I Introduction

In the previous content, we discussed the transition frm the first to the second generation of thrombectomy stents and understood the principles behind different stents’ ability to capture thrombi. However, with further research into how thrombectomy stents interact with thrombi, there have been more adjustments and changes in their design. The third and fourth generation thrombectomy stents mentioned later do not have strict official definitions; rather, they are more like shorthand for different conceptual stents.

II Further Analysis of Thrombectomy Stents and Their Interaction with Thrombi

The development of medical devices aims to solve clinical problems more effectively, and the driving force behind this development is a deeper understanding of diseases. To clarify the relationship between stents and thrombi, Anouchska et al. conducted a prospective study.

▲High-Resolution Imaging of Interaction Between Thrombus and Stent-Retriever in Patients With Acute Ischemic Stroke

Through micro-CT and electron microscopy, mechanical (C, D) and adhesive interactions (G) were observed. E and F are magnified images of the blue and red boxes in C and D, respectively, showing porous filamentous and dense surfaces. Histological staining showed that the thrombi contained regions rich in both fibrin and red blood cells. Fibrin is pink in (H), red in (I), and purple in (J).

▲High-Resolution Imaging of Interaction Between Thrombus and Stent-Retriever in Patients With Acute Ischemic Stroke

The observations mainly identified the following different types of thrombus surfaces and thrombus-thrombectomy stent interactions:

Two Types of Thrombus Surfaces

1. Porous Fiber Surface: The porous fiber surface, visible under a scanning electron microscope at a magnification of at least 200x, resembles the fiber network described in previous literature [2] (Figure A below).

2. Dense Thrombus Surface: The thrombus surface, where the porous fiber network cannot be distinguished under a scanning electron microscope at a magnification of at least 200x (Figure B below).

▲ Thrombus surface by SEM

Thrombus-Stent Retriever Interaction

1. Mechanical interaction: The thrombus is entangled around the struts, with gaps between the struts and the thrombus material (Figure A; Figure C is an enlarged view).

2. Adhesive interaction: The thrombus adheres to the struts of the stent retriever, similar to water droplets adhering to a thread (Figure B; Figure D is an enlarged view).

▲ Stent-thrombus interaction

A total of 79 interaction sites were photographed and analyzed across 7 stents. Among these, 44 (56%) thrombus-stent interactions were adhesive, while 35 (44%) were mechanical.

Thus, the thrombus-stent interaction is primarily adhesive rather than purely mechanical (direct clamping between the stent retriever struts, similar to mechanical interaction). This perspective refines the mechanism of stent thrombectomy compared to the conclusion drawn in our previous discussion.

▲ thrombectomy stents

III Thrombus to Stent Length Ratio

In addition to the interaction mode between the thrombus and the stent, the thrombus to stent length ratio (TL/SL) has also become a focal point of research. Belachew et al. conducted a retrospective analysis, using SWI to measure the length of thrombi and correlating it with the stent length used during treatment to summarize the impact of TL/SL on first-pass recanalization (FPR).

▲Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke

Finally, the conclusion was drawn: TL/SL affects the patient’s FPR, with a smaller TL/SL resulting in a higher FPR. In other words, longer stents may have a better first-pass recanalization rate under the same conditions. This pattern also applies to vessel recanalization rates (the smaller the TL/SL, the better the vessel recanalization).

(TL/SL Quartiles)

▲Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke

IV Impact of Tortuous Vessels on Stent Retrievers

Longer stents not only increase first-pass recanalization but also improve the overall success rate of the procedure. Besides the attributes of the stent itself, the anatomical characteristics of the vessels can also influence the success rate of the procedure to some extent. J.H. Kim et al. conducted an in vitro vascular model thrombectomy simulation experiment. They focused on observing the performance of different thrombectomy techniques (including aspiration thrombectomy, stent retrievers, combined techniques, etc.) in various vascular tortuosities .

▲vascular models

In experiments with different vascular models, both aspiration and stent retrievers produced poorer outcomes in more tortuous models. This suggests that the tortuosity of cerebral vessels may affect EVT techniques. Considering the stents, physical stretching or compression of the stent (which can make the stent thinner and flatter, potentially pushing the thrombus out) could be factors affecting the success rate of thrombectomy.

▲In Vitro Analysis of the Efficacy of Endovascular Thrombectomy Techniques according to the Vascular Tortuosity Using 3D Printed Models

V Emergence of Third-Generation Stent Retrievers

Let’s summarize the conclusions of the aforementioned experiments:

1. The relationship between the stent and the thrombus involves not only mechanical action but also adhesive interaction.

2. Longer stents, without affecting the vessel, can achieve better thrombectomy results.

3. Second-generation stent retrievers are prone to stretching and compression in tortuous vessels.

Possibly based on these considerations, or perhaps for other reasons, third-generation stent retrievers have emerged (there is no strict definition between second and third generations here). A common feature of third-generation stent retrievers is the availability of longer models, which can be divided into two main categories.

‍

First category: Primarily mechanical grasping, with enhanced embedding ability into the thrombus. This includes devices like Solitaire X, Trevo NXT, Tigertriever, among others.

▲Solitaire X (thrombectomy stents)

▲Trevo NXT (thrombectomy stents)

Among them, I personally find Tigertriever to be quite representative. This stent system allows the operator to adjust the radial expansion degree of the stent according to the diameter of the target vessel. The adjustable outer diameter size enables it to better adapt to the size of the target vessel. During the retrieval process, the stent size can be moderately contracted to reduce the risk of vascular injury. Whether this manual control method can grasp the thrombus better than self-expanding stents is something I am not sure about and cannot conclude rashly, but this design theoretically addresses some of the pain points.

▲Tigertriever (thrombectomy stents)

Second category: Primarily adhesive clasps. Compared to self-expanding stents that mechanically embed into the thrombus, this design emphasizes adhesion to the thrombus, incorporating more metal wires within the stent. To address the issue of wall adherence in tortuous vessels, the stent is designed in segments, resembling a train. This design not only prevents compression in bends but also ensures the stent opens more effectively (not being influenced by proximal or distal landing points).

▲train

Products in this category include EmboTrap, Eric, 3D Revascularization device, etc. Whether it’s the improved functionality or the stent’s design, I believe that this category of stent retrievers embodies the characteristics of third-generation thrombectomy devices (of course, this does not necessarily mean they are clinically superior, but their design has indeed made significant improvements addressing specific experimental pain points).

▲Eric (thrombectomy stents)

▲3D Revascularization device 

▲Embo Trap (thrombectomy stents)

Here, the most representative example is Johnson & Johnson’s EmboTrap stent, originally developed by Neuravi. In 2017, Cerenovus, a division of Johnson & Johnson focused on neurovascular treatments, announced the acquisition of Neuravi. EmboTrap features a dual-layer stent design with an inner closed-loop stent providing high radial support and an outer open-loop stent with more mesh wires. The benefit of this design is that the large openings in the outer structure can trap the thrombus in the middle, while the high radial force design of the inner layer quickly creates a flow channel after stent deployment, achieving rapid recanalization. EmboTrap III further designed the outer open-loop part to be flared to maintain wall apposition during thrombectomy. The closed distal end is designed to capture any potentially escaping thrombus.

▲Embo Trap III (thrombectomy stents)

We all know that thrombectomy is a race against time. One critical aspect of mechanically based stent retrievers is that once deployed, the stent’s opening can create a passage allowing partial blood flow, achieving immediate reperfusion to some extent, and using the flowing blood to aid in thrombolysis. Segmental stents mainly rely on thrombus adhesion and physical interaction between segments, typically not forming an immediate passage. The dual-layer stent design of EmboTrap theoretically combines the advantageous characteristics of both stent types.

▲The Inner Stent Design of EmboTrap

Beyond the theoretical design effects, one of the most representative studies on EmboTrap—ARISE II—also provided excellent results. Whether in terms of first pass effect (FPE), three-pass recanalization, or 90-day modified Rankin Scale (mRS) scores, EmboTrap demonstrated significant advantages of third-generation thrombectomy stents .

▲Primary Results of the Multicenter ARISE II Study (Analysis of Revascularization in Ischemic Stroke With EmboTrap

▲ARISE ll Angiographic and Clinical Outcomes

VI Is the fourth-generation stent retriever the future?

Whether it is the mechanically focused Solitaire or the EmboTrap with its numerous designs, today’s thrombectomy procedures can solve most problems. However, mechanical thrombectomy (MT) can still face challenges when dealing with organized or hard fibrin-rich and sticky clots, which are common pain points in clinical practice. To address this, Vesalio designed the fourth-generation stent retriever—NeVa.

▲Neva (the fourth-generation stent retriever)

A notable feature of the NeVa stent retriever is its functional zone design. The proximal end is responsible for embedding and adhering to the thrombus, while the distal end is designed like a mesh pouch to ensure fragments remain within the stent. NeVa also features a unique Drop Zones technology. Drop Zones technology uses different sizes of mesh to change thrombus interactions, capturing the thrombus within the stent rather than relying solely on embedding and dragging along the arterial wall. During the procedure, each Drop Zone increases the likelihood of thrombus embedding into the stent.

▲Drop Zones technology

Beyond the innovative design, clinical trials have shown impressive results. CLEAR is a prospective, multicenter, single-arm study designed to evaluate the safety and efficacy of NeVa in recanalizing large vessel occlusions (LVOs). The trial results, whether in first pass recanalization (73.8%), three-pass recanalization (90.7%), or 90-day favorable outcomes (65.1%), have been remarkable.

▲Reperfusion results in miTT population 

(Clinical outcomes in mITT population)

▲Primary results from the CLEAR study of a novel stent retriever with drop zone technology

Despite the impressive results, Vesalio has not rested. Recently, they launched the latest NeVa series stent retriever—NeVa NET. This time, they focused on the risk of distal embolization by integrating a microfilter net to prevent clot fragments from migrating to new or distal areas. Whether this design will better help reduce the risk of thrombus migration remains to be seen with more clinical trial results.

▲the latest NeVa series stent retriever—NeVa NET

VII Conclusion

In recent years, the development of aspiration catheters has progressed rapidly, while stent retrievers have been relatively low-key. With the maturity of combined techniques, more practitioners are focusing on the performance of aspiration/intermediate catheters, often considering stent retrievers as an auxiliary tool (essential but not requiring the highest performance). However, with upstream research providing more detailed studies on thrombus properties, it is believed that future stent retrievers will be designed more specifically to help solve clinical problems better. Although the article discusses the development from the first to the fourth generation, it does not necessarily mean that the fourth generation is superior to the third or second. The best tool is always the one that fits the job well.