This roundtable discussion brings together several key physiology thought leaders as they discuss the recently released 1 year results from the DEFINE PCI study. Listen to Drs. Allen Jeremias, Andrew Sharp, Manesh Patel, Ziad Ali and Constantin von zur Muhlen as they review the study results and ask, “Are we using physiology the wrong way?”
Welcome to this. T C T Connect E Symposium sponsored by Philips. My name's Andrew Sharp. I'm a consultant cardiologist from the University Hospital of Wales in Cardiff in the UK I'm joined by a world class faculty today to talk about defined PC I one year results of which are being released A T C. T connect in 2020. We're also gonna talk about fr pull back on a fire call registration and how they can help us in PC I procedures. I'm now gonna introduce the faculty first. We'll start with management. I'll manage. Hi. How you doing? Great. Thanks. Thanks for having me. We also have Theodoli from Colombia in New York. I Andrew, how are you? We have Allen. Jeremiah's from across the water. Long Island, New York. Any and on we have Constantine introduce yourself. Constantine. Yes. Hello. My name is constantly transforming from the university Heart center. Private causing in Germany. Well, we're going to start with our own Jeremiah's. So, Alan, we're gonna be talking a bit about defined PC I today tell us about the study. Why was it performed? Tell us a little bit about the early results that we've already published. Thanks, Andrew. Maybe I can recap quickly. The original findings off defined P C I A Z. You all know the purpose off the study was to see in what percentage off patients that we still leave significant skinnier behind. And we have some information from multiple studies with FFR that were done post PC I, which demonstrated that about 10 to 20% of patients still haven't FFR below the schema threshold off 200.80 after what appears to be a successful and geographic P C. I. The issue with those studies were that they all retrospective, um, and the data set that we had I think, wasn't helped the highest quality in terms of the scientific aspect of it. So the fine p. C. I was a single arm observational study off 500 patients where we checked by fr before to make sure that we had in fact, patients who have significant ischemia. But then everything was guided by the angiogram. And when the operators felt they had a good and geographic result, and normally they would have concluded the procedure. What we asked them to do is to do a blinded post PC II fr. And then I fr pull back with the question, Um, what percentage of patients still have significant ischemia? And importantly, when we do the i f pull back and we're gonna talk a lot more about that shortly, we can also localize where the ischemia is coming from which potential regions are causing, um, residual ischemia. All of that obviously was done in the blinded fashion. After that, the study was concluded. Onda reason we did it this way is to basically assess, you know what I said. What is the state state of the art after we feel we did a good job with an angioplasty, but importantly also to follow those patients. And Monash is gonna talk more about the one year outcomes, but basically follow these patients and see what the natural history is. This is how how the study played out. This is the individual I fr game post PC I And as you see on the left, there was some patients starting off with a knife are around point to obviously huge amounts off ischemic burden in those patients. And after that they basically normalized off the PC. I so you can you can imagine that those patients derive a significant benefit from PC I. But then there were plenty patients that had kind of borderline I frs with very, very marginal improvement. And our hypothesis was that those patients might not drive the same amount of benefits. So I'm going to show you a case example in the in the study. As you see, there was a pretty hi great significant distal led stenosis on the right thing is how the final angiogram look reasonable and geographic result, and the procedure was concluded. We did a blinded by a far as I mentioned before afterwards, and this is the physiology. So before I fo 0.39 again indicating that there was a critical amount of Kenya after spending the distal lady, it improves the 0.74 And when we lived the pull back, you see that actually, they did a good result in the stand. There is no step up at all, so that's not the problem. But what the problem is is that there was a I would say, very, very mild and geographic cyanosis in the mid section off the lady, which had a huge physiologic radiant off off, you know, 25 points or so leading to a still significantly impaired by fr and the The idea would be if the investigators or I guess, in clinical practice, if we would do this pull back, um, on a routine basis. And we would recognize that off course to put a short stand in that middle i d. And six, this problem would be very, very easy. So these are the results in aggregate. A total off the 500 patients, 467 of which qualified for analysis. And we found that 24% of these patients still had significant ischemia. Post PC with an i r r off 0.89 or less. The good news is what we did. The pullback. We found that the majority more than 80% of these had focal lesions, which potentially could be fixed. And this is the breakdown imagery Will 38% had focal lesions within the stent, 31% proximal and 30% distance. So about a third of 33rd. It's really kind of hard to predict, but when we do this, pull back on the systematic and the systematic fashion. What we find is that we leave behind lesions, pistol to the stand, approximate to the stand. And also the stand is not optimized in most cases. And then this is kind of the provocative part, which obviously we don't know and we didn't need to do more studies. But theoretically, if all of these folk allusions could be addressed with additional PC, I we could reduce the residual ischemia rate from 25 to 5%. Andrew, back to you. Thanks, Alan. And I think a lot of people, when they hear these results, they say, Well, you just didn't look at the angiogram properly. But we did a call of analysis, didn't we? Looking at the Lumen Ah, graffiti and doing QC A of the Lumen just to see whether the operators eyes weren't working or whether these were truly silent lesions. And do you have any comment on that? Yes. So there was no correlation between the angiogram even. But you see a and the most PC I physiology. So it's exactly what you said that basically, you can't predict based on the angiogram, where you're gonna have a focus step up from, you know, from the physiological. I'm gonna bring Ziada. Lena, we're going to talk a little bit with you about what we've known before this study about post PC physiology. What the significance is X Andrew will, of course, post PC PC I physiology is nothing but old. In fact, the original work by grunting, who is truly a physiologist. He used to measure the the physiological Grady Int both pre and post any intervention. And so there's a very long precedent for assessing post PC I physiology. I think it's clear that the role of post PC I physiology is very important. So, you know, I guess one of the questions is, you know, how did we evolve over time from, you know, using originally tubes and then wires. And then I think a big move in our field was when we started to see some of the data that came out from post PC I FFR, which clearly showed that the more ischemia you resolve, the better you do. And that we could even dichotomies to some degree ah, post PC FFR that had an improved outcomes. And so why do we switch to a non hyper emmick pressure ratio of why I fr well, really. It's the same reasons that we use I fr for any other reason. I mean, because it's less patient discomfort. Certainly you don't want to give the patient a second or third round of a dentist in which could make them uncomfortable. It's faster, which is also very important. And finally, it's cheaper. So I think the value of post PC I I f r is, uh it really tells you whether you did a good job. Yeah, I think in addition to what you just said, it's also important to recognize that I think I have far Pullback is superior to metaphor pullback because doing arresting pullback will minimize the crosstalk between multiple lesions, which, of course, happens when you induce hyper Renea. So the I F. R is not just easier to do faster, cheaper but also, I think, potentially more accurate. No, I think that's a great point. And of course, you know, maybe when physiology we started to use physiology, we were doing, you know, perhaps a little bit simpler lesions where there's just one Grady into pull across. But in the current era of PC I, there's a lot more diffuse disease. There's a lot more burden of disease and the pullback sort of the how to treat rather than just whether to treat is is a major major advance in the field. Great, we're now going to bring in manage to talk about the one year results of the defined PC I study so managed. Tell us about what these new data show. Yeah, maybe I'll show you the data and then put it in context of the wonderful sort of conversation of Z Odd and Alan just said of Why do we think about not just how you know should we treat, but how do we treat and what did the one year defined PC results show us? We had the pleasure of describing, as you can see here, the one year results, and I describe these on behalf of all the investigators and, most importantly, the patients on DSO. I do wanna acknowledge that these are my disclosures, and certainly there was research funding from Philips. Allen's already talked to us about the overall trial designed to define PC I and the what I'll call the acute results. So the results of what did we learn when we let investigators do the PC to the best of their knowledge and then to a blinded pullback. What percentages you saw. Patients still have residual ischemia or physiologic reduction. So, you know, one would ask, what were the goals of the one year results and the one year results, as you can imagine, or to follow those 500 patients. And you can see here that we had 500 patients enrolled and we did a post I far a data in 535 vessels in 480 patients. And that's because there was some drop out of a Z, you know, from the original study. And so we had analysis data set of 467 patients in 520 vessels so still fairly robust set of group of patients. And, as I said, the one year outcomes that we were looking to identify where first and maybe importantly, to recognize and 500 patients demonstrating clinical outcomes is often difficult, certainly even at one year. And so we know that angioplasty can reduce symptoms, So we were looking both for the clinical outcomes, but also the symptom improvement And then we also recognize that these air hypothesis generating it's a 500 patient important study that tells us about physiology. But we recognize, as we get these data that they will help us better understand and think about treatment algorithms. That, of course, would need to be tested. I'll just cut to the chase and sort of say, How did we get and what did we see? We analyze the entire data set, and we looked in the people at one year and said, Are there post talk cut points that can help us best identify where people have differential effects in their clinical outcomes and symptom outcomes. And we're going to go deeply into this cut point of 10.0.95 or greater in a second. But you can see here it least in defined PC. When we looked at patients who achieved a post PC II fr 0.95 or greater, this KM curve shows you clinically driven target vessel revascularization, my cardio infarction, Um and and certainly you can see that there's a statistical difference in the range of outcomes is between one point, um, 8% versus 5.7% and we recognize that this is important. We also went further and said, What about cardiac death? Spontaneous semi something that is not even a decision point for any of us is just did the person have a spontaneous myocardial infarction? Did they have cardiac death here? You can see a very low number and those that had an ion far greater than 0.0.95 or equal to it and 3.2% against small numbers but encouraging and certainly with the hazard ratio that's elevated in some statistical significance, it starts to make us think that this might be meaningful. I'll show you one final piece of data. This is a complicated slide. By now, many of us having looked at the ischemia trial and other results have started to look at these curves to see how do people symptoms get better over time. And I just want you to this slide. Um, the first is that the total group is is in the first column and then the second column, or people that have daily angina and then sort of weekly to monthly. And then the far right is people who had no engine or no symptoms, and then, as the curbs go from right to left, people get better or their annual score gets better and you can see that at one year those people were having daily angina. With this cup, point seemed to get better with their symptoms, and certainly those that had monthly engine, it got better. It helps us understand how people are doing so. At least I conclude this portion of saying in defined PC at one year, despite an geographically successful PC, I, in highly symptomatic patients at Baseline without residuals, gave me a post PC IR for had a greater improvement in their annual symptoms. And that that cup 0.2 point 95 we're gonna talk about in a second compared to patients who had residual scheme. So we saw that if you could achieve a cup point or an i f. R off 0.0.95 or greater, it was associated with event free survival and improvement in symptoms, and we're going to be studying this prospectively. Um, so I think these air certainly important findings and help us understand where we might need to go in the future. But maybe the Z odd sort of example. I might take it beyond turning on the light switch. I might say that we often if we weren't thinking about an intervention, we would say, Should I use a drug? Yes. Then, after I think about using that drug, I often have to know what dose should I use. And so we do studies to identify which dose we should use. So another way of thinking about our problem here is Should we do rebound authorization? Yes. And then we did the best we could. Then the question is, what dose do I do or how do I do it? So I get to an effect that improves the patient outcome. That's great, Manisha. I mean, we have seen signal across many PC I studies going back decades that there are proportion of patients who do not respond symptomatically to P C. I. I'm Suddenly the curtains were opening and way could probably do the metaphors to death here. But we're starting to see that there's 2025% of patients who didn't get better after a PC. I and all of these studies we're starting to see a signal of one of the possible reasons, Father and it becomes increasingly intuitive that if we are leaving behind the problem that we set out to fix, we may end up with a less effective result, particularly and also the most to gain with high symptom Burton. Yeah, I guess I would say that there's no there's no perfect answer for any patient we're always trying to in digital, individualized care. But But as I sort of used with the other analogy, I think what we know is we, as we heard already, that forensic originally thought physiologically getting people is close back to normal as possible would be the goal. And even in that New England Journal original publication, we saw radiant improvement. We saw Angel's Symptom Improvement. So we've known this story for a while. It's just maybe we haven't had the mature technology to deliver it. A Z I think we've already described we now have technology until, such as pull back, we're gonna talk about poor registration. Second, we're not only can we say okay, there's a risk benefit to re vast arising. This patient with angioplasty should we be doing it? How and where should I do it and then does that lead to better outcomes from my patient, both symptomatically and clinically, and I think I have another's have said early on before we had all of this technology inability. It seems like a higher bar for in asymptomatic patients make them feel better, obviously. And so there. Therefore, you know, the lowest bang. You're going to get the asymptomatic patients. But as you get more symptomatic, you have lower physiologic baseline scores or you have more residual schema. You have opportunity improve our patients. And so I think, is you're saying here hopefully the defined PC. When your albums are starting to show us, How do we build those targets to improve our patient of I'm going to bring in Constantine here for his thoughts. Constantine, what do you make of these results? Are these going to influence how you practice PC? I thes results from defined PC. I shows that guiding piece I buy eyeballing simply relying on the in geographic result belongs to history. We know from studies like Rush that post PC angina is common and it's a rather than a problem for the patient's quality of life. And maybe we now have a solution for this problem. The remaining stenosis and up to 24% off all these patients as found in the study. And indeed, this is a very relevant number of patients and shows us that we still have a huge potential to improve interventional technology and quality with the aim to improve the outcomes as we have just seen. And we have to think about maybe a new cut off. Is it 0.0 off 0.95? Is that the higher the better? So maybe we conduct discuss that later on, but to continue On the one hand, that means that we have to use physiology before doing a P C. I in order to detect all stenosis that are relevant to the Haitians, as we have seen on the previous example, and, as we have already discussed by far, is the perfect, too, for set for that, since it can not only detect single lesion, but it can also evaluate Syria lesion and even discover visions that are not detectable by the pure and geographic view. And later on, I also have an example. On the other hand, these data should also encourage us, of course, as he had mentioned to perform post PC I'll for the routine base to see if the lights which works in order to recognize how to treat the individual patient and its analysis and not only who to treat. I think, however, that it will take sometimes to introduce post PC II are into the clinic routine since every interventional list thinks that he has done a great job after putting a standard s. So I think a change of mind really has to take place. And these data absolutely encourage that. You know, sometimes there's something we can do to fix it and to further improve physiology, and sometimes there isn't. But at the very least, you understand that you leave some ischemia behind and you might treat that patient different medically afterwards, at least you have the knowledge, and you don't think you did a perfect job when in fact you didn't. Yeah, I think that's really important island. You know, uh, knowledge is power. If we're ending up with a pattern of diffuse disease left behind after you've dealt with a critical lesion, you're gonna continue your vessel dilator, uh, set the patient expectations if we're getting a final result from a focal lesion of another fire of 1.0. I think we can have increasing confidence that we can withdraw those Anton giants if there's no other substrate on, manage the patient differently. Eso These have riel implications for the real World Day stay management of stable angina patients. They don't like their drugs. They want to be off their drugs. That's one of the reasons they're having P. C I. Onda. Why wouldn't you want to know if you've abolished the problem that you set out to treat what we're really dealing with might be something we see in all of medicine, which is inertia. We're used to doing things the way we were treated and the way we've been trained to do it and the way we treated every day. So the change practice, what I often say is we need the rational brain to show us the data, and then we need emotional or case examples that show us where we've done something wrong. So I know we're gonna get two case examples, but I would say that you know, it's almost like we are, and I've used this analogy since we've used different analogies. If if you're if you're in the cockpit and you have a light that's really important to taking care of this flight, this patient's care journey and you don't look at it, then certainly, I think that's an opportunity missed. And so what I worry about with what we've just described is we're starting to now have a very important set of data that shows us that continuing post PC physiology is going to be important. We're gonna have to change the culture, even though let's say that there's some of those data being existing that that's gonna be important. And we need Thio ensure that we do that with science. But certainly we also do that with rigorous sort of continued push. To say that you're angioplasty may not be complete until you've done intravascular imaging and intravascular physiology to confirm both the stent and potentially the physiology in that vessel. Allen is your routine. Have you built these findings already into your clinical practice? Well, partially be honest. Um, you know, I think every time I do measure physiology before and the wire is available, obviously, you know it makes sense to use it after more and more. To be honest with you now, actually, with the release off the new wire, which is fantastic in terms off the handling when we can discuss it later as well. I basically use that as as my you know, routine angioplasty wire. There's no need to change anymore. And then obviously the wire already is in place, so it's easy to check afterwards. You know, in cases where the measure physiology, I still don't open necessarily. You know, why are afterwards Thio check. Although, you know you can make the argument that you should, but certainly in all the cases where you where you check before and you guide your procedure based on the physiology based on the I f. R pull back, it makes no sense not to check. Yes, this new wire that we Europeans can't get yet. So, yeah, tell us a little bit about this new wire and how it's handling and performance might just encourage us to go back and check the f r at the end of the procedure. So that's actually an interesting story, Andrew. So Alan and I decided toe live record the first use of the Omni wire so that it was completely genuine and uh, it is really, really good, E actually, why are the Legion was No, no, I mean it. We did a multi vessel case. We use the same wire in multiple vessels. We went into side branches and the drift was very little. And we could perform the PC I over the wire. The connection is much better. I mean, it's pretty rare when I come away saying this is really, really good and a major iteration. And to be honest, one of the things we can discuss together is why didn't we all do post PC I physiology before? And the truth is that it was a really pain, right? The wire turns into a piece of shrapnel. You don't wanna go put it down the artery. It's getting stuck behind the stent. Now you've broken it. Now you need to get another one. It's another cost. Somebody has to go and run and get it for you. The angel looks fine. Let's just get to the next case. And then now we're getting to the point. I mean, that's why I think this is such a major iteration that the wire handles so well you can actually do the PC I on that wire, the connection and disconnection is really seamless. And then you could just, you know, reconnect get a result to see whether you did a good job, do a pull back and you're done. So all the things that I talked about before in terms of making the procedure faster or making it safer make it more efficacious, it really, uh it really matters. I mean, one thing that you guys have probably heard me say before is that physiology was a science that was ahead of the technology. And I think we're finally catching up on the technology side so that it becomes more utilitarian in the cath lab. Well, that's high praise Manager. Have you had a chance to knock this way around yet? I using as a workhorse. Yeah, we were just getting our hands on it. And I agree. I think that the wire is starting Thio Aziz accident, Not just the wire. The wire is fantastic, but I think the entire field is now going from where we might say for all the reasons described, um, you know, second administration of a dentist, seen how easy and how hard is it to hook up. What does it look like after you've done the first intervention? Um, now co registration that we're going to talk about in a second? How does it look for even where the world's going for both I vis physiology, wire and non wire based technology. So I think the impetus. Actually, I would save by many on this screen and others to say that we shouldn't accept. You know, poor technology. Physiology should drive our revascularization. We have to push, and thankfully, companies have followed. But we have to push our colleagues and others to demand better techniques and technology to get the things done that we want. So I do think it's a step forward. I do think that these data and these types of sort of iterations have made the entire field go forward. If you just take a step back and get Thio Nana Dennis, Ian based physiologic measurement like fr and see what that's done to the field, it's dramatically changed what's going on the corner of physiology, where one could argue before that there were 8% of angioplasties at most, maybe 10 in the United States that we're getting some sort of physiologic assessment in the Catholic that's changed, and that's changed for all the right reasons, I think. But I think it should continue to be database driven and certainly demanded by our colleagues and others who are saying, Listen, you can't expect us to do a volume that we want to with the care that we want to without technology, that's going to be very easy to finish. Can I just clarify for anybody watching? We've talked about two different numbers here. We've talked about less than 20.9, which is the ischemia threshold that we've used in defined flare. I far sweetheart on then. We've also talked about a different number from the five D C, which is 50.95 So can you just a simply as possible for people who maybe aren't high uses of physiology? Explain what the two different numbers of signaling and how we use them. Yeah, I want to be very clear that the 0.89 number is the most evidence. Base number 2.95 number that we're talking about right now is a hypothesis generating number as we start to test this and we also know that this physiology is a continuum, right? So we recognize those data. But the 0.8 night number is the number that we're using to say. Should I re vascular eyes? This vessel is there a significant reduction in physiology that likely will lead to improvement in that number has been Now, as you've heard tested, um, potentially more than almost any other number outside of the FFR number of point a dough which was studied head to head And you know, you know I have are two trials now defined and see sweetheart. So I think people should feel very confident about the 0.89 number to say. Should I do something and back to my analogy, how far do I go? And how far do I need to go to do something or what's the dose or how how do I do it? That's the 0.95 numbers saying, What's the target now? That target of of 0.95 is what we've seen in Define PC I one year we need to study it prospectively in a randomized fashion to say If you get to that target versus doing what usually do, do people get better outcomes. Yeah. What do you think? How do you interpret this 10.95 number? That's a good question, I guess. I guess it depends like in all things in life, right? It's It's always the gray zone. But just just two minutes. This point, I think the bottom line is this when you go in, you want to see is the ischemia or not? Should I do a P C I Once you made a decision to do PC, I you want to get to as high off the number as you possibly can get, right? Ideally, if I if I was able to I'd like to get everybody back to one point out right one point. Oh, Then there is no even at all. That would be the ideal. Based on the post talk analysis from the fine PC, I will identify this number of 0.95 or greater is kind of the optimal result, knowing that in many cases you probably won't be able to get there, But at least you have something to import. Now the question is okay. If we can get 2.95 and everybody, you know what should be what should be doing and how should be guided by. And I think that's where it's really, really critical to do the iPhone pullback post PC I because that will tell us instead opportunity to do additional PC. I may be optimized stand or maybe find another focal lesion like I showed you in the case that we can maybe do another stand and eliminate the radiant. Or is it all the fused to these, In which case we understand? Okay, there's no additional PC that could help the patient, but at least we know what we're dealing with when they come back. You know, 23 weeks later to the office, they still have chest pain. I don't have to run an order. Another stress test, you know, burden the health care system with additional testing because I expect them to have some degree off of angina. And then we also understand how much potential benefit in the PC I would we can get. In some cases, I didn't show you those examples, but in some cases, three i fr before and after is the same. Obviously, in that patient, I wouldn't expect any change in their symptoms right in some cases, the 23 it goes to 230.6 point seven. You know, in that case, I would say, Well, yes, there is still a Femia, but maybe let's go and maybe we have some benefits. So it's really important to understand these nuances and and put this together, um, to kind of make the best decisions in follow up when we see these patients back the beauty of the pullback technology and it's new iteration, the car registration application of it is that we can get this information before we put the stent him. So we're going to come to Constant and now who's got a couple of cases that really illustrates this, That, uh, yes, we really need to know what that final result is. But we can actually predict this in advance now of putting a stent in using the courage stray shin technology. Constantine, Have you got a couple of cases? You could shows that just really illustrate how we can be forewarned of some of these scenarios of residual ischemia or an geographically misleading lesions. It's sure that's a very good point. And as already mentioned, it's important also to do physiology before putting a standing? Ofcourse. Okay, so I brought you two cases too short cases on. But I just want to show you what we experienced there in the Catholic. So he's my disclosures on dumb. The case Number one is on a 62 year old male patient with a history of multiple PC ice. And he also has an I c D. Implanted do Thio sudden cardiac arrest that he had. And in 2017, he suffered from an end Stemming s with RCs stenosis which Waas standard with a good result. And now he has read the progressive angina in the C C H C. C s three stage and in the echo he has a new hypercane Isha in the posterior war. So this patient directly went on the calf table and you can see the image. And to be honest, I was first distracted by this the no sis in the segment 12 on the left hand side on. Since we did not have an evidence of ischemia so far, I of course decided to do a knife are And here is the core registration and the result was very surprising. So we did the pullback and finally, the stenosis that was suspicious to me in the beginning. So in the beginning, off segment to wasn't relevant at all. So if you look at the yellow dots here, it's just 0.5 points that we would increase the measurement here by putting a standing. But the real problem is in the proximal lady. And I hadn't seen that on the first view on. Of course, I did some more projections with high definition images. And now you can appreciate here that there is an instant restenosis, which is indeed severe on. Of course, we, uh, treated this vessel and this lesion with the drug eluting balloon did the final I have are in this patient and it waas 0.96 and year. So this is a perfect example that you sometimes miss lesions when you're distracted. Maybe about other lesions on a case. Number two is on an order patient. He's 82 years old, also made patient with multiple PC ice and all coronary vessels. And he has a high bleeding risk. So he has severe recurrent G i beatings and also his taxes and now also has progressive in China. with the CCS three stage and we performed a stress echo in the other condition the interior ward at 100 watts. And these are the images. So in the left corner is the right Connery outward was fine And here you can appreciate that There's something going on in the left main and on the left seen. You can also see that there might be some region in the lady just behind the diagonal branch. On the right hand side, you have a different projection in this patient. It was actually difficult to project the lead, but anywhere we did a sink vision core registration in this patient and this is the result. So we have more or less diffuse disease. This distal ideology lesion that we have seen on the previous scene isn't relevant at all for the patient on what we see, if we have to have a closer look and start doing a virtual PC, I s that we have a left main stenosis there. But it doesn't contribute at all to the human dynamic significance in this patient and by the way, we also do the measurement into the L. C X obtained the same result, But you can see that the proximal lady is a significant legion. And remember, this patient has a high bleeding risk, so you don't wanna plant him full metal jacket with five centimeters off stand. You may be really want to selectively treat the area causing an ischemia just in case that you need to stop dual anti platelet therapy earlier due to the new bleeding's. And we did that and implant understand 24 millimeter Islam. And this is the beauty off the virtual PC I that you can estimate in advance the improvement off coronary physiology and that you also can define how long, substantially in this case we chose the 24 millimeter long stand. So in this case, you put a pressure wire this Lee, you've demonstrated that there's a substantial drop in pressure across the vessel, but we've then done a pullback, and that's mapped the areas of pressure loss onto the angiogram, thus allowing us to draw where we would put our stents on the image on it will tell us what to expect from the fire after the case. How accurate is this in your experience? Is it is it giving us a sort of broad estimate or is it really quite accurate? It's very accurate. I couldn't believe it. But there is, Let's say, in this one patient there was an estimate off 0.95 and we obtained 0.96 And it's really amazing how these results can estimate what you reach after PC I. So it's very accurate indeed. So this is giving us this power really of saying I haven't put a stent in yet. I know that that leaving residual ischemia might be a bad thing. Uh, if I put the stent in there in your case near the RV branch in the first case, I'm actually not gonna do much. I'm gonna lift by five points, and I'm still going to be below on a fire of 50.9 on. It really does allow you to map out the length of the stent to within a couple of millimeters. Andi give you that knowledge before you commit, which I think is a is a really key part of this technology. You don't have to go ahead and put stenting if you find that it's a diffuse pattern that's unlikely to relieve ischemia. Absolutely so it's a great tool and it works very well and it gives us it gives us important information before doing the P C I in diffuse disease, especially in Syria legions. And it gives us surprising results Sometimes, as you've seen in the first example. And in important point is that also, this technology really is very convincing as you're challenging yourself. You everyone is missing lesions. It happens in clinical routine. But this tool really helps us to get a very good reside and to do a very, very accurate planning in advance and see how you're an expert in in country image ing. This isn't a surprise to you, is it? That we're gonna find these and geographically silent lesions. Angiography is just not that good a way to assess Conrad disease. You know, it really begets you to use the planning tool. Why wouldn't you want to do that? And what we know from multiple studies is that if you put in very long segments of stent, it increases your stent thrombosis rate and your target vessel failure rate. So if we can sort of minimize the amount of stent that we need to maximize the amount of gain. It should Onley improve long term physiological out, and it's an individualized therapy for the patient. Of course, as you have seen in the example, you have a high bleeding risk patients you don't wanna put too much stent in. It's a perfect tool you can plan. How much sent you want to put in and what are you want to reach at the end? And I would track on. What constitutes said is that you know, you can end up doing a beautiful and perfect image ing guided PC I, but still have ischemia. So it's really not that one modality or the other answers all the questions. It's just like you know, you need a toolbox. And it's really to answer the question with the best available tools that you're trying that we're all trying to achieve. And, you know, I think they became this sort of false sense that well, I've already used the pressure where I can't use an image in catheter now, right? I mean, I don't know where that came from. E understand that cost implications are important, but the most important thing is that you do the right job for the person on the table, right? It's not like they came in with a budget at the beginning. The patient didn't do that. It's our responsibility to use all of the technologies to really optimize the PC. I yeah, I was just gonna add to that. I mean, I think we're so acutely aware of the costs inside the procedural room, which I think is important. But, you know, we're engaged in a PC. I bundle here in North Carolina, where we we we said, This is what will deliver the care out to 90 days and soon six months for and and I can tell you, having that patient come back or not knowing that the patient has engine are not being able to manage with that patient's expectations are are much more costly than I've this character or a stent failure or a stent amid led when there's really a scheme and approximately D or actual total mischaracterization of how you should treat the patient a Z, I think Alan said, you know, maybe maybe Lima is with this patient needs rather than a PC. I vocally, with continued pain and PCR again given example that Constantine just showed You have a patient, you end up standing the wrong lesion. They come back. You don't know why. So you don't do another angiogram because you just look at your last angiogram. You're like, it's perfect. This guy's crazy. And so you send them back home, and then they come back again to the hospital, and then they come until the point at which they end up going through another hospital. And so I think doing this. I know Alan likes to say this all the time, you know, sort of doing this right. The first time really saves you in the long run. You know, with data that's showing that we have, like, a 20%. Am I right? In the first year after your first A CS and a 20% residual chest pain. These air, not small numbers and even impacting them on a small scale can have a profound implication on the cost. Just to correct you the lioness. Sometimes you have to do the right thing by the patient. Yeah. Yes, Alan, I think you've got another example to show us having. You're using this technology to plan PC eyes? Yeah. Thanks. Andrew. Eso your constant ensure that some some nice cool wretch cases. This is another way of using it. This is the case. Actually, the and I did together San Francis. This is an ultra low contrast angiogram and somebody with advanced renal dysfunction. What we do is we always separate the diagnostic angiogram from the actual PC I. So the patient had an angiogram with nine cc's of contrast. And what we found is, you see, is a pretty high grade stenosis off one. What we typically do in this case we stopped the case will bring the patient back a couple weeks later. And then the goal of the procedure was to do this with zero contrast. Just to show you how we engage the guiding catheters by injecting sailing. Then we're looking. Or if you're changes, to know that we actually engaged and then what we do is we cannot recreate a metallic silhouette off the vessel by basically wiring all the branches. And then what we do is finally wire believe the pressure of fire and as you stay here with way will pull back and we actually do an I f. R. Corange just based on the metallic. So it off the wires without injecting contrast. So that's possible Also. And in this case, Aziz pretty clearly indicated there is a very, very hydrates, um, stenosis with a huge radiant I collision. And the I f r is 0.54 obviously pretty critical. Um, ischemia. The next step, of course, is then, um Thio Instance, We can't inject contrast What we did in this case where the trial registration by adding on in Tabasco ultrasound and what we do here is we find the landing zones, um, disability approximately, and based on the tool the concept in already showed you guys, we kind of figure out how long the stand we need based on the on the isis pullback and co registration, and then basically, just execute, um, placing the spend. We kind of have this template from the previous procedure so we can have a rough idea of what we at where we're located. And then based on the I, this image ing and the S are pulled back way, place to spend and then follow up, Of course, with isis and physiology. And this is the final result I have for basically normalized back to one, Um, in this case. And of course, we also make sure with intravascular ultrasound that there is no extra section that the stand is fully expanded. And if all this works and the patient is dramatic and there is no e k g changes, we basically conclude the procedure without shooting any angiograms. So this case with this, with zero contrast, it's a really impressive use of the technology and also speaks there to your comment about how these old distinctions of who to treat how to treat on do you use Iver's for one physiology for another. It's all going now. It's All these core registration technologies are changing the way that we can handle these very, very difficult patients. I think that's exactly true. I mean, I remember doing my first zero contrast PC in 2015, the patient had an elevated creatinine, and I had measured the FFR and CFR before the case proved there was a ski mia. Then I did a pullback, mapped what part of the artery was in then sort of marked the distal reference with the knives. Catheter marked approximate catheter with an Irish catheter put the stent in post dilated it, and then the nurse asked me goes, Are you gonna take a picture? And I just thought why I measured the pre PC I physiology. It was a scheme IQ. I put in a stent, the edges air perfect. It's fully expanded. I measured the post PC I physiology, and it's perfect. I'm done. And really, that was sort of the evolution of this. And now when you have the technology where you can do things like try registration to see, not Onley Where, uh, you that you can see the artery from the inside out and the outside in, but also have that in coupled with physiology. I mean, it really is, in many senses, eliminating the need for ferocity and angiography other than to be a guide for where you're going to need to go, you know, managed. I heard she had once referred to contrast his poison, uh, Onda at any tools we can use that can reduce contrast administration like the courage stray shin tools we've just seen. That's not a trivial impact. If we can keep someone's GF are 20 instead of 10 following a PC. I, uh, that's a really major difference to that patient's life. Yeah. No, Absolutely. I mean, I think you know what you've just seen is again. I think what we when we think about the world of interventional cardiology, there's always people who are pulling and pushing us to places we need to go. So zero contrast PC is fantastic. And what you've seen is a great example of how these tools help us get there. And you know where the world is is very far away from you even zero contrast PC. But there's a lot to get to by just saying, Hey, can you do PC with one shot for fewer shots and then grow contrast? Right. So what? What I would argue is much like that nurses reaction is Yeah, the audience in general is gonna have a belief system so tied to angiograms, right? And so to move them from angiograms to know angiograms, the first step might be just to say, fewer, safer angiograms and reducing that that risk. I would even argue that, you know, based on the data we just discussed from defined P C I the angiogram really is overrated. We rely on it 100%. You know, but I feel like we relied it way, way too much. And so we actually use the procedure and inject contrast, really, for no good reason when we have much, much better tools to assess which regions needs to be treated and also to assess the final outcome. So I think, you know, honestly, it's not necessary in most cases to do as many pictures as we do. So Alan 500 patients defined PC and we've got some strong signals here of clinical benefit. But we need more. What's the next steps for this area of research? Tell us about the trials that are coming. So the follow up study off the fine PC is gonna be the fine GPS, and it kind of builds on the data we just discussed Aziz we all talked about. Obviously, it's important to do physiology, post PC I, but maybe even more important to do it before and just by Constant showed us, you know, in the cases that were guided by physiology, that's kind of the concept off. Define GPS, what we want to be doing a pull back, and I fall back with core registration ahead of time and really fully plan out the procedure. We've mapped the entire vessel. From the physiological standpoint, we have certain goals we want to achieve, you know, in optimal results being 0.95 But unacceptable is point mental because I recognize we don't get there in every patient. And based on those goals, what we're trying to do is to really plan the procedure ahead of time and then execute in the GPS on if you will. And we're going to compare that strategy to ah, standard and geographic approach plus minus image ing. Interest imaging is optional. Um, in both groups to see if we can, uh, in fact, show that we're gonna have the reduction and hardened and the study is gonna be somewhere between 2500 to 3000 patients. So it's gonna be adequately power to show us hard at points. And I think, and I hope frankly, it's gonna be the definitive honey to show that physiology guidance is helpful in reducing major cardiac events and then become the standard of care. So we've seen that if you treat a vessel with a low fr or FFR on your guided by that finding that you have a better outcome then if you're guided by the angiogram. So the difference with this study is that we're going to not just get the vessel level valley. You know the 0.82 down the bottom end of the lady, we're gonna do a pullback co registered, as we saw with your awesome Constantine's cases on. Then we're gonna use that data to plan and execute PC I and to try and ensure with post PC I physiology that we've achieved the goal of abolition of ischemia and hopefully this'll perhaps higher standard of result with an eye, a fire of 0.95 or above. But is that right? That's the idea because of not honestly, I think we were somewhat convincing in this Webcast to say Look, it makes intuitive sense and we have some degree off evidence to support this. But in all honesty, for the skeptics out there, we need to produce a randomized trial to demonstrate that there is in fact, a reduction in the hard endpoints. When we use the strategy because it is a bit more involved, it is a bit more complex to do a procedure in this way and we have to kind of justify both the complexity and maybe also the resource utilization. So if we can show that, in fact, that will reduce outcome bad outcomes for the patients and we reduce repeat hospitalization in the end, we're gonna also save costs. And the secondary endpoint of the study is gonna be an economic analysis. Um, putting both in the part, if you will, right, the resource utilization and but also obviously the follow up to see if, in fact, patients get admitted less frequently, and we might actually save cost with the strategy. Well, I think that's set you up nicely managed for your takeaways from this discussion and the results of defining peace at one. Yeah, I guess I would say that the best findings that I would say that we now know. And I reiterate some of what Allen has already shown us that I think defined PC and its most basic form, um taught us that even in the best of our practice, we have patients that have up to a quarter of patients, have residual ischemia in the vessel. And then the question is, what does it mean? And at one year What we've seen is that there's a signal that that those that got a higher post P C I f R and we did a post talk analysis losing the cup point of 10.0.95 Those patients had better symptom reduction and less clinical events. So it fits with how we think about what we are aiming to do. And we're now hopefully gonna have prospective randomized data to confirm that a strategy of doing that will lead to better patient outcomes on that's powerful because, like any technology or clinical care, I use the example of dose finding. You have to get to the place where you get that. I'm gonna use that. Want to go prove that when I do that, enough people, they do better. So that's where we are with the findings from one year to find peace, great. And, yeah, it feels like every time I open a journal, there's something new in this area. There's new innovation. It's quite an exciting time, really. To be an interventional cardiologist, you're pretty good at horizon scanning. Where we gonna wind up if we can really get this NGO based physiological assessment right? It's a game changer. I think the same things that made I fr advantageous toe FFR will be iterated forward. It'll be safer. It will be less uncomfortable or less discomfort. It'll be cheaper. Eso and it just fits in the workflow with things that operators around the world are very used to. So I think that's to me. That's the next big sort of blue sky thing. I think there's some problems that need to be rectified in that field. Is everybody on this call knows? But in the meantime, I have to say, I think this improvement in the physiological wires is a really big step forward. I mean, it's very rare for me to say that I was truly surprised at how different this made a single case. It was just super quick, fast, utilitarian. There wasn't a lot of messing around. As we know we've had to do for years with physiology wires, so that improvement innovation. I think it is a true advantage and lastly, you know, let's not forget that we're gonna have continuous iteration in the software. It's gonna become even easier. I'd like for the computer to tell me what's diffuse. What's focal? Where's the lesion. What's I stayed? Should I put back if I have residual disease? All of these things can be iterated with a i with computational algorithms. A za future comes to the president. You manage your involved in several guidelines, I presume this is gonna feed through into future iterations of the guidelines. Well, as you know, guidelines and appropriate scratch era, complicated documents. I like to call him living documents. And they sometimes don't change fast enough as we know. My response to this is I think so. I mean, yes, he's done a wonderful job in the chronic CD guidelines as we just heard about. And, uh, I'm sure the U. S H A. C C guidelines and the criteria gonna hopefully evolve quickly. I think, to take home from this program, hopefully for our colleagues and our patients are that, uh there's continuous innovation and, you know, health comes when that innovation gets applied to the right patient. So we're going to keep working on it, for sure. And I'm I'm excited to be working with a lot of the people on this screen, but also just thinking about a different sort of partnerships. We have to help this happen for our colleagues and our patients? Well, patients is a great way to end. So manage Constantine Islands. Yeah, thanks very much for joining me today. So I want to thank Philips for sponsoring this symposium. Uh, thank t c t Connect for giving us the opportunity to embed it within their really groundbreaking new meeting. Onda, thanks to all my co commentators on goodbye.
