Percutaneous Aortic Valve Replacement

When did you first start using the Cribier-Edwards percutaneous aortic heart valve? We received FDA approval in August 2003 for a one-time compassionate use. Dr. Alain Cribier, who did the first human clinical implants with the valve, had started using it about a year earlier in Europe, also just for compassionate use. Our first patient at Beaumont Hospital was a 73-year-old man with no other treatment options. He came into the hospital with recurrent heart failure, previous bypass surgery, multiple admissions for heart failure, severe aortic stenosis and was deemed to be high risk for surgery three cardiac surgeons had turned him down. We did the procedure using the antegrade approach, and were able to deploy the valve successfully; it looked like the patient was going to do well. For 24 hours, he did spectacularly, and then 36 hours after the procedure, he abruptly decompensated, and four days later he died. At autopsy, we found that the anterior leaflet of the mitral valve had been torn by the catheter as it had gone around the mitral valve. Three days post-op, the patient developed severe mitral regurgitation, which was the cause of death. We had been negotiating with the FDA for months to get started, and they initially had given us permission to do three cases. After the death of the first patient, the program was put on hold. At the same time, there was a lot going on with the percutaneous heart valve itself. The company that made the device, PVT, was undergoing acquisition by Edwards Lifesciences. This further delayed any U.S. testing. Edwards also realized that it was going to be very difficult to do the procedure from the antegrade approach. Beaumont Hospital had an institutional IDE, which is a permission to experiment within the United States. When Edwards bought the company, they took over the IDE, and changed the design of the trial. The FDA then approved our site to resume the protocol. After August 2003, when we did our first case, it then took a year and a half to start again. In February 2005, we resumed the protocol, and that was when our first long-lasting survivor occurred. His procedure took place in March of 2005. The FDA had given us permission to do five cases, and another U.S. center was allowed to start as well. However, due to some case complications in both centers (procedure learning curve), Edwards withdrew the IDE to wait for a further refined retrograde delivery system. Per HIPPA guidelines and confidentiality reasons, case details may not be released. Right around the same time all this was happening, Dr. John Webb (St Paul’s, Vancouver) started doing procedures from the retrograde approach, starting in January 2005. The antegrade approach (see diagram) involves advancing the catheter through the right side of the heart, from the right atrium across the septum to the left atrium through the mitral valve, and then up and around into the aorta. The antegrade approach was the original way pioneered by Alain Cribier. The retrograde approach is a more direct approach, involving advancement of the catheter into the aorta, then back down through the aortic valve where the valve is implanted. Edwards decided to focus its efforts solely on the retrograde system for the short term to help make the valve easier to place. They developed a new delivery catheter that would optimize the retrograde technique. Since January 2005, Dr. Webb has been the most active implanter in the world, and I think he has done more than 50 cases since he started his program. At our site, we were able to resume using the catheter in the retrograde approach, and we started our trial again here in the United States in December 2005. Both our site and Columbia University are open, as well as the Cleveland Clinic. We now have permission from the FDA to do a total of 55 patients, and they will review the results. Ultimately, the plan is to do a randomized trial. How does the procedural technique differ from balloon valvuloplasty? You begin by doing a balloon valvuloplasty on the patient. We use an undersized 20-mm balloon. We advance the balloon through the femoral artery, across the valve and dilate it. We pre-dilate the valve to make sure we can identify just where the calcium on the aortic valve is and how that fits into the leaflet apparatus. A valvuloplasty balloon is used to deliver the Edwards valve, which is a stainless steel skeleton with the valve sewn on the inside. The valve is crimped onto a balloon, and then the whole apparatus is delivered over a wire across the aortic valve. Thus, we start by doing a catheterization, then put a catheter across the aortic valve, make pressure measurements, and then we leave a long exchange guidewire in the ventricle. We put a valvuloplasty balloon across, and once the valve has been prepared, then we bring the stent valve across the aortic valve, and deploy it. The sheath is 24 Fr in size, so we actually have the surgeons do a cut down on the iliac arteries in order to advance. It is too large to be able to close without surgical closure, so the sheath is placed and after the procedure, the sheath is removed, and the surgeon closes the wound with surgical closure. The procedure itself takes an hour and a half, and then the patient goes to the CCU for recuperation. Is there any need for overdrive pacing? In order to implant the valve, you have to have the heart not contracting. If the heart contracts, and pushes any blood forward, it will take the valve out of the place where it is implanted. In order to prevent this, we pace the patient between 200 and 220 beats per minute, causing such rapid pacing of the heart that there is no forward cardiac output for anywhere from 15 to 45 seconds. That’s how long it takes to implant the valve. Could you talk about the role played by size the patient’s own anatomy and that of the valve itself? That’s a very good point. We basically are putting a circle (the valve), into a triangle (the trileaflet aortic valve). You have to slightly oversize the valve itself to make sure you don’t have a leak on the outside. There are two sizes available right now: a 23 mm and a 26 mm valve. The 23 mm is being used in patients with smaller vessels and valve diameters, and the 26 mm size is being used in valves that are larger. If the valve is greater than 26 mm in diameter, then we think it’s too large and are excluding those patients. So we currently have a range of annulus sizes of 19-26 mm. What medications are the patients receiving, both during and post-implantation? Patients during the implant have general anesthesia. They get antibiotics prophylatically and then they are anticoagulated with heparin. After the procedure, there really is no special treatment. Most of these patients have severe heart failure, so they are on beta blockers and ACE inhibitors, but there are really no specific additional medications required during or post procedure. What are the clinical criteria? The patients have to be older than age 70, have an aortic valve area less than 0.7 cm2, and they have to be considered to have a high operative risk for surgical valve replacement. We are using a risk-scoring system, which is a calculated formula for cardiac operative risk evaluation obtained from large patient registries. The operative mortality risk needs to be greater than 20% for a patient to be receive a percutaneous valve. Do you consider percutaneous aortic valve replacement a true potential alternative to surgical repair? Not yet. I think the procedure is really in its infancy. I mean, it would be analogous to saying that balloon angioplasty was an alternative to bypass in 1980. It’s really not an alternative yet, because there are a lot of patients that are very good surgical candidates and there is no reason to use this experimental procedure on them. Surgery has had over 50 years of experience. With some of the bio-prosthetic valves there are implants that are now almost 20 years in duration. Until we have a better idea of the durability of the percutaneously implanted valve, I think it is way too premature to consider this an alternative. It’s a very good treatment for patients who are not good candidates for surgery. There are a lot of patients with severe aortic stenosis who simply are not suitable for surgery because they’ve got co-morbidities; for instance, severe lung disease, porcelain aortas, which are very heavily calcified aortas that the surgeons can’t cut into, and/or other co-morbidities like renal failure or liver failure, which makes surgery technically unfeasible. What do you think about the balloon-expandable versus the self-expanding valves? That’s a good question. There are probably going to be five different kinds of devices that are actively going to undergo trials. Physicians in the marketplace are going to decide which is easiest to deploy and which is the most durable. CoreValve is the other valve being used in humans and is a self-expanding device that is currently being tested. Dr. Eberhard Grube appears to have very good experience in Europe and Germany, and they’ve got a lot of experience with implants there. I think the self-expanding valve is going to be a very interesting strategy to look at. There are other devices that I’m aware of using other technology, but I think that everything is going to be in a state of rapid evolution. Edwards has now demonstrated the technical feasibility of percutaneously implanting aortic valves, so we know that we can do it. Now there will be a rapid onslaught of trials of different devices and techniques to try to treat aortic stenosis. What’s the greatest danger to the patient during the procedure? Well, there are lots of risks. The sheath itself is very large in dimension, and laceration or rupture of the iliac vessels could occur. The valve itself needs to be meticulously placed. If it is implanted too low, you can have fatal, catastrophic aortic insufficiency. If it’s implanted too high, the valve can embolize, and it will basically just sit in the aortic root. These are all potential complications. There is going to be a learning curve where physicians figure out how to deploy the device safely, and we will see the technology is going to improve a great deal. The valve will become smaller and lower profile, but that’s why it’s not really appropriate to say this procedure is an alternative to valve replacement, because it’s all still in the infancy of design and technique modification. Surgeons are involved with the procedure. What are your thoughts on the increase of multi-disciplinary involvement in percutaneous procedures? I think the successful programs are going to be the ones where the surgeons and cardiologists collaborate constructively. Everybody’s going to benefit. Patients in particular are going to benefit. You have to have the collaboration with the surgeons for this procedure. First of all, you must have superb surgeons, so that some of these moderate-to-high-risk patients can be treated surgically, and it can be done safely. And then you need to have the surgeons available for complications that can occur during the valve implant procedure. Basically, a multi-disciplinary collaboration is essential. There are going to be technologies where surgical approaches are an integral part of the procedure. Already, in Vancouver, they are using a trans-apical approach, where the surgeon is actually cutting down in the apex of the ventricle and implanting the valve under fluoroscopic guidance. The most powerful catheter labs and surgical suites are going to be redesigned so that there is a fully functioning cath lab and a fully functional operating room in the same room. Could you talk about your future plans for work with the valve? In the short term, we have finished the 20-patient pilot feasibility trial, and have been given an extension to do an additional 35 cases at three active centers. This is so we can get the technique really well-established and all the technical problems ironed out before doing a multi-center randomized trial. That is the path to approval in the United States. We’ll try to get this device approved for patients that are high-risk or inoperable for valve surgery. The big question is going to be the path to approval for all of these devices, because everyone is really trying to figure out the safest way for percutaneous aortic valve implantation to evolve. The FDA is requiring randomized trials, which may or may not be the best approach in some of these situations. Dr. O’Neill can be contacted at woneill@med.miami.edu

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