The State of Carotid Embolic Protection and the Role of Flow Reversal
A panel of carotid stenting experts engages in a candid discussion of data, devices, decisions, and the future of embolic protection in carotid stenting procedures.
DATA AND DEVICES: WHAT HAVE WE LEARNED?
Endovascular Today: Based on your experiences and the data so far, what are some of your broader observations regarding the various types of embolic protection devices—both occlusion and filters?
Dr. Clair: As the field has progressed, there has been a significant decrease in the profile of filtration devices, making them easier to use. There has also been improvement and experience on the part of the operators after using filter devices over a period of time, and these devices continue to be the primary method of protection in treating patients with carotid disease.
I think distal occlusion is much less frequently used now than it was before. It offered a profile advantage and potentially an embolic protection advantage because it stopped the flow completely. Flow reversal does that, but it also provides the ability to treat almost any kind of anatomy distally that you may encounter. This is one critical area in which flow reversal in particular adds something to the procedure.
Dr. Gray:I agree. On the whole, filters have significantly come down in size and profile as well as ease of use. Some of the newer technologies in filters have been alterations in approaches—nets, etc.—but even the original filters that we started with have generally seen tweaks that improved their usability. In spite of that, there are still patients for whom filters are not the ideal option, so proximal occlusive protection is reasonable in those patients.
I have not frequently used distal occlusive protection, so I don’t speak about it very often. We have used proximal protection though, and from a clinical standpoint,it has been a lifesaver with occasional patients in whom there is just no way to do the procedure otherwise.
This instills a comfort level because we do not have to perform the procedure unprotected, which was the only other option before if the patient absolutely couldn’t have surgery. Proximal protection has really allowed us to access a lot of patients who were otherwise considerably difficult or for whom placing a filter could be more problematic and dangerous than completing the procedure without protection.
Dr. Hopkins: This instills a comfort level because we do not have to perform the procedure unprotected, which was the only other option before if the patient absolutely couldn’t have surgery. Proximal protection has really allowed us to access a lot of patients who were otherwise considerably difficult or for whom placing a filter could be more problematic and dangerous than completing the procedure without protection.
I’ve been working with the brain for 35 years, and there are still huge areas of this organ that aren’t fully understood; they don’t function at a level that we can detect clinically, and that leads to one of the other issues about embolic protection. There hasn’t been enough attention paid to mental status changes associated with carotid artery disease, and the guys at Columbia did some great studies with endarterectomy
What they showed with endarterectomy is pretty conclusive, including that you can expect to see a dip in mental status function for a period of 30-plus days after endarterectomy in a significant number of patients. It usually returns to baseline within 3 to 6 months. What we really need are more data on stent patients with mental status changes pre and post.
Dr. Clair: What they showed with endarterectomy is pretty conclusive, including that you can expect to see a dip in mental status function for a period of 30-plus days after endarterectomy in a significant number of patients. It usually returns to baseline within 3 to 6 months. What we really need are more data on stent patients with mental status changes pre and post.
Endovascular Today: Based on the data available, can comparisons be made between specific embolic protection devices or types of devices?
Dr. Gray: I’m not aware of any direct data that compares these devices in a prospective, randomized study with sufficient numbers to really make a differential decision between specific devices in terms of embolic protection. All we really have are the data that were developed for the IDE trials, which are probably the most rigorous data available on each individual filter or embolic protection device.
We’ve seen a pattern of reduced stroke and death at 30 days over the course of the last 7 or 8 years, since the beginning of these trials having been reported, with SAPPHIRE and ARCHeR being granddaddy trials. More recently, EPIC and EMPiRE are more robust. The data have gone from about 7% or 8% complication rates to about a 3% complication rate, which is a significant reduction. The question really is, is it something inherent in the newer devices, or is the field itself improving?
Independent of the devices, we’ve seen a reduction in overall complication rates. Part of this is based on better patient selection and improved operator technique.
Now, having said all that, there are data that suggest that if you take a look at some of the secondary, nonclassic endpoints of stroke and death, such as TCD or DWI, Flow Reversal may show a differential compared to distal embolic protection. The challenge here is to determine whether the results will translate into a clinical outcome, and we all just talked about the fact that we think it’s important. Intuitively, it makes sense; it feels better not to have any embolic material in somebody’s brain.
Dr. Clair: I completely agree. It is pretty clear, though, that Flow Reversal in particular, at least in any study that’s looked at it, has had an advantage in soft markers of what are potentially cerebral events, meaning fewer DWI infarcts on early postoperative scans and fewer microembolic HITS or signals during the performance of the procedure.
Dr. Hopkins: There’s a clear trend of improvement in terms of morbidity and mortality as more and more experience has been achieved and newer devices are coming along. How do you look at the most recent data where you have the EMPiRE data, which are superb, and you have the EPIC data, which are also superb. They’re all getting better. We are learning—as each trial gets published and the data get scrutinized, we learn something new. I mean, what Bill did with the CAPTURE data is phenomenal. You learn so much from just really scouring that entire database and finding things like, 18% of the strokes occur in the contralateral hemisphere—how about that? And, only one-third of the ischemic events occur during the procedure. What are we doing about that?
We learn from each dataset. We now know that symptomatic patients are problematic when it comes to filters, for whatever reason. For Dan and me, having spent a number of years doing endarterectomies, it doesn’t surprise me at all, now that the data have hit me in the face. Because when you operate on symptomatic patients, very often you see the ugliest plaques. So it’s no surprise to me that filters are overwhelmed by the amount of thrombus and plaque debris that you see when a plaque ruptures and the patient becomes symptomatic from carotid artery stenosis.
The evolution toward something to do a better job, toward proximal protection, is a natural evolution. Whether or not proximal protection will be the answer for all symptomatic patients, I have no idea, but it certainly seems to be a step forward in terms of our ability to clean up the plaque debris. It’s almost like an endovascular endarterectomy.
The evolution toward something to do a better job, toward proximal protection, is a natural evolution. Whether or not proximal protection will be the answer for all symptomatic patients, I have no idea, but it certainly seems to be a step forward in terms of our ability to clean up the plaque debris. It’s almost like an endovascular endarterectomy.
Dr. Gray: We have also learned from the people who have more experience than we do in some of these fields. The European Flow Reversal trialists won’t do a symptomatic patient with anything but Flow Reversal because they feel like they’ve already lived this experience, they don’t need to go back and relearn the filter experience.
There are some tantalizing data from EMPiRE looking at the outcomes between symptomatic and asymptomatic patients, and there really wasn’t much of a difference. That is unique because if you look at most trial data, there is a difference in outcomes between symptomatic and asymptomatic patients.
Dr. Clair: I’ve had a couple of patients with very tight lesions that we have treated with the GORE Flow Reversal System, such that when we initially inject, there is no flow reversal because the lesion is tight enough that it can’t generate a pressure head. When we dilate those individuals, and even in pre-dilatation, it reverses and goes out through the filter. I have to admit, as an interventionist, it makes me feel a lot more comfortable than what I would have to do in this situation if I were using simply flow stagnation. And, for those individuals, when I put a stent in, again, I get that same situation where I’m watching the flow I’ve injected just come right back through the sheath and through the filtration system. From my standpoint, you’re not going to get a better protection situation than that. Those are the patients in whom filters or simply flow interruption won’t offer the same kind of protection.
Patients with lesions so tight that I don’t think I can get a filter through them without predilating are ideally suited for Flow Reversal because as you do that predilation, you want everything to start being filtered. You obviously can’t do that with a distal protection device, and I don’t think you can do it easily with flow stagnation either.
Dr. Clair is showing the thought process of a vascular surgeon. He was thinking about how to reproduce the experience that we have when we perform a carotid endarterectomy. We are meticulous in making sure we’ve stopped all flow when we do an endarterectomy, and we always ligate the superior thyroidal temporarily. We don’t leave anything going besides that, with a clamp distally. There’s no doubt
that Flow Reversal comes closer to that than flow stagnation because you are not actually reproducing the
endarterectomy ligation, but you’re overcoming that one branch that can provide some antegrade flow.
You’re overcoming that by reversing the flow. I would imagine that most vascular surgeons will feel a little
more comfortable when they’ve shut everything down because that’s what they’re used to. And, for symptomatic patients, my hope is that proximal occlusion will achieve better outcomes to the point where we can clearly say it’s equivalent or better than endarterectomy.
Dr. Clair: Really, it’s almost any patient with a complex lesion, such as one so tight you don’t think you’re going to be able to get a filter through it or at best you’re going to struggle to get through it, or distal tortuosity, or there is symptomatic or ulcerated plaque present, especially if you can see it on the angiography— I think those patients in particular are ideally suited for a Flow Reversal protection system.
Dr. Hopkins: And it may be that the elderly patients fit into that category, as long as they don’t have a very difficult arch. Any patient with difficult perilesional anatomy is clearly a potential problem for a filter, particularly if there’s a major kink in the artery at the lesion or just distal to it. The cases where we’ve had the most trouble are severe kinks in which we place open-cell stents; even though you need an open-cell stent for a kink, those are some of the cases when you’ll sometimes have trouble retrieving your filter device. If you have proximal occlusion, you don’t have to worry about all that. You just perform the procedure and go home. So, as Dan says, difficult anatomy is another great indication.
These procedures—stenting and surgery—are quite complementary. I keep saying that, but everyone keeps wanting to push comparing one to the other. We should no longer be looking at randomized, prospective trials comparing the two. Previous trials have taught us enough that we now can select very well between the two procedures and decide which is best for the patient. We’re now accumulating more data on which type of protection is probably best, and eventually we’ll get to the point where we’re very comfortable in determining which procedure overall is going to be best for the patient.
I think what you said is really important, that there are clearly patients we know ahead of time are high risk for surgery or are high risk for stenting, and the concept of randomizing those patients just seems crazy.
As a cardiologist, I have listened to you say that, and only in the last few years have I really come to understand the true place of these procedures relative to each other. I look at it like coronary angiography. I do a coronary angiogram, and I know I can place a stent in just about anybody, but that doesn’t mean I should. There are patients with coronary artery disease for whom bypass surgery is the appropriate procedure; carotid disease should be approached with a similar mindset to get the best outcomes for our patients.
That’s such an important point because back in the days of CREST lead-in, our attitude was we can stent anything.
That’s my concern about CREST—that we did not have that selection pressure, that we felt we had something to prove, and we did, and we didn’t have the data that suggested that we couldn’t stent everybody.
A CRITICAL LOOK AT THE CLINICAL DATA
Endovascular Today: Have EVA-3S and SPACE had a long-term impact on your practice?
Dr. Clair: Patients are told by their physicians not to let us put a stent in because the data argue against it or the data show that it has higher stroke risk. It’s turned people who are potentially very good candidates for stenting away from seeking that therapy or from even accepting it at times, and it’s made it extremely difficult to randomize patients who really should be included in trials like CREST to look at carotid stenting versus surgery in asymptomatic individuals who are good candidates for both procedures. We have seen an overall decrease in the number of patients we’ve stented since that data came out.
Dr. Gray: I agree. EVA-3S was the one that hurt most. I look at SPACE as a positive study for stenting—1,200 patients, no difference. It’s hard to make a negative out of that. The conclusion that SPACE reached was that they failed to show non-inferiority. That’s the wrong conclusion. They failed to complete the trial, and that’s an important difference. It was never powered properly.
Dr. Hopkins: They didn’t have the funding to complete it, and then they didn’t have the data to say that there was anything other than equivalence.
Dr. Gray: And, only 25% of the patients were stented with embolic protection. Those studies were published in the New England Journal of Medicine and Lancet—well-respected journals—but if we thought in this community and the US, or in England for that matter, that those trials were well done and gave us a specific answer that we could rely on, then we would have shut down ICSS, we would have shut down CREST, and we would have shut down ACT I. We didn’t do that because we didn’t believe those trials were well conducted or gave us the answers that we needed, specifically about symptomatic patients.
Dr. Clair: Despite the fact that SPACE has not really shown the same problem really that EVA-3S did, the challenging aspect is that the conclusion is the headline of the study. I’ve presented the SPACE data a number of times as part of a talk and always reached the same conclusion—that the ipsilateral stroke and death rates were similar. You’re talking about four events in 1,200 patients. There really is no difference.
Dr. Gray: Lost in SPACE and EVA-3S to some extent is that both looked at long-term stroke outcomes between stenting and surgery; EVA-3S was four years and SPACE was two years. If you take away the procedural 30-day outcomes and you just do a landmark analysis, which basically sensors all the events before 30 days and just looks at the events after 30 days, you see that there’s no difference in stroke prevention between stenting and surgery. Both had very low event rates. It’s all about the 30-day data, because in the end, the stroke prevention efficacy is very good for stenting, as good as it is for surgery, and better than the natural history at least as we have it now for medical therapy in many of these patients.
The other thing that wasn’t really highlighted in SPACE that came out in subsequent publication, which was, again, prespecified, so it’s not just data dredging, was an analysis looking at age as predictor of outcomes. If you look at these data published last January, almost two years ago now, patients under the age of 68 do better with stenting, statistically better with stenting than surgery. Ridiculously low rates of 2.8% stroke and death at 30 days, compared to surgery, which had a relatively flat by-age stroke and death rate of about 5% or 6%. Over the age of 68, surgery looked better than stenting, but not statistically different.
So what that tells us is, we’ve been attacking the most difficult patients with stenting, the ones who are the elderly, who are older and sicker, and what I’d hate to see is a therapy that is just tuned beautifully for the youngest patient, even potentially better than surgery, wiped out by a lack of appropriate analysis.
Endovascular Today: Next on the radar is CREST.
Dr. Gray: With CREST, we will have the biggest body of carotid stenting prospective randomized data available to us, and I think it’s critically important we get the data analyzed appropriately by time from symptoms to treatment, age, symptomatic status, operator specialty, and any number of different things. If we don’t do that, then we’ve done the entire field a disservice and potentially our patients, denying them access to what could be for certain patient subsets a very useful and safe alternative.
Dr. Hopkins: We’ll never get a more complete, comprehensive study than CREST. But we have to stop talking about which is better and start talking about what we can learn about each subset of patients from these trials as we go forward. CREST will teach us something about symptomatic patients, and it may be that surgery in that group with that protection device is better. However, that is a first-generation device, and nobody would use it anymore.
Dr. Clair:The other problem is that when CREST was designed, we didn’t understand completely what the differences were between subpopulations of patients getting carotid stenting. In order to move forward with CREST, you have to believe there is clinical equipoise between the two procedures. The fact is that there isn’t clinical equipoise in certain groups of patients, and we know that now, and any trial that would be done from this point forward should clearly take advantage of the data that have already been generated about risk related to, number one, natural history. We know that patients with different comorbidities have different natural histories of their lesions.
Dr. Gray: If, in the early era of coronary angioplasty, in the ’80s, coronary angioplasty had been forced to compete in a randomized trial versus coronary bypass, we would not have coronary intervention today. Period, end of discussion. We would have only really been able to address a small subset of the simplest lesions in such a trial, and without stenting would have had excessive acute and late failures. The point I’m trying to make is that you can’t kill CAS before it’s been fleshed out. The problem is that CREST was conducted in a revolutionary time with carotid stenting, beginning at a time when it wasn’t a stable platform. And, it has the potential to be the last word.
We haven’t talked about ACT-I, which I think is a very important trial because it is a randomized trial including asymptomatic patients, 3:1, hopefully in a more modern context of carotid stenting with better patient selection. We hope there’ll be a second shot on goal for the asymptomatic population. We’re halfway done with that trial now, at 900 give or take, and until we see the results of CREST, especially for the asymptomatic cohort, which is the majority of patients undergoing procedures in this country, I think that trial is very important to continue.
Dr. Hopkins: Medicare is sitting on maybe the greatest opportunity it has ever had to shoot itself in the foot. Stroke is the most expensive disease that we treat, hands down, and if Medicare figures out a way to distort the data to a point that allows them to, in their own mind, rationalize shutting down carotid stenting, it’s just a tragedy.
Another frustrating aspect is that many companies have invested considerable money, time, and effort into this technology, which is clearly valuable. The biggest tragedy would be if Medicare figures out a way to make it so it’s not worth industry’s time to continue to go after this market, not only for the companies, but for the population at large. Sadly, it’s happened in some ways already.
CMS CONSTRAINTS AND FDA MANDATES ON EMBOLIC PROTECTION CHOICE
Endovascular Today: As we have discussed, some of the limitations regarding CAS procedures and technologies have little to do with the the details of the procedures themselves, and more to do with their regulation and reimbursement. How does the current CMS coverage decision impact the use of specific embolic protection devices, such as distal filters versus Flow Reversal?
Dr. Gray: Both devices are approved by the FDA for symptomatic and asymptomatic patients who are at high risk for surgery as defined by a list of fairly standard high-risk criteria. CMS, again, as I understand it, reimburses the use of those devices only in the symptomatic population at high risk. So the asymptomatic population would not have access.
Dr. Clair: And, unless there were registries involving those devices, there currently is no way to treat asymptomatic individuals with these devices and get reimbursed for it.
Endovascular Today: So, absent a change in CMS’s position, as soon as these post-market surveillance studies and registries are concluded, these devices will all be in the same situation as far as reimbursement is concerned— limited to the high-risk symptomatic patient.
Dr. Gray: We treat them in one of two ways: They get treated and the hospital takes a loss, or the patient gets a bill. For some patients, it’s one of those options, or not get treated at all. That seems fundamentally unfair to patients who can’t afford to pay or to hospitals who shouldn’t have to pay for approved device
Dr. Hopkins: There’s a lot more we could learn about Flow Reversal in a postmarket surveillance setting.
Dr. Clair: True, and we already have information from Gore’s submission for approval indicating that there are differences between Flow Reversal and what’s recorded in previous filter registries. That makes it even more interesting in terms of gathering additional information about how beneficial this might be in certain populations of patients undergoing carotid stenting. It makes it even more imperative in my mind that we have this option available. We may not have enough data to say it for sure, I think there clearly are advantages for this in certain subpopulations, but we really need to have the ability to use it to define those better.
ADVANTAGES OF THE GORE FLOW REVERSAL SYSTEM
Endovascular Today: What are some of the primary advantages of the GORE Flow Reversal System?
Dr. Clair: One of the major advantages is in complex lesions, which would include ulcerative lesions. In a patient who has thrombus, I think it’s hard to justify not using this system when treating them. Severe stenosis, such that you think placing a filter through the lesion is going to be difficult, mandates the use of this type of protection. And, obviously, I think tortuosity in the vessel makes this an outstanding option.
Another advantage is that you get to choose the wire that’s going to be best to cross the lesion, and you have protection beforehand. In fact, we have had situations, some of the patients enrolled in the EMPiRE trial, where I had trouble getting a .014-inch inch wire to cross the lesion and needed to actually put a micro catheter in with the wire in order to get across the lesion. I would never have tried that with a filter device. I believe it’s just completely impossible to do that with a filter device.
This system provides a level of protection in those complex lesions that you can’t match with anything else.
Dr. Hopkins: You can break it down into categories; the anatomical issues for which a proximal device is clearly a better choice with difficult perilesional anatomy, and then the symptomatic patients for whom we know there’s a higher risk of a lesion having a large plaque burden that may be fractured, therefore posing a greater risk of embolization and a greater risk for overcoming a filter. Those are some of the patients for whom we think there may be an advantage to embolic protection proximally with the Gore device.
As Dr. Clair mentioned, any complex anatomy in which you don’t feel comfortable or you know there’s a greater risk using a filter is the kind of patient where the Gore device is a much better choice.
The downside, of course, is just that there is a real or perceived difference in terms of the ability to get a larger device that is used for proximal protection around a more difficult arch. I say “real or perceived” because I think that it’s a lot easier to use than most people think it is. It is a 9-F device, so it’s bigger, and it can be more difficult to navigate. It’s a little more bulky at the tip, but I’m impressed with how flexible the distal end is.
A difficult arch comes with its own set of challenges, and there are a lot of people who, in my own shop, were using the Concentric balloon catheter for any situation in which we wanted to occlude the common carotid until Gore came along. Now that we have the Gore device, it’s taken a lot of encouragement to get the guys away from the Concentric device even though it is not nearly as good a device, and it doesn’t have anywhere near the stability that the Gore device has. Most of the difference is perception rather than reality. It’s a pretty easy device to use, but we have to first get past people’s natural concern about the fact that it’s a bigger device and it has more paraphernalia on the end of it, and, therefore, it may be more of a challenge to get it around a difficult arch.
Dr. Gray: I don’t think it’s more difficult to place the sheath itself. I like the sheath design. I think the sheath is among the best I have used. Although a bit larger in terms of French size, it has a nicely graduated taper of the stiffness, such that the durometer of plastic is very nicely segmented and matches its placement in the aorta and common carotid anatomy. I find that it goes places I didn’t think it would go, so I’ve been favorably impressed with that.
The only real challenge to the device is getting the external carotid balloon into place, when occasionally there are external lesions or a very proximal superior thyroidal artery, as well as hooking up everything in the back end to make sure it’s all flushed and ready to go. Once it’s established, it’s a very quick procedure, and it doesn’t require the release and recapture of filters. Also, a wire specific to the patient’s anatomy can be used. It’s very helpful in those aspects.
I think we’ve gone over the lesion sets, but the other thing that I’d say about that is, although we do use the device for certain lesion sets—either symptomatic or difficult tortuosity or so on—I also think it’s probably important to use beyond that, because if you’re only pulling it out for the most difficult lesions, it’s going to be tough to maintain an expertise. So the last thing you want to do is pull out a complicated device in a difficult lesion that you don’t have a familiarity with or the last time you did it was a year ago.
I would encourage people who are getting this device into their labs to use it randomly on a few patients just to maintain their level of expertise so that they don’t just have it during the most difficult cases. I think that’s probably good advice. We’re trying to follow it in our lab too.
Dr. Hopkins: The other enormous advantage for the Gore device is in patients with acute ischemia who either have an occluded carotid or have thrombus in a carotid. We use that device, or something like it, all the time. So in acute stroke, it’s enormously valuable if you have an occluded carotid because you can put that device up, go through the clot, open the carotid artery, aspirate the debris, and then go on upstairs if you need to. But for patients with acute occlusions, this is a wonderful device. Because if you have an acute occlusion and you don’t use this type of device, you invariably run a high risk of having distal embolization into the intracranial circulation when you open the carotid. So this is a great device for that.
Endovascular Today: How would you summarize the importance of tailored stenting—choosing which stent and embolic protection device to use?
Dr. Hopkins: We’re way behind our European colleagues because we cannot tailor our choice of devices to the patient the way they can in Europe. We’re entering patients in registries, and the FDA mandates that we put a system in rather than tailor them. So I think we’re at a significant disadvantage because we don’t have that freedom. It’s clear that there are differences between the various types of devices. Navigability of a device, appropriateness in a curved lesion versus a straight lesion. There are all kinds of variables. There’s still a big a debate as to whether open cell is better than closed cell. All these things may have a role, but for now, we’re stuck with what we have.
That’s why the Gore EMPiRE clinical study was wonderful—because you could choose the stent you wanted.
Dr. Gray: We’d have much more creativity. Also, without tailored stenting, we’ll reach a plateau in our outcomes at some point. We haven’t had any integral changes in the devices, stents, or anything else because of the marketplace we talked about before; we’re forced to use systems rather than mixing and matching what we might think is the best thing for the patient. Now I recognize there are compatibility issues there, and I’m not suggesting that we shouldn’t take those into account. However, it does limit our ability to do what we think might be best for the patient.
Endovascular Today: What issues are there with regard to access when using the GORE Flow Reversal System?
Dr. Clair: I think there are cases in which it could be an issue, but the fact is it’s never precluded us from being able to use the device, and in any patient in whom we’re choosing to do carotid stenting, we haven’t had an issue with accessing the carotid with this device. It’s probably just about as easy as any of the other sheaths that you’re going to place into a carotid.
Within the trial, I think we had one patient with a high-grade iliac stenosis that we simply angioplastied and then proceeded to use the device. And, honestly, this is the equivalent of a 7-F shuttle sheath, which is very similar. It currently has to go in through a 9-F sheath, but the fact is the device itself is like what we were using 6 or 7 years ago to treat carotid disease anyway, only it’s more flexible and I would say easier to get where you want to, and to Bill’s point, with the balloon up, it’s more stable once you get it to where you want it to be anyway.
You don’t have the ability to catheterize the vessel like some of the systems, where you can catheterize it and then take the sheath in over the catheter. That would be a nice thing to see with this device, but right now, I don’t see getting access as an issue with this device.
Dr. Gray: We’ve actually done that with the 125 Cook Shuttle—we’ve been able to do that using this device over that system. So it can be done. And we haven’t had a patient in whom we weren’t able to deliver the device due to difficult anatomy.
Dr. Clair: And, like you said, the distal tip of that is extremely flexible.
Endovascular Today: Are incidences of access-site hematoma an issue?
Dr. Clair: One impressive element in the EMPiRE trial was that the access complication rates were very low, particularly from what we’d expect to see with 6-F sheath access sites. I think that’s a function of physicians learning how to deal with larger access sites, and closure devices have dramatically reduced the issues with this. Physicians have learned how to use closure devices well in this situation, such as in methods where the closure system is delivered initially, and then the working sheath is inserted.
It’s impressive that the groin access complication rates are very low, and despite the fact that we’re using a 9-F sheath, physicians are obviously very comfortable dealing with sheaths of this size. Because these patients are aggressively anticoagulated with antiplatelet therapy, we’re all very careful in dealing with the access site. There are pretty good data that access-site complications worsen outcomes, so if you have one, you’re at much higher risk regardless of the interventional procedure. In carotid intervention in particular, that recognition has led to a lot of attention being paid to the groin access site in minimizing those complications, and I think this is a good example of it. Dr. Gray: I agree. We use a 10-F sheath so we can watch our pressure—and some of the 9-F sheaths can do that too—but we just go to the 10-F sheath anyway because it’s either a ProGlide or a Prostar. And the fact that the sheath is in for about 30 minutes, I think the duration of dwell is a very important part of hematoma management. We pull the sheath right after the procedure, tie it, and we’re done. That really limits complications to a large extent as well. If you don’t have a dwelling sheath in for 6, 8, or 10 hours, that makes a big difference. We learned that a long time ago in our coronary experience.
POSSIBLE LIMITATIONS OF THE GORE FLOW REVERSAL SYSTEM
Endovascular Today: What would you say about the learning curve associated with the GORE Flow Reversal System?
Dr. Hopkins: I think there’s a learning curve with anything. With this though, there’s a mental block because everybody’s used to a 6-F Cook Shuttle, and you see a 9-F and say, “Wow.” There’s a psychological barrier that has to be overcome, but once you get past that, the reality is that it’s really not any more difficult to use. It’s just a matter of getting over it as a psychological hump.
Dr. Gray:The learning curve issues are not in the placement so much, although there’s some learning there. It’s not really “learning,” it’s just experiential. Putting a balloon in the external is not a big deal, and working with the balloon, making sure you have stump pressure—that kind of assessment. It’s not a big deal. The bigger technical issue is the back end of the device, making sure that the entire device is flushed adequately, the Thouy ports are closed, that Flow Reversal is established, and that you manage the procedure in a systematic way—that you aspirate after critical parts of the procedure, and when you actively aspirate, that you don’t aspirate during an open Thouy, and so on. Those kinds of things take a procedure or two. It really doesn’t take more than that to get a sense of how to manage everything, and you get your own stylistic way of doing it. But once that’s established, the rest of it is very easy.
With the technical parts of using the device, there’s actually not much learning curve there at all.
DEVICE INTOLERANCE AND ISOLATED HEMISPHERE
Endovascular Today: What can you tell us about patients in whom there is intolerance for Flow Reversal?
Dr. Clair: We had three patients in the trial who had intolerance in one way or another, and in each one of those situations, we were able to complete the procedure by performing it in steps. We predilated and stented, then released the Flow Reversal, and postdilated. After each point before opening it up, we did active aspiration, and then were able to reperfuse the patient. The total time for the procedure itself, once you have the sheath in place and initiate Flow Reversal, is normally no more than about 10 minutes. It’s usually not a large portion of the population of patients who can’t tolerate flow reversal for 10 minutes.
There is also a group of patients, and we didn’t see this in the trial, but it’s been published before, in which adaptation occurs—if you occlude a patient initially and they have intolerance, the next time you occlude them, there tends to be a smaller number of patients who are affected.
For some physicians this is one of the things they are initially concerned about, but the fact is, if you’re treating any patient who has carotid disease, you will have periods of time where you’re doing inflation and a patient has an ischemic event while you’re occluding that ipsilateral carotid. It’s a small number of patients. I personally think it’s pretty easy to deal with if you’re used to dealing with this process. If you’ve done carotid endarterectomy with a patient awake, it’s pretty easy to deal with this sort of thing, you put a shunt in.
Functionally, you’re doing the same thing here; if you have a problem while the patient’s awake, you just open up the carotid after you’ve done some active aspiration and those steps of the procedure that you’ve completed to that point.
Dr. Gray: The trial data Dan is reflecting on is pretty impressive considering that we thought it would be more like 5% or 10% of the patients who wouldn’t be able to tolerate Flow Reversal when we started the trial. I think it turned out to be 2% or 3% who had some intolerance. Part of that is because there was some selection going on there. Patients who clearly had an isolated territory problem were not entered into the trial.
I’ve also been impressed after the conclusion of the trial and the approval. I’ve used the system in a couple of patients in whom I cannot identify a collateral circulation for the life of me, but I try it anyway because there are not a lot of options for these patients. And when we do it, they get a little starry-eyed, but they don’t lose consciousness, they don’t have a seizure; they get quiet, but they don’t really have a lot of trouble. You just move through your procedure quickly, and it goes fine. I’ve been very impressed, and I’m not sure how that happens. With literally no identifiable collaterals, they seem to do okay. That was in the right hemisphere, so that probably makes a difference.
Dr. Hopkins: I don’t think I can explain it, but I can just tell you from an observational standpoint, we’ve been doing balloon test occlusions of carotid arteries for many, many years, and I can’t ever predict them. It’s sometimes the patient who has an isolated hemisphere who will have symptoms, then sometimes they won’t, and I don’t think there’s any way to be sure. I suppose if you were doing Xenon flow studies, you might be able to get a better preoperative sense of whether or not they will tolerate it. But as Dan says, the important thing is that you know how to deal with it. Fortunately, we’re keeping these patients awake, so if the patient has symptoms, you know it right away and you can deal with it.
The disadvantage to endarterectomy is that you may have an intolerance, and if you’re doing it under general anesthesia, you won’t know about it, which may be one of the causes of stroke in endarterectomy. Here, we know right away, and we can aspirate and re-establish flow. And, very often, I don’t know why this works, but if you re-establish flow for a few minutes, give the patient some fluids, let the pressure come up a little bit, and try it again, then usually the second time around it works and the patient tolerates it. So it’s something that is (1) infrequent and (2) fairly easy to deal with. All things considered, it doesn’t seem to be an issue.
Dr. Gray: And there’s a third part to that, which is it doesn’t appear to have any clinical sequelae. If a patient has some intolerance, there doesn’t appear to be an outcome related to that, be it stroke or other outcomes.
Dr. Clair: It’s usually pretty easy to identify the patients who are intolerant. There may be some who are having relative ischemia because they’re a little bit sleepy and that may be their manifestation, but for people who have significant ischemia, you know pretty much right away—they’re having some kind of noticeable alteration in their mental status. We have the balloon in with the wire before we initiate Flow Reversal. We initiate Flow Reversal, cross the lesion with the wire, and take the balloon right behind it, predilate the lesion, and it’s no more than 5 minutes before we have the stent in place after initiating Flow Reversal. It’s usually at about that point that they begin to manifest something. If so, we simply do active aspiration and open it up. It’s pretty straightforward.
Dr. Hopkins: That’s part of the learning curve—having everything prepared and ready to go minimizes the time that you’re occluded, and you minimize the risk of having to have actually stop, aspirate, re-establish, and then start all over again. If you’re well along in the procedure and the patient begins to exhibit some level of intolerance, usually you can just finish off the procedure and then re-establish flow.
Endovascular Today: How has the GORE Flow Reversal System changed your practice?
Dr. Hopkins: It has very definitely expanded our ability to treat patients, and it has improved our overall CAS safety profile because we can now avoid using filters for patients whose anatomy is not conducive to using a filter. It’s a wonderful addition to our armamentarium for treating carotid artery disease. There are patients we’re treating now that we simply would not have attempted before.
Dr. Clair: The only problem right now is that we can only use it in symptomatic, high-risk patients. There’s a large population of patients in whom this device isn’t currently usable, and naturally we’d all like to see that change soon.
TIPS FOR SUCCESS
Endovascular Today: What technical tips would you give to people who are going to embark on this? If they’ve never done a single Flow Reversal procedure before, what would you recommend?
Dr. Clair: I think the key issue is using the sheath just like using any other sheath. I would take a few minutes before the performance of the procedure to just confirm how it functions within a patient to ensure that you understand the concept of how to do active aspiration, the steps you need to take before you do that, such as tightening the Tuohy-Borst adapter at the back end of the sheath so that when you aspirate, you’re not aspirating air from the back end of the sheath.
Those are things that are pretty routinely done by interventionists who are comfortable using Tuohy- Borst adapters, but if you’re not routinely using them, you need to make sure you’re taking that into account. Then it’s just a matter of management—actively withdrawing through the sheath and then transmitting that fluid or that blood back into the patient through the venous system and through the filter. Doing that once or twice before you’ve actually even accessed the carotid, just so you’re comfortable doing it, is not a bad thing to do. I can understand that before you do the procedure, you might feel uncomfortable. But after two cases with this system, you can manage it comfortably in any situation. It’s a very short learning curve, and it really all focuses on dealing with the back end of establishing the Flow Reversal.
Dr. Gray: I agree, that's where the learning curve is.
Dr. Hopkins: The most important thing is to accept the initial concept that it’s no different than anything else, getting the system up there. Once you accept that, I think you’re over the hump.
Dr. Clair: Gore has been pretty good about providing on-site, preprocedural training with the back end, which I think is the biggest issue for people to get over. Doing that ahead of time was very helpful for me. It didn’t necessarily even involve a simulator, but rather just looking at the device, understanding how you need to manipulate it in order to do active aspiration, return that blood to the patient through the filter, and then continue the procedure with imaging and pressure monitoring.
One of the neat things about this device that we really don’t have with anything else is to assess the intracranial back pressure in the patient. It’s actually kind of neat to be able to do that and to see how systemic hypertension actually can affect that. Driving patients’ blood pressures can drive their collateral circulation up, and we’ve used that intraoperatively in some patients to manage what appeared to be the early mental status changes. The other thing is just understanding that this really is a significant issue for people, whether their collateral flow is adequate to that region or not.
Dr. Gray: In terms of tips for success, one thing we do for all of our stent procedures that I think is especially helpful with Flow Reversal is that we stack our equipment on the table towel, and we go top down. So if we’re going to use a balloon and a wire, we get everything established, we turn on the Flow Reversal, the balloon and the wire are already in the patient, but there’s a stent on the table all ready to go. We select it, and under that there’s potentially a second balloon if we want to use it postdilation.
We’re not waiting around, pulling stuff off shelves, and prepping it. It’s all on the table ready to go. We can cut our Flow Reversal time down to less than 5 minutes—I mean very quick procedures once Flow Reversal is established because there is no filter to go get, there’s nothing to clean up afterward, if you will. It’s just basically in and out.
THE FUTURE OF EMBOLIC PROTECTION FOR CAS?
Endovascular Today: What do you believe is the future of embolic protection in carotid stenting?
Dr. Hopkins: I don’t know if there’s a future without embolic protection. We’ll never muster a trial enrolling the number of people to do a study that will tell us. It will be impossible to get the average person who has any common sense to be willing to undergo the procedure without it. We don’t need a trial to tell us that embolic protection is necessary, and most people who have any understanding, clinicians who have taken out a filter and seen debris that would have gone to the brain, are going to opt for embolic protection in every case.
Dr. Clair: I agree. There no longer exists equipoise in the community of people doing carotid stenting that there may be no difference between filter and no filter, or protection and no protection. If you polled 100 people, I doubt that even 50 percent of them would say there’s no difference, or that they believe a randomized trial would be reasonable.
Dr. Gray: Much of the trial data we’re seeing from EVA-3S, even ICSS, reflects a time in the early 2000s when carotid stenting was still very much in the early steps of its evolution, and the standardized technique had not been either developed or accepted in terms of filter protection, or available embolic protection. The data reflect an era that I think has largely passed, even in Europe, and certainly in the US. I don’t think you’d find equipoise here. There are not enough people to do the trial who would believe that there’s no difference between CAS with and without embolic protection.