Current Treatment of Bifurcation Lesions and a Dedicated Stent

How prevalent are bifurcation lesions? Bifurcation lesion incidence ranges from 30 to 40 percent of the lesions treated today with percutaneous intervention. There are some studies (such as the upcoming trial from Boston Scientific, SYNTAX) that are looking at complex multi-vessel disease plus or minus the left main, where the initial demographics have shown that up to 50% of treated lesions have at least one side branch related to the stenosis treated in the main branch. True bifurcations, where both segments of the bifurcation — meaning the main vessel and the side branch vessel — are involved are between 10 to 30 percent. Disease in the main vessel, in and around a bifurcating vessel that may or may not be diseased, occurs in up to 60 percent of cases. Bifurcation lesions are thus an important contributor to everyday intervention. The problem is that it is often technically challenging to treat both the main and side branches and, at the end, have good angiographic results for both. As a result, a variety of techniques have been promulgated, none of which have absolute superiority over another, which makes it more difficult for the average operator to know which technique to adopt when the lesion is in, around or involving a bifurcation. Generally, for the sake of simplicity, a so-called “provisional” stenting approach to bifurcation has been advocated. Provisional stenting means that you treat the main branch as definitely as possible, and only then deal with the consequences of that treatment to the side branch. If the main branch is treated well but then the plaque shifts into the side branch, with the side branch ostium becoming pinched with the appearance of slow flow, then it needs to be rescued. At this point, a variety of techniques using two wires can be adopted. Perhaps a balloon and a stent, or a stent alone, is used. Certain trials, the most commonly quoted being the NORDIC I and II trials, have examined provisional stenting of bifurcations, and it has, as a result, become a preferred approach — i.e., take care of the main branch, and then respond to the side branch according to what happens during the procedure, following proper treatment of the main branch. Can interventionalists make an assessment as to what that plaque is going to do when the stents expand? If there were a way to predict plaque movement, then it would be very easy. I don’t think we have a way to predict, which has led most operators to wire both branches, treat the main branch, jail the side branch wire, and then come in and reconnect everything if there is disease. That is where the difficulty lies in side branch stenting, because there is a great deal of wire movement, jailing of wires and recrossing of stent struts. If we could predict which lesion was going to be a problem and which was not, it would be a lot easier. We would be prepared with appropriate equipment or would use a bifurcation-dedicated stent beforehand. But there is no such ability. It is an unpredictable situation. What if the side branch is too small for a stent? If the side branch is too small for a stent, then it is usually only ballooned. In small vessels that are less than 2.5 mm in diameter, the NORDIC trial and other data have indicated that it may be best to do nothing to the side branch that is less than 2.5 mm. Ignore it, or just balloon the side branch in case it gets into trouble, i.e., the “keep open” technique. This is a hypothesis that’s never been tested and would be very difficult to test in a clinical study, obviously. Is there one area of the coronary tree where it is more common to find bifurcations? The challenge of bifurcation lesions is that they are very common throughout the coronary tree. It’s not like in the legs or anywhere else in the peripheral vasculature, where the vessel is usually a straight segment and then, at some point, one or two branches occur. The entire anatomical disposition of the coronary tree is a tortuous and bifurcated system of arteries. Bifurcation prevalence is common everywhere: in the right coronary, in the circumflex and the left anterior descending artery. All of these arteries present one, or more than one, side branch. One of the more interesting theories is that atherosclerotic disease develops more predominantly at the side branches because it is where laminar flow is altered and shear forces are also different in terms of blood flow — minute after minute, year after year and decade after decade. Laminar flow is blood flow without any impediment. Imagine putting a rock in a riverbed. The water gets more agitated, and instead of running smoothly, you can see turbulent jets develop, called non-laminar flow. These turbulent jets occur in a similar fashion at bifurcations. When these forces hit the arterial wall, over time it becomes irritated and starts to create atherosclerotic predisposition. Thus the argument is atherosclerosis is more common at the bifurcation because of non-laminar flow. Are the high restenosis rates that we see with bifurcation lesions a result of an inability to adequately treat the plaque at the lesion site? The pendulum has swung dramatically in terms of how to optimize treatment. Initial research has focused mostly on the acute result. Now, the second question is how to optimize the treatment of bifurcations for long-term patency, which is where we look most closely at restenosis. From the beginning, it was well known that bifurcation lesions with bare-metal stents, whether you did one or two stents for bifurcation disease, was associated with significant restenosis. Then came drug-eluting stents, and it was thought that they would solve the problem, but indeed drug-eluting stents do not, because either the main branch or the side branch, depending on the technique you use, still has a significant amount of restenosis. As a matter of fact, one of the most disappointing data sets, involving the Cypher stent, was in bifurcation disease. There was a small study published showing that even with two Cypher stents, in the main and side branch, the restenosis rate was not in the single digits as was the case for main vessels, but was actually at about a 20-25% rate when you considered the side branch as well. A great deal of investigation and published literature ensued, examining whether the cause of the double-digit restenosis rate was the disease, stent malapposition or the techniques in use. It came down to the fact that no matter what the technique, the main problem arises from the angle of the side branch. If the side branch takes off at a different angle from the main branch, anywhere from 70 degrees or greater, it is very difficult, no matter what technique you use, to fully and adequately cover the ostium of the side branch. This is probably where the restenotic pattern begins. Trials next sought to determine whether the crush technique was better than the Y-stenting technique, the Y-stenting technique better than the provisional and/or provisional better than the culotte technique. Today, there are three main techniques in use. First, provisional stenting, meaning first treat the main branch, then wait and see and treat if necessary the side branch, using a modified Y- or T-stenting technique. The second technique is an a priori treatment of both the side and main branches, called culotte, where you angle into the side branch and then add a stent into the main branch. The third technique is called ‘kissing’ stents or V-stenting, which is side-by-side stents in the main branch and the side branch, creating a new carina in the main branch. An extension of the NORDIC trial found that the ‘crush’ technique probably results in the most restenosis, so it is being abandoned as the ultimate or preferred technique. Restenosis remains an issue, independent of the approach, independent of the technique, and perhaps independent of the device, because there is no dedicated bifurcated stent on the market that has optimal coverage of both the main and the side branch. As a result, the field of what we call dedicated side branch stenting is developing, with an effort to develop devices specifically designed and optimally suited for coverage and treatment of bifurcation lesions. You are working on one of these devices, the Stentys stent. Can you describe it? The Stentys stent is a takeoff on the idea of the provisional stenting approach, with its focus on stenting the main branch first. Instead of being balloon-expandable, it is a self-expanding stent, with the idea that self-expansion is a kindler and gentler approach, so less plaque shifts into the side branch. After placement of the Stentys stent in the main branch, the side branch is examined. If there is disease or plaque shift into the side branch, then a wire can be threaded through the stent into the side branch. A balloon is advanced through the struts, which look like very large cells. Once the balloon is inflated, it disconnects “bridges” between the stent struts, creating a large, unimpaired orifice with access to the side branch. A second stent can be advanced into the side branch with great freedom and ease, facilitating good apposition and placement. As a specialty stent, the Stentys stent allows for perhaps less plaque shift, but if that does not happen, the stent permits a ready-made rescue situation, where any common wire, threaded through an enhanced opening to the side branch, allows for treatment of the side branch with greater ease, higher success, better coverage and ultimately, perhaps, a better restenosis rate. You note the stent design is comprised of large cells. Are there any strength issues with such a design? There have been a lot of preclinical bench data as well as animal data that addressed this obvious question about a potential shortcoming in the integrity and strength of the stent. However, the stent has a special, patented design and is also self-expanding. These two characteristics permitted the engineers to create a product with similar hoop strength to regular balloon-expandable stents, including some non-disconnectable links at the edges. In comparison to standard balloon-expandable stents, at least in the in vitro model on the bench, the Stentys stent possesses the same scaffolding and radial strength, a must in order for it to meet any regulatory requirements. In placing the Stentys stent, is there any special positioning in the main branch that needs to be done by the interventionalist? Yes, an excellent question. For the last few months, we have focused on optimizing an area we call the “disconnectable zone” so it can be easily placed in and around the side branch. In other words, there is not just one disconnectable cell requiring complicated maneuvering, but a 15-mm disconnectable zone in a 20-mm stent. All the interventionalist has to do is put the disconnectable segment in and around the bifurcation branch, and then it allows him or her multiple rows of disconnectability to access the side branch and thread the wire through as needed. If there is no need to treat the side branch after placement of the stent, then the procedure is over. If, on the other hand, disease is pre-existent in the side branch or is worsened by distortion of the anatomy or plaque shift through treatment of the main branch, then that 15-mm opaque zone of disconnection can be targeted. A wire is passed through the branch, the struts are disconnected by balloon inflation, and a second stent is advanced, at will, if needed. How many human procedures have been done with the Stentys stent? It is obviously a day-to-day tally, but at last communication, it was at about 12. It is important to also note that a bare-metal version of the stent was implanted. The company has drug-eluting versions in development as well. Two drug-eluting stents are being studied, one using paclitaxel and the other sirolimus. We are currently evaluating both drug systems in the animal model. What were the inclusion criteria for the patients done thus far? Inclusion criteria for the Stentys stent include any bifurcation, meaning Medina classification 111, 100, or any combination or permutation. The Medina classification rates the bifurcation just before the side branch, just after the side branch and the side branch itself. A 1 or a zero is assigned if there is disease or not, respectively. A true bifurcation is one where the plaque is above the side branch, in the main vessel (“1”) below the side branch in the main vessel (“1”) and in the side branch (another “1,” for a Medina classification of 111). The Stentys cases were on any and all types of bifurcation lesions. We are planning for 6-month angiographic follow up because, remember, this is a bare-metal version of the stent and will be associated with a typical bare-metal stent restenosis rate. The main aim of our initial study, called OPEN I, is not to look at the restenosis rate, but mostly to look at acute outcomes. Primary endpoints are procedure and acute outcomes, and immediate and 30-day major adverse cardiac events (MACE). Secondary endpoints are restenosis rates. As the drug-eluting version of this device comes online, then late loss and restenosis of either the main or side branch, or both, will be considered as a prime endpoint for the study. What are future plans for work with the stent? Mostly we will be looking at ease of use, primary success rate of implant and what happens to the side branch. Our first hypothesis is that a self-expanding stent at the bifurcation is a kinder, gentler treatment of the main branch that may affect the side branch less dramatically. The second hypothesis is that this stent will make the procedure easier to rescue, and the third is that if you have to rescue the side branch, since the stent can offer a wide opening, the second stent can be placed with greater accuracy and ease. Restenosis of the main and side branch will be important endpoints. The company expects a European launch next year of its bare-metal bifurcation stent, and possibly the DES iteration as well. Dr. Buchbinder can be contacted at mbuchbinder@fcvmed.org

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