Richard Myler: I have always believed that you don’t read history, you repeat it. You may never have heard about Richard Schneider who was the chief of Werner Forsmann in Germany. In 1929, a 24-year-old man who worked with Schneider had the idea to catheterize himself. Richard Schneider recognized the genius of this young — and perhaps crazy — man’s idea. Schneider stood behind him and interventional cardiology was born. Don Effler stood behind a young man from Argentina who didn’t even have a license to practice medicine in the U.S. Then René Capalero performed his first interventional cases. And so things progressed. Andreas Gruentzig had a failed early case — about his seventh, I believe — and had to send the patient to surgery. There were a lot of sharks in the water at that time, young cardiac surgeons who wanted Gruentzig to fail so bad, they could taste it! Andreas was broken emotionally oftentimes as a result of this animosity. The head of surgery at the time, Dr. Sening, asked his young men: “What was the plan for this patient if Andreas hadn’t done the procedure?” They replied that the plan was to perform bypass surgery. Dr. Sening said, “He had his bypass operation; he had to go emergently. The patient did very well.” Sometimes it’s not a bad idea to enlist the support of some gray-haired people in your department, or even someone from outside your department. It’s wonderful to have the support of another physician who has a high regard for the imagination and courage of those who are trying new things, especially in neuroradiology since it is such an emotional area. I remember when Gary first taught, we were all thrilled about it, but we didn’t have quite the “umph” needed. It sure would have been terrific to have someone like a neurosurgeon at the time. Eberhard Zeitler: In the past, approximately 90% of all neurology procedures were diagnostic. This will hopefully change with the arrival of new diagnostic imaging methods, especially in the area of early stroke treatment for which accurate and rapid diagnostic methods are needed. I have several questions for our young neuroradiologists: Can CT scans be done for most strokes instead of MRIs? What is the decision-making process today? How do we decide which patients should go to the interventional lab and which should receive active, conservative treatment? Nick Hopkins: Based on the available evidence which, as you know, is very limited, we know that if a patient has a very low NIH stroke scale — that is, less than 10 — and the patient is within three hours of onset, then the patient may benefit from intravenous t-PA. It is very difficult to get any neurologists to agree to treat those types patients aggressively. At our institution, we asked the question: How about the patient who we know will do poorly with intravenous t-PA? The odds ratio of a patient doing poorly when his NIH stroke scale is over 10 rises, I believe, to > 75% — a huge number. For every increase in the stroke scale number, the odds of that patient recovering are correspondingly lower. Thus, we established an arbitrary cut-off point at 15. If a patient’s NIH stroke scale is over 15, we don’t care how fresh he is, if he is one minute post-stroke, we will treat him aggressively by taking the patient directly to the angio suite. If, however, a patient’s stroke scale is 10 or less, we treat him with intravenous t-PA. We have been tweaking this method as we go along based on what we’ve learned from cardiology as well as from our own mistakes in order to come up with a protocol that makes sense. We are starting a new protocol now, in fact. Thus, we are making progress with each step along the way, but we are learning the hard way because we don’t have the numbers that cardiology does. This is a real problem for us — not having the numbers. The floodgates will open when more neurologists and neurosurgeons get trained in this area and enter the fray. Howard Cohen: We have a very active stroke program at the University of Pittsburgh under the guidance of Gary Roubin who encouraged our cardiologists to get involved in stroke treatment in cooperation with the neurointerventionists, neurosurgeons and vascular surgeons. We undertook this form of collegial teamwork with carotid stenting as well. Some of my colleagues are on the bandwagon while others are not. Every institution seems to have its own local politics: some people want to work together, while others are rather territorial about their work. In my view, we need significant involvement from cardiology, particularly in the areas of intracranial and stroke interventions, and it will require an incredible commitment. An interventional cardiologist simply cannot expect to get an occasional call from the neurointerventionist at his institution inviting him to help treat a stroke patient. Obviously, the head is a different discipline with many challenges; the circulation and the way it responds are different. It’s not something a cardiologist can just dabble in occasionally; there must be a commitment like that shown by Gary Roubin. Interventional cardiologists have experience with urgent acute interventions to offer the huge population of patients who require acute stroke or intracranial intervention. As was pointed out earlier, things are a little different in the cerebral circulation and there are times when intervention is appropriate and other times when it is not. Neurologists, from my perspective, tend to be more conservative in treating their patients, while cardiologists tend to be more aggressive. The two disciplines need to join forces to strategize and develop new techniques because as Paul mentioned, we are spending a significant amount of money in the wrong place. We need some new ideas which would come more readily if we worked together. Cooling, for example, is a very exciting area, not only in intracardiac applications, but in the area of intracerebral intervention as well. Nick Hopkins: I think you are absolutely correct. In reality, our differences are not as great as we think. What we do in the head is not terribly different from what you do in the heart. Working in the head is little more delicate, thus we need industry to continue providing the tools that will enable us to work effectively in the brain. I can guarantee you that the catheter skills you interventional cardiologists have today in the area of intracranial stroke management, including the treatment of atherosclerotic disease in the head, are far greater than the skills of most neuroradiologists. I will probably get shot for saying that, but it’s true! You aren’t going to publish that comment, are you? Gary Roubin: I would like to encourage interventional cardiology groups to identify a young, aggressive member of their practice who would focus on the array of procedures related to the cerebro-vascular bed and stroke, starting with vertebral intervention, which is like ostial intervention, saphenous vein grafts in the right coronary, subclavian intervention, and carotid bifurcation intervention. More than 10% of the 750,000 strokes annually are due to patent foramen ovale — a lesion that cardiologists are most qualified to treat. We treat these lesions in our invasive cardiology group. Cardiologists know a lot more than neurologists, vascular surgeons, and neuro-radiologists about the pharmacology, disease management, adjusting the ACT with Angiomax — which most outside of cardiology have never heard of, but which cardiologists are very familiar with — using IIb/IIIa agents, dosing of aspirin and Plavix, and so on. Cardiology truly has so much to offer. I was invited to the neurologists’ annual meeting to talk about what we do in the cardiac cath lab. The neurology community wants us to approach their department chairs and determine how we can help them. As one of the speakers said two weeks ago at this meeting, “All we have to assess our patients who present with stroke is a clinical NIH stroke scale. We don’t even have electrocardiograms. We can’t assess how much injury is occurring at the time.” Imagine if we had no EKG, let alone the ischemic penumbra! The neurology community has no idea about the vascular anatomy. Everything depends on the collateral supply to the affected area. Over the past ten years or so, Jiri Vitek has taught me how to assess these stroke patient. And yet, there is no way to assess collateral supply in the case of acute stroke. In the typical case, a CT scan is performed, an NIH stroke score is determined, and then the patient is put to bed. It’s absurd compared to what we are doing in interventional cardiology! Imagine if we could take the acute stroke patient to the cath lab for an imaging study which would show the status of the collateral supply to the brain and help us determine how to rescue the patient. Nick Hopkins: I understand that neuroradiology spends 90% of its time dealing with aneurysms, arteriovenous malformations, arteriovenous fistulae, and other assorted malformations of the brain. Up until a few years ago, neurologists never performed intracranial angioplasty procedures. Never. It’s all brand new to them. Angioplasty is something cardiologists obviously have been doing for years now. That is why I say that interventional cardiologists are probably better suited to the treatment of acute stroke and intracranial atherosclerotic vascular disease than most neuroradiologists. Jeff Werner: Our institution recently implemented a teamwork strategy to launch a brachytherapy program. It was mandated that the team be comprised of a radiation oncologist, a radiation physicist, and a cardiologist. From the very start, the team members accepted the fact that each person contributed a particular set of skills and expertise. The radiation oncologists, once we got to know them, were very happy to be working as a team and were very interested in this program. It seems to me that this teamwork approach involving one or two successful therapies or a couple of types of clinical situations, is an effective way to move things forward. Nick Hopkins: The team concept is certainly the best approach. Raoul Bonan: I agree with what Paul and Jeff said. Even the neuroradiologists and radiology oncologists at certain institutions will not be in the lab anymore; they will delegate someone else to do the procedures. Through specifically focused studies, such as the one involving 50 sites in the U.S., we have been able to spread the notion in the U.S. and Canada that these radiation therapy programs represent a new approach to therapy. Reginald Low: Why don’t we form a committee whose task would be to establish a core curriculum for cardiologists to train in neurointervention work? If industry would help support this effort, we could have the first world course on the core curriculum for cardiology training in neuroradiology and neurointerventions. I have been involved in some animal pre-clinical testing with wires, balloons, and stents for neurointerventions. I find it interesting that companies in the industry have not developed cooperative working relationships between their neurology and cardiology units. There are numerous wires, balloons, and stents available for neuroradiology applications that industry has not fully explored in terms of possible cardiology applications. I have used stents that are so much more trackable than anything we have presently in cardiology and that could be very important niche products for certain cases. Michael Lawrence-Brown: Politics aside, I find this a fascinating subject. I have seen a patient recover four hours after total loss of consciousness. The patient underwent carotid endarterectomy with total occlusion on the other side and two hours post-procedure, he lost consciousness. The ultrasound showed complete occlusion. I placed a sheath in the carotid artery and infused with heparin, then took the patient down to the angio suite where I diagnosed a dissection which extended right up beyond the siphon. I successfully got around the siphon and then placed a Wallstent all the way down, completing the patch at the bottom. The patient then regained consciousness. He did experience some deficit, but it was very interesting because it involved the collateral circulation and the situation we’ve discussed here regarding acute coronary syndromes. We may have more time than we think to recover these patients when their artery occludes. The second important factor was that we reduced our shunt rate from 12% to 2% by allowing the brain to control the blood pressure (under a local anesthetic). Thus, there is more coming out of the brain than we know, as far as I can determine. We frequently see changes in hypertensive medication and difficulty controlling blood pressure for hypotension following carotid endarterectomy. Thus, there is a pharmacology of the brain that is not yet fully understood, but it has implications for all of us because if you treat patients with strong hypotensive agents to control the strain on the heart, you may actually be reducing cerebral perfusion if the patient has a carotid stenosis or an occlusion — and this could lead to stroke. Carotid disease therefore becomes very important in that context. But the process is even more interesting in that we can really look at the whole of atherosclerosis by looking at the carotid bifurcation which features a mobile section and central forces on the curve, as well as a fixed area. Another fixed area appears at the base of the skull where traumatic dissections commonly occur. Interestingly, those traumatic dissections of hematomas do heal. No artery bifurcation in the body better demonstrates the sheer forces that occur in the wall and the rotational forces that occur at a bifurcation better than the carotid bifurcation because there is a high-resistance vessel in the external carotid artery and a low-resistance vessel in the internal carotid artery. This means that every time it pulses, it rotates and is thus a perfect setting for fatigue fractures. Yesterday we touched on the idea that there is more than just the intima associated with the generation of atherosclerosis. Why is it that carotid occlusions are such isolated lesions? We know in most cases, except in some diabetics, that we are going to get to the end of the lesion. There is something mysterious about the bifurcation that we have yet to understand. In 1993 we looked into materials to use in stents for stent grafts in the aorta and found much of our technology in the field of dentistry. Before Andreas Gruentzig, there was Dodder, and before Dodder, there was Stent. This is accelerated testing — one hour = one year. An ideal metal, with electron potentials and current, will give a nice line straight up and then when it goes beyond the electron potential, it will deform. A good metal will come back to the same point. The stainless steel material is shown on this slide in red. This slide shows a titanium alloy, a wonderful metal that comes from dentistry. Here are examples of nitinol, nickel, and titanium metals. Stainless steel is a little better, but when it deforms it does so completely, and once it deforms, it does not return to its initial shape. Nitinol, on the other hand, is a memory metal, so when it deforms it returns to its original point. Nitinol’s slope is not straight, however, which means that every time it deforms, its crystallized structure is slightly changed. Thus, over time, nitinol changes its memory so that it becomes brittle and fractures. When we study stents, we take plain x-rays. If a nitinol stent is going to be placed in a carotid bifurcation, plain x-rays will routinely need to be taken to check for stent fractures. This slide demonstrates how we thought that if we gold-plated the stent, it might give better protection, but gold-plating makes it worse. The memory might be slightly better, but the slope means that it will corrode very quickly — a phenomenon which I believe has been observed in the heart as well. Finally, if bare-metal stents are placed across orifices, there is no accretion; it will not substantially interfere with flow, especially if the artery orifice is > 3 mm. I can’t take you down to 1 mm because the technology we had did not offer sufficient accuracy. The blood helps because it is a sheer, thinning fluid with vortex shedding. But at the edges, if intimal hyperplasia occurs, it may grow to cross the lattice, which might be seen with the Wallstent. This is a weld or a solder: there is greater corrosion there and some eluting may be occurring, but it is not eluting a substance that decreases intimal hyperplasia. Instead, it increases intimal hyperplasia. Therefore, what we use — especially in the final frontier of the brain, the intracerebral circulation, and the carotid arteries — is very important. Perhaps the drug-eluting stent will be the answer, but it needs to be a self-expanding one because it will have to be able to negotiate around the curves in many instances. You saw the image Nick showed of the stenosis that was right on the apex of the curve. We obviously have a lot to learn yet and we must work together to arrive at a better understanding of vascular disease. John Anderson: What I’ve heard today is excellent, but that’s not where we are. There is not even a perception in the general medical community or in the general public that a treatment for stroke exists. We need to start with education and refer back to the excellent work that has been done in the past and that will hopefully continue in the future. We have trained paramedics to use defibrillators, but for most people, stroke is not an emergency; rather, it’s often considered “a done deal.” People don’t tend to rush stroke patients to the hospital because they are not aware that there still might remain a therapeutic window of time during which the patient could be salvaged. Education of the public and the medical community is thus where we should start. Until we take that step, we will continue to see a large number of patients who are simply not retrievable no matter what innovative techniques we try on them.