Good afternoon, everybody. Thanks for joining us this afternoon. We've got a great set of talks. My name's Neet Sandhu, and to lead off, we'll have Dr. Santangeli discuss modifying ICD risk with ablation for those with ARVC. All right, thank you very much, and welcome, everyone. First day of HRS. It's been already quite busy for everyone, so it's great to be here. So my task was to answer the question whether VT ablation can obviate or defer the need for ICD in arrhythmogenic cardiomyopathy. Now when we look at the natural history, this comes from the ARVC registry of Johns Hopkins. We do see that, of course, the clinical spectrum of patients with ARVC tends to be slightly heterogeneous. So there are some patients that present mostly with VT, but it's also important subgroup that will never have VT, and will have mostly heart failure. So of course, the ones that do not present with arrhythmias, of course, in those ICDs are really not indicated. The problem is that we don't really know how to identify these patients. So now if you look at the efficacy of antiarrhythmic therapy, again from the North American registry, the conclusions are that beta blockers were not protective, not harmful. So is it really a wash here? Sotalo was not effective, despite the classical teaching that it may be effective from those observational studies. And of course, amiodarone was effective, but it's not very desirable in young patients with ARVC. And there is a recent evidence mostly coming from Dr. Scheinman's group, and there is another study going on from NIH, actually sponsored by Rochester, using flecainide in addition to beta blockers like metoprolol or even sotalo, which is, of course, an antiarrhythmic, to reduce the event rate for VT in patients with ARVC. Now, when we talk about ablation, of course, the old data were a little bit disappointing here. They were endocardial VT ablation from the Johns Hopkins series here in 2007. And again, things have changed, of course, since then. But if you look at this curve here, the conclusion was that the ablation was only at best a palliation or a treatment over last resort. Now, as we moved on to understand better the substrate of ARVC, thanks to the studies mostly from Frank Marchionisky, University of Pennsylvania, and other groups as well, these are actually cases from UPenn. When you see that there is a large evidence of scar here in the epicardium, much more than the endocardium, and if you end up ablating the substrate, endocardial and epicardial, takes a long time. These are long procedures, but you can make the patient non-inducible for VT with a lasting effect in most patients. And these are the data. This was actually old data. In 2015, it had been updated now to more than 100 patients, I believe, or even more than that. But here, the data are quite clear. If you approach patients with an endoepicardial approach, you can achieve very long-term suppression of VT in the large majority of patients. And I think here, an important point that is still the approach that I still use, of course, we go to the epicardium only when it's necessary, not in every one. Because if you look at the second curve here, one might argue that 50% of patients do well just with endocardial ablation. So in 50%, maybe you don't need to go epicardial, but in the remaining, you will need to go to achieve long-term success. So if you have persistent VT inducibility with endocardial ablation only, you go to the epicardium. If you have clinical recurrence, then you take a look at the epicardium as well. Results in terms of drug therapy here, amiodarone was essentially abolished. It was only one patient that was waiting for transplant here. Most patients are only on beta blockers or no endothelial therapy after endoepicardial ablation. This is a graph that we all like to show. It doesn't make a lot of sense to me, just because in order to have a median episode of zero, you need to have 51% success rate. But here, it went from median episode of 13 to zero. This is only a few patients that ended up having less VT. This patient was the one that was on amiodarone that, I don't know if you can see my, oh, I realize you cannot. Sorry about that. Maybe, OK, anyhow, the last patient that you can see here, the one that goes from blue to red, is the one that was on amiodarone right before. Oh, here we go. Sorry about that. Right before the transplant. Now, with this in mind, we try to look at the efficacy of ablation as a standalone therapy in patients that do not want a defibrillator. So for patient preference, essentially, it was a multi-centre international registry between here, the US and Asia, in particular, 32 patients with RVC. All patients presented with monomorphic VT clinically, they were all hemodynamically stable, although in 13%, so it was one or two patients that had history of syncope, not necessarily associated with VT, so it wasn't clear to what extent it was really VT related. Pretty much all of them tried antiretroviral drugs before the ablation procedure. And again, all of these procedures were done with an endopikoidal approach. As you can see, this is patient number one with three VT induced and extensive epikidial substrate that was targeted here. And these are the results here. Median follow up, 46 months with a range of 26 to 65 months. There was no deaths just with ablation here. 81% patients with freedom for recurring VT. Recurrences were still hemodynamically stable, so we could potentially reablate them. There was no syncope of cardiac death. These data have been replicated by other centres. This was all data actually from 2014 from Philippe Maury in Europe, where you can see that 20 patients in this group of ablation patients without ICD were ARVC. And again, none of these patients recurred over time, nor had death or syncope. And this is more recent, from the same group and for Philippe Maury, where you can see that there is a group of patients of, I believe it was 65 ARVC patients were treated with ablation as a standalone therapy with no background in ICD therapy, and pretty much the same result that we've shown in our multi-centre registry. Now, this has also been seen in the registry arm of the PAWS Southern Cardiac Death Trial for Roderick Tang, where you can see the large majority of the registry patients were managed with ablation without ICD, had actually in fact ARVC here. And this was actually managed just with ablation. And if you see at the composite endpoint of VT recurrence hospitalisation on death, registry data, the ARVC, there were zero deaths here. If you look at the supplement, mostly with VT recurrence or hospitalisation because of VT. Now, is ablation really something that can be used in alternative to an ICD? Now, we need to look at progression of disease. This is, again, data from University of Pennsylvania. When you remap patients with VT pre and post with a timing between different maps of 50 months, so a significantly long time follow up here, you can see that the scar size in most patients doesn't evolve, really. So it's not necessarily progressive in terms of the electron atomic scar. And if you also look at bipolar and unipolar scar, only three patients here were really progressive in terms of the of the scar size compared to the remaining like 28 that were remapped, which is really a good outcome. So now the big question is, these are the data. The only data we have, small centres, small numbers from multi-centre registries. There is no randomised control trial. These are my conclusion. First of all, ARVC is not always progressive, arythmogenic disease, and the VT substrate can remain stable for years. We know that from remapping data. Long term outcome seems excellent with ablation approach that targets endopikidal substrate and VT. And there is data suggesting that it's safe to do an endopikidal ablation of VT without background ICD therapy. However, there is only observational evidence. Nothing is randomised and is affected by relatively small sample size and variable follow up duration. So VT ablation with no background ICD at the present time should not be recommended, but can be considered in select cases after shared decision making. Thank you for your attention. Any quick questions for him? All right. You'll stick around. Yeah. OK, great. I have the pleasure of introducing Dr. Frank Marshlinsky from University of Pennsylvania to speak on the topic targeting substrate and catheter ablation of ventricular fibrillation syndromes. Chairman, ladies and gentlemen, I've been charged with talking about targeting substrate and catheter ablation of VF syndromes, and here's what I'd like to cover, VF in structural heart disease, including primarily ischemic cardiomyopathies, but also talk about VF in unique VF syndromes, such as Bregada syndrome, J-wave syndrome, idiopathic VF, and long QT syndrome, and I'm going to emphasize ablation targets, strategy, endpoints, and expected outcome and be quick about it. I want to start by saying the concept is an old one, actually. It was first published by Len Horowitz in 1981, several of the patients, a sub-study in this group of patients he was talking about that had, quote, torsades de poids, or polymorphic VT, but it was followed up years later by Al Buxton and Penn Crew at that time, and we talked about using surgical ablation of the substrate guided by mapping a VT on procainamide, and so this was the typical scenario, patients presented with polymorphic VT, cardiac arrest, had inducible polymorphic VT, had sustained monomorphic ventricular tachycardia on procainamide, which was mapped pre and post, intraoperatively, and the induced ventricular tachycardia was then targeted and ablated and end up with non-inducibility. Now our current approach in patients with VF in the setting of a prior MI is shown on this slide, and of course in the early post-MI period includes targeting of the triggers that are frequently present once the triggers have been eliminated and sinus rhythm restored, actually doing program stimulation, and if there's rapid inducible ventricular tachycardia, targeting the substrate with the goal of ending with non-inducibility of ventricular tachycardia. Here's another example with a variation on the theme where we induced or identified a VF trigger and extensive substrate, and in this patient, after eliminating the trigger and targeting the substrate, tried to induce ventricular tachycardia and then mapped and ablated the induced ventricular tachycardia and end up on the lower right with a pretty extensive ablation of the large septal scar, and that's fairly typical. Here's just a brief comment on the AVATAR study. It was a small study, but it was one of the first attempts to actually map induced ventricular fibrillation. A small number of patients, six, compared to a reference group, but the patients that were mapped, ablated, made non-inducible, had a good outcome. Let's move on and talk about the specific unique VF syndromes like Brugada syndrome, described in a series of patients, first by Nadamani, who identified a substrate on the RV alfalotract epicardium, don't have really a pointer, I guess we're, okay, oh, oh, there it goes, no wonder, I got it, I got it, thank you, so we're good, okay, and identified substrate on the RV alfalotract epicardium, targeted that substrate for ablation, ended up with elimination of inducible VF and inducible ST segment elevation, and the patients had a good outcome. This was further refined by Brugada and, Joseph Brugada and Paponi and colleagues when they used potential duration maps with the administration of ashmaline to identify a fairly sizable epicardial RV alfalotract substrate and then targeted this substrate for a fairly extensive but superficial ablation and defined further the endpoints that should be used including the elimination of the abnormal electrograms with residual dense scar, loss of the Brugada BCG pattern, and the change of VF inducible to non-inducible. This has been associated now with this strategy, been associated with a good long-term outcome by, as evidenced by the BRAVO study, patients, particularly those with elimination of Brugada ST segment elevation, had an excellent outcome during long-term follow-up and it has become more or less the standard of care. Then you have J-wave syndrome, unique syndrome that's occasionally associated with recurrent ventricular fibrillation identified in accompanying these infralateral ECG changes, so-called J-waves, and it's been associated in selected patients with scar that primarily is localized to the epicardium and the inferior RV, and not uncommonly it coexists with Brugada RV alfalotract changes. And the authors, primarily Hasegawa and Naramani, have described a technique that they focused on eliminating the fractionated electrograms, eliminating the J-waves, preventing inducibility, and that has been associated with a long-term outcome after the last ablation procedure of 91% success. And more recently, there have been two nice reports, one on primarily patients with idiopathic VF. This is our, in general, we just target the trigger, as most of them sit in the, associated with the moderator-bander LV Purkinje system, and that's been associated with a very decent single-procedure ablation outcome. But this is a unique report in patients who didn't have triggers, and the investigators described this arborization of Purkinje-like potentials that was rather unique in terms of not following a linear distribution for the potentials, but rather these clusters that were associated with abnormal Purkinje-like potentials, and would target fairly extensively the entire area of arborization with ablation, trying to eliminate the evidence of these abnormal potentials, and documented over a 24-month follow-up, primarily in patients with idiopathic VF, but also applied to some non-ischemic and mixed cardiomyopathy patients, a low recurrence rate. So moving from just trigger ablation to substrate ablation in this subgroup. And then finally, this early report by Dr. Poponi, initial report in Europace, and then a follow-up report in the European Heart Journal Supplement, where he's actually taken patients, primarily those with at least syncope, some of them with VF arrest, a lot of them with genetic, a clear-cut genetic mutations, and identified abnormal electrograms in these patients in the RV outflow tract region, targeting these abnormal electrograms and eliminating them, shortening the QT interval, and then following these patients with good clinical outcome. So more to come and more evidence to support this, but pretty exciting information. So in summary, rather than just targeting the triggers, which are there frequently and need to be targeted, there's the ability to target the substrate. In coronary disease, it's possible to administer some procainamide and transition polymorphic VT to unimorphic VT and target that, and it seems to be successful. More to come with multipolar mapping. And then there's the recurrent unique VF syndromes with very specific ablation targets, typically in the RV outflow tract region for Brugada syndrome, J-wave syndrome, J-wave syndrome in the bottom of the RV, and then Long QT syndrome over the free wall of the RV more extensively, and eliminating that target has been associated with good clinical outcome. And then finally, this arborization of Purkinje-like potentials, particularly in patients with idiopathic VF, but gives us an opportunity to improve outcomes in these patients. Thank you for your attention. Any quick questions for him? Yeah. Go to the mic. You can also send questions via QR code. Sir, I just wanted to know that LQT syndrome, it's applicable to all the three types, or any specific syndrome, plan ablation? Yes. I tried to put the genetic syndrome, so most of it is Long QT1, but all of them were represented in the list of patients that you did. Still relatively small numbers, 11 initially, then extended to 18. About a quarter of them, third of them, had no identifiable genetic abnormalities, but two-thirds did, and it was all the syndromes identified. Any other quick questions? Dr. Markczynski, I might have a question. These can be challenging cases, and there's a balance between cardioversions that are necessary and trigger analysis. Have you approached these with general anesthesia, usually, or with conscious sedation or MAC? Well, typically, it will be general anesthesia, but it really depends on the clinical scenario, so if we know that the patient's PVCs and triggers get suppressed with general anesthesia, we won't do that, and then we'll bring them with conscious sedation and heavily sedated into the laboratory. We won't hesitate to supplement what we're doing with boluses of lidocaine, knowing that it'll wash out if we have to wait a little bit, and if they're very unstable, try to get them stabilized, and usually, you can make that work. Again, we start off every case by making sure we have an assessment of the 12-lead of the trigger and very specific targets in terms of the anatomic region, so if nothing else, we're still left with an anatomic target, even if we have to use general anesthesia, high doses of lidocaine, suppress them, we'll at least give it a go in terms of trying to eliminate all the VF triggers anyway. Dr. Marsalinski, in LVAD patients, I frequently find triggers in the hisperkinesis system in the septum. Yeah. What are your, what's your experience, even in patients with CAD, scar-related VT? Yeah, I think it happens much more than we've previously recognized, and whether it just is a cause for PVCs that then act as the intermittent trigger and they're scattered and they're less predictable, or you can establish some reproducibility, I think as we get better monitoring techniques, more 12-lead monitoring, more jacket monitoring and other multi-lead monitoring, we'll be able to have a starting point that gets us to a region much more reliably established reproducibility of the trigger and find something to regionalize a specific target. We'll focus on the Purkinje system, whether it's to look at this arborization that's occurring, I still think that the triggering mechanism is very important, of course, that if you find an early trigger, you surround it by later triggers, if at all possible, or later sites of activation so that you, because you can get fooled in the Purkinje system, where we had a very nice case where it actually was exiting from the bottom of the posterior fascicle approximately, but after we ablated that exit from that region, didn't completely block the posterior fascicle, just from that region, it exited all the way to the anterior fascicle. So it can run along the road of the Purkinje system and you can get fooled. So, again, it means you ablate a little bit more extensively, and if you can, the key is to stay calm, which is hard, I mean, but stay calm, and if need be, repeated cardioversion, if need be, try to take a break with some lidocaine and a little bit more sedation, then reverse. Obviously, it's frequently a very long case with a lot of challenges in young patients that nerve-racking, but fun. Thank you very much. Next, we'll have Dr. Thala Khanahalli from the Minneapolis VA talk to us about bipolar ablation for refractory ventricular tachycardia. Chairman, ladies and gentlemen, thank you HRS for inviting me to speak on the bipolar ablation to control refractory ventricular arrhythmias. So these are my disclosures. So the next few minutes we'll be talking on the overview of this particular topic which I want to discuss regarding why bipolar ablation is performed for ventricular arrhythmias. Then I would like to emphasize some aspects of the understanding intramural ventricular tachycardias and how is bipolar ablation performed. So why bipolar ablation? As you can see, the substrate can be quite complex. Not only the complexity of the substrate exists but also the question is how deep the substrate is located. When it is located something like that, one of the problems is the energy source really matters whether we can penetrate that deep, you know, with the current available technology. So how do we improve the tissue penetration of ablation lesions? One is to alter the impedance, the impedance modulation by various methods. One of the methods to do is changing the osmolality of the irrigating fluids. Other one is changing the patches. Now if you have a one patch to two patches, positioning of the patches in a different location closer to the area of interest may actually improve the conductance of the current. So despite doing all these things, we have a significant limitation. As you can see in the case sequential unipolar in this particular as opposed to the simultaneous unipolar, you still have a core of tissue where you cannot really reach that area. So the bipolar ablation traditionally has a better way of actually conducting across the tissue. So understanding intramural ventricular tachycardias. So if you thinking in terms of the VTs which is suspected intramural, one of the few things to do as a pre-procedure is to make sure that we have a good imaging technique to start with. So if you can demonstrate MRI or the CT, even the delayed enhancement and the PET scans which gives us some ideas with respect to intramural substrate as whether we need to plan for bipolar ablation. We have been doing quite frequently the VMAPS which actually may give some insight into looking at these VTs ahead of time by doing a NIPS procedure and figuring out if the VTs indeed an intramural location. We've been doing one more concept is the transmural fusion pacing. In the left panel is the VT as you can see and the right panel is actually pacing on either side of the ventricle septum with the catheters too and we have validated using a vision wire in the septal perforator. If the morphology matches, it gives an idea even in the absence of a septal perforator by pacing with this technique which may give some clue as far as where you really want to target these ventricular arrhythmias. This is another concept of doing the transmural fusion entrainment, I would call it. In this case, the LV septal overdrive pacing is done and the RV septal obviously looks more like a manifest and in this case, the stem to activation is quite long, 350 milliseconds. One is still suggestive of involvement of the entry site at 80% cycle length and when you do the transmural fusion pacing, it's dropped to 250 milliseconds stem to activation which drops to about 64% that falls into the isthmus range. So this gives an idea that what we are dealing is an intramural ventricular arrhythmia. We've been doing one more thing which we have a poster in this Autrhythm Society meeting looking at the frequency maps. When you look at the frequency maps among in this area of successful ablation sites when we did the bipolar ablation, we found quite the focus is on the dominant frequencies, the low frequencies. There is a cluster of dominant frequencies seen in this area and this can also be demonstrated by looking at the areas of ILAM and then the 5 to 6 millivolt voltage, unipolar voltage area and the emphasis maps of the low frequencies fall exactly into the same region. So this gives an idea of where to really target the substrates. So if you cannot induce the VTR, it is an unmappable VT. One more technique to do is to do the pace maps. So in this case, in the unipolar pacing on the LV septal site is about 75% range and when you do the transmural fusion pacing here, it jumps to 93% and the V maps showing evidence of septal activation and one more problem is this one is this CT scan is a little bit obviously generic, so because of the specific is currently not available at this time. So in the same patient where we had the best pace map, you can see the low frequency signal which is clustering less than 200 hertz, so just what we are seeing is the dominant frequencies in those regions where the substrate is of importance. So once you have that, then you look at if the activation mapping is possible, you can do the activation. In the top right corner, you can see there are some missing isochrones in this region. The reason why the isochrones are missing is because it involves both sides. So in that case, it is already giving us idea what we are dealing with the VT is involving both sides of the septum. So why bipolar ablation? So because of the bipolar ablation, how we can do is in this is our setup because of the substrate what we have actually dealt with and essentially ablation catheter is on one side and the return of the grounding electrode which is replaced by from the patch is on the other side and it is connected to the EP recording system where you can actually visualize this catheter and the electrogram and once the ablation is turned on, it turns out down to the ground and hence you can actually perform the ablation. So how do we improve the lesion or reduce the risk of a complication is changing the electrode size on the return electrode. That actually does two things. One thing is it dries the current very well and also reduces the temperature as well, the return electrode. Hence the tissue pops are less likely to occur. And one of the key things to look at is the orientation of the electrode. If you cannot, by the 8 millimeter electrode can be parallel to the septum and that may actually minimize the risk of tissue pops as well. So as you can see, the current driven in this case, one of the cases that we did was 664 millivolts, milliamperes and then you actually have this, the impedance drop you can actually clearly see that is happening 20 to 30 ohms. So this is an example of this bipolar VT which you saw earlier and it terminates very quickly once you are in the right location of the target. So ablation parameters, once the substrate is identified is to test the ablation by starting with the lower watts. That's an important thing in my mind. The 15, start with the 15 watts. When the impedance is going in the right direction, that means you are in a good situation. Then you can titrate the watts. You know, typically what we have noticed is 35 to 40 watts is more than sufficient to most of the times to get the transmural burn. With that in mind, we have a multi-center study. We collected the cohort studies among five centers across and we have a total of 55 patients that we have collected and it is to be published shortly. We have quite a long-term data. In this group of patients, the mean power used was only 32 watts to have an efficient lesion. The impedance drop is about 25 ohms and the acute success rate was 94% and very few complications were seen. But the long-term success, this is the four years data, was about 55%. Remember these patients are quite sick patients actually with multiple VTs and intramural is one of them. And so I think this paper will give us some insight into the effect of what we have seen with the bipolar ablation. So in summary, when sequential unipolar ablation fails, the bipolar ablation is useful. And deeper intramural substrate needs to be defined just to make sure that where we are dealing with. And if there is a dense scar, obviously the bipolar ablation will be helpful mainly because of the fact that penetration will be a challenge. And the substrate identification using the unipolar voltage is beneficial to locate this particular area of scar where we can hone into that particular area. Missing isochrones is an indirect clue to tell you that there is some other location which is causing this problem. And lower frequency maps, as we have the dominant frequencies, forms the substrate in the intramural location, which I think will be very useful in identifying, especially with current available technology. Thank you very much for your attention. Thank you. Any questions? So Venkat, have you tried SBRT for deeper substrates? No. We don't have the facility to do that in our center. But I do acknowledge that I think some people have used that one. So far, I didn't get a reason to send a patient at this moment of time. I think there are obviously some group of patients which may be beneficial to use them. So the bipolar side, do you use a non-irrigated 8 millimeter catheter? Well, that's a good question. The return electrode can be used. Irrigated also penetrates lowest temperature, one reason. Non-irrigated, if it is 8 millimeter, is probably beneficial mainly because of the fact that temperature goes down. That's one good news. The other reason is also the tissue lesion will be bigger. And in that way, I think one thing is for sure, we should never use a non-irrigated on the LV side. You can clearly see sometimes child formation in this case situation. Any other quick questions? All right. Thank you very much. Thank you. Let's check up here. There you go. I would like to introduce now Jacob Karruth to give a talk on Pulse Field Ablation for Refractory Ventricular Arrhythmia Ablation. Thank you for the introduction. Thank you to HRS for having me here today. And these seconds are so painful. Okay. There you go. All right. So my task is to talk about Pulse Field Ablation for Refractory Ventricular Arrhythmias. These are my disclosures and a special acknowledgement to Drs. Bhattana B. Srinohar and you who are responsible for many of the pictures that I'm going to be showing you. Challenges for VT ablation. You just saw many talks on VT ablation. And coming from the perspective of technologies that make big lesions, knowing where to ablate may be as or even more important than a powerful ablation tool. Nonetheless, the lack of a safe but powerful tool has limited catheter ablation for VTs for a long time. We've already heard about radio frequency. We are currently limited by the 3.5 millimeter tip. We can give long lesions. We can do all sorts of things that you just saw to enhance our lesions. The advantage of radio frequency is seeing slowing before termination that has prognostic value. But if you look across the publications, there are limitations of radio frequency. Most of the papers get you to depths of five to six to maybe eight millimeters, despite using other techniques other than bipolar ablation, which is the only way to get really deep. The lesions are often of limited width. You sometimes get surface pairing. You need really high quality contact and force to get really good lesions. And then you have to worry about the limited efficacy in scar. Oftentimes the lesions go only three to four millimeters deep, and then a host of safety issues that have plagued us for almost a decade. Steam pops, char formation, et cetera. The current generation of PFA catheters that have been tested in the ventricles are limited by two things. Both small tip catheters and large focal catheters that have been published on is that with PFA, although you can get deeper in scar, you're not limited to the three to four millimeters, you can get six to seven millimeters. All the technologies have depths that vary between five to eight millimeters, and this is after repeated applications going up to four to five applications. And this may not be the final answer for our difficult VT cases. So what are our options? I want to first talk about something that is more opinion and maybe not so data driven, but I think is really relevant in the world of PFA. Remember the 3.5 millimeter tip catheter in most situations is inherently unstable, which is why contact force is so important. And as you build the contact force, these catheters will either compress tissue when it's thick or stretch tissue when it's thin, like in the ventricle or the atrium. But as the force increases, you get improved stability, you get some improvement in coupling. But with PFA, what you really make a difference in, although a little bit controversial, is you get more depth. You don't really impact the width with the classic small footprint catheters. When you talk about large footprint catheters, things are a little bit different. And I'm talking about this because you'll see both these catheter forms enter the world of VT ablation. These large footprint catheters are often compressible and are inherently stable. When the contact force increases, you get some tissue compression and tenting, but not as much with small focal catheters. The cage itself compresses a little bit, and what that does is to increase the coupling, which leads to more width, but the depth doesn't go up by that much. And in my opinion, force cannot be the solution to make deeper lesions. We just need better generators that make bigger electric fields to get deep lesions. We all know that if PF is repeated, you get some improvement in depth. After repeating it four or five times, the yield is pretty low, and this is consistent across most waveforms. We also need to remember that every time you deliver PF, and if there's live tissue somewhere close by, you will activate the myocardium. So in ventricular cases, it's important to appreciate that occasionally, if you mistime it onto a PVC or a T wave, you will get ventricular fibrillation. This rapid pacing that you can only see on ice because the EGMs are lost during a PF pulse sometimes helps with stability. So it's not always bad. Intracavitary mobile structures, PF is really the ideal technology as long as sedation and general anesthesia doesn't mess up PVCs. In this publication, using a lattice-tip catheter, we show really effective lesions, both in the papillary muscle and even structures such as the moderator band, and you can see all these little branches that are oftentimes so difficult to ablate with radiofrequency or cryocatheters, and PF, because the field needs to involve the tissue and your lesions just last for a few seconds, you're much more likely to get an effective lesion with pulse field ablation. In the world of VT, the way I look at it, we have small and large-tip RF catheters, and then the lattice-tip is the large RF-tip catheter. We will have small-tip and large-tip PFA catheters, and then there's this big discussion about, is RF with PF in either order going to be better than PF alone? Some thoughts. Lessons to be learned, PF and scar, multiple investigators have shown that PF goes right through scars. Scar is conductive for the electric field, unlike temperature, and you can see this lesion going right through this porcine infarct, and here you can see where the scar and normal tissue is side-by-side, the lesion looks pretty symmetric. If the scar is made by prior pulse field, you see the lesion go right through. These are examples of histology specimens, and I'm showing you this because I want you to be convinced that PF is the answer for scar tissue. Here's example of a PF lesion outlined in yellow going through RF scar, but this is what I want you to pay attention to. I don't know whether you can see my cursor. Oh, I guess you can't. In the right upper region, you see these black arrows shining? That's basically showing you these spared muscle bundles right in the thickness of the scar being ablated by PF. So everything bright is spared myocardium, and everything light pink is ablated. So you get the endocardium above the scar, some endocardium past the scar, and you see these three bundles marked with PFA, PFA, PFA. These are ablated bundles, and to the left of that, you see where the yellow asterisk is, is spared muscle bundles because we haven't applied PF in that region. And I think this is convincing evidence that whenever we are dealing with scar, PF is going to be the better option. What about fat? On the left upper corner, you can see an application right on top of the LAD. Yes, we cause some fibrosis and internal hyperplasia. I'm not saying it's benign, but you can get through fat, which is oftentimes very difficult with pulse fields. Now, what if the fat is in the thickness of the scar? We only have modeling data from Dr. Gonzalez's group in Spain, and what they basically show is that it's not all bad news. Sometimes the fat interface allows for the electric field to be concentrated, and sometimes, at least theoretically, can lead to even a deeper or bigger lesion. What about bipolar ablation? Just like with radiofrequency, you can do this with pulse field, but the beauty about pulse field bipolar ablation is you need a few applications. Prolonged contact over many seconds is not needed. You never have to worry about steam pops or char or coagulum if the catheter is designed right. And there have been some cases of septal rupture with RF bipolar ablation, and this is unlikely to happen with pulse field because there's no destruction of the connective tissue. When you're in the free wall doing LV endo to epi, you need to worry about coronary spasm, but this is just an example of a bipolar lesion across the interventricular septum. What about epicardial ablation? If it can ablate endocardially, it surely will ablate in the epicardium, and because there is no blood stealing the electric field, for the same dose, you get a deeper lesion. You just need to know for whichever catheter you're using how far away you need to be from a coronary to safely deliver, and if you're close, you need to give nitroglycerin if you choose to ablate with PF in the epicardium. What about combining RF and PF? There are two ways to do it. Use it sequentially or actually deliver a PF dose that heats up tissue, something that we don't want in the atrium, but when you're using irrigated catheter in the ventricle, why not let PF heat tissue? And you can see in this particular example, you get a PF lesion. The whitish area is PF ablation, and the darker area that's white on top is the RF portion of the lesion, and the RF portion of the lesion, by making the impedance drop, likely allows for the PF to be driven deeper. If the catheter can look at temperature from the surface, like the lattice-tip catheter, you can look at the temperature format of a PF lesion, which is one way to understand whether PF energy is being driven into tissue. So these are three examples of scar VT cases treated with PF, and you can see in this case, the temperature rises like this. In this case, it rises, drops, and rises again, and in this case, it rises much more steeper, and I know that this is going to be my best PF lesion, this my worst, and this is somewhere in between. So there is a way to track these lesions. Idiopathic ventricular arrhythmias, just remember the overall experience has been fairly similar to radiofrequency, the same success rates, 85, 75%. You see repetitive firing, you see late terminations, some cases, the data, the PVCs come back, but more work needs to be done, particularly when you're close to coronary arteries, and we need to really decide whether RF or PF is the best choice in some of our younger patients. This is data kindly shared by Fred Sasher from the Bordeaux Group that basically presented at IRA, the European Affair Registry, and I'm sharing this data because I want you to get a sense of where we are in the world of VT ablation and PF. These examples of PF applications for VT, 37% of the time, 17% RF, and 45% both, mean number of applications with PF and RF, so clearly in Europe, they're using both approaches for VT termination with this particular catheter that can do both. Some complications, I think one thing that we need to worry about with large RF catheters is strokes, and remember, these patients had a 70% absence of recurrence at six months, which I think is pretty good for a population of redo procedures. I'm gonna end with what I really think is maybe the future of how we will tackle VT ablation. This is a catheter that delivers a monophasic waveform. We're going backwards in a sense, but this is because this is the most effective way to electroporate tissue. This catheter is a deflectible, force-enabled, sensor-enabled catheter that uses blended micro nanosecond deliveries, and more data will be shared by Vivek Reddy at the late-breaking trial on Sunday, but, oh, let me just go back. You saw those lesions. I wanted to show you those big lesions, but they were about 15 millimeters deep, and this is work from a case in Prague where we are treating a patient with epicardial late potentials, and you can see them right over here in the epicardium. We then look at the endocardium, and as you can see, as we tilt above, you get a sense of the inferior scar. This is an inferior wall MI, and what we are doing is to ablate in the inferior wall in the hope that we target the epicardium, and I'm gonna show you the last post-ablation map, so we're giving discrete lesions, and you see all these late potentials are completely gone, and you have the decapolar catheter in the same location where you had these really interesting signals, and while you can argue that I may have just destroyed a channel, we have seen this across multiple patients, and we really think that this has significant promise because we are truly utilizing the right energy source for scarred myocardium. Thank you. Thank you, Jacob. Will all the speakers come up here so we can have questions from the audience? I have a conflicting session. Okay. I have a question. What catheter do you use? What catheter do you want to be, and what catheter are you using now? Thank you. Okay. Jacob had to go, but please. Any questions from the audience? There are a bunch of questions here in the chat. I lost those questions, but one of the questions was, there's a patient with ARVD and the patient does not want ICD. Is it okay to just ablate? That was one question. Yeah, it is okay. Based on the data that we have, the question is, if the patient doesn't want it, there is nothing for us to do, right? So we cannot really force him into, we can just say that it's not the best idea because it is still 30% recurrence, 20 to 30, depending on different series, even after endo-epi. We can predict the one that recur very, very easily. So but then yes, if they don't want it, they don't want it. Another one is epsilon waves and risk of sudden death and ventricular arrhythmia, question mark. Can I just make a comment? Obviously I think all of us would like to eliminate the VT and certainly get it to the point where the risk of having recurrent monomorphic VT was so low, you can use a non-intravascular device. And I think that that should be the goal currently. That makes sense. And especially in that RV, that gets a low flow. So if you're adding leads into the ventricle, more likely to get thrombosis, more vulnerable if you alter any part of that tricuspid valve that you'll accelerate the RV failure. And so that it makes sense to be able to do that as a goal and see if that helps patients in terms of prevention of heart failure and need for transplant. Here's a guy with some experience. What do you say? I just wanted to make a point on not having a device in ARVC. I think we were talking about not the same of a pediatric ARVC, somebody who presents at the age of 17 with rapid VT, their profile is different compared to somebody who's 40 years old and comes in with sustained monomorphic. I just want to make the distinction. I don't want people to go home and say ARVC can be managed without, it has to be taken on a patient-by-patient basis. I think the risk of sudden death is pretty high in the early, you know, second decade and third decade of life. It's totally different from the usual patient who presents with monomorphic. I just wanted to make that distinction. Yeah. Yeah. Totally agree. I'm not recommending. Actually, even in the older one, it depends. When you say 40, it's still relatively young, I would think. But I would still recommend ICD. Yeah. But what I'm trying to say, ICD is always recommended for secondary prevention. But just some patients don't want it. And then we can manage VT with, ablation is better than medications in that sense, especially endopic ideal ablation. But of course, background ICD should be the standard. Yeah. I don't think we should recommend it at all. So we're not standing up and recommending no ICD. ICD for everybody. That's exactly what I'm trying to say. They seem to behave as two different animals. The one early pediatric ARVC seems to behave very differently compared to the adult ARVC, which is scar-based re-entry and whatnot. A lot of triggered VTs and earlier automatic VTs, which are pretty rapid, degenerative VF. I think the second point also wants to make that ARVC, again, not being a progressive disease, is all the literature is from older ARVC patients that we actually do. There's not much of a data on ablation in patients with 15 to 21 years of age. And if you actually do repeat ablations on them, there's a lot of progression between that 15 and 21. Once they go there, they reach a plateau. And you can follow them for years and years and years together, don't seem to change, either because they have inherently changed their behavior or we've asked them not to indulge in physical activity or whatever it is. But the rate of progression seems different. I don't know what Dr. Marshalsky's view is on that. I think the following is true, is that it doesn't progress uniformly. Yes. That's an absolute. And then when you look at the data, it is, with long-term follow-up, my sense is that between 25% to 35% will have some element of progression. And that's what you actually see with echo imaging, MR imaging, when you look at segmental wall motion. There's a lot of consistency with other data other than what we found with electroanatomic mapping. So, I think that's true. And the issue is some have just minor degrees of changes, which I think are due to wall stress and mechanics. Other will have more dramatic changes if they have a new inflammatory process that actively involves a lot of the new areas of the right ventricle. And they're the ones that will present with recurrent ventricular arrhythmias. So, I don't think we're, you know, I think the good news is that the progression is not uniform and not rapid, certainly. And that it's an unusual patient that actually progresses with large amounts of new scar. And that's consistent, even if you use imaging techniques. So, I think that's where we are. Plenty of exceptions to being absolute about any rules. Perfect. Yes. Thank you. I have a couple of questions for Dr. Venkat, sir. So, in a patient bicuspid aortic wall, I've seen a couple of cases with intramural VPCs. So, if we're able to go through the coronary sinus and one through the cusp, we can do bipolar ablation. In some cases, we are not able to negotiate the CS catheter up to the end. So, is there any other thing? The second thing, the second question is, a patient with post-childhood replacement having VPCs coming near the wall. So, how do you approach it? Good question. I mean, the one thing is, one thing is we're always limited is the anatomical proximity. And if you can, I'm making sure that, you know, defining the coronary venous anatomy, if not possible. Sometimes veins are very positive. There's positive veins. You may have to use the arterial approach in order to really map or probably target those. Bipolar ablation, you know, I think it's just like anything else. You know, if you have the proximity, there is, I think, a couple of papers. Wendy actually published, Dr. Wendy Zou just recently, looking at the, one thing is the far-field potentials in those areas. You know, the earlier, I think, Frank Bogan said, well, if you're in the proximity in that area, potentially you can target them. It's not the earliest activation. But, in essence, you know, retrospectively looking at it, it looks like the far-field potentials make a difference. If you can identify them, then maybe the target may be different. What you actually suspected as a coronary cusp, as a lesion is one side, and the LV on the other side may not be the case. Maybe you have to go in the area where you need to specifically target the far-field potentials in those aspects. Arteries are another location. I've repeatedly done mapping in the septal perforators. Obviously, we are limited. And pace mapping, as I mentioned, may give some ideas, if you can see, can reproducibly see that kind of a thing. That may give some idea where maybe, even if the activation may be late, you can potentially target the bipolar in that region. For prosthetic aortic valve, means biometallic aortic valve, and BPC is coming near that valve? Yeah. You know, we had another case very similar to that. The transeptal approach, you know, going through the transeptal approach and targeting that area, you can actually curve around that, come back to that location is one way to do. Sometimes you may end up doing alcohol ablation, depending upon where you are in that region. Yeah. There's a question here. I think it's meant for Dr. Marchalinski. For patients that have ischemic cardiomyopathy and ICD recording suggestive of VF without identifiable triggers, how do you approach those folks in the lab? Well, I mean, one, it's, first of all, a relatively speaking unusual case, but I think that what we used to do as a standard was if we could induce polymorphic ventricular arrhythmias, actually administer procainamide, and even some patients without inducible arrhythmias, when we gave them procainamide, we got monomorphic VT, and there was a scar, a substrate. We targeted the monomorphic ventricular tachycardia with activation and entrainment mapping, and patients had a good time, a good outcome. I'm not sure if they had a good time. And so that's the typical standard. I think that if you say they didn't have a trigger, you'd have to say, well, I got a recording of it, and it started off as a late coupled monomorphic ventricular arrhythmia that then became quickly polymorphic tachycardia in VF, and that's the kind of patient that I think that you sort of know that there's some element of circuitry that's focusing on an anatomic area. And I think you can also do that with non ischemics in the basal septal area, so that they start off, if you look at the VTs that you induce that are polymorphic with non ischemics, they almost always start off at the base, basal septum, where they have their scar, and then it quickly degenerates. And some of them do very well when we targeted the basal septal region very aggressively. So I think that that is an option. But as I said, I think our standard is, especially since we deal with a lot of referrals of patients who are very unstable with VF storm, those patients almost always will have a trigger, and then we still try to target at least anything we can still induce if it's monomorphic ventricular tachycardia, and not uncommonly extend lesions to include most of the abnormal, dramatically abnormal substrate in the region. So there's a question on brugada. There's a patient who had a brugada ablation seven years ago and has not received any shocks. Device is due for replacement. Should we go ahead with a replacement or extract the device? Yeah. It's like the ARVC patient. I think that until we have very, very long-term follow-up that most patients, we just replace their device, and we learn from that monitoring that they provide. Dr. Marcenski, in patients undergoing VF ablation that you cannot induce PBC, when do you indicate modulation of the VT or VF substrate versus de-arbolization of the hispokinesia? Well, I'm going to ask Dr. Santangeli to answer the latter part since he's been focused more on it. I had a very nice young patient who had that. He was an interesting kid. He was a kickboxer, and he ended up getting post-matches, got an infarct. Then he developed this incredible arborization of his Purkinje system. I've never seen it, much like the one that's in the paper that they reported. We targeted that area because I was inducing repeated polymorphic ventricular arrhythmias, and it's in the area of his scars, so it wasn't all associated, but very specifically targeted and eliminated that dense area of Purkinje abnormality or what appeared to be a Purkinje abnormality. I just saw him in follow-up, and he's still physically active, bungee jumping and doing all kinds of crazy things and getting VF all the time until we did that ablation, and then he's not had anything. I think if you're lucky enough to see it, we do need to characterize what's normal because I do think that there are some patients that may arborize, and how much arborization is abnormal? Are there clues? Does it need to be within this area of at least a voltage abnormality or at the edge of it? I think all of that's open to study and needs to be explored, but there's some method in madness. We have to figure it out. All right. Any other comments? Yeah, I was going to add about the VF aspect. I think it's much more sorted out for ischemic that tend to be at the border zone of the septal scar. It can be infero-septal for RCA infarcts or antero-septal for anterior MI. For non-ischemic, it's fascinating. It seems to be this patient tend to be wired differently than the normal, at least that sense. They have much more Purkinje potentials in the distal septum area, but we need to have more normal data for that. In fact, I wanted to map 100 F patients, but then PFA came about, and we don't map anymore. We've never done that study because I think it would be really interesting to see the density, let's say per square centimeter or something like that, of the septum density of Purkinje potentials in patients with VF compared to the one, the normal patients. I think we may find a difference there, but again, we need to get the normal ones. We don't map normals anymore. I guess PVCs, we can do them, but it's still, I guess, ventricular arrhythmia skewed, I would say, biased in some ways. Yeah, and what we don't understand is the depth of the Purkinje involvement into the subendocardium and even midmyocardium that's been reported, and that Intramural junction. Intramural, yeah. Yes, exactly. You know, we had data earlier looking at the infarct-related ventricles. It looks like some of the VTs which exit towards the infarct-related artery seem to have hemodynamic instability as opposed to away from that area. I always wondered that, you know, one of the questions. There's some data looking at when nerve sprouting angiogenesis happens, whether or not it has anything to do with what you were talking about, the potentials you are seeing. Are they truly the nerve sprouting issues causing the… Yeah, is Purkinje looking at… It's like a mimics of those… Yeah, I mean, the way… Yeah. The reason why we call it Purkinje, there tend to be high-frequency discrete potentials pre-QRS. They may not be Purkinje, maybe something else, but we don't really know. Dr. Josephson, Dr. Anselemi would know this. He would be very upset if we called it even close to Purkinje. How does he call it? No, no. He said, well, you don't know what you're talking about. Okay. That's fine. It's accurate. They're pre-QRS or whatever that is, so… No, no. I don't disagree with you, but I refuse. Adamant. I think we're just about out of time. I'd like to thank all the speakers for their presentations, time, expertise. Thank you all for joining us this afternoon.

ventricular arrhythmias

refractory cases

VT ablation

ICDs

ARVC

bipolar ablation

pulse field ablation

Brugada syndrome

mapping techniques

individualized therapy