The Dark Side of Embolic Protection Devices
These devices will play an important role in CAS, but their use involves some trepidation.
To view the figures and tables related to this article, please refer to the print version of our September issue, page 54.
There is considerable evidence, both clinical and experimental, that embolization takes place universally during all carotid artery stenting (CAS) procedures. Currently, there exists a consensus among specialists that some form of embolic protection device (EPD) with the ability to capture emboli and prevent intraprocedural neurological complication should be routinely used during CAS.1 However, each additional step to an existing procedure possesses the possibility of an additional risk to the procedure. The use of EPDs may not be an exception.
VARIOUS DISTAL EPDs
There are two different types of distal EPDs.2 The first approach is the use of a distal occlusion balloon to temporarily occlude the outflow from the distal internal carotid artery. The PercuSurge GuardWire (Medtronic, Santa Rosa, CA) is currently approved in the US for use in degenerated saphenous vein grafts. The second approach is the use of a filtration device placed distal to the lesion. An alternative to distal EPD is a method in which a proximal occlusion balloon is used to reverse the flow in the internal carotid artery (ICA).
LIMITATIONS OF DISTAL EPDs
There are a number of failure modes for distal EPDs. These include (1) failure to cross the lesion with the EPD, (2) failure to capture all emboli, and (3) other failure modes (Table 1).
Failure to Cross the Lesion with the EPD
Deployment of an EPD may not be a problem in a straightforward case with simple anatomy. When dealing with patients who have tight stenosis and/or tortuous vessels, however, it is not only technically challenging, it can also be dangerous. The cause of failure to cross the lesion includes the large crossing profile of the EPD, abrupt change in stiffness, and lack of torquability.
Large crossing profile. The crossing profile of various EPDs is summarized in Table 2. Each device has a relatively large crossing profile, especially when compared to the profile of a 0.014-inch guidewire, which was the standard device used for crossing the lesion before EPDs became available. This larger crossing profile has resulted in the inability to cross the lesion, especially when the lesion is very tight. Predilatation with a 2-mm PTA balloon has been used to overcome this problem, but this maneuver not only makes the procedure more complicated, it also contradicts the concept of cerebral protection. Manufacturers are developing second- and third-generation devices that have a lower crossing profile and will hopefully minimize the need for predilatation.
Abrupt change in stiffness. The problem with all distal EPDs is that there is an abrupt change in stiffness, from the floppy guidewire attached at the tip of the device to where the protection balloon or the filter is placed (Figure 1A). This change is especially important in dealing with a tortuous ICA and has been responsible for some failures. Straightening the vessel with a separate wire (buddy wire) prior to the introduction of the protection device facilitates the deployment of distal EPD; this maneuver may however cause embolization. Design improvements in second-generation devices have made this transition more gradual and have contributed to their safer and easier deployment (Table 2) (Figure 1B).
Issues Related to Capture Efficiency
Capture efficiency is one of the most important aspects of any protection device because the whole purpose of using the device is to capture emboli and to prevent procedural neurological events. The capture efficiency can be hindered by a number of different mechanisms and is dependent on which type of device is used (occlusion balloon vs filter). However, one common mechanism for missing emboli takes place during the initial passage phase. Whether it is a distal balloon or a filter, the brain is not protected from emboli at this time; this is an inherent shortcoming of any distal protection device.3,4
Failure to Capture All Emboli With Distal Balloons (PercuSurge GuardWire)
Incomplete occlusion of the ICA. The PercuSurge GuardWire accomplishes brain protection by occluding the ICA, thereby preventing the emboli from traveling toward the brain. Gradual deflation of the balloon resulting in re-establishment of prograde flow has rarely been encountered. This phenomenon can be prevented by constantly monitoring the balloon with the fluoroscope or by injecting contrast into the ICA during the procedure. Unfortunately, it is often too late at this point to detect the problem. On the other hand, excessive overinflation will increase the risk of vessel spasm or dissection.
ICA-ECA communication. Although the PercuSurge GuardWire may effectively protect the brain from emboli from the ICA in the vast majority of cases, the external carotid artery (ECA) is not protected. It is well known that the external carotid artery has collateral communication with both the intracranial ICA and the vertebral artery. This communication may allow the emboli to travel to the brain.5
Suction shadow. Tubler et al have reported on their experience with the PercuSurge GuardWire.6 They experienced a 5.2% periprocedural neurological complication despite the use of the GuardWire. The authors speculated that suction shadow may have been responsible for this phenomenon. Suction shadow occurs when the aspiration catheter fails to aspirate all the emboli due to the fact that some emboli may have been too large for aspiration, or due to the fact that blood column adjacent to the GuardWire balloon may not always be effectively aspirated.
Failure to Capture All Emboli With Filter Protection
The pore size dilemma. The strength of a filter device compared with an occlusion balloon is that it can preserve flow during the procedure. This not only maintains flow to the brain but also permits angiography to be performed during protection. However, preservation of flow may mean preserving the possibility for the emboli to travel to the brain. A number of groups, including ours, have evaluated the efficacy of a filter in our ex vivo model and, although the filter was able to capture the vast majority of particles, especially the large ones, it did not capture 100% of them.4,7 Particles are released during the initial passage phase, and particles smaller than the filter pore pass through or around the filter. From experience with the PercuSurge GuardWire, it is known that the 50% of the emboli released during CAS are smaller than 100 µm.8 Interestingly, all filters currently available have pore sizes larger than 100 µm, which may explain why there are significantly more particles captured with the PercuSurge balloon than with filters.9,10 Although it may be argued that such small emboli missed by a filter may be inconsequential, there is also enough evidence in the literature to suggest that microemboli result in neurological dysfunction, including deterioration in cognitive function and memory loss; although such patients may not always present with a stroke or a TIA.11,12
Smaller pore size may decrease the chances of microembolization, however, it also resulted in a higher incidence of filter thrombosis. Filter thrombosis is related to filter plugging as a result of capturing too many particles and/or fibrin deposition.13 Some manufacturers had to make the pore size of their filters larger because the thrombosis rate approached 20%. Currently, most filters have a pore size of 100 µm to 150 µm.
Particles flowing around the filter. In addition to particles flowing through the pore of the filter, some particles may flow around the filter. This is especially true when a filter device is placed in a tortuous ICA in which the filter may not appose the vessel completely, possibly allowing the particles to embolize (Figure 2).
Embolization during retrieval. Embolization with the use of the filters can also occur during the retrieval phase. This is due to the fact that some filters have limited volume, which will decrease further if the filter is collapsed during retrieval (Figure 3).
Mathias has reported experience with various distal EPDs. Although brain protection reduced the perioperative stroke rate by 60% compared to unprotected CAS, 10% of patients undergoing protected CAS had new silent infarcts based on diffusion-weighted MRI.14 This study clearly underscores the need to improve the emboli capture efficiency of these protection devices.
Other Problems Associated with Distal EPDs
Detachment of the filter components. Although extremely rare, detachment of the filter from the guidewire has also been reported. Detachment occurs when the filter is caught on the stent during retrieval. Similar events have occurred with other components of the EPD system, including a retrieval catheter that detached and embolized.
Problems associated with the aspiration catheter or the filter retrieval catheter. All distal protection devices require either the aspiration catheter (PercuSurge) or the retrieval catheter to be introduced prior to retrieving the protection device. Both catheters have a large lumen at the tip because it needs to either suction the particles (aspiration catheter) or to collapse the filter. Difficulties in introducing these catheters have been encountered because of this large opening being caught by the struts of the stent. With increasing use of nitinol filters, this has become a more frequent event because nitinol stent struts have a tendency to protrude into the lumen. In some cases, surgical conversion has been required.
Dissection/spasm in the distal ICA. The distal ICA is a relatively delicate vessel with regard to dissection and spasm. Because any distal protection device exerts some degree of force on the vessel wall to achieve complete apposition, it will irritate the vessel.9,10,15 The degree of irritation increases with frequent movement of the protection device, which is inevitable even in experienced hands. Although most episodes of spasm are self-limiting and do not result in clinical sequela, the long-term effect of such spasm in the development of intimal hyperplasia is unknown.
Prolonged procedural time. Because the use of EPDs adds more than a few extra steps to the procedure, as well as the previously mentioned technical issues, it is not surprising that the procedural time with EPDs is significantly longer than that without. According to the global survey by Wholey, the mean procedural time with the use of EPDs was on average 30% longer.16
THE REVERSAL OF FLOW APPROACH (THE ArteriA PARODI APPROACH)
When analyzing the limitations of distal EPDs, it becomes apparent that there is room for an alternative method. The proximal occlusion and reversal of ICA flow is one such example. The Parodi anti-embolization catheter (PAEC) (ArteriA, San Francisco, CA) is a guiding sheath with an occlusion balloon attached at the distal end of the catheter.15 The main lumen has an inner diameter of 7 F that allows the passage of balloons and stents.
Once the PAEC is inserted in the common carotid artery, the occlusion balloon attached on the outer surface of the PAEC, as well as the ECA occlusion balloon, is inflated, thereby occluding inflow to the carotid bifurcation while maintaining access to the carotid bifurcation lesion through the main lumen. The side port of the PAEC is then connected to a sheath that is percutaneously inserted into the femoral vein to create a temporary A-V shunt. This A-V shunt, along with the external carotid occlusion balloon, will create reversal of flow in the ICA. Thus, particles of all sizes will flow retrograde through the PAEC and can be captured. Once reversal of flow is established, CAS can be safely performed with a guidewire of choice. Of note is that the lesion is not manipulated with any device until cerebral protection is achieved, and that particles of all sizes are recovered with the reversed flow.
This approach also has disadvantages, which include (1) interruption of flow during protection, (2) the potential to cause dissection or spasm in the ECA or CCA, and (3) it requires a larger puncture site hole in the groin. In addition, the somewhat bulky sheath (10-F outer diameter) may make its introduction into the common carotid artery challenging if the arch anatomy is complex. Although this approach is not perfect, it is noteworthy that it eliminates many of the issues related to distal EPDs.
EPDs: A MORE COMPLEX AND DIFFICULT PROCEDURE, BUT MUCH SAFER
There is considerable evidence, both clinical and experimental, that embolization takes place universally during all CAS procedures, and it is the Achilles’ heel of carotid stenting. EPD requires unique technical expertise to avoid unique complications and, therefore, adequate physician training for its use will be beneficial and probably mandatory. Despite the fact that first-generation EPDs have a number of shortcomings, there is increasing evidence in the literature that shows their benefit in reducing embolic events during CAS. Although not scientifically sound, the overall complication rates after CAS with and without EPDs appear to show a clear benefit for the use of EPDs (Table 3).
Routine use of a cerebral protection device, whether it is a distal EPD or a proximal EPD, has become the standard for CAS procedures. Recently, the preliminary result of the SAPPHIRE trial (PRECISE and AngioGuard EPD, Cordis Corporation, a Johnson & Johnson company, Miami, FL) was presented.17 The SAPPHIRE trial randomized 307 high-risk patients to either CAS with EPD (first-generation AngioGuard filter) versus CEA. The 30-day major adverse clinical event rates (stroke, death, and myocardial infarction) for CAS and CEA were 5.8% and 12.6%, respectively. Based on this SAPPHIRE result, it is expected that FDA approval will be granted by the second quarter of 2004. This author has worked with Morgan Stanley to estimate the future of the carotid market (Figure 4). It is estimated that CAS will play a major role in the treatment of patients with carotid stenosis; and EPDs, as well as patient preference, will play a major role in this paradigm shift.
Takao Ohki, MD, is Chief of the Division of Vascular Surgery and Associate Professor of Surgery, Montefiore Medical Center, New York, New York. He is a consultant for Cordis. Dr. Ohki may be reached at (718) 920-4707; email@example.com.
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