Wait, thanks doctor. I'm excited about very innovative approaches of application PCI as part of this webinar. I'm delighted to introduce Doctor Carlos Kalei from ALST. He is very well known for his groundbreaking work with coronary CT guided PCI and today we're looking forward to your case based discussion and talk on bifurcation PCI involving coronary CT in the context of the P4 study. Over to you, Carlos. Excellent. Thank you very much. I think just to double check that you're hearing me well and you see my full screen. Yes, we are. Excellent. I think that, you know, the more that we learn about CT and the interaction that it has with the assessment of bifurcations, the more I believe that in the future for every complex bifurcation plan in CT will become a very important or an essential tool to understand not only the bifurcation itself and all the geometrical information that we know from the past matters, but also the distribution of the plaque. This is a key element for predicting, for example, the risk of a cybrane seclusion, for understanding what are we doing, the multi-layer stenting, for example, in the leaky crush where that is at the level of the calcium away from the calcium. So there's a number of things that you will see after this presentation, and I just want to provoke your thoughts to see the potential of CT in the way that I'm going to show it today for bifurcation planning. Okay? These are my disclosures. And then, again, Tanvir asked me to basically do it around a case, and I think this is very appropriate. And what I'm going to do now is basically, this is a typical case in our lab, 70-year-old male in this case, CCS class 2, under medical therapy, normal renal and ventricular function. And it comes to the lab, basically, let's say the classical routine, the patient lies on the table, you do a couple of shots, and this is what you get. So you're at the table, basically you see lung disease in the LED. I'm going to stop these two pictures just to give you kind of more time to understand the disease. And there's a number of questions, of course. And then you are saying, okay, it looks LED. There is something that distal left main. I'm not sure how significant this is. It looks long, it looks significant. In the right side, you see the caudal. It looks like there is a trifurcation, a high marginal. So yeah, it doesn't appear to be so simple in terms of the approach. So basically, we need to take a decision, and that's basically the way we actually work. And you can have imaging or physiology, but at the end of the day, it boils down to a treatment strategy. And in this case, you can say, well, the disease looks fairly restricted to the LED. We can perhaps do a LED PCI. Some people might say, oh, spur the left main because of trifurcation. Well, that's a consideration to have. Some people will say, no, listen, there is some disease at the level of the circumflex. It's better maybe to go up front with two stents. But some colleague will come around and say, listen, it's a trifurcation, very good distal beds. This is a very nice case for surgery. And then you might say, okay, that's a consideration as well. And then you might say, okay, but if you look at the trials, some people will say, well, basically, you can manage this patient medically. So a number of options on the table. And basically, if you're an interventional cardiologist and you're at the table, this is what is happening in your brain. You're trying to think, well, should I cover that plaque? How should I modify that plaque? From where to where should I extend? Which vessel, which size is that vessel? How can I assess the side branch? If I'm going to modify the calcium, which is the best tool to modify this calcium? And basically, we have around 30, maybe 60 seconds in this type of PCI to take a decision about the coronaries of that patient. And well, if you start taking decisions without the correct amount of relevant information, this is what is going to happen. If you put this patient under the hands of three, four, five different colleagues, everybody will do something different. And when everybody's doing something different, basically, this is what happens. This is data, a landmark data from Professor Soroy's syntax one trial, basically showing the variability in the distribution of the outcomes, which is basically a direct consequence of the variability in treatment or decision making. So basically, you see here, for example, every little sphere here is basically one hospital, one side. And you see here that there were sites that were very, very high rate of maze with surgery and very almost zero rate with PCI and vice versa. So really, this is one of the biggest problems that we have today in interventional cardiology is the variability in treatment. And no wonder why. The reason of this variability is basically we're taking most of the decisions based only on an angiogram. And we know that when we look at an angiogram, we basically have no real understanding of the plaque characteristics. We don't understand the disease burden. You cannot assess vessel remodeling. And if you think about the physiological component, well, you can guess whether that lesion is producing the ischemia or maybe something else. We have demonstrated that you cannot assess the pattern of disease looking at anatomy alone. So you need physiology for that. And you have absolutely no clue about the status of the microcirculation that given patient. So of course, there are solutions for that. And we all are familiar with the fact that we can, of course, use invasive physiology or physiology in general. But we also need to realize that the penetration of the adoption of this is quite low. Even we have Bimmer in the Netherlands, is one of the highest countries in Europe for physiology adoption. They have like 28, 30% of the PCIs, they're using physiology. But even in the highest countries of uptake, this remains relatively low. On the other hand, we have the use of intravascular imaging that, of course, will inform about the plaque characteristics. But again, this is limited by the penetration. And although we have seen spectacular double-digit numbers in terms of growth of intravascular imaging the last couple of years, this remains to be very, very low when you account for the total number of PCI. So the question is, how can CT help? And there are a number of ways that CT can help you. And of course, everything starts with the first slide, which was basically, what are the patient characteristics? Where is the clinical scenario? And what is that geographic picture? But again, CT can also shed light on what are the plaque characteristics of the lesion that we're targeting to treat? And of course, what is the physiological component? And this brings us back to the patient. Again, I showed the angiograms again, and I'm going to explain how CT will add information that will, again, help us take the decision of the doors that I showed before. And let's start by assessing the plaque. When we assess the plaque by CT, we have developed this framework of understanding of education. This is basically the only four names that an interventional cardiologist needs to remember in terms of using CT for PCI planning. On the left side, you see the 3D MIP, which is basically a gross understanding of the anatomy with an emphasis on the calcium burden. Then we have the axials, which are basically used to select which type of guiding is best to have enough support to do intervention in that particular vessel. Then we have the NPRs that inform us about the severity of the lesion, the length of the lesion, and also the plaque distribution, and the cross-sectional view, which in my view is one of the most important reconstructions because it's very similar to why it was an OCT. And basically, you can understand what is the arc of calcium, what is the plaque burden, et cetera. I'm going to show, of course, examples in the case that we're talking about. So let's go back to the case. Now we're pulling of the previous slide, basically the NPR. And the NPR we see here, the first thing that I see when I look at these NPRs is the fact that this is not an LAD disease. This is a left main disease. The plaque extends towards the mid-portion of the left main. And when you look at this piece of calcium here, you see that if we're going to treat this lesion percutaneously, the stent has to be extended to at least the mid-part or the proximal part of that left main to cover the complete disease. Now, when we measure this distance, and we can do that in any of the commercially available softwares, and we are trying here to understand what would be a healthy landing zone, the same as we do, for example, with intravascular imaging, we measure from, let's say, this mid-portion of the left main, and then we go until the mid-LAD. That appears to be very, very normal. And this gives us a length of 48 millimeters, which is perfect because we have a stent of 48 millimeters. So theoretically, this could be covered completely from normal to normal with one stent. I want to make here a short comment, and it's the fact that CT has a negative predicted value for disease of around 98%, 99%. So one of the things that I teach my fellows when they're learning CT is that if you see a normal cross-section by CT, 90% or 80% of the times will be normal, and 100% of the times will have certainly an adequate landing zone with a plaque burden of less than 30%, 40%. So that's an important detail to keep in mind. Now, the beauty of CT is that we are looking at the pictures, of course, in the three-dimensional space, but you can go in any branch. So in this particular case, we're talking about a left main trifurcation. So of course, it's relevant to understand how is the distribution of disease in the circumflex. You see the circumflex here in the middle. And although you see some disease in the proximal circumflex, this is very, very little amount of disease. So basically, the risk of this branch or to have a problem of the option is very, very low. Then we look at the ramus, and the ramus, again, there is no disease at the level of the option of the ramus. There is some disease in the proximal part of the ramus, but again, favorable for, for example, a provisional strategy. Now, what has really changed, and I think Yanis will explore this in depth in the second part of this webinar, is the fact that we're not looking anymore at these pictures in this gray scale as the radiologists or the imagers used to do. We're basically now taking these pictures and creating three-dimensional meshes of the disease. So of course, we have the lumen, and then we just plot in three dimensions the plaque on top of it. What you see on the right hand of the slide is basically calcium, the white spots are calcium, and you see again, the rest is basically the vessels and the non-calcified plaque. So if we go to the case that we have on the table, basically, we're looking at the fact that, again, the calcium extends to the left main, the circumflex basically takes off an angulation of about 90 degrees, and there is this ramus, which again is large, and you see here the distribution of calcium in the proximal part of that ramus. So this is an unprecedented assessment, and I think that it's extremely intuitive. You don't need to be an expert in CT to understand what you're looking at, and I believe that any interventional cardiologist without any training in CT will quickly understand what are the characteristics of this particular disease. Now, what we're doing in the trial, because this is, I have to say, we're almost finishing the P4 trial, is that we are putting these geometries, these reconstructions inside the lab. And these pictures, these geometries are synchronized with the CR. So every time that you move the CR, you will know exactly what you're going to see in the angiography without putting your foot on the pedal. And that, of course, you can imagine the consequence of that. You'll basically be reducing directly radiation and contrast. But the most powerful part of this is that you can see the plaque in the three-dimensional space in the three vessels during the procedure, and that adds a layer of information that is very, very powerful, especially when you have complex disease with a lot of calcification. There are a number of studies already showing the accuracy of the CT when you're trying to look at either plaque volume, plaque burden, or even calcification arc. I just showed you a picture. I will not show you data. I just showed you a picture that basically shows how you can basically, with CT, understand what is the calcification arc, what is the plaque burden you see here, for example, in the cross-section, the four from left to right, that you see this allo, this is basically a fibrotic plaque, again, identified by IBUS and in this case, VH. And again, identifying plaque composition by CT is quite straightforward. We have basically the same components. And the key, in my view, element that facilitates the understanding of plaque by CT is the fact that the intensities of the plaque can be measured for free in any screen, basically. And if you have Hounsfield units below, let's say, 50, this is most likely to be lipidic. The Hounsfield units are between 50 and 180. This is what we call fibrotic tissue by either pathology or VH. And if you have high intensities, typically above 300 or 400, these are calcified lesions, which are very easy to identify also visually. Now, this, in my view, the way that CT actually helps looking at calcium is basically solving one of the biggest needs that we have in the field. And this, of course, applies to the field of bifurcation. And the reason is because we are not good at looking at calcium within geography alone. This is a landmark work from Gary Mintz, basically showing that around a third of vessels with severe calcifications more than 180 are invisible in angiography. And why this is important? Well, the major predictor of external expansion is basically calcium. If the calcium is not well prepared, this would likely lead to a standard expansion again, shown again by Gary in a similar work. But what is really important is the fact that when we treat patients with severe calcification, this basically is associated with a three times or 30 percent or increasing mortality compared to those patients treated with PCI without calcification. Now, if we go to the case, now we look at basically the distribution of the calcium. And we see again that the calcium at the level of the left main is a 90-degree calcification. So this is not really a severe calcification. And then you see the other pieces of calcium basically in the proximal part of the LAD, some on top of the, I would call this the polygon of confluence of the trifurcation, and then some proximal calcium in the LAD. But again, not really severe calcification requiring an advanced plaque preparation. And CT, in my view, will become one of the most important tools to assess calcium. I would explain why. But basically, you can characterize calcium morphologically, the same as you do with IBIS or OCT. You can understand calcium with the three-dimensional space that makes assessment of calcium very, very intuitive. And you can assess how hard the calcium is, which is something that is specific for CT. And that is basically due to the fact that you can assess the calcium density. And I will not talk today about wire bias. This is something that we're working as well, basically trying to identify which are the cases that rotablation might be the best treatment strategy. Now, how can we do that? Well, very easy. You have here the assessment of basically the circumference of calcium. And here you see that IBIS and OCT on the left side. And you see how it looks in the cross-sectional view with CT. So again, quite easy to identify the circumferential calcification, semicircumferential calcification. The same applies for thickness. You see here on the top a thin calcification, in the bottom a thick calcification. And here you can also measure, of course, the length of calcification. Now, by far, the most novel aspect of all this characterization is the fact that you can derive what I call the degree of compactness of the calcium or how hard the calcium is, as I mentioned before. Now, I'll bring your attention to cross-section F, G, H, I, and perhaps J. And if you look at these cross-sections, you will tell me, well, this is basically circumferential classification. And that is true. If you look at this by IBIS, it will be just a shadow around it. And OCT will be the same. But when you measure the density of this calcium in their respective quadrant, so every 90 degrees in this case, you see, for example, that cross-section G, there is hard calcium at 3, at 6. But the calcium here on this quadrant, on the superior quadrant, is basically less hard. I don't want to call it soft, but less hard. And then you see more or less the same here applying. And so using the certification of density, you can basically understand, we have understood already that most of this circumferential ring of calciums is not homogeneous calcification. This is just basically, it depends, of course, on the patient, depends on, in my view, on the age of the calcification, but you'll see here that this is most likely to be heterogeneous. Now, imagine that you have this three-dimensional map that you can, of course, plot that on top of your angiogram, and you can understand where the calcium is located. And again, you will see, we have spectacular cases where we have seen that this concept of density basically plays a big role in understanding where would be, or what would be the likelihood of extended expansion using here a case of the bifurcation with this diagonal, where you have the distribution of the calcium basically away from the bifurcation or in the other part of the bifurcation. The Hounsfield unit were extremely high. We deliver in this 120 pulses of IVL there, and even after that, we could not expand the step properly. Now, let's continue to the case because we have to take a decision based on basically on how to treat this gentleman. And the other piece of information that CT can add is basically telling us how big is that vessel. Not in terms of the length or the diameter, but basically the mass that that vessel subtends, which is basically essential information to decide even on technique. And we see here immediately that the LAD basically subtends here about 25% of the mass, but look at the Ramos. The Ramos is as important as the LAD in this case in terms of the mass that it subtends. And then you have here the circumflex, which is a very small circ with about 10% of the left ventricular mass. Now, we have a complete analysis from the morphological point of view with the plaque, with the calcium, and on top of that, we can also add physiology. And how physiology can help in this case? Well, of course, we have to consider physiology in the traditional use of physiology, which basically has been defined by all the FAME trials and is in the guidelines, which basically is to detect if the lesion is flow-limiting or not. But the reality is that today, we're not using physiology anymore in that way. Of course, we use physiology to understand if the moderate lesion is significant or not, but the big change in the use of physiology is the fact that by looking at the pattern of the pressure drop of the distribution of resistance at the level of the picardial vessel, we can predict what is going to happen after PCI. And this is a new way of using physiology, in my opinion, is more clinically relevant than before because now we're adding a guidance component with the use of physiology. And when it comes to CT, it's basically you can do many, many, many things, and I will show you basically what you can do. Of course, on the left side, the classical use, guidelines, positive, negative, but in the middle, we have this ability to understand, again, in every single point of the coronary tree, how the pressure is being lost. And this changes the procedure many times in the way that PCI is basically the mechanism of action of PCI, you're required to have a resistance that you need to basically reduce or eliminate. If you don't have a resistance from the physiological standpoint, basically PCI is not indicated. So if you do this pullback curve and it's completely fused, well, basically the PCI will not be addressing any pressure drop, and that's an important concept that needs to be kind of discussed. And basically with this technology, I think that we have evolved to a place where we have something called the FFRCT planner that we can basically do virtual PCI. I will show all of this in the context of the case. And I just want to kind of emphasize here the fact that you can derive these virtual pullback curves in the same way that you can do an FFR pullback or an IFR pullback. And then you basically understand that the case on the right is a perfect case for PCI. The case on the left is a very, very bad case for PCI. Because what we also understood recently is that we cannot increase flow with PCI in diffuse disease. But that's for another time. Now, if we go back to the case, this is what we see. This disease that looks long in the LAD from the left main is basically focal disease. All the pressure losses are located in that very, very austere LAD. If you do a pullback curve, this is how it looks with a very high PPG, 0.62. Again, all the pressure loss is located at that particular place at the osteum. And again, imagine that for every single case that are coming to the lab, the CT analysis will provide you with basically a complete map of the anatomy, including the plaque in three dimensions in the three vessels. And I'm talking about the plaque and, of course, the volume of the plaque, but also the composition of the plaque. And on the right side, a complete map of the physiological situation from, of course, the flow limiting decision, yes or no, but also the location of pressure drops. And again, you can mimic the PCI in this case. What would happen if I put a 48 coming from the left main to the mid LAD? Well, basically, you will increase, you will be increasing the flow and putting that patient above the ischemic threshold, 0.82 in the distal part of the LAD. And that basically will certainly make the patient feel better. Now, what was a very complex and difficult decision-making process now becomes an extremely simple procedure. Now it became seven fringe, radial, three wires, a 48, and what could have been a very complicated long procedure from both the strategy part and the technical part becomes a straightforward procedure with a provisional from the left main to the mid LAD, landing on normal landing zones, but post-PCI-FFR, 0.88, and that's it. So everything that you have seen in this case, basically I took this case from before, is what we are basically doing in the trial. We're basically randomizing patients to CT or IVUS to be treated following that, with that guidance. And in the CT arm, we're basically doing everything that you see on the screen, a complete understanding of the anatomy before you go in the lab, a specific patient-specific guidance, so you don't have to change the guidance anymore because you choose the one that basically is most fitted for that particular anatomy. You understand the severity of the calcification, understanding right away whether advanced plaque modification needs to be done, the mass at risk, which in my view is crucial in bifurcation lesions where you're trying to define the best technique, and of course also in the lab, assessing the best view. And the best view, again, is important because you need to find a view that is good to see the ulcer of the sour branch or to see other characteristics of the bifurcation. I think having that information in the lab really, really helps. And the whole physiological part, which is basically, again, understanding the pattern of disease and the significance of the lesions and also predicting what would happen if I do this or that technique. I'm very happy to say that we have included 952 patients as of yesterday. It was the last time I looked at the numbers. We think that we're going to be finished before aorto-PCR, which comes in a couple of months. We'll see. But basically, what we're doing is we're randomizing, again, a little bit more than 1,000 patients with CT, with everything that you have seen in the last few slides. And again, the control group is IBS-guided PCI with a non-inferiority design with MACE as an input at one year. So to conclude, and we have a few minutes still to have a good discussion, I think that CT has evolved in a way that is able to characterize CAD both morphologically and functionally. It's not anymore a rule-out tool. This has really, really evolved. And I didn't show any of the new CT scanners, but that is just mind-blowing to see how the hardware is evolving. The second point is that we're testing all this in P4, where we're basically integrating CT for two things. It's important to kind of dissect what we're getting from the CT. The first one is the planning part. So going in the lab, knowing exactly what you're going to find, with a clear map of where the calcium is, where the problems can be, where the bifurcation, basically what is the characteristic of the bifurcation, actually before you do the first injection. And that changes the way you approach the case. And the second element of the P4 is the guidance, the online guidance, basically having the plaque or the map of plaque in front of you during the procedure. That really helps. And we firmly believe that if this approach shows to be beneficial, I think this is going to become the way they will be doing procedures in the future. Thank you very much for the invitation and for your attention. I'm happy to address any remaining questions. Thank you so much. That was so informative. Dr. Rapp, if I might ask a question, and I agree, I think having the information, particularly the mass at risk in identifying a side branch that is important enough is so crucial in terms of planning. As part of your P4 trial, Carlos, is there, do you allow the use of IBIS periprocedurally for anything? Particularly, I mean, in bifurcation stenting, it helps, intravascular imaging is helpful for rewiring and particularly when you find points like that where it might be difficult. Is IBIS allowed within the protocol? No. So if your patient is randomized to the CT arm, basically if you do IBIS, it's a protocol violation. When we started the trial, we thought that, you know, we were ready, really, we knew that all these trials looking at intravascular imaging will be positive based on historical data. So we said, listen, we're really testing whether this can have the same outcomes as IBIS. So we sampled, when we did the sample size calculation, we did an assumption that we said, well, at least 10% of the cases, the colleagues will use an IBIS because, you know, sometimes you really want to check. That number today is 2%. So we don't have a lot of people looking for the IBIS and the reasons are two. From the pre, let's say, imaging part, so the IBIS before implanting the stat, I think CT offers comparable and sometimes better information than intravascular imaging and easier to interpret. The post-PCI part, where we're mandating the trial is to use device detection. So you have to use a stent boost, a clear stent, whatever you have in your lab, 3D stent, doesn't matter, to be sure that you are not leaving any under-expansion behind, okay? And we're also, it's mandated by protocol, the bifurcation lesions to do this, to be sure that, and again, you have a very well-extended expansion at the level of the bifurcation. Thanks very much. Carlos, if I could ask you a question, we've been using a lot of CT as well in the Netherlands and I agree with you that it's an amazing technology because it allows you to have the complete three-dimensional anatomical information, not just the luminogram, which we get with the coronary angiography, but actually information about the plaque itself. In my experience, and you already mentioned this, the negative predictive value is extremely high, but the positive predictive value can be a little bit disappointing at times when there can be a lot of disease on the CT, but you take the patient to the lab and it's still relatively moderate. So I guess my question is, there's two parts to the question, do you think that there's ways that we can standardize the CTCA with particular settings for the CT scanner in terms of KV, that more standardized the houndstooth units that we get out on the other end to optimize the standard CTs that we have, and do you think that the higher resolution that photon-context CT will offer in the near future will change the game even more? Yeah, so, Bimmer, thank you, there are two super relevant questions there. So the first one is that we, you know, one of the reasons that I like to do clinical trials is because you always learn something that makes you practice in a better way. And one of the big things that we learned from before, very early on, was the fact that the way that we were doing the scans, we were doing rule-out scans. And if you do rule-out scans, you cannot see what I showed you in the pictures before. These are cases where basically if you have calcium, you have to increase the energy of the tube, you have to increase your kilovolts, because otherwise you're going to get a lot of blooming. And these are the typical cases, Bimmer, you're saying, you know, they put in the report, we cannot determine the lesion's significance, or it's very significant, they do an angiogram, you see nothing. The reason of that problem is because from the radiology side, the radiologists have been trained with this concept called ALARA, which means basically as low as reasonably possible radiation, which is good for a 45-year-old woman with atypical complaints. But when you have a patient that has a very high likelihood of coronary artery disease, in P4 you need to have a lot of disease to get in, you need to go with higher KBs, and that allows you to see through the lumen and have lower or more specificity in the assessment of the disease. Now, this is with normal scanners. Now, we have three sites in P4 with photon counting, and the difference is it's like another world. So if you are not following what is happening in the CT field, two years ago with the photon counting CT, the resolution doubled. So we went from 0.4 to 0.2 millimeters. And in addition to that, there is a specific way that you can remove the calcium, so calcifications are no longer a problem. I have recently, I'm involved with a team of St. Francis in the U.S. assessing the agreement of photon counting with OCT in terms of vessel size, unbelievable. So even in the future, we'll be able to size very precisely photon counting, the calcium will not be a problem, and I think we will be able also to look through stents. So I think that's certainly the future. We're going to wait a little bit, I think we'll wait a couple of years until this becomes mainstream, but I think that's the future, certainly, of CT-guided PCI, the photon counting approach. Nick, do you have any comment before we go to Yanis? Yeah, just make a brief comment. Excellent presentation, Carlos. Obviously, you get so much information from just CT, pre and post. You know, my experience has been in modeling CTOs and chronic total inclusions, and we use CT a lot for ambiguous proximal caps, and I get exactly the same information that you were talking about. Unfortunately, we don't have photon counting in CT, but I've seen images, and 0.2 millimeters is just incredible. I mean, this is better than what most centers have. You know, one other comment I was going to say on the P4 that's randomized, which is going to be great information to see in non-inferiority or even superiority to IVAS, but sometimes what I like to do is post-stenting. I like to look at the edges of the stent, and on IVAS or OCT, if sometimes you miss a dissection by angiography, but you see that on IVAS or OCT, and that makes you change your strategy a little bit. And with your randomization, I guess that's not possible, because you can't use the post-imaging either. Is that correct? Yeah, that's correct. So indeed, you know, it's a trial. There's a question. We are trying to be rigorous here from the scientific point of view, and some people say, well, but the trial is biased towards CT, because you have all this information that you cannot get from IVAS, and you got the physiology, and then you got the prediction. Yes, that is true, but you also don't get what you're saying. You don't get a very deep assessment of the edges. So I think this is where we're testing. I have to say that I'm pretty curious. You said superiority. I think that we're not aiming at superiority of CT at the PCI, but that's going to be P5. In P5, we're going to do superiority of planning with CT versus no planning, because in the meantime, Nick, we kind of understood that there is a big value, as you said, to plan the procedure. It can be a CTO. It can be a left-main. It can be a bifurcation. But if you go in already with a deep understanding of the disease, that changes the procedure from the decision-making, also from the technical part.

coronary CT

percutaneous coronary intervention

bifurcation cases

P4 study

plaque distribution

intravascular ultrasound

photon-counting CT