Well, good morning, everybody. Thank you very much for being here on, you know, the final day of HRS 2025. My name is Philip Kukulich. I'm fortunate to be co-moderating this session. I'm supposed to read something before this, as if you haven't heard it before, but it is my pleasure to welcome you to St. Louis Heart Rhythm 2025. If you haven't already done so, please download the app. In the app, you can participate in the live question and answer session. I have an iPad up here for the questions and the answers. So if you wish to put a question in the app, I'm happy to read it out, and we'll have those questions answered by our experts up here. If you don't have the app, we were going to invite you during the question and answer session to the microphone up front here. We really hope to have an engaging Q&A session at the end. The structure of this format, we're going to have four excellent talks. We'll keep the questions to the end. With that, let me turn it over to my co-chair to introduce himself and start the proceedings. Good morning, everybody. Welcome to this session. My name is Martin Bernier from McGill University. So it's my great pleasure to introduce our first speaker, Dr. Packer, who will tell us about particle therapy for ventricular tachycardia, proton versus photons. We have to wait for the disclosures and I can insure you that I have no idea where they came from. So, I thought we'd spend a little bit of time talking about some of the differences between protons and photons. Over time, there were huge differences and I think the thing that's happened with time and as we've done things, we have a little bit better idea that maybe we're not as far off as we thought. Now, this is more of a realistic concatenation of my disclosures. So, I'm going to talk really in more general terms than I usually do to begin with. You know, whenever we're doing this sort of work, you have to do two things. You have to do structural and you have to do arrhythmia sourcing. You have to be able to be in a position where you put both of them in position. And this is a slide that I'd like to show and you've seen it but it's the source of arrhythmia we're seeking and we can do that with a variety of different things. For example, 12-lead ECG, 12-lead holters or any other mapping thing that you want to do or extra corporeal mapping of a cardio mapping. But you want to get some kind of a signal, some kind of an idea of what the arrhythmia looks like. I find it quite easy to use a 12-lead holter. There are a number of other things that you can do. You can do mapping. You can also do cardio insight type mapping. And there are now another two or three different kinds of insightful mapping capabilities that gives you a shell. You know, it's a little bit easier to work from the outside in than it is from the inside out. But when you're doing proton beam, it really doesn't matter. You should be able to get them both. But if you're looking from an outside point, you got 252 electrodes on the body surface. Then that's not necessarily going to be right for where your arrhythmia is. But hopefully it gives you an idea. So then it comes to the structural sourcing. Now here is a CT. I like CTs, particularly in ischemic heart disease or coronary artery disease. We'll go through this one more time. You can see that there's a kind of a longitudinal coaxial. There's a collateral sagittal and looking down axial. And as we run through those, again, you'll see that we go from the mitral annulus. And they can slide all the way down to the end of the apex or to the tip of the apex. So you get, with all of these, you get anterior lateral, lateral medial. You get valve down to apex. And now I might do it. Well, we had our shot. And if you look at this, then again, you get the idea that you have to scan the entire view and you have to build the construct such that when you're going to combine it with whatever you're doing with your arrhythmia sourcing, then you get where you need to be. Now the one thing we have to thank Bill Stevenson for is he was part of this era in HRS clinical consensus statement, really volume definition for STAR. And what we're trying to do is we're trying to decide what kind of a volume can we set. There are different ways you can do it. You can do a cardiac structural set and get that target volume in that way. Or you can use the target volume to be created from anatomy and then at the same time with some kind of a map. You can do it endocardial or epicardial. And all of those give you a pretty good idea, I think, of where it needs to be. And here you just put it all together to come up with what you think is going to be your treatment volume. Now, Phil, who cares about treatment volume? Me. Yeah, the whole world does. You know, if you're looking at oncologists or radiation oncologists and they're trying to do their treatment volumes, then they like to put in something we call a little additional ring or a margin so that they can ablate a little bit more than what they probably need to for that bit of cancer. That's a really bad idea for what we do. We want to be just as small as we can possibly to be. And we want to be able to get what we need to get and nothing more than that. Now, when we talk about particle therapy and photons, let's just look at this. You know, photons look like photons, little packets of energy, sometimes sine wave issue. And then if you look at particle therapy, it really is a stream where you shoot protons or carbon or helium or anything else. Well, with the photons, sometimes you'll get an entrance dose loss. But Phil assures me that if you put in enough beams over the course of about 180 degrees, you're going to get the beams where you need to get the beams. I agree with that, although I do think that you lose some in entrance loss sorts of effects. With protons, you shoot those in and you see something that's a little bit different. Photons go beyond your target. Protons tend not to. When protons go in and they fire off, and that has to do with the energy and it just blasts, it stops right there. And if this is our target over here, you don't want to be going through your target. You want to hit the target, but you don't want to go through it. Now, the black and the red are really telling us what's life, what's real in life. And then there's a penumbra around it. That's the other colors that you see. You don't see as much of a penumbra as you do in protons as you might see in photons. There's some there, and you have to watch out for it. And putting it all together, you have to make some final decisions. Well, the final decisions are you have to do contouring of your target. You want to know where every single pixel of that target happens to be. Epicardial surface, endocardial surface, mid-myocardial surface, and then you do simulations where you think that you know that you've been able to target carefully and you've been able to do a pretty good job of getting, you know, there's a coronary artery here. It's not here, and you're staying away from it. And then you do treatment planning. The treatment planning really lets you lay out where your volume is going to be. And when I say volume, it's laying out whatever energy you're going to apply. Now, there's a couple of things in here that are important. You can use any energy you want. And this idea of a dose-volume histogram applies to all of them. Now, it applies better with photons and better with protons. And this is the net dose that you're going to deliver, and it's the volume you're going to deliver on top of that. So when you look at all of this stuff together, you don't want to be hitting these things down low because that's things like esophagus. It's hitting things like liver. It can hit colon. It can hit the brain. There are a whole bunch of things that you could hit, and you just don't want to do that. And so what you're doing is you're going to be aiming out with a greater, in the case of protons, you're going to be aiming further out here, and you're kind of in a V95 or D95, depending on how you think of it. You want to deposit that much of your dose in a place where it's supposed to go. So then you've got 30 gray protons, which is what we do typically. We've done some with 40. But see, your tissue's also scarred by myocardial infarction. That's what you saw all the way down at the tip of that CT scan that I showed you. And it's, you know, a little bit of misery. And then you've got normal tissue. So when you do this Venn diagram, I call Venning up. When you Venn up, then you have to keep track of scar. You have to keep track of what energy you're going to be delivering, what it's going to do, and then normal tissue. And it usually stacks pretty well. So let's just say it stacks. Well, the cellular outcomes. What we saw in the work that was done in my lab with Kostas Tsiontis and Hirao is that if you look at conduction velocity, we found the conduction velocity over the course of delivery in some place that has tissue. This doesn't go down very well, but it drops over time. It gets slower and slower and slower, depending on what the dose is. We see the same thing here with connections. The connections that tie everything together also decreases, progressively slower and slower. You also see caspase turning into kind of an apoptotic sort of a thing. And this was a little bit of a surprise, because every time we did something, things got slower. And then we went to St. Louis, and we found, for all intents and purposes, that things got faster. Which things? Sodium 1.5, increased. Connections, increased. Velocity, increased. Conduction times, increased. And they mapped it out, and they looked at other things that gave indication that you'd really wiped out the various components, nuclear components. We didn't figure that out, but we kind of thought, they're using mice, and they're using very tiny amounts of energy, and so the Murian model may not be the same as the Porcine model that we used. Now, maybe our Porcine model was too big. We were shooting too hot. And so Philip and I had a variety of conversations, and I don't know, it looked somewhat like Animal House, near as I could tell. But the details were, is we went on and then looked at tunnel cells, and basically, tunnel-positive cells give you an idea of where the DNA really has been trashed. And we looked at that, and you can see that it drops off in the upper, but then where it drops off down below, is you get an initial peak in that tunnel cells, and they tend to drop off over the course of four or five or six weeks. So our sense is that you would have something occurring very early, and that's the apoptosis that you see. Peaks early, goes down. Fibrosis comes along later. Now, this drawing that Hirab did kind of looks at three months of time. I don't agree with that. You start to see that earlier than that, maybe, you know, 16, 18 weeks. And then what happens is the connections start to break up, and all of the things that make life slower makes life slower. It just makes sense. This has also been something that's been done at the University of Utah, and Ravi Ranjan, looking at delivery of proton energy, finding exactly where it goes, seeing how it increments over time, and as you go along a little bit further, the thing you see is that there's progressive slowing, not progressive speeding. So, you know, what happened? Well, we went back, and we looked at the same thing. We went back and looked now at Utah, what's going on. So we looked translationally, and if you look translationally, this slows over the course of about 16 weeks, and then it really flattens out. But if you look at the volume, whether you're looking with eyes or whether you're looking with tissue, it's pretty straight. And if you look a little bit further, then as we did this translationally, you could see areas that were in Farks scar in the blue. You could see areas that were the actual energy delivery from protons in white, and then more or less regular tissue in gray. So the point for that is very much that there were marked changes in three-dimensional conduction velocity, and three-dimensional conduction velocity we think doesn't lie. Now, I just need to do one more thing, and then I'll get out of here. If you look at the clinical experience now, there's been a lot of studies that have been done. These have wound up most ideally shown in what was seen in the ERA and HRS studies and documents. You see 3D, how you develop scar and VT. And then as you do your delivery, then you get to the point where that is likewise delivered. In another study, conduction velocity drops. But in St. Louis, VT goes away. Not all of VT. And if you look at Kauser's data, then the KM curves go off to about drop off 25%. And if you look at them carefully, then there is even more problem altogether. If you are very careful about how you drop the beads, not really beads, then you can have very little damage. But in terms of looking at what this means now from the standpoint of mortality or heart transplantation recorded 12 months by forest plots, we don't have the answer yet. They're liners. They're liners if you're looking at a 12-month look at mortality and subgroup analysis. According to age, it's all the same. And I think that that basically says that we don't have all of this yet, and I'm going to stop here before showing you how photons and protons can actually get rid of heart failure. We'll get to that maybe some other time. But the point is, I think, Philip, at this point, I think we've kind of figured this out. There are going to be things that happen early and then things that happen late, and they're all relevant. So I'll stop there. Thank you. Thank you. Thank you very much, Dr. Packer. On to another form of energy. Now Dr. De Potter will tell us about ultra-low temperature cryoablation for ventricular tachycardia. All right. So also on my behalf, very good morning to all of you. So also on my behalf, very good morning to all of you. And what I would indeed like to go over with you is results on using ultra-low temperature cryoablation for the purpose of ventricular tachycardia ablation. Of course, the predominant energy used in VT ablation is RF ablation, and RF ablation has its merits and also its limitations. Main limitation obviously being that lesion depth is ultimately limited to some degree and that there seem to be issues with creating deep and solid lesions, particularly in unhealthy tissue, in scar tissue. This means that there is an ongoing search for improvement in VT ablation, both by improving the biophysics of RF ablation, for example, changing the properties of the cooling or changing the properties of the impedance and alternative energy sources, several of which you will hear about in this session. For this particular presentation, one specifically interesting technology, I believe, is the use of cryoablation. Cryoablation is well-established for VT treatment, of course, and is mainly in the surgical context, a technology that has been used for decades with very high efficacy. Cryoablation in percutaneous settings has also been used and has been shown to be safe. For example, it has been shown to be not associated with injury to the coronary artery and has been shown to provide excellent stability due to the fact that the catheter sticks to the tissue once it is frozen, which leads to a very common application of cryoablation for the purpose of trying to eliminate papillary muscle PVCs, but the fundamental limitation of percutaneous cryoablation until now is that the energy sources available simply do not lead to a very efficient lesion formation because the temperature does not reach the threshold you would like it to reach. For this, you need to open surgery with powerful coolant sources. Now, through technological innovation, the use of liquid nitrogen has become available in percutaneous settings by hypercompressing the liquid nitrogen. It becomes feasible to use liquid nitrogen at its theoretical boiling point of almost minus 200 degrees Celsius and to apply these two catheters to the human heart in a percutaneous setting in a beating heart context, of course, and this is the essential innovation which allows ultra-low temperature cryoablation in a human setting, which was developed and tested in the studies that I will show you in a second. So this is what the system looks like. This is the ablation catheter as it is currently available. It has a 50 millimeter long ablation element and also contains eight electrodes which are useful for recording, which can be used for navigation purposes in an electroanatomical mapping system using impedance-based tracking, and which can be used for pacing if needed. There is no irrigation on the catheter itself, and here you see a typical lesion formation. You see a typical ice ball formation on the catheter in a bowl of body temperature water. Results so far, preclinically, have shown excellent lesion formation and have shown fairly deep lesion formation both in healthy and, importantly, equally in scar tissue. You see here in this example both in terms of lesion depth and lesion width, lesions exceeding 10 millimeters both in healthy specimens and in scar specimens. Interestingly, in this study, a bit outside of the scope of this particular presentation, the technology was compared using only ultra-low temperature cryoablation as well as combining the cryoablation with a post-field application which is feasible through the ongoing cryoablation. And interestingly, here is a clinical example of this property or this ability of lesion formation in the setting of preexisting scar. This is a single published case report, but a few cases have been performed and a six-patient series is currently under review. You see a patient with sarcoidosis with preexisting septal scar formation on the MRI which is typically a very challenging setting for RF ablation to achieve good lesion formation. And you can see here after the cryoablation, you can see clear change in the late gadolinium uptake on the MRI post-ablation, indicating lesion formation in the septum despite the preexisting presence of scar. Here you see another property of the technology where you can see an ongoing ablation in the endocardium with simultaneous recordings on the epicardium. You see here ongoing ablation. You see the freeze artifact on the electrograms on the ablation catheter. But importantly, you can see on the epicardial recordings, you can see elimination of the near-field electrogram on the recording during the application, indicating transhumeral lesion formation. And we've also recently shown to further confirm this property of lesion formation in the setting of non-healthy myocardium. We've shown that the technology is feasible, is capable of creating lesions in a bench setting only so far in the presence of synthetic materials. Synthetic materials such as patches after a congenital surgery, for example, is another typically very challenging scenario for RF ablation. And what we've shown is that despite the fact that both RF ablation and cryo ablation, both thermal modalities experience a reduction in efficacy in the context of a synthetic patch. The reduction in efficacy is far greater for RF ablation and there is a loss of over 50% of efficacy for RF ablation, whereas the attenuation of the freezing effect is relatively modest and we documented a more than 50% loss of efficacy for RF and a slightly less than 20% after the second freezing cycle loss of efficacy for cryo ablation, indicating a potential for this technology, for example, in post-surgery congenital heart patients. Now, as mentioned before, the technology has also been studied in a first in human clinical trial, the CryoCure VT trial, which studied patients with both ischemic and non-ischemic cardiomyopathy for which a six-month follow-up was the primary endpoint. Freedom of VT events at six months was the endpoint of the study. In the CryoCure VT study, recommendations for freeze duration were provided based on estimated tissue thickness, although the ultimate decision on the duration of cryo application was left to the operator and the CryoVT cohort has been reported in some case studies and smaller cohorts and then finally we published the full six-month outcome last year in EuroBase. So these are the demographics of the 64 patients treated in CryoCure VT, fairly standard characteristics I would argue for a VT trial with the majority of patients being ischemic cardiomyopathy patients which were treated in nine centers as you see on the slide here. Procedural characteristics show a procedure time of about three hours in our very first human experience with this technology. You can see here different mapping strategies that were used to treat the patients, a majority of patients undergoing a substrate-based mapping strategy and mapping approach, some patients being treated with additional base mapping for example to target specific sites of clinical VT morphology. In the CryoCure VT study, the vast majority of patients received a two-minute freeze plus a two-minute bonus application after the thawing phase and as you can see on the slide, the average number of lesions per patient was nine lesions with an average duration of freeze time of just under four minutes. There were zero protocol-defined major adverse events in the study and the adverse events that were recorded are also shown in this slide, did not lead to specific clinical consequences or any need for particular intervention. In terms of the acute efficacy, in terms of the acute inducibility of the 64 patients that were recruited in the trial, 54 were assessed because seven patients were not inducible at baseline and three patients were not re-induced because they were considered too unstable for re-induction by the operators. Of the remaining 54 patients, 51 out of those 54, 94% of patients did not show inducibility of their clinical VT which was a primary acute success endpoint and 46 out of the 54, 85% of patients did not show any inducible VT which is the secondary endpoint. In terms of clinical outcome, what we reported earlier which you see in the middle of this slide is the six-month outcome and what Atul Verma has shown just yesterday in one of the sessions here in San Diego is the ongoing follow-up and we now have reported the 12-month follow-up, so the one-year outcome of these procedures. These are all the events in the patients reported at six months and now at 12 months you see a 73% freedom of ICD shocks in our population and a 44% freedom of any VT event in the population. If you break this down and look at the patients with VT recurrence, with any VT recurrence or with ICD shock, you see there is no substantial difference, no significant difference between etiology of the cardiomyopathy, both ischemic and non-ischemic patients seem to do equally well and we see an ongoing follow-up that there is an ongoing reduction in rate of new VT recurrences and ICD shocks. You can also appreciate on this slide which gives an overview of the VT burden pre- and post-ablation and again on the left hand of the slide you see the six-month outcome, the primary endpoint of the study and you can see the pre-ablation burden and you can see the very substantial reduction in ablation six months post-ablation. What you can now appreciate from this part of the slide in the ongoing follow-up up to one year is that overall the VT burden remains unchanged versus the burden of zero to six months and you can appreciate also that in those patients with early VT recurrence there is certainly not an ongoing increase in VT recurrence. You can also see from this slide that five patients were retreated and one single patient died of heart failure at day 183 just over six months after ablation. Looking a little bit different at this burden data you can see from this slide that the majority of patients had recurrence without an ICD shock and fewer than four ATP events, three ATP events or less is the recurrence mode for the majority of the patients which If you compare this to existing publications compares, I wouldn't say favorably, compares equally to existing trials of course. This is for reference only. All these trials have different endpoint definitions and none of them is randomized. And finally on the use of antiarrhythmic drugs we've observed a significant and sustained reduction in antiarrhythmic drug use both immediately after the ablation as well as in the ongoing follow-up up to one year. So to conclude I'd like to point out that the technology is being studied further in an ongoing U.S. IDE trial which is an extension of an early feasibility trial that was already completed which is again studying patients with ischemic and non-ischemic cardiomyopathy which has already reported its acute endpoints of the early feasibility data at HRS 2024 similar to the cryo-cure VT data. And I would also like to point out that improvements in catheter technology are being developed with the goal of improving catheter maneuverability with the goal of making the catheter compatible with existing sheets and with the goal of making the freeze duration even shorter. In conclusion our trial data I believe has shown that endocardial ultra-low temperature cryo ablations are safe and effective in patients with both ischemic and non-ischemic cardiomyopathy. There is more real world and trial data on the way. In particular the U.S. IDE trial is recruiting substantial amounts of new patient data and there is technological iteration under development targeting better integration in routine workflows and allowing potentially even faster lesions. Thank you very much. Happy to take questions. Thank you very much. That was fantastic. As a reminder you can log on and send in Q&A, send in some questions online. I see a couple of questions already that have popped up. We're going to save the question and answer to the end. Also if you're standing on the side we've got some seats off to the left and in the front it's Sunday of HRS so don't stress your legs any more than you need to. So please get comfortable. Thank you. With that we'll continue with our next speaker, Dr. Korut, who will tell us about pulse field ablation, radio frequency or both for VT ablation. All right. Morning everyone. Thank you for HRS. Thank you to HRS for this opportunity. My disclosures and a big acknowledgement to our postdocs who are responsible for many of the slides that you will see and the experiments that we did. The way I look at scar related VT in the world of PFA and current catheters except the ultra low temperature catheters is that we have large and small tip PFA catheters. We have large and small tip RF catheters. And then there's this concept of RF before PF or PF before RF. And that's the armamentarium that we have in the world of RF and PF for scar VT. And I think one advantage of this form factor is that it's a form factor that we've been used to for many years doing AF ablation, PVC ablation and VT ablations when it comes to using small focal tip catheters. I'd like to start off by talking about two concepts, the differences between a small footprint catheter and a large footprint catheter. We have shown recently in Jack EP that things like contact force dynamically change as you deliver RF. We have shown that contact force increases as you deliver an RF lesion because the tissue is getting stiffer. So contact force is a very complicated topic. Now what I want to point out is that the small footprint 3.5 millimeter tip catheter is inherently unstable and that's why contact force is so critical to enhance stability and coupling. Remember as you increase contact force in thick tissue what it does is to compress tissue. Something we've all believed but no publication to support this data and we will have a paper addressing this soon. In thinner tissue like the atrium the small footprint catheters stretch the tissue and that's what keeps it stable. But with large footprint catheters things are a little bit different. These catheters are inherently unstable and contact force increases make little tissue compression or stretching as compared to focal tip catheters. And this is important because when you deliver energy using large footprint catheters the dose has to be correct because you can't force the catheter and get the lesion deeper. Remember with these large footprint catheters as you increase force there is some improvement in stability but what really happens is that the catheter compresses a little bit and the coupling increases which is why these lesions will generally be wider maybe not that deeper and in the former you get deeper lesions with less impact on width especially with PF. That said, let's talk about the only large tip focal catheter that can deliver RF lesions. And there's been lots of publications telling us why this increased surface area of this catheter in the low current density is critical to why this catheter is the only way you can deliver large amounts of radio frequency current without running into issues. Moreover, these surface thermocouples that this catheter has allows us to deliver temperature controlled radio frequency. And this irrigated temperature controlled radio frequency and in this in my opinion is really the only way to deliver large amounts of current into the tissue to minimize things like char and steam pop which has always plagued us as we've gotten more aggressive with radio frequency. Some preclinical data and I want you to really focus in on these little red rectangles because this is in vivo data. Yes, vivo data always looks good, difficult to reproduce in clinical practice. But with this particular catheter, you can deliver radio frequency out to 30 and 60 seconds reaching depths as deep as 10 millimeters. And this is far better than the 5 to 7 millimeter in healthy tissue, the 3 to 4 millimeter in scar tissue that we are stuck with in the world of radio frequency with small focal tip catheters. Using that, let's switch to what the large and small focal tip catheters in PF currently, the first generation catheters do in the world of lesion creation. We are stuck between this 5 to 8 millimeter depth and you get to 8 with multiple repeats. And yes, this is better than radio frequency in getting through scar. But 5 to 8 millimeters deep is not going to solve most of our problems. All we can do today is to repeat applications. And it's my conviction that unless we have a second generation of PF generators, we can't cross this threshold which I think will limit our success going forward. Remember for some structures that are mobile and difficult to place, PF is the ideal energy source. It may not be relevant for scar VT, but here you see a papillary muscle, a moderator band and all of its tiny branches, all of them effectively ablated with pulse field. Briefly about idiopathic VA, it gives you some sense of how PF can enter the world of focal arrhythmias. And both these publications by Della Rocca and Ruwald basically tells us that PF seems to perform almost similar to radio frequency with about an 85% success. You get late onset of success just like we see with radio frequency. So I do think PF will play a role even in idiopathic VAs and cases can be done under sedation. Two slides about scar, multiple authors, Dr. Gerstenfeld, Elad Anter, everyone has published that PF goes right through the scar. The conductivity of the scar does not prevent PF from crossing over the scar region. And you can see this yellow dotted line showing you how this lesion goes right through the scar at the same depth as a layer without scar. Look at this PF-induced scar that we created in swine and six weeks later via blade and you see the PF go right through this PF-induced scar. The same lessons, I think you can't see my cursor, but on the left panel you have scar, PF above and below. In the bottom panel you have radio frequency scar, PF going right through. But pay attention to this section on the right upper corner. These three, so the black flashing arrows shows you three surviving bundles labeled PFA, PFA, PFA. Now these have been ablated by PFA. You see PFA, everything dark red is spared by our cardiomyopathy. Everything light pink is recently ablated with PF. And you can see the lesion, you know, destroying the surviving sub-endocardial scar common in ischemic cardiomyopathy going right through the scar and these three bundles have been ablated but the bundle with the asterisk has not been ablated because we haven't applied PF on that portion. And it's important to appreciate that of all the technologies out there, PF is particularly suited to seek out surviving muscle bundles because the interface of healthy tissue and scar is where the electric field concentrates itself. So if there was a substrate specific technology, it's PFA. What about fat? We think of fat as an insulator but preclinical data from the Cleveland Clinic and from our group basically says that if the dose is high enough, clinically relevant amounts of fat may not be as much of a barrier to PF as it is with radiofrequency. And in this modeling study from the Spanish group, Dr. Gonzalez-Suarez shows that fat within the scar in some instances can even amplify the field and cause a bigger and wider lesion. Moving on, one of the big advantages of PF is the fact that it does not destroy connective tissue. So if you wanted to go deep and do bipolar ablation, you can get great depth, 16 and 17 millimeters across, but what's most important is that, yes, you have the speed of PF but you don't worry about steam pops. You don't have to worry about char and coagulum. And more importantly, I think you will never see a ventricular septal rupture with PF because the connective tissue is not destroyed with pulse field applications. Yes, for the free wall, you have to worry about coronary spasm. In the epicardium, you make lesions just like radiofrequency does. I don't think epicardial ablation is a missing need. You just need to know that, yes, the PF lesion will be deeper than the endocardium because blood's not stealing the current away from the tissue. And just remember, for every catheter, you need to know how far you need to be from the coronary arteries to get through. This is data from Dr. Verma talking about RF and PF. So that's a PF lesion acutely. This is an RF lesion acutely. And these are the combinations. And you can see the coagulated center and the hemorrhagic core. And it's a little bit unclear to me which, whether this hemorrhagic zone is all effects of the typical hemorrhagic zone we see with RF and what combination there is with PF. But if you look at the data, the PF and RF or RF and PF combinations definitely were deeper than PF only. But I don't think sequential ablation is the answer. By the time you switch your generator from PF or RF to PF, you lose valuable seconds. And that heated tissue starts to abate. I think the better way to do this is to use high-frequency biphasics, which we know create too much heat, which we want to avoid in the atrium. But if your catheter is irrigated, you can actually create an RF lesion at the same time as you create a PF lesion and get really significant depths. Remember with PF, catheters that can detect temperature on the surface are very useful not only to understand whether you've gotten contact, but you can grade your lesion. These are temperature profiles in PF applications in scarred myocardium. And you can see how the temperature rises here steep. Over here, the rise of temperature is shallow. And over here, you see the temperature go up and get flat. And you know that this was your best lesion, here a reasonable lesion, and here a lesion where there was some catheter movement. Now, these behaviors may change between areas of scar and healthy myocardium. So more work needs to be done. But certainly a metric that we can use to assess quality of lesions during PF, given that all the EGMs disappear so quickly. This is another catheter that will be presented by Vivek Reddy at a late breaking shortly, a monophasic waveform. Each application is only 150 microseconds. So that's one tenth of a second. And you can repeat up to five applications. It's contact force sensor enabled. And you can get lesions as deep as 15 to 16 millimeters. And this is one approach to PF in the small footprint form factor, a form factor that we've all been familiar with that creates rapid deep lesions that can take out epicardial substrate even in the endocardial application. A few words about the European Affair Registry, courtesy of Dr. Fred Sasher. And essentially, this gives you a sense of 126 patient multicenter registry of redo patients. People are using PF only, RF only, and about 50% of the cases, RF and PF. These are sequential applications. You get a sense of how many PF and RF applications are being used. 82% acute success, 11% failure acutely. And these are the risks, risk common to all catheters. Every time you use RF with these powerful tools, you have to worry about embolic events. And two thirds of these were redo procedures. These are the safety issues, efficacy, 68%, which is pretty good at six months for patients with redo procedures. Thank you. Thank you very much for that. And on to the last but not least presentation for this session, Dr. Stevenson will tell us about enhancing RF energy delivery for VT ablation, needle, bipolar, or multimodalities. Dr. Stevenson. Yeah, well, thank you very much. Boy, this is an exciting session. I'm going backwards to RF now. But as you heard from Jacob, RF still has a role, even with the new catheters and technologies, that there may still be a need for RF. Let's see if we can get this guy coming up. Okay. so, you know, as has been alluded to this morning, the issue that we're kind of discussing is that it's very common to have intramural portions of reentry substrates or foci of ventricular arrhythmia that are a common reason for failure of ablation. And one of the things that happens with a thermal injury, with RF injury, is that initially you get some little core area of necrosis surrounded by edema, and then over the subsequent several weeks, that edema gradually resolves. So we've all seen the situation where you had acute success in the lab, and a few days or a few weeks later, the VT is back, and that likely relates to this resolving edema. So what can we do to increase the area of permanent thermal necrosis? And first, let's just talk about what we can do with, right now, with your standard regular old RF catheters that you have available. So the necrosis that occurs is a result of the increase in temperature. Any tissue that gets to above 50 degrees for any period of time is probably irreversibly injured. And what's causing that is resistive heating of the current passing through the tissue. So anything that you can do to increase the current into the tissue has the capability to potentially increase your lesion size. However, you can't just crank the current up in an unlimited way, because if the surface tissue gets to 100 degrees, you'll get steam pop, steam formation and pops that can rupture through the tissue. And if the electrode surface or the surface of the tissue reaches 75 degrees or so, you can get coagulant formation from blood proteins on the tissue, and that can be a source for embolism. So you want to maximize current delivery into the tissue while maintaining those temperature parameters. So to increase current into the tissue, you can just crank the power, as I mentioned, but with the available generators for irrigated catheters in the U.S., our maximum power delivery is 50 watts. So there's some things we can do with that limited maximum. We can increase tissue contact. We can try and reduce the impedance, which will have the effect of increasing the current. And we can try and reduce current loss to the surrounding tissue and the blood pool to have more of the current go into the tissue. Then we can lengthen our RF applications. I'll show you a little bit about that. And then bipolar RF ablation is also an option. So power, watts, is the product of resistance times the square of the current. So if you set your power to 30 watts and the impedance is 106 ohms, you have 360 milliamps of current. If the impedance is increased to, say, 184 ohms, you can see that the current here fell to 190 milliamps. Now most of the patients in your EP lab, our average impedance is probably in the 120 to 140 ohm range. Every now and then you get somebody who's 180 in Tennessee in particular, and sometimes you'll have somebody who's 100, and that makes a pretty big difference to the amount of current that's going into the tissue. You can modulate that by reducing the impedance of your system by adding a second ground pad. And there's also some thought that if you put the ground pad closer to the heart and in the direction where you kind of want the current to flow, that that may also increase the current delivery into the target tissue. So second ground pad, ground pad on the thorax, ground pad on the anterior chest wall if you're targeting LV outflow tract sorts of foci may be helpful in increasing current delivery. Now what happens when you increase current delivery is that you're going to increase the chance that you can get a steam pop or coagulant formation. So one of the things that we're going to come back to in a moment is how do we, if we're going to try and increase current delivery, how are we going to monitor for these issues? Another way that we can increase current delivery into the tissue is by reducing current loss by irrigating with low osmolar irrigants, so half normal saline or some laboratories have even used dextrose in water with no sodium ions. And that also increases current delivery into the tissue. And in this series, again, there was an improvement in outcomes in these patients who had failed standard deblation, but there were 12 steam pops, although those pops weren't associated with complications. Now the other thing we can do is we can prolong the duration of the RF application. So these are, this is from data from Hiroshi Nakagawa's very nice study that shows you in these different curves, oh, you can't see my pointer, I'm pointing away up here on my screen. Sorry about all that pointing that I was doing vigorously that you couldn't see. So this is the temperature at the surface in bright red, 3.5 millimeters below the surface in darker red, and 7 millimeters below the surface of the tissue. And you can see that the time course of heating is slower the further you get below the surface. So here at the surface, right up to 70 degrees relatively quickly, 3.5 millimeters below, it continues to climb, 7 millimeters below, it continues to climb, takes a while to get to 50 degrees and then continues to climb. And we actually don't know what the optimal duration of RF application is for irrigated RF. So the duration size can increase beyond 90 seconds, it can probably increase beyond one and two minutes. So there are a lot of examples now of long duration, three and five minute RF applications for deep foci in, for example, the left ventricular outflow tract that can be helpful. Now how do you monitor this? So intracardiac ultrasound can be very helpful looking for tissue whitening and bubble formation. And if you watch this video, you see these little bubbles here, and at one point they're going to increase pretty dramatically and then you're going to see a pop. And it turns out that most pops you do hear, there's the pop, that big flurry of contrast there, and you see there's this marked tissue whitening, the cavity's filled with bubbles. But almost 20% of steam pops that occur during RF, in our lab anyway, are not audible. And we don't think it's because we have bad hearing at the table. You know, you really don't, it's possible. Something could happen or you could think something fell on the floor or something, but we don't recognize audibly about 20% of pops. But things that are useful are that contrast formation and a sudden increase in spontaneous contrast formation. And the other thing that is useful is watching the impedance fall. So it is very unusual to get a pop with an impedance fall below 8 to 10%, and the chance of a pop goes up quite dramatically when you get impedance falls that are more than 12 to 16%. And this is, of course, because the impedance is proportional to the tissue temperature, and it's a good marker of that. So watching with ultrasound for bubble formation, backing off when you see a marked increase in bubbles or tissue whitening, and then titrating the power to maintain the impedance below an impedance fall of 10 to 12 ohms is a very reasonable thing that probably, we hope, allows the safe application of the greatest power that you can apply safely for a long duration of RF application. Okay. Now you can also apply bipolar standard RF. This was already alluded to, and this certainly makes larger, deeper lesions. And then I want to get to the – and then there's data that bipolar ablation certainly can be effective when unipolar ablation at both sides fails. There's also some examples of septal rupture related to bipolar ablation. So with any of these tools where we're going to make larger lesions, there's the potential for a greater risk of complications. Another interesting approach is a kind of a modification of bipolar ablation where the RF current is applied between the standard irrigated ablation catheter and two or more electrodes on a mapping catheter, two or more small electrodes on a mapping catheter. And the feasibility of this approach was reported in Jackie P. a couple of years ago by Fernandez. And this allows you to potentially apply RF in small venous structures in the epicardium aiming at those from underneath with a standard RF catheter. And then in the final couple of minutes, I'll just show you the needle catheter. So RF ablation can be applied on a needle, and we had a lot of experience with this needle, which is an end hole irrigated needle. And the nice thing about needles is it allows you to do some degree of intramural mapping. You can pace and record on the needle electrode, and that was helpful in some cases in helping guide where to go. You can certainly make, when you irrigate and apply RF, it can make intramural lesions. And we used that catheter in 114 procedures with no procedure related mortality of 3.5 percent incidents of pericardial effusion, freedom from any VT at six months of about 47 percent in a group of redos pretty similar to what you heard from the cryo ablation experience a moment ago from Dr. DePotter. There is a modification of the needle, which is the saline-enhanced RF ablation. It's a project that was led by Doug Packer and Michael Curley of Thermedical. This modification heats the saline in the needle. And so it's heated saline going into the tissue, which is more efficient at transferring electrical energy into the tissue, and it can make very large ablation lesions. And Doug Packer reported the initial experience with this catheter in a pilot study, and it was expanded to 41 patients, and with quite remarkable decreases in VT frequency, again favorable. However, the major concerns were that there were three deaths in this study related to thromboembolic events and cardiogenic shock. That was probably related to large areas of ablation and one dissecting intramural hematoma. And those can occur with standard RF and even with transcoronary alcohol ablation that has been reported. So intramural needles can repeatedly be inserted into the ventricles for mapping and help locate intramural arrhythmias, which has some appeal. They can certainly create large lesions, and with the increase in lesion size, there are going to be increase in risks. And I do worry about this scenario where our mapping technologies need to keep up, because if we have a situation where here's your endocardial breakthrough, but the circuit's really over here, and so you apply RF at the earliest, or a large ablation tool at the earliest site, you have to take out all of that before you really get to the circuit when what you really want is to take out just this little piece. Thank you very much. Thank you for that. These fascinating times that we live in with all those modalities available to treat our patients. With this, we have a couple of minutes for questions. Great. We have some online, but I get to ask mine first because I'm sitting up here. And I appreciate, Dr. Stevenson, you finishing with really where the question should be. Whether you get your information from Voltaire or Spider-Man, the story is with great power comes great responsibility. And we have all discussed important ways to create more damage inside the heart. And that last slide, that last concept was important. So maybe very briefly, if I could ask each of the speakers to tell me, what is their most important concern with the particular type of energy source that you have reported? What keeps you up at night? And how, in particular, how can we mitigate that risk? So Jacob, let me start with you. What do you worry? And Affera is probably the closest for PFA for most of us. So what keeps you up at night about the Affera system in the ventricle, and how do you think we can mitigate that risk? OK. I think it's still important, as everybody knows, that we need to know where to ablate. These systems aren't tools to ablate and see whether it works, because you'll take out a lot of myocardium. I think what we need for Affera and for other PF catheters is two things, titratability, so that you can have small doses and big doses, so you have a whole range to choose from. And for PF in particular, you need to be able to constrain the field and be able to direct PF. And I'm not quite sure what the answer will be. But without those two options, we'll be a little bit indiscriminate using PF in the ventricle. Perfect. Perfect. Dr. Packer, your thoughts about both SURFneedle, which you've worked with, and then with protons in particular. What keeps you up at night, and how do you think we can mitigate that risk? I think that you have to have some experience. You know, with the SURFneedle, it actually works very well. But one of the things that was learned is you don't want to be pushing the needle eight millimeters or 10 millimeters into the tissue. If you've got good contact and you're putting the needle in, then there's kind of a double contact situation. So I think you just have to decrease, in some cases, particularly thin walls, you have to decrease the depth of the needle. Power behaves like power. That's the thing. Now, as far as protons and photons, it's new, it's different, you have to learn about it. And I think that we've come a long way in the last couple of years with that. I think as far as the protons go, it's all about treatment planning. Treatment planning where you don't put in margins. That's what oncologists do, we don't. The treatment planning, you have to have a very good sense as to how much you're going to drop in areas that you want to drop. You know, your V-95s and D-95s, I think that has to be very, very carefully orchestrated. And I think there are similar things, you know, with photons. They behave differently, but I think we're coming to the point where we understand that ultimately the mechanisms are quite similar. I think that there's nothing like a little bit of experience. This is one area where you need to have done it, and you can do that in animal models, you can do that also in other areas. Good. Good. Bill, you brought it up, you left it with the last slide. What do you think we have to be worried about with aggressive RF? Yeah, so I know a lot of people will be doing substrate ablation. Some of these tools that you've heard look like they'd be wonderful for the patient with the great big anterior wall scar, and so you just homogenize that, and maybe you're going to be done. But what's going to happen, I think, in a fair number of people is that you'll homogenize it and then there's still a VT left, and now what do you do? So what you'll probably do is you'll look at the morphology, you'll do some pace mapping, you'll go to that quadrant of the scar, and you'll say, okay, we need to do a bit more here. But now you're in the border area. And if the tool that you use produces a large lesion that extends out beyond the border area, you're starting to take out normal functioning myocardium. And that's kind of my worry. So I wonder if, as we start to have these tools available, it could be that we'll want to do a bit of a staged approach, where first, if you're going to homogenize a big scar find, take out the low voltage stuff where you know it's all there, and then if something's still Maybe you just wait and see if anything recurs before you decide what to do to go back, or take something that's a more targeted approach, because I do worry that we're going to run into some troubles. Yeah, that's an excellent point. And Tom, do you have any thoughts about biggest risks and ways to mitigate? Well, my biggest unmet need, let's say, is what Professor Stevenson just said, and I'm not going to repeat it. He said it, explained it way better than I ever could, but it's technology independent, of course. Specifically for the cryoablation, I don't lose sleep over it. I'm a good sleeper to begin with, but the cryoablation is a very well-known quantity, and we very well know from surgery what we can expect from it. So I'm not concerned with the technology per se. I think the room for improvement, or what can help us do better procedures, is more in terms of developing the catheter, which for all cryo catheters has always been a pain point, is the maneuverability and the steerability of the catheter, which is continuously evolving, and stuff like integration in 3D mapping systems, and things like that. It's more ancillary aspects of the technology. The technology itself, frankly, I don't have major concerns. Great, great. There's a series of questions, and we're pushing our time limit, so I'm going to ask our speakers to give us the shortest answers possible. Here we go. Dr. Stevenson, how do you feel about the use of ablation index to help guide the depth and size of the ablation? Ablation index has been very well validated with RF in the atrium. I'm less convinced about using it in the ventricle, and I just use the fallen impedance in the measures that I showed you. Perfect. Nice short answer. Well done. Doug, give a short answer. Do you want me to give you a short answer? Short answer, Doug, about ICDs and using protons. Are you concerned about any interactions between the protons and the ICDs? If you're driving with protons, no. Where you just start slinging neutrons, that's a big deal. The bigger problem is not that you're going to have an issue with the generator, for example, it's that if you're ablating at the tip and you damage that myocardium, you lose sensing. So it's not neutrons, it's not protons, it's the whole issue of damaging your sensing capability. Good. Good. Last question. Jacob, I've got to call you out on a potential disadvantage of PFA and AFib ablations is the vagal sparing, the nerve sparing component. So there are data that link vagal nerve denervation with RF and better outcomes. And so what are your thoughts about adjusting the autonomics to the heart or sparing the autonomics to the heart using PFA? Yeah. So it seems like it's mostly a concern in the atrium, but if you go to all the late breaking trials for the last two years with PF, I don't think the data bears out that PF is doing a bad job with AF controls. So I'm not convinced taking out ganglia is necessary for most people. Thank you. Thank you to our distinguished panel. Thank you, my co-chair. Thank you all for attending. I hope you enjoyed the last few hours of this meeting.

ventricular tachycardia

VT ablation

energy sources

proton therapy

photon modalities

cryoablation

pulse-field ablation

RF energy delivery

intramural needles

lesion depth