So, Dr. Collette is the PI for the PIV4 trial, which is a pivotal trial who's going to examine the role of CT for PCI planning, 1,000 patients, almost completely enrolled, and we're super excited to hear from you, Carlos, and the update on the study. Wow. Manos, thank you very much for the introduction, and I have to thank also the team of Sky for preparing this webinar. I think it's very, very timely. You have heard from Dr. Sandoval that we're releasing an expert consensus or expert opinion document in the next Sky session, which is going to be very insightful and practical. So my role today is to update you on what we have done in the PIV4 trial. As Dr. Brilaki said, this is all of us finished in terms of recruitment. Let me start showing my disclosures, and I want to approach this today more from a philosophical perspective and explain to you what actually we're trying to achieve where we do a CT-guided PCI. And to do that, the best approach is basically to put ourselves in daily clinical practice. This is my daily practice, 70-year-old, angina class two, comes to the cat lab with sometimes ischemic test. It lies on the table, and then you make a shot, and this is what you get. You start thinking about the disease. You start thinking about what am I going to do? It looks like a traffication of the left main, longitudinal LAD. You start analyzing the angiogram, and then you have to take a decision. The decision, you can say, well, it looks pretty suitable for a crossover to the left main. Maybe, maybe, you know, the side branch is a bit diseased, so maybe I go to two steps up front to be sure that I don't lose a side branch in the meantime. There is always a consideration about surgery. This is a left main disease with proxal AD, although it looks straightforward for PCI. And if you think about it, none of the trials have really shown a huge advantage in this type of patient, so it's not unreasonable to think that you can match this patient medically. But the problem is that we're at the table. We're thinking about the case. We have a number of questions. What is that plaque? How long is the plaque? Is that plaque calcified? It's not calcified. Which size of stent I require? Which is the length? Where is the disease starting? Where is the disease ending? If I modify the calcium, which tool should I use? And then we have around 30 to 45 seconds to basically decide what we're going to do with that patient's coronary, and that is a problem. In my view, this is one of the biggest problems that we have today in interventional cardiology. Everybody's doing something different, and even in my own cat lab, if you land on my table or a different table, perhaps the approach will be different, and that leads to treatment variability. And if you think about it, this is data from the SYNTAX-1 trial, where every little circle is a hospital participating in the trial, and you see the variability in the different outcomes when you compare the outcomes with surgery versus the outcomes of PCI. So this variability in clinical decision-making is translating into variability in patient care and is translating into variability in treatment outcomes. And it's not a surprise. It's not a surprise because we're taking decisions based on an angiogram, and we don't know anything about the plaque. We don't know anything about the disease burden. We don't understand vessel remodeling, and when you think about either ischemia or the presence of focal versus diffuse disease or even the disease at the level of the microcirculation, we have absolutely no clue because we are not being informed by an angiogram. And of course, we have technologies that overcome these limitations. We can use invasive physiology. We can use invasive imaging, but these technologies are not used in the vast majority of cases. So we remain, in the majority of the cases today, being approached from an angiogram. And here is where I think CT plays a big role. And as Dr. Sandoval mentioned, this tool is not anymore a rule-out tool, a tool for low-risk patients. It's a tool that can stratify patients with coronary artery disease, and it's extremely relevant for PCI procedures, and I will explain to you why. And the reason is simple. Here, of course, we have access to either the angiographic and the clinical information, but CT also can shed light to the plaque characteristics and, of course, the physiology. So before we embarked in the trial, we designed a full educational program to teach the interventional cardiologists how to read CT. What is important to recognize here is that the approach that we are taking for interventional cardiologists is completely different from the approach that you normally see with radiologists or with imagers, because the clinical question is a different one. We're not interested in knowing whether that patient has coronary artery disease or not. That's the diagnostic question. Now it's a new question. It's a question about planning, how to approach the disease. So this is the framework. Basically, this is the only four names that you need to remember when you look at CT with PCI, our PCI mindset, 3DMIP, actuals, NPR, and cross-sections, and I think Dr. Sandoval had explained how to use this in practice. Now the reason why I believe that CT is going to become a major tool in the cat lab is the fact that with CT, you can stratify calcium in a way that no other image modality can do. You can understand the severity, look at the morphology. You can see the calcium in 3D, which completely changes the game in the way that we have thought about calcium until today, and it gives you information about density, which basically reflects the hardness of the calcium that has direct implications in terms of advanced vessel preparation. And in addition to that, you have access to physiology, physiology in the classical way. So the left side of the slide is basically what the guidelines suggest. Look for depressive ischemia based on FFR, but you can also look at the focality of diffuseness with these virtual pullbacks, and now you can make a prediction of what's going to happen. That's very important in medicine today, that we can predict the outcomes and that influence the complete decision-making process, and I'm going to talk about that later. So let's go to the trial. So with that in mind, I think I will explain to you what we're doing in the trial, and if you are in the randomization to the CT-GaN-PCI, this is what the interventional cardiology will receive from the core lab. So this, we call this planning package, and here you see first is an overview of the complexity of disease on the right side. Then we tell the physician taking decisions on their own, but we're making also recommendations We recommend which guiding is the best guiding to get support. We assess the calcium and understand whether it needs to be modified with either a balloon or IVL. We provide the mass at risk for every single vessel in the coronary tree, which is extremely helpful in bifurcation PCI. We suggest the best projections, extremely useful for osteal PCI as well, for either right or left main, and the full map of physiology, physiology in the classical way, but also physiology in kind of this new way of thinking about physiology, which is what can the future disease and the prediction outcomes. So let's look at a case, and imagine that this is the next patient in the cath lab, and you have the access to the CT beforehand, and this is the MIP. This takes, in my experience, 20 seconds to read. This is a fully automatic reconstruction from any single scanner, and then you say, okay, this is the next patient. Well, I see a lot of calcium in the aorta, I see a lot of calcium in the right coronary. The right coronary has two bends, very tortuous, with calcium. So that prompts you to a number of things. You're thinking about access, you're thinking about support, you're thinking about guiding, and with an osteal lesion. So keep that in mind. Up front, you understand that this is a significant lesion with a focal disease, PPG 0.89, very focal. Okay, that's important, that's very good for PCI. And then you have this unprecedented visualization of calcium in the three-dimensional space, understanding that the calcium is, again, at the level of the osteum, but you see the location of the calcium as well in the proximal part of the right coronary, and you see that after the lesion, there is small calcifications there that might need to be over with the you can rotate, this is a three-dimensional geometry, so you can basically do whatever you want to do with it, and understand the distribution of the calcium in this way. Now what we have expanded the field to is the analysis of the density, and here you see that the density is above 1500 Hg units, basically reflecting the fact that this is a very hard calcium, at least of the osteum. The more proximal part is less dense, that basically means that it's softer at that place, and then you go to the lab, and then you're thinking, okay, I'm going to do an osteo-RCA-PCI, I know the projections to be completely perpendicular at the time of the stem delivery, I know that there's a significant lesion there, I need support because it's calcified, I don't want the guiding to be too deep, so I'm going to perhaps go for IL 0.75, I know the measurements, I did the measurements to cover the complete plaque, I'm going to need a 48, so you get all this information before you step in the lab. So imagine what happens, so you're in the lab, 0.75 IL, just put it there, this is not a surprise, you just wire the vessel, IVL directly, that calcium needs to be modified, so you're already in the mindset of calcium modification, then you perform the procedure, and then you end up having these type of pictures after the 48 millimeters in the Proxyl-AD, with extremely good angiographic results. But what is important to realize is that if you're going to a complex case, and you already know what you're going to do, the cognitive overload that you're going to have, the cognitive load that you're going to have in the catalyst is reduced because you already know what you're going to treat, and that actually frees space from your prefrontal cortex to improve the decision-making capacity, and this is one of the key things about CT-CAT and PCI, is that the ability of planning, the ability to know what you're going to do, which in clinical practice we don't know, this is what we're trying to change actually, it's helping you taking better decisions. And don't forget that we are in the cat-lab, as I showed at the beginning, we have 200 things in our mind, what are we going to do, do we need to modify, how to look at the intravascular imaging, etc., etc., etc., you don't need to have more things in your mind, so this really, really helps, again, putting you in the best shape to take the correct decisions when they need to be taken in the cat-lab. And this is what I was referring to in the decision-making process. So basically we process information, we take this cognitive processing and we make a plan, and then we execute the plan and we have an outcome. If you know what the information is before you go in the lab, that gives you sufficient time to analyze it, and if you have all these tools that are basically predicting the outcome, you're taking a decision based on an accurate prediction, and that improves the complete decision-making process, and I think that's one of the solutions that we have to address this problem of readability. Now it's not only about planning, because the second part of the CT-Guided PCI is the fact that we are embedding the geometries in the cat-lab, I'm going to show you a video in a couple of minutes, but having that information again with these novel tools also enhance the execution of the procedure. And the reason is as follows, so we are used to see these pictures, these pictures are I think it's something, I consider that almost already from the past, because for us in the cat-lab we will get these three-dimensional geometries with three-dimensional calcium, two-dimensional coronary tree that are extremely easy to interpret, and we put those in the lab and the white is calcium, the red is blood, and then basically interpretation becomes very easy. And then you got this calcium analysis with, again, it's extremely intuitive to understand, and even if you are doing systematic intravascular imaging, having the understanding that this is the morphology of the calcification facilitates the interpretation of any intravascular imaging. And again, you put this in the lab and you see for the first time a complete map of the plaque in three dimensions during the diagnostic procedure, and this, again, increases the understanding of the disease that you're about to treat. So imagine that for every single case that you do in the lab, you got a complete map of the disease with the plaque composition, plaque extension, plaque burden, and next to it an understanding of the physiological component, not only significant, not significant, where are the pressure losses and whether this is a case for PCI, and you can even model what would happen. So this is the design of the trial. Again, a little bit more than a thousand patients, as Dr. Zbrylacki said, we're almost at the end of recruitment. You see here that we're randomizing all these patients with significant coronary artery disease to either be treated with CT-guided PCI or IVUS-guided PCI, which in our opinion is the control group, but I think it's the best way that we have today to do PCI procedures. We're looking at a one-year outcome, we're not in priority design. And where are we here? Well, this is data from a couple of weeks ago, 930 patients, so around 100 to go, 92% of the patients are included. I'm very thankful to the team of Minneapolis, but also all their colleagues from the U.S., the U.K., Japan, and Europe, including this challenging trial to execute because the number of rigor control there is at every step, but I think we'll certainly be finishing recruitment in the next few weeks. So to conclude, and I think to start the discussion, CT has evolved in a way that today it can characterize coronary artery disease completely from the morphological space, including the calcium analysis, to also the physiology with the PCI planning capacity. Where we're testing before, again, there are two major components of the strategy. The first one is planning the procedure in a similar way that we do for structural interventions, and second, having the information at hand in the lab during the case with all the information of the plaque that, of course, is missing from the angiogram. We firmly believe that if this trial is positive and the next studies that we're planning are also in the same direction, we will be seeing that planning stable PCIs will become the standard of care. And with that, I would like to thank you all for your attention, and I'm more than happy to have a discussion. Wonderful, Carlos. Thanks again, and congratulations. I think that's an amazing achievement to get almost 1,000 patients already. I know it was a lot of effort and many sites, but I think everyone is thrilled to see the results of the trial when they become available. And maybe open it to our panelists, Dr. Jaffray, Dr. Moran. So, Farouk, you've been doing this for a long time and on CTOS and other complex lesions. How does the technique and the systematic approach that you heard from Carlos fit in what you've been doing and with the future of the field, you think? Thanks for the question. Great to be here, and what a great talk. It's really quite inspirational, and I think this is really…I think we've had our head in the sand a little bit just because, as Yada mentioned, we have not been able to really automate this process of just image display. Everyone is absolutely so comfortable with image analysis from being in the cath lab, but the CT information hasn't been digestible for us until more recently. With that, it's like any roadmap. We love roadmaps for all the work we do. If we have a CT roadmap ahead of time for all the wonderful reasons about optimal triage and optimal planning, why wouldn't we use it? So, as long as this information becomes increasingly automatable and just as there as a roadmap coming in, we're going to see adoption. And so, while I have focused on real-time CT fusion with you, Manos, for CTOS, there's so much more for setup ahead of time. Just understanding the actual compositional plaque burden, physiology, gut orientation of guide catheters. So, it's a very exciting time to see this evolve. Wonderful. Thanks, Feru. And Arash, I know you've been also one of the early believers on the area. What are your thoughts, and how do you see the present and the future of the field? I think we've just hit it at the right time, Manos, because with the advent of AI and AI coming everywhere, it is truly helping us all understand the CT even better. So the more, you know, AI is not artificial intelligence for me, it's augmenting our own intelligence. So, the more protocols are being written based on AI to help us in the cat lab, I think that's one place. The other thing is I also like the fact of we're getting a lot of different methods of training right now, and the training is not what it used to be. There are high-level operators, mid-level operators, community operators who are not very comfortable, and this could be used as a triage tool and say, hey, this is a really complex case. I don't think I want to do this in my ambulatory surgical center without surgical backup. So I'm going to put this in another day, or I'm going to get a second operator. So it can be an excellent safety backup for complex cases planning as well. Not just in the cat lab, but even before. Which cat lab should the patient have this procedure? And I think that could also be a very effective place. Wonderful. Thank you, Shazia. I think some questions are coming, but I think in the interest of time, maybe we'll have Farouk present his presentation about calcium, which we thought was actually a weakness of CT, but turns out to be a strength. So Farouk, very excited to hear about your thoughts about how to analyze calcium. Already Carlos showed a lot, but look forward to your thoughts as well.

CT-guided PCI

coronary artery disease

interventional cardiology

plaque characterization

predictive tools