 Welcome to Texas Heart Institute Educational Series on Innovative Technologies and Techniques, featuring science in treatment of cerebral vascular disease. I'm your host, my name is Valmarie Crazier. I'm an international cardiologist at Texas Heart Institute and CHI Health, Baylor St. Luke's Medical Center in Houston, Texas. Joining me today is Dr. Miguel Montero Baker, he's an associate professor of vascular surgery at Baylor College of Medicine and also divisional chief of vascular surgery at Baylor St. Luke's Hospital in Houston, Texas. Also joining us today, a special guest, Dr. Gary Rubin. Dr. Gary Rubin is a world renowned international cardiologist, recognized for his groundbreaking work in development of the first FDA approved coronary stent, as well as in pioneering the techniques of carotid artery stenting and embolic protection devices. Dr. Rubin has published more than 250 manuscripts in peer review journals and as many abstracts also in journals. He has also edited three textbooks and contributing to other textbooks as well. In his 30 plus year career, he has gained a tremendous reputation in the field of cardiac care and particularly in the field of coronary interventions and the carotid artery interventions. Dr. Gary Rubin is currently the medical director at Cardiovascular Associates of Southeast in Birmingham, Alabama. Welcome, Gary. Thank you. So Gary, I would like to ask you with your tremendous experience, 25 plus years in performing carotid artery interventions, what is a typical scenario of carotid intervention in your hands look like? Thank you, Dr. Krazier. It's a pleasure to be here. Carotid artery stenting was developed almost 20 years ago now in an effort to minimize the invasive requirements for treating carotid stenosis since they are one of the important courses of stroke in our patients. We began by trying to figure out how we could do this with percutaneous techniques that we'd used in the heart. And as it evolved over the years, now decades, we have been able to develop a technique that requires very little time in the interventional suite. It does not require general anesthesia. The patient is awake or can be completely awake during the procedures done under local anesthesia. And it's a technique that we have tested now rigorously in many prospective randomized trials against our competitor, which would be the standard technique of endoterectomy surgery. And we have been able to show that this is a safe and effective technique for treating carotid stenosis. Thank you, Gary. As you have mentioned in the last several decades, significant progress has been made in endovascular treatment of cerebral vascular disease. Dr. Miguel Monteiro Baker, can you summarize for us what progress has been made in technology, techniques, and patient selection for carotid artery stenting? Of course, Dr. Kreischer. I think that when we look at where we were and how it's evolved slowly over time, we definitely came from a rather imperfect stance to really smoothing out all the technical needs that we required. So there's been a very interesting evolution on just the catheters, the material of the catheters, the tips of the catheters to make them as less abrasive as possible. A lot of effort and a lot of investigation has been put on how can we avoid some of those particles going through the brain? So all the embolic protection, be that distal or proximal embolic protections, that has evolved flawlessly. And then I think stents themselves, the technology that we're using at the implant, be that open cell, closed cell, hybrid cells. I think all have been adding more and more to the safety of this procedure. Another very important thing is that we've understood that a lot of what happens when somebody's trying to maneuver their way from the bottom all the way up to the carotid, is it's a treacherous path. So we've understood a lot more about what adequate anatomy we need, what could be a high risk patient for carotid artery stenting, what could be a low risk patient, what type of curvatures would you need. And all of that has been now obviously added to advancement in perioperative imaging. I mean, we have now more information than we have ever had in the past leading to the safety that we have now with as Dr. Rubin mentioned many of the studies published. Excellent, thank you Miguel for this update. Now we're moving to the segment of this presentation that talks about science in carotid artery disease and treatment of carotid artery disease. There are a lot of skeptics, these believers and critics of advances in carotid artery interventions what Miguel has just mentioned. And these believers that we have made a significant progress. So Gary, I would like for you to summarize to us the results of these clinical trials that have validated carotid artery stenting. And as answer maybe why is there still a dispute among societies and different individuals that promote one treatment or the other and lack of acceptance from payers for carotid artery stenting. As a reasonable alternative to a carotid end direct me for a certain subset of patients. That's a great question. Thank you, Dr. Crazier. And I think we can look at the science and they have been now two, three, four studies that have been published, two and one combined meta-analysis in the New England Journal of Medicine, very reputable journal, peer reviewed journal that has illustrated the scientific rigor that we have subjected coronary artery stenting to in attempting to validate this against the standard of care which was carotid end direct me. So there was the Crest One trial that was begun about 14 years ago now. Then there was the Act One study which looked at asymptomatic patients. That was launched about seven or eight years ago. We've now have 10 year outcome data from these studies. So what we have here is rigorous scientific data. So there is opinion, there is commentary, there is bias, but we need to turn as we are now in this era of COVID-19 to the best science and the best advice from the scientists who have done the work to randomize patients in these prospective trials to screen them carefully to make sure we are comparing apples to apples, not apples to oranges, to make sure that the follow-up is not biased, that we're measuring the end points with great rigor. And that's what we've done. In fact, carotid artery stenting has been one of the most carefully studied medical procedures at this time, probably on the second to coronary intervention. And I'm delighted to show you now some of the results. And the bottom line is that no matter how you look at this, that the outcomes, the primary outcomes in all of these trials, where we looked at stroke, death, we looked at myocardial infarction complicated in the procedure. And we looked at the incidence of stroke out to four and then to 10 years. And as you see from these slides, let's go to the next one. And you can go to the next one that we have in these rigorous prospective apple to apple comparisons demonstrated that carotid artery stenting in terms of stroke prevention is equivalent to carotid endarterectomy surgery. So this resulted in independent statement an independent statement from the National Institutes of Neurological Disorders and Stroke. Scientists, neurologists, without any, as we say, dog in the hunt, to declare that these trials have shown that surgery and stenting are equally safe and effective. Now there are a couple of caveats to this. And that is that in the earliest of these trials as Dr. Montero Baker so rightly pointed out, we didn't quite understand the best patients to be treating with stenting. And so the results of generally minor stroke, neurological events were a little bit advantageous for surgery. But over time, both were very effective in preventing stroke. And I am quick to add that we will discuss data later in this discussion that shows that the outcomes in 2020 compared to 2000 and three are very different. And therefore the outcomes have significantly improved. And I would also add that what is not shown on those slides are the operative complications from surgery. And they were not insignificant. There was approximately 5% of the patients had damage to the cranial nerves with the neck surgery. And so this is a secondary endpoint that was studied in these trials. So the bottom line here is simply that this much less invasive, much less painful, percutaneous procedure has been shown in terms of stroke prevention to be as safe and efficacious as I wrote me. So that's where we stand today. And that is what the rigorous science has shown us. Dr. Ruben, let me interject for a second and ask you, you've obviously been part of this from the very beginning with such amount of effort and energy put into Crest 1, what was really the driver for Crest 2 and what was its uniqueness and the necessity for it to exist? That's a wonderful question. And let me address it because it's very important. Over the decades that we have been using, firstly, endoderectomy and secondly, parodistenting to take care of these blockages, there have been significant advances in medical management of patients with these blockages. Now there have been trials in the past that demonstrated that it was better to remove the blockage of surgery than to use simple medications. But the medications back now 10, 20 years ago were not the medications that we have access to today. And so it is extremely important that we turn now back and answer the question again. Can we now prove that removing the blockage with either stenting or surgery is still superior to medical therapy? I would then move on to this major Crest 2 trial. I was part of the planning committee and among the executive committee have been credentialing operators. As we planned this trial, it was very clear that the unknown that the test treatment was going to be medical therapy. And the medical therapy we are using is truly state-of-the-art. That is targeted medical therapy looking at targeted reductions of blood pressure, of LDLC cholesterol, of hemoglobin A1C for diabetes, for smoking cessation, for weight reduction, for improvements in nutrition. So this is really five-star medical therapy. And we are now comparing endarterectomy and stenting against this best medical therapy. And it needs to be said that both endarterectomy and stenting have become safer again over these last 10 or 15 years we're talking about. So this is a very important trial. And it's a trial that we are well into. And we have now close to 1600 patients already randomized. Now, let me perhaps move on to talking about where we stand with carotid artery stenting in 2020. To make sure that we have the best carotid artery stenting and the best endarterectomy to compare to this five-star medical therapy, we said about credentialing pressed to stenting operators and surgeons who are going to be doing endarterectomy. Let me talk about the stenting operators. The committee which was comprised of interventional cardiologists, vascular surgeons, neuro surgeons, neuro radiologists, neurologists and other neurologists interested in the quality of the trial, then looked at the outcomes and the way certain interventional cardiologists and carotid stenting operators, vascular surgeons, neurologists performing the procedure. Very, very importantly, this was a quality assurance for carotid stenting. We have been able to credential now close to 200 operators in over 160 sites, so many hospitals, community hospitals, academic centers and smaller institutions around the country. And so we got a chance to look at how they were doing, not in the randomized trial where the outcomes are blinded, but we looked at the outcomes in the cases they were doing that they must submit to our registry. And of course, all of these cases are covered by full CMS reimbursement. So let me ask you a question. Where are we now with pressed to registry? Do you have any preliminary data that you could discuss with us? Yes, let's look here at this slide because this was the results of the operators performing cases in this pressed to registry. Let me emphasize again, this is not the randomized trial results, but we looked at this very carefully. So let's begin by thinking about a patient where he comes to our office with a very severe stenosis. And it's only severe stenosis that we're treating, greater than 70% narrowing. We have a choice of putting them on best medical therapy, which we do for every patient. That's a statin. That's very good blood pressure medicines. That's controlling their diabetes. That is anti platelet therapy. Then we consider randomizing them to medical therapy or end artiracomy or stenting. But we looked at the patients that were not randomized, but were in this registry. And the outcomes that we saw from this very large number of operators are superior to anything which we have ever seen published from credible prospective registries over the last 20 years. So the outcomes in asymptomatic patients were 1.4%. In symptomatic patients, 2.8%. Even the best of any other revascularization technique that's done prospectively and rigorously does not come up with better stroke and death outcomes in the periprocedural period. More interesting to me was when we looked at those patients who would have been eligible for the randomized trial, but for some reason live remotely, didn't wanna participate, just wanted to get the revascularization done. The stroke and death rate was 0.8%. So this was published in the Journal of the American College of Cardiology just a month ago. These demonstrate the safety of carotid stenting when performed by credentialed operators of which there are many. And they include vascular surgeons and urologists and neurosurgeons and radiologists as well as interventional cardiologists throughout the country. But these outcomes are really superior. And this, to me, is telling me that since we know that strokes are very rare after you do an endarterectomy or surgery, that we have a good chance of demonstrating in press too that medical therapy may be hard to beat revascularization, even with this very good medical therapy that we're putting the patients on in the other arm of the trial. Thank you, Gary. The results are very impressive. I'm quite convinced that this is one of the best results that we have seen so far with carotid artery stenting, particularly because 45% of those patients were symptomatic. So another important issue is, is there cognitive decline associated with carotid artery stenosis? Is it only present with symptomatic or can it be also present in asymptomatic patients? And also, how does a carotid intervention play a role in this scenario? Can you comment on some of the information related to the press too trial? Yes, this is a great question. Thank you, Dr. Frazier and one that's very important. The press too trial is state of the art medical therapy and state of the art revascularization with stenting or endoderectomy. They're really two separate trials, the endoderectomy and the stenting arm compared to medical therapy. One of the things we're looking at very carefully with cognitive testing of all the patients, including in a subset MRI imaging before and at follow-up and cognitive testing at follow-up is to test whether removing these blockages is an important way to diminish cognitive decline that we've seen anecdotally in patients with high grade blockages that this slide shows in light brown the cognitive status of patients who have had high grade blockages and the cognitive status of patients who do not have high grade blockages or have had the blockages removed. And this is in different domains. This is just one of a number of studies and this is what we would call preliminary evidence that there is a strong signal that perhaps removing the blockage apart from preventing stroke that may improve cognitive decline. So this is another very important reason why we must recruit patients to the Crest II trial, why we must complete this trial because not only will we answer the question, is revascularization still superior to best medical therapy as it was in the past? Is it still? And in addition, can we improve cognitive function in patients who are revascularized? So this is a very important issue for us to be discussing. Thank you, Gary. So to summarize scientific evidence as far as carotid interactions of concern and your personal experience, you've been doing this for more than two decades. What is your approach as far as treatment is concerned? Who are the candidates for carotid adrestenting in your experience and who are better candidates for carotid endoterectomy? Thank you. That's another very important question for all of us to be thinking about. In 2020, when a symptomatic patient who's had a stroke or a more commonly TIAs, transient ischemic attacks, when they present to us, the evidence is that we should take care of the blockage after we start them on this intensive medical therapy. And so what we do is we start them on statins, dual anti-platin therapy, and then we look at the anatomy and Dr. Mantero Baker has very nicely pointed out that we have advanced imaging now. Many patients are suitable for a stent and quite a large number of patients, when we look at the anatomy, we think that alternative techniques such as endoterectomy or a new technique called trans-carotid stenting, T-car, is the best option. So in a symptomatic patient, then we move them on to the best option depending on their anatomy, as Dr. Mantero Baker pointed out. Now for the asymptomatic patient, we're in a totally different ball game. For asymptomatic patients, we don't know whether we should revascularize immediately. Certainly we understand today that there is no emergency if someone's having no symptoms. And so for these patients, my practice and what I think is the best current therapy is to approach these patients to be in the Crest II trial where they have a 50-50 chance of getting either endoterectomy or surgery on one hand or a 50-50 chance of continuing with the medical therapy, which we follow them very carefully. And should they have the worrisome symptoms, we can also move them on to revascularization. So in 2020, my advice to all my asymptomatic patients is participate in the Crest II trial. This will give us so much information about how to manage these patients going forward. It will give us the best scientific evidence that we need to understand how to treat these patients. So Gary, this is as a follow-up question. I cannot resist not to ask you this question. A few months ago, we had a visiting physician and Abbott from Australia visiting us and actually recorded a program with her. And as you know and you know her well, she adamantly disagrees that the carotid artery stenting has any role for treating a patient with cervical vascular disease. So I ask her a very pointed question. I ask her, is there any role for carotid artery stenting in patients with severe carotid artery disease? And I said even 99% stenosis of a patient that needs urgent cardiac surgery. And she said no. So I want you to answer this on the basis of scientific evidence. This is a rebuttal and I think it is appropriate for you as a leader in the field to give this statement. Well, that's a great question. I would say that some commentators have very strong opinions. I'm not sure that that necessarily makes their opinions correct. But in the area of high grade carotid stenosis, there is now best evidence from previous studies that revascularization is superior to medical therapy and particularly for a patient that's undergoing the hemodynamic extremes of, for example, coronary artery bypass surgery. The standard of care is to take care of this lesion until we have scientific evidence to the contrary. And we do not have that. So if we fall back on the science, if we fall back on our experience and the work that we need to do, then the standard of care and the recommendation from the vast, vast majority of those of us taking care of these patients is that revascularization is in order in these patients. And of course, we are studying this very carefully in press two and we will have additional answers in a year or two when we finish that trial. So that's my thoughts on that particular previous opinion. Thank you, Gary. I share your views. Well, this is very informative and I would like to thank both of you gentlemen on your very valuable and meaningful and scientific contribution to Texas Heart Institute educational programs. Thank you very much. Thank you.