The importance of embolisation in atherosclerotic vascular disease has recently undergone a major change in mindset. In the 1990s, it was considered a rare event confined to degenerated and aged saphenous vein grafts (SVGs). Lately, however, embolisation has become a major issue to contend with, not only in SVG but in all carotid artery stenting, in acute myocardial infarction (AMI) and in percutaneous interventions in other coronary and peripheral arteries. This growing importance has been echoed in certain task-force guidelines recommending the use of embolic protection devices (EPDs) in percutaneous coronary interventions (PCIs) of carotid arteries and SVGs.
The Many Facets of Embolic Protection
Deployment Position of the Device
EPDs can be deployed in various locations relative to the target lesion. Most are deployed at the distal side of the target lesion, such as the distal filtration device. Proximal devices include a distal occlusion balloon with a flow-reversed and aspirated debris system. Thrombectomy devices are active across the entire target lesion, excising and aspirating the tissue emboli. All distal and proximal devices require a proper landing zone, which may be limited due to vessel anatomy. For example, the circumflex anatomy limits the use of distal protective devices. Other position limitations include device size range and side branches between the target lesion and the protective device.
In some cases, flow preservation through the target vessel is of prime importance, for example if the vessel is providing uncollateralised circulatory output to a large area of the myocardium or in cases where even a brief period of ischaemia may not be tolerated (e.g. left ventricular dysfunction). Potentially, all protective devices have negative impact on flow preservation, ranging from total occlusion of the vessel for several minutes by some occlusion-based systems to reduced flow through filters sometimes clogged with trapped emboli, which may lead to complete or partial filter occlusion.
In case of AMI, the extra time required to deploy the EPD may delay reperfusion. There is a lack of meaningful clinical benefits in this setting, despite the debris retrieval and improved flow characteristics.
Pore Size Optimisation
Electron microscopy studies show that the diameter of particles ranges from 3.6 to 5,262μm; 50% are less than 100μm in diameter. Optimising the pore size of filter-based devices is vital in order for two counterobjectives to be balanced: smaller pores would limit the flow, capture significantly more debris and are therefore more likely to cause filter thrombosis, whereas larger pores would allow much more debris to pass through and cause damage downstream. Additionally, smaller pores may require a larger capacity to hold entrapped emboli or risk overflow of debris. The pore size of today’s filter devices, ranging from 80 to 150μm in diameter, represents a compromise that is dictated by these opposing requirements and may pose clinical risks.
Embolic Protection Timeline
While some of the existing protection devices may be in place before the stent is deployed, all of them are removed at the end, thereby limiting the protection to the duration of the PCI procedure only. This is a significant shortcoming and is particularly critical in carotid stenting, where about half of stenting-related strokes occur post-procedure. It is reasonable to believe that a similarly high rate of post-procedure embolisation occurs in coronary procedures as a result of the delayed outcome of plaque layer destabilisation.
The relatively large crossing profile of distal protection devices and thrombectomy devices adds a complicating factor when advancing through a partially occluded artery or in a tortuous vessel. In addition, the unfavourable crossing profile of the catheter makes the retrieval of the device technically challenging as it may get caught in the deployed stent struts. Both of these potential scenarios increase the risk of device-related vessel dissection, perforation or other injuries. Some of the devices come loaded on their own delivery system, adding a level of complexity to the entire process, prolonging it and requiring training and experience.
A New Approach to Embolic Protection
A new approach to embolic protection has recently been introduced. This approach attempts to block the debris at source, preventing it from entering the bloodstream in the first place. The first product based on this approach is now commercially available as MGuard™ (InspireMD), which is based on a stent covered with an ultra-thin, micron-level, flexible mesh sleeve fabricated by circular knitting. During stent deployment, the net stretches and slides over the expanding stent struts, creating custom-designed pores parallel to the arterial wall. Once in place, MGuard captures embolic debris between the fibre net and the arterial wall and isolates the pro-thrombotic intima components from the bloodstream.
Advantages of the New Concept
The protection net is deployed simultaneously with the stent, as it reaches its position and expanded size upon stent deployment. No specific distal or proximal landing zone is required, nor are special considerations required for side branches beyond the target lesion. There are no limitations on vessel size, and the range of sizes fits all standard diameters and lengths of target lesions.
As the net follows the vessel topography, it has no impact on blood flow. In AMI, as the net is deployed simultaneously with the stent, reperfusion is accelerated compared with protective device deployment. The net may also have a positive impact in preventing no-reflow in AMI in lesions with a specific composition of plaque.
The size of the net’s pores can be controlled. Due to the position of the net, the amounts of entrapped debris, overflow or filter thrombosis are no longer limitations on minimising pore size. Thus, a level of freedom has been gained in terms of designing optimised pore size.
The net serves as a built-in, permanent EPD, extending the protection time beyond the end of the procedure. It falls short of extending protection pre-stent deployment, and does not protect against embolisation when crossing over the lesion or pre-dilatation.
The net has minimal effect on the stent’s crossing profile and is delivered on a conventional delivery system with no impact on dilatation pressure. Hence, simple deliverability is achieved, eliminating the need for special training.
Following an animal trial in which the safety of the device was established, MGuard was and continues to be tested in clinical trials to assess its deliverability and safety in a high-risk PCI cohort of native coronaries with acute coronary syndromes and degenerated coronary vein grafts. Since embolic debris is captured in 98% of vein graft interventions, this serves as a good model for MGuard.
Thirty patients have already been enrolled and interim results show that the device and the procedure were successful in all patients using conventional PCI equipment. No device-related safety issues were encountered. Additional clinical data need to be collected to reach statistically meaningful conclusions regarding the safety and efficacy of the device.
Other Potential Clinical Benefits and Applications
The net may play a role in reducing the impact of stent expansion on the arterial wall. By diffusing the pressure, the net may reduce the injury, thereby reducing intima hyperplasia and, eventually, reducing restenosis.
Drug Delivery Platform
The net can also be used as a potential platform for drug delivery systems. The net provides better and more uniform coverage of the arterial wall than a conventional drug-eluting stent (DES); therefore, it may elute the active ingredients more efficiently, thereby lowering the dosage. The net may also facilitate the use of drug molecules with reduced diffusion capabilities. This potential application is particularly appealing in view of the delayed healing and imperfect stent strut endothelisation observed with currently approved platforms of DES.
Incorporating the concept into self-expandable systems without altering the crossing profile or compromising flexibility, coupled with the inherent permanent embolisation control, may provide an important contribution to the current arsenal of carotid stenting.
Perforation and Bleeding
Perforations are among the most feared complications of coronary and endovascular interventions. Currently available covered stents are bulky and inflexible and frequently require upsizing of the guiding catheter. The new concept could be designed to become occlusive by employing a denser polymer mesh or impregnating the net with pro-coagulants.
This new approach to embolisation control may potentially improve several facets of embolic protection. MGuard, the first product developed under this concept, is currently under investigation in human coronary and vein graft trials. Subject to supporting clinical data, this concept may have a wide area of potential applications and may contribute significantly to embolisation control in various settings. Ôûá