Thanks, Tanvir. We're excited to be here tonight with a host of faculties who have extreme expertise in instant restenosis. You know, I was excited when Tanvir and the team asked us to present on this topic because instant restenosis is a problem in and of itself that, as we know, you know, can be recalcitrant in patients and can be difficult to treat in a durable fashion. It's particularly complicated when it involves bifurcations, and as you know, one of the problems with bifurcation stenting is that we have higher rates of TLR related to instant restenosis. And so, I think, you know, upfront imaging and doing a good job to get your first stent in well should be an edict, but that doesn't always lead to good results despite best efforts in modern practice. And so, we've got three case presenters today. We've got an expert faculty, including, as Tanvir mentioned, Ron Waksman, who's really been a pioneer in treating instant restenosis for many years now, and I've learned a lot from Ron, who I'm co-moderating with. So, the lineup today is we're going to start with Dr. Sanicera, who's with us from a trip in Minnesota on his way back to Emory, and then at the end of the session, Dr. Lisko, who's Dr. Sanicera's partner, is going to talk about their efforts to set up a focused ISR clinic to help treat patients that are afflicted with this problem. So, without further ado, we'll try to keep this conversational and Pradak, go ahead and take it away. Great. Thank you so much, Kevin, and thank you, Dr. Rab and Sky, for this opportunity to present. It's great to be here with a very esteemed group of colleagues. So, I'll start off with a case here of an 80-year-old male. He presented with class 3 angina, past medical history of CAD, had a PCI, the LAD-DIAG, verification in 2021, issue of hypertension, hyperlipidemia. He had a SPECT, which showed anterior ischemia, and has normal ejection fraction on echocardiogram. This led to a cardiac catheterization, which basically showed, you know, I just have one image here of the problem area, and you can see there's a stent extending from the prox to the LAD, along with the bioplication, DIAG stent, and then if you look on the image here on the right, so you can see severe ISR here in the osteodiag. This is actually a distal edge of the LAD stent. There's a gap, and then there's another stent further downstream in the mid-LAD. And you know, so we have a very algorithmic approach, which is image-guided for management of ISR, and so for this, we predilated both the LAD and diagonal branches with a 2,5-NC, which was followed by IBIS imaging, and here's the IBIS pullback from the LAD, so you saw that distal stent, and there's a gap here in between two stents, and you'll see some dropout with some de novo disease in between the two stents, which leads into severe myeloma hyperplasia at the distal edge of the old stent. Here's the diagonal branch coming in at 10 o'clock, and then you see again more myeloma hyperplasia and incendiary stenosis in that LAD segment proximal to the diagonal branch, and we're continuing the pullback all the way back to the proximate LAD. You see some calcific neophthala as well as some underextension in that proximate segment of the LAD stent. I have some reference numbers on the right-hand side, so the distal vessel is 2.5 millimeters in diameter, and a reference of 4.94-millimeter scope. The MSA was 1.96, and that's marked out on the right-hand side here, just proximal to the takeoff of the diagonal branch, and then I have some other still images of the new lesion distal to the mid-LAD stent in that area, in the gap area, and then the distal reference segment at the very bottom right-hand panel in the distal stent. So this is, and I'll let this IBIS run from the diagonal branch again. Basically we're pulling back distal to proximal. You'll see the stent's well-expanded. You see a significant amount of neonatal hyperplasia right here as we're coming back into the LAD coming in from your 1, 2 o'clock, and then you can see that, again, the disease in the LAD, just proximal to the takeoff of the diagonal branch there, again, pulling pullback all the way back to the prox LAD in the left lobe. So from a diagonal branch standpoint, the distal reference diameter was 2.5 millimeters with an area of 3.32 millimeters squared, and the MSA was 1.62, which is marked with the area of severe ISRE that you can see in the graph that we have on the right-hand column. So Kevin, I'll pause here if there are any comments from the panelists about thoughts on how to approach this. So one clarification, this is the first time ISRE hit only one layer, is that correct? Yes, just one layer. Yeah, I think you nicely outlined in product there's a couple different mechanisms of action here, probably to some degree undersizing, correct? And then additional to that, there's tissue inside the stent, some of which is more benign-looking neo-animal tissue, and there's some evidence of calcific neo-atherosclerosis, correct? Yes, yes. It's a potpourri of ISRE mechanism, which is quite nice. Yeah, exactly. What are your thoughts, I guess, how you'd start off? Yeah, the hard part about calcific neo-athero is that there's really no place for it to go. So outside of the scything issues of the stent, you kind of have a compliance and a bulky tissue with no home to go as you start to stretch this thing. And so a lot of times, we're inclined to either use some sort of plaque modification. There is potentially a value play here to softening everything up with IVL, including the neo-animal tissue, to see if you can get an adequate MSA on expansion in the calcified neo-atheros segment. And if you can't, it's one of those scenarios where sometimes we just need to go ahead and drill it with a roti-burr or with Orbital. Admittedly, Orbital is contraindicated, but it does work quite well with debulking calcific neo-athero. The amount of calcific neo-athero in this case isn't so awful product that I might not try some IVL massage therapy, see if you could make things bigger. I'd be loving to not have to re-bifurcation stent this, and so I'd be interested what Evan thinks. But if there's a way to get this open to a place where, at worst, you have to stent the LED main branch, but DCB out the diagonal in some way. And a lot of the decisions of what your final therapy is is really going to be driven by how much recoil, what sustainable MSA you gain based on doing ballooning, plaque modification, whatever you decide to do. I'd be interested, Evan, Ron, or Khaled, do you guys have any other thoughts? Yeah, I may chime in for a second. This is interesting because it's not only ISR, it's including also a segment that was never stented, which didn't come into our classification. We have biological, mechanical, mixed, neo-athero, I mean, all those A, B, C, D. But this one is also including a segment in between that's never been stented. So that may change the approach. And I agree with you that there is a modest neo-athero, and I think that you definitely don't want to re-stent the diagonal. So my approach would be to wire both, to do just POBA, try to get the best imaging-guided outcome just with balloon, then to go with DCB to the diagonal and to finalize with re-stenting the LAD, including the unstented segment. I think that probably would be the best approach in this situation. Now, should we don't feel that the balloon is fully adequate, I would apply all the other modalities that you have suggested. Great thoughts and comments from everyone. And yeah, that was our thought as well. And Kevin, as you said, yes, there is some calcitic neo-athero, but I felt like it's not really too overwhelming. And I thought there's a ton of neo-animal tissue. So basically, my thought process was to maybe start off with laser for the neo-animal hyperplasia after we just did 2,5-NC to kind of open up some room for the ibis. So we did laser with saline for both 1,4-fiber on both the diag and the LAD. And then this was followed by just Wolverine cutting balloon for 2,5 in the diagonal branch, 3,0 in the LAD, and then 3,5 in the entire proxy LAD segment proximal to the diagonal branch. It's a nice picture in the middle there, Pradeep. I always kind of, it piques my interest when the Wolverine's up at a reasonable pressure and there still seems to be a space between the stent metal and the balloon itself. Kind of like, you know, you see that you've got some tissue there and it's just a matter of whether that stuff compresses and stays compressed or is going to expand. I think your approach to debulk is a good one. The way you overcome this problem is by stretching the underexpanded stents and making them huge and getting acute luminal gain that makes the final kind of tissue that's left behind maybe not be that bad from 8% diameter stenosis. But your thoughts to remove some of it with a laser is good, especially, you know, it doesn't do that well for debulking calcific neo-athero, but it can help with more rubbery stuff. That's a nice application of the technology from a mechanistic standpoint here. Also, I was just going to add with the cutting, you know, it's a lot of things in addition just from plaque modification in the areas, if you're considering DEB, I really find it's helpful theoretically just from greater drug delivery. But you also learn, as Kevin mentioned so much about, are you ready for the next step, be it drug-coated balloon or another drug-coated stent based on that expansion. And you can see it here even on just the gap between the prior stent and the cutting balloon in the middle image. With any of the advanced fluoro, things like device detection, stent boost, you can really hone in on that, particularly for bifurcation lesions. It's great just so you can see how you're getting expansion. One thing just to your credit with the IVUS before, just because one of the focus of this session's bifurcation is because you so nicely did IVUS from both arms, the LED and the diag, you see it was a perfect bifurcation. You see two perfect osteo. There was that one image that kept looping where the osteo, it was the implant, like that's perfect. It is a perfect double barrel. I think it's so helpful having that image and really understanding that you don't need to put another double layer of stent across this, particularly in the diag. And I think agreeing with what the other said, hopefully just if you get good expansion, drug-coated balloon for the diag and then really focusing in on the LED. Yeah, great points. So Kevin, I see what you're saying with the gap there in the middle panel. And I hit that area, actually. It's just approximately the diag with a 3.5. And then we talked about that gap. So my thought was maybe treat that middle segment with a short stent not crossing the diag. And so I put a 2,518 DES in that middle segment to treat the de novo disease, a post-dilated. And you can see a really good expansion here on the image. And so the question now is, are you ready to do DCB or break you? And so we went ahead with the kiss just to make sure we're conforming the carina, the bifurcation. And then here's the image angiographically after treating that distal de novo disease, kissing with inflation, cutting boolean laser. Yeah, the one nice thing about a cutting boolean product, and I don't know that this has been proven, but one of the main problems with rubbery neo-animal tissue is recoil. And it can happen, it can look OK initially, and then you get to take your final angiogram, and this stuff sort of bounces back at you over time. Yes. I think Jeff Potma once pointed out that Roxanna, I wouldn't be surprised if Ron was a co-author back then, had a paper in Cirque apparently that was an instant resynosis. It was instant A-A-T-A-N-T, because they brought a patient back for a relook and the angiogram looked good at the end of the case, and two hours later it had sort of recoiled back. And so the nice thing about a cutting boolean is I hope when I use it in these scenarios that by the fact you're slicing the neo-enema, you're creating some discontinuities in that tissue, which just hopefully separates it a little bit that the fibers are a little less likely to recoil back at you. So having defined what was inside the stent with the initial ivus is super important, because I think you employed two technologies in sequence, laser to hopefully debulk and maybe soften a little bit. Soften is better when you use contrast, but then a cutting boolean to mitigate hopefully a little bit of the recoil, which can be prone in these cases. And you did one-to-one sizing based on the ivus, which is nice. And at least your initial picture there looks like substantial recoil is not a major problem right now. You've got a reasonable angiographic result here. And so I'd be hoping like, oh, maybe this can be a kissing DCB or a DCB case. I don't have to re-stent the part of the LED that involves a diagonal. But your use of imaging and I think choice of device based on it has been really nice thus far. Hey, Kevin, how does imaging up front affect your choice of cutting boolean technology, be it with a Sculpt or a Wolverine? Yeah, so I think it boils down to a couple of things. I'll show a little bit of the algorithm that Evan and I developed a couple of years back related to my case. But the main question is, is the stent well-sized or well expanded or not? And if it's big, what's inside of it? What is that tissue made of? And so if it's under-expanded and focal, I'll usually use a Sculpt because you can crank on them to 25, 28, and they typically are rupture-resistant and stay put. And if it's neo-animal tissue that I'm worried is going to recoil, I'll take a Wolverine and try to slice it so it's a little less likely to be connected and come back at me. I mean, that's sort of a back of napkin approach I have. But all of it's driven based on what the IVUS or OCT tells you is inside the stent, and whether the IVUS or OCT tells you the stent is expanded or not. I want to make a comment here on the instant restenosis. I think that even with cutting boolean, you're going to have the tissue falling back. And you're not going to prevent it. So the only trick is really to use antiproliferative technology, which could be, obviously, drug-eluting stent, which we're trying not to. We use brachytherapy a lot. And when we use brachytherapy, the tissue will disappear. So you don't have to worry what's going to happen the next 24 hours. If you're using just POBA, you have to worry. But if you use DCB, it can work like brachytherapy. So I think DCB, both arms post, will take care of the tissue over time. And you don't have to push too much, eliminate the tissue, because you're not eliminating it. It's going to fall back. And again, it's just a question. Maybe another 30 minutes, another one hour, if you'll wait, you'll see the tissue coming back. Yeah, we see that in brachy cases, right, Ron? You know, the endogram looks good. You call for the brachy guy or gal. They come from wherever they are. They do their time out. You prep the catheter, you put the catheter in. You keep the catheter for 10 minutes. If you're doing 212s, maybe a little bit longer. And then, like, your final picture looks awful again. I find it very frustrating. So you've got a reasonable angiographic result there. It looks nice product. What did you do next? Well, so I have both limbs just to see how we modified everything. At least based on kind of the post-ivus to the diagonal, it came out to be 98% expansion just after all the modification. And here's the run. I mean, you know. And the LED should be coming in. Right there. And, you know, the bifurcation looks great. And, you know, the LED, I think, with a one-to-one size Wolverine and NC, I mean, it looks a lot better from an expansion standpoint. Here's the LED. Yeah, you fixed the undersizing, which is nice. I mean, your stents are one size now, which is sort of the improvement. So if you drill those stents up, it's going to look a lot better. Drill those stents up. You can tolerate a little bit of tissue recoil because the entire artery is larger. So the relative effect of that recoil becomes less because you've now got one-to-one size stents where you didn't start that way. So it's a really nice imaging example of that product. It's great. So, yes, I mean, you see the stents are a lot better expanded. The carina looks great, again, for the LED. And so I ended up doing kissing bone inflation with two agent DCDs. So 2-5 in the Diag-3-0 in that LED. And then I took a 3-5-30 for that Prox LED, just based on imaging and sizing for 60 seconds each. And this was our final result. Looks great. Yeah, it's a really nice use of imaging to define what the problem is, what the tissue is, apply two technologies to help address it, get a short step to fix the gap distal to the bifurcation. I think confirm with imaging that you've got a really nice prep result, and then apply DCB to avoid re-stenting. It's wonderful. The thing that I think we're all cognizant of is that the residual percent diameter stenosis, at least in the perspective looks at when people fail DCBs, if you've got more than 30% diameter stenosis, you're a little less likely to remain patent with a DCB treatment for ISR. So trying to get things well-expanded and get a good angiographic result seems to track with better DCB outcomes. And I think you applied that algorithm beautifully in this case. What do you think, Evan, would you have done anything differently? No, I think this is great. And just building on what you mentioned is that the benefit of serial imaging is there's very limited data on the different lesion preparation modalities. So, you know, head-to-head based on the type of instant re-stenosis. So by using imaging, it's the only way to know that you've achieved what you set out to do. You modify the plaque, you have adequate expansion that you can move on to that final step. So I think very liberal use of intravascular imaging, particularly in ISR, is essential. And that's basically what with Agen and the Agen IDE trial, they had over 70% intravascular imaging there. So, you know, to get DEB results like Agen, you know, it's key that you're using systematic imaging like this, where it's not just one imaging run at the beginning or one imaging run at the end, but really using it to guide your management. Hey, Khaled, I anticipate that in Kuwait, you've probably had DCBs longer than we have. And I was interested, you know, if you're going to try to do a DCB strategy, you know, are there things you see on the angiogram or the IVS you apply in a systematic way that, hey, this isn't going to hold with a DCB, I'm going to have to re-stent it? Because I figured you had access to these and probably have more experience than us U.S. colleagues have now. Yeah, we've been using DCBs for some time, and we have both types, paclitaxin and serolumus. Usually, ISRs, we try to go where they just are coated balloons. But sometimes, if there is a stent fracture or you have GAB, like Watek had in his case, or if you have a new atherosclerosis and clear plaque rupture in the stent, you may have to stent that segment. Otherwise, you try to go with DCBs as much as you can. With all, you know, plaque modification techniques, you try to use whatever is needed in a specific region. You said something very important regarding the calcification. So when you have a calcium, whether it is in the plaque, inside the stent, or behind the stent, you usually don't stent that segment anymore. But if you use DCB, you have to use two. Because you want to use one for the diagonal, one for the LED, and it's going to be a cost of $14,000. So I don't know if the reimbursement would allow us. The beauty when we did brachytherapy is one catheter for all. If you do a combination, it's tough. I mean, I think that, you know, we have to admit that it's costly, but you cannot do it with one drug-coated balloon. You need two. Yeah, Ron, we used brachytherapy in the 90s. And then, for some reason, and because of the data is that we're weak at that time, we stopped using it, I guess, in 2003. And now I think we have to get it back. Yeah, we use it primarily for those who really failed DCB, failed DAS multiple, not first-time restenosis. I think DCB will take some of the role. But we would like to have it in their memorandum. It's always helped to have it. So we are using it, probably 150 cases a year still. Yeah, we have about the same volume, Ron, and we're already starting to see people referred for DCB failures, not for brachy. And that's going to happen in a third of cases with DCBs, the European data shows. So there's a couple of comments from the chat, you know, with regard to Wolverine and Angiosculpt, gimmick or value proposition in instant restenosis. You know, I think, Evan, you may have mentioned, you know, at least some preclinical studies to facilitate drug delivery. Other thoughts on these two technologies and instant restenosis, other than the fact that they stay put and don't watermelon seed. Do you like them in this scenario? Yeah, I like it. But, you know, we have very limited data. It's observational data. There's some initial data, a small observational study showing with cutting balloons the impact of potentially greater drug delivery with DBs. But we certainly don't have randomized trials looking at it. I think the reality is, you know, we don't know. And, you know, what we know is with instant restenosis, you know, as Kevin mentioned, is they come back. It's a revolving door pretty much no matter what the treatment is. Another stent, another, you know, DB, brachytherapy, very high. Once someone's had ISR, it's tremendously high rates of recurrent stent-related events. And you just want to be as aggressive as you can each time they're in the cath lab to try to delay that next time they're there. So I think if, you know, Alex had mentioned before about why not start with an NC. I think that's appropriate if you image it. And you have great expansion plaque modification. Oftentimes, you can stop with an NC. But the key is you need to make sure you really reach that end point. If not, I would just have a very low threshold for using specialty balloons. And even if that's not working, then for IVL and laser and sometimes mechanical arthritis. Great. Well, thanks, Padak. That was a great case. We're going to move on now to Dr. Khaled Elmari who's presenting from Kuwait. Thanks for being here, Khaled. We appreciate it. Go ahead and take the form and load your slides up.

instant restenosis

bifurcations

plaque modification

drug-coated balloons

imaging diagnosis

treatment techniques