This article originally appeared in MPO.
Thrombectomy innovations are addressing the needs of physicians trying to get a handle on challenges with clot removal techniques
Stroke treatment and prevention is a hot market. According to Allied Market Research, the global thrombectomy devices market generated $1.3 billion in 2020 and that figure is expected to double to $2.6 billion by 2030—a compound annual growth rate of 7.4%.1
Drivers of this market include the increase in sedentary and unhealthy lifestyles, resulting in higher rates of deep vein thrombosis (DVT), peripheral artery disease, acute myocardial infarction, and pulmonary embolism (PE). Other factors are a growing geriatric population and advanced medical technology improvements that allow stroke to be treated quickly and more effectively, with improved patient outcomes and shorter hospital stays.
“Over the past decade, advancements in technologies have allowed for the development of safer, quicker, and more efficient clot removal in both large and small vessels,” said James F. Benenati, chief medical officer at Penumbra, an Alameda, Calif.-based global healthcare company focused on innovative therapies for stroke, peripheral and coronary blood clots, and aneurysms. “These advancements have shortened the time to treat strokes and made single-session arterial, DVT, and PE therapy routine in the U.S. Additionally, high thrombus burden coronary lesions can now be treated more safely and quickly than in the past, using continuous aspiration thrombectomy. Advances in catheter design provide catheters that are more torqueable and trackable, enabling physicians to reach target vessels rapidly and safely.”
In the past, the treatment of choice for stroke by many patients and physicians has been anticoagulants and thrombolytics. “However, given the associated risks with these therapies, such as bleeding, mechanical thrombectomy devices have been developed,” said Jason Belzer, divisional vice president for the U.S. coronary division of Abbott’s vascular business, based in Santa Clara, Calif., which provides products addressing heart disease, cardiac arrhythmias, peripheral arterial disease, and more. “These devices provide rapid thrombus removal, thereby restoring blood flow while minimizing bleeding risks or other complications.”
The two main types of thrombectomy devices for removing clots are aspiration catheters and mechanical thrombectomies (stent retrievers). A survey by the Society of Neurointerventional Surgery revealed roughly 40% of neurointerventionalists identified catheter aspiration thrombectomy as their therapy of choice. Approximately 30% opted for stent-retriever mechanical thrombectomy, with the remaining 30% favoring an approach that combined both methods.2
Both methods are proven to be safe and effective. In mechanical thrombectomies, a catheter is inserted into an artery and is then directed to the clot. A stent retriever is then inserted into the catheter, captures the clot, and both clot and stent are pulled back through the catheter and out of the body. Aspiration thrombectomies are best for smaller clots—when the catheter reaches the clot, a negative pressure is created that pulls the clot into the catheter; the pressure is maintained until the catheter and clot are removed from the body.
Because these methods are quick, effective, safe, and easy to use, some hospitals and medical centers services are establishing Pulmonary Embolism Response Teams (PERT). The goal is to have a single multidisciplinary team of experts in thromboembolic disease who can respond rapidly to patients with acute pulmonary embolism and have the tools to provide a full spectrum of therapeutic options. “PERT teams were modeled after rapid response teams and are meant to generate a prompt, patient-specific plan for patients with pulmonary embolism without having to consult multiple individual specialists,” said Belzer. “PERT teams require the latest tools that provide rapid solutions for clinical manifestation, including aspiration catheters and mechanical thrombectomies.”
Latest Trends
Another tool in the stroke intervention toolbox is balloon guide catheter (BGC) technology. BGCs help with clot retrieval by creating proximal flow arrest, reducing embolic burden, and shortening procedure time. In mechanical thrombectomy, flow reversal through the BGC as the stent retriever is being retrieved helps pull in loose fragments of the clot, removing them from circulation. BGCs can also help with recanalization during aspiration thrombectomy.
Although BGCs can lead to improved patient outcomes, they have historically been limited in their ability to reach targeted anatomy. CERENOVUS recently launched its first balloon guide catheter—EMBOGUARD—after years of stroke science research and rigorous model and real-world case scenario simulation testing. “The result is a BGC that is highly navigable, which can potentially improve revascularization,” said Mark Dickinson, worldwide president for Irvine, Calif.-based CERENOVUS, part of Johnson & Johnson MedTech, and a leader in the endovascular treatment of hemorrhagic and ischemic stroke. “We’re excited by continued advancements in this space and, ultimately, how they can translate to improved patient outcomes.”
Thrombectomy is a highly competitive market, which also drives innovative research and development (R&D).
“We work with many small but very innovative companies that are racing to the thrombectomy or aspiration market,” said Doua Vang, vice president of business development for VitalPath, a Minneapolis, Minn.-based provider of highly complex catheter solutions for the cardiovascular, peripheral vascular, neurovascular, and structural heart markets.
Much of this R&D is focused on miniaturization of devices and ease of navigation to make it easier to pass through torturous anatomy more quickly, or to reach more distant targets in the body. Key mechanical characteristics for these products and their components include low friction, flexibility, and pushability without kinking.
“More companies are chasing after a larger inner diameter (ID) to increase the ability to aspirate a clot, while keeping the outer diameter (OD) as small as possible so the device can be used in a wider range of patients, making for a very thin wall,” said Vang. “But at the same time, you don’t want the catheter to kink and you want pushability to traverse through the anatomy. So physics is working against us. These challenges mean that we have to be even more clever at material selection to safely manipulate the catheter to where it needs to be.”
Expert navigation and manipulation to reach cardiovascular targets quickly is also dependent on the guidewires in thrombectomy devices and their mechanical characteristics, including material properties, diameter, tip design, and surface coatings.
“There is an increased acceptance of polytetrafluoroethylene (PTFE)-coated guidewires that can be either 314 stainless steel or made with nitinol,” said George Osterhout, president of Surface Solutions Group, a Chicago, Ill.-based provider of non-stick, low-friction coating technologies specifically for the medical device industry. “This is because the diameters of the wires continue to get smaller and require a coating that reduces friction so they can be more easily pushed through the blood vessels, reducing the risk of vascular damage.”
What OEMs Want
OEMs want to be involved in thrombectomy innovation because it is such a rapidly growing market that positively impacts a huge part of the population—almost half of all U.S. adults are afflicted with some type of cardiovascular disease.3
“What our customers are looking for most is speed to market,” said Scott Olson, vice president of engineering for VitalPath. “Everyone asks us how fast we can help them get to a concept and start building product. Customers are also really focused on how we can help with supply chain issues.”
“Given the current supply chain situation, customers and contract manufacturers have to be very creative in material selection to avoid bottlenecks,” added Vang. “Customers are always asking us what can we substitute for certain materials that have been hard to come by. There is a lot of problem-solving required for material selection—whoever can solve that problem is going to win the game.”
For guidewires, OEMs increasingly want coatings on reel-to-reel continuous wire spools or cut-to-length guidewires. This helps reduce their work-in-process costs because they do not have to do all the cutting and grinding prior to sending the wire to a supply chain partner for coating, such as Surface Solutions Group.
“There is also increased interest in adding a white banding marker on guidewires versus creating a band by having the PTFE ablated down to the metallic substrate, without damaging the wire,” said Osterhout. “The white banding provides greater contrast than the bare metal reflection against the coated area of the wire.” This higher-contrast banding helps surgeons know the depth of the wire during procedures, which provides greater accuracy in navigating to the target area. The band is relatively smooth on the PTFE surface and the tolerances on the length of the band are more accurate than with the ablation banding method.”
Design Considerations
Interventional cardiology devices and their components follow the same general design considerations as other types of medical devices. Design for manufacturability (DFM) is especially important. A properly designed part, regardless of the material used, is essential for a trouble-free and stable production process. “Unusual shapes or exaggerated proportions often require precise design adjustments,” said Chris Becker, director of sales for life science applications for Plastic Design Corporation, a Scottsdale, Ariz.-based provider of micro-molded components for the medical device market, including interventional cardiology. “For injection molding, draft angles on the side walls of the part are extremely important in order to allow the part to be ejected from the mold.”
DFM is best applied at the beginning of the design process; however, part design engineers are usually not familiar enough with production details to fully design toward that method from the start. As a result, DFM tends to be an ongoing process throughout the part design phase between the part designer and the manufacturer, culminating in final design changes that are made before the final design review. “It is important for medical device companies to not only engage with partners that understand and value DFM, but also promote disciplined engagement—early and often—throughout the process,” said Becker.
DFM includes the careful consideration of the following qualities that are “absolutes” for any cardiovascular equipment:
- Cleanliness—For long-term implantable and short-term in vivo interventional devices, medical device companies (MDMs) are responsible for meeting stringent product requirements for cleanliness, including aspects of both viable and non-viable cleanliness. “These requirements translate beyond component manufacturing to procedures for cleaning, storage, and handling of tooling, equipment, and product,” said Becker.
- Dimensional accuracy and control—Due to the incredibly precise nature of cardiovascular intervention, MDMs must maintain extremely tight dimensional tolerances for their interventional devices, especially those that navigate through complex anatomy and narrow blood vessels. “Component suppliers must meet these stringent criteria at the initial qualification of the product and throughout the lifecycle of the product,” said Becker.
- Flash—Flash is excess and unwanted material that may be deposited on a surface during injection molding, which can result in unintended consequences if not completely removed. Flash can also add to or distort dimensions on the area of the component where it appears. Such material is often irregular and may have a rough surface or sharp edges. “Flash is often impossible to see with the naked eye and requires advanced optical scanners or imaging systems to ensure none is present on the components,” Becker said.
New Advances and Technologies
CERENOVUS established a world-class stroke science arm—the Neuro Thromboembolic Initiative (NTI)—to collaborate with physicians and academics to investigate and understand neurovascular disease. By gaining practitioner perspectives and better understanding unmet clinical needs, these insights inform CERENOVUS’ research and development process. Coupled with company-sponsored clinical studies, these findings contribute deep insights on the histology of clots and the technological advances that will help physicians achieve better patient outcomes.
The output of this research has resulted in several new thrombectomy technologies, including EMBOTRAP, a stent retriever. The EMBOTRAP device is placed through a microcatheter less than half a millimeter in ID across the clot. The microcatheter is unsheathed and the EMBOTRAP device opens up and traps the blood clot. The physician then withdraws the device and microcatheter while engaging the blood clot, often times with co-aspiration. It is a very fast procedure—sometimes less than 10 minutes from puncture to revascularization. The stent device is made from nitinol or nickel-titanium alloy; the superelastic and shape-memory properties of nitinol make it especially well-suited for this application.
VitalPath has opened a design center for product development that will accelerate timelines and drive new technologies. New equipment includes a laser, extrusion line, and braider. “Our new laser-cutting equipment greatly enhances our ability to make new thrombectomy catheters,” said Vang. “For example, instead of a traditional braided or coiled catheter, we’re seeing a trend where the entire shaft is a laser-cut tube. We can manipulate the laser-cut pattern to meet exact performance specifications and still be able to snake the catheter where it needs to go.”
This also has the potential to reduce the number of processing steps. Instead of adding multiple jackets, sometimes the laser-cut pattern can be manipulated so it only needs one jacket material. “Our team also recently came up with a concept for a steerable microcatheter,” said Vang. “Microcatheters are typically not steerable—it is such an extremely challenging design. We developed it as a proof-of-concept and showed it at MD&M West, where it received a lot of attention. We are now tinkering with the design for a large OEM.”
Surface Solutions Group can currently process banded guidewires up to 24 inches. Most OEMs want white banding on green or blue PTFE-coated guidewires. In response to this trend, the company is developing a system that will provide white banding on PTFE-coated cut-length guidewires up to 72 inches long. “Our tolerance on a 10-mm white band width is in the range of ±0.5 mm,” said Osterhout. “We are in prototyping stages at this time and have excellent adhesion of the white band to the green or blue PTFE.”
Surface Solutions Group has done this type of high-contrast banding with hypotubes up to 15 inches long, but never on a 0.013-inch diameter guidewire that is 72 inches long. “Although the much smaller diameter guidewire banding is indeed a challenge, our R&D is showing that the white banding is possible, as long as the bands are located within a 20-inch area on the guidewire,” said Osterhout. “We can also do the banding with good repeatability on longer parts than originally thought.”
A downside to traditional aspiration catheters is clogging. Substantial clot burden can lead to potential clogging during a procedure. To solve this problem, Abbott developed an innovative hydrodynamic aspiration catheter that sprays a high-pressure saline jet located in the distal part of the catheter. “This jet macerates the captured clot within the catheter, allowing for more efficient aspiration while reducing any clogging issues,” said Belzer.
The system can also selectively infuse/deliver diagnostics or therapeutics intra-procedurally. Its high single-session treatment success rate leads to improved patient outcomes and reduces the length of costly hospital stays.
In 2021, Penumbra launched its Indigo System Lightning 7—a minimally invasive catheter-based aspiration system that uses continuous aspiration to remove blood clots throughout the body. “Our Lightning Intelligent Aspiration System is a unique, computer algorithm-aided, clot detection technology that can differentiate between clot and flowing blood,” said Benenati. “This is designed to reduce blood loss and the need for clot-dissolving drugs, which helps to lower the risk of bleeding complications. The Lightning technology highlights advances in both catheter and pump aspiration design, allowing safer and more efficient methods to remove clots.”
CERENOVUS’ NIMBUS system, approved for use in Europe in 2020, was developed for tough clots that refuse to budge by using proprietary models that simulate difficult anatomy and clot histology. In approximately 25% of thrombectomy cases, tough clots cannot be removed and each attempt increases the risk of vessel injury. Nimbus is designed with two different features to maximize tough clot removal: a proximal spiral section and distal barrel section. The spiral section maximizes blood vessel lumen coverage and device-clot interaction. Through this unique design, NIMBUS can improve reperfusion rates and reduce the number of passes required in tough clot cases.
“This innovation demonstrates our commitment to ensuring physicians have the most advanced tools in their hands to change the trajectory of stroke,” said Dickinson.
Moving Forward
“When we look at thrombectomy, we see opportunities to drive outcomes through innovation by treating challenging disease and doing it less invasively and more efficiently,” said Belzer. “This space is getting a lot of attention from companies such as Abbott, so it’s fair to assume we’ll continue to look for ways to bring incremental value to patients and providers alike. Those options could include addressing higher clot burden with smaller devices, addressing older (chronic) clot, and making the process more streamlined through technology—for example, smart catheters with embedded sensors.”
Another R&D goal is making devices smaller, more flexible, and more pushable to penetrate further into the body, or through narrower and more delicate blood vessels. For example, the FDA recently cleared Israel-based Rapid Medical’s Tigertriever 13 device, which was designed to remove clots from delicate brain blood vessels resulting for ischemic stroke.4 What makes this stent-retriever device unique is its adjustability; using advanced 3D braiding used in aerospace engineering, Tigertriever can be precisely controlled to capture the clot and also remove the tension from the vasculature before removal.
New advances in thrombectomy are not always technology-oriented—they can be related to software as well. In an effort to address unmet clinical needs, Penumbra has partnered with RapidAI to enable faster clinical decision making for pulmonary embolism diagnoses and procedures. RapidAI provides a clinically proven, data-driven artificial intelligence platform that empowers clinicians to make faster, more accurate diagnostic and treatment decisions for stroke and aneurysm patients. “Penumbra and RapidAI have worked together to develop several clinical and communications modules for pulmonary embolism,” said Benenati. “The modules are aimed to streamline triage and decision making by processing computerized tomography (CT) scans and delivering clear, easy-to-interpret CT images directly to the physician.”
As medical technology advances, and thrombectomy devices continue to evolve, patient outcomes will improve and patients will have shorter hospital stays. Several years ago, thrombectomy for venous and arterial disease was hardly a consideration; today, for many physicians, it is now the front-line therapy for ischemic stroke throughout the world.
“Looking into the future, we see the advent of next-generation aspiration catheters and larger lumen devices that remain highly navigable,” said Dickinson. “Until now, physicians have had to make trade-off decisions on size versus navigability, with navigability invariably winning. After all, you need to be able to access the clot to remove it. But the lure of a larger device and the increased hope of clot removal through it has always been desired. This combination—navigability and size—has always been an engineering challenge, but we are confident to have overcome these factors and anticipate major developments in this area in the future.”
References
