
An anatomically accurate cerebral flow model (Model H+N-S-S-002; Elastrat, Geneva, Switzerland) was used as an in vitro simulator for cerebral arterial thrombectomy procedures (figure 1). The model is designed with a mild (39% by diameter) stricture in the distal M1 to generate consistent clot localization. The model generates pulsatile anterograde normal sinus flow at 120 mL/min, with 120/80 mm Hg pressures, maintained with a dual output solenoid diaphragm pump (Model #76302-70; Cole Parmer, Court Vernon Hills, Illinois, USA). The working fluid was saline without distal vascular resistance. Forty-five separate 5×5×5 mm proprietary experimental emboli were inserted into the model to simulate acute arterial emboli. Emboli were created from a proprietary surrogate material that represents a heterogeneous composite of hard and soft components of an organized thrombus. The surrogate is allowed to soak in saline for approximately 1 h before being injected into the proximal internal carotid artery of the vascular model. Fluid flow is allowed to carry the thrombus surrogate to the restriction in the M1. Due to the viscoelastic nature of the surrogate, it is able to conform to the size and shape of the M1.
The cerebral flow model with surrogate thrombus material lodged in the M1.
Embolectomy
Stratified block randomization was performed following embolus injection into one of three cohorts: Solitaire stentriever (ev3, Plymouth, Minnesota, USA) plus guide catheter (figure 2); Solitaire stentriever with guide catheter and proximal Funnel placement (figure 3); or Solitaire stentriever with guide catheter and distal Funnel placement (figure 4). Proximal position was defined as 5 cm from the most proximal turn in the internal carotid artery segment. Distal position was defined as just distal to the anterior cerebral artery origin in the middle cerebral artery segment of the model. Embolectomy was then performed using only one pass of the stentriever and/or Funnel device per trial. Adequate recanalization, defined as restitution of flow in the M1 branch of the middle cerebral artery (MCA) and >75% removal of clot burden, was assessed by a blinded observer following embolectomy. Distal embolization was defined as the presence of thrombus fragments in distal MCA branches. Previously uninvolved territory embolization was defined as thrombus fragments in the anterior cerebral artery branches. Time to perform embolectomy was also recorded. Statistical analysis was performed using χ2 tests for independence and trend.
Solitaire stentriever and guide catheter during thrombectomy.
Thrombectomy with Solitaire stentriever and proximal Funnel placement. The Funnel was advanced through the guide catheter to the desired location in the internal carotid artery and then the guide was retracted to expose the Funnel.
Thrombectomy with Solitaire stentriever with distal Funnel placement. The Funnel was advanced through the intermediary guide catheter to the desired location at proximal M1 and then the intermediary guide was retracted to expose the Funnel.
Results
Forty-five thrombectomy trials were performed: 15 with Solitaire and guide catheter; 15 with Solitaire, guide and proximal Funnel; and 15 with Solitaire, guide and distal Funnel. The average time required for thrombectomy with the Solitaire stentriever and guide catheter (without use of the Funnel) was 8 min 26 s. Mean time for thrombectomy with the use of the proximal Funnel was 11 min 0 s and with the distal Funnel was 9 min 24 s (ANOVA, p=NS).
Recanalization results are shown in table 1. Use of the Funnel was associated with significantly improved recanalization compared with stentriever alone (p<0.01). Use of the proximal Funnel resulted in a 25% increase in successful recanalization and use of the distal funnel resulted in a 200% increase in successful recanalization. Distal embolization rates are reported in table 2. Use of the proximal Funnel resulted in a 20% reduction in emboli into previously uninvolved territories, while use of the distal Funnel resulted in a 60% reduction in emboli into previously uninvolved territories.
Recanalization rates in the three trial groups
Distal emboli in the three trial groups
Discussion
Revascularization results after stentriever thrombectomy have been excellent, with reported TICI/TIMI 2 or 3 recanalization in as many as 92% of patients.1–4 However, one major limitation of these devices is the tendency for the thrombus to fragment, resulting in a 16–22% risk of distal emboli.5–7 This phenomenon is probably due to three main contributing factors: (1) initial fragmentation of the thrombus by the stentriever lattice; (2) pulling the construct proximally against the stationary vessel wall and the direction of blood flow, generating significant shear forces acting on thrombus fragments; (3) the proximal recovery of the stentriever into larger caliber vessels than those in which the stent was originally deployed (eg, pulling an M1 clot proximally into the larger internal carotid artery), resulting in the expansion of the stentriever from intrinsic radial forces while in the larger artery and the resultant loss of tight apposition between the stentriever lattice and thrombus.
The Lazarus Funnel was developed to sheathe the stentriever in a protective cover that captures the thrombus contained within the stent, thereby removing the potential for thrombus fragments to be released during device re-capture as it is pulled proximally against the flow of blood into vessels of increasingly larger caliber. It can be used with any thrombectomy device delivered through a catheter of ≤0.027 inch. The device added only 50 s to thrombectomy time when used distally in conjunction with the Solitaire stentriever and is simple to use. In this flow model simulator, distal emboli occurred 60% less frequently with use of the distal Funnel. Furthermore, recanalization was significantly higher with use of the Funnel. Although these data are experimental in nature, the improved recanalization and reduction in distal emboli are encouraging findings. Further study in an animal model is necessary to document efficacy in vivo.
There are several important limitations to this study. While review of recanalization and distal emboli was blinded, proceduralists could not be blinded to the device and therefore device maneuvers and time to perform thrombectomy were potentially subject to operator bias, though extreme care was taken to perform all procedures in a uniform manner. Furthermore, the flow model simulator and proprietary emboli may not fully reflect in vivo vessel, thrombus and device interactions.
Conclusions
In this acute ischemic stroke embolism flow model with Solitaire stentriever thrombectomy, the Lazarus Funnel was associated with a 200% increase in successful recanalization and a 60% reduction in distal emboli compared with the Solitaire stentriever alone. Although preliminary, these data suggest that the Lazarus Funnel may enhance mechanical thrombectomy and warrant in vivo studies. Furthermore, these data suggest that the concept of early clot containment may provide benefit in reducing embolic events.
Footnotes
Contributors All authors contributed to the manuscript through data acquisition, data analysis, manuscript composition, and/or through critical review of the manuscript. All authors provided final approval for publication.
Competing interests JM serves as a consultant to Reverse Medical, Lazarus Effect, Pulsar, Medina Medical, and Edge Therapeutics. He has investor interests in Blockade Medical and Medina Medical and is on the Advisory Board for Codman Neurovascular. YPG is a stockholder and President of Lazarus Effect.
Provenance and peer review Not commissioned; externally peer reviewed.