Welcome, dear colleagues. Today, Heart Rhythm Society, the BEAT, is proud to host our first live webinar on pulse field ablation. This is a free CME event. The disclosures for all the faculty have been shared in the previous slides. And I am Kamala Tamarisa, clinical cardiac electrophysiologist from Texas Cardiac Arrhythmia in Dallas, Texas, United States. And I'm the co-chair of this program. The goal of the webinar today is to provide you with the background, animal and human studies and practical application of this novel technique that uses electrical pulses to ablate myocardial tissue. We have two esteemed speakers today, followed by an excellent group of panelists. And our two esteemed speakers are Dr. Andrea Natale and Dr. Amin Alamad. Dr. Natale was born and raised in Italy and completed his training in cardiology there. After completing training at the University of Wisconsin and Canada, he joined Duke University's faculty and was the director of EP and section head. He then became the medical director at the Cleveland Clinic's Center for Atrial Fibrillation and was named to the task force for atrial fibrillation at the FDA. Dr. Natale is the recipient of numerous awards and a highly regarded expert in the field of EP. Dr. Natale integrates innovative technologies that advance our field. His attention to detail, patient-centric focus, and use of specialized devices and ablation catheters support advantageous outcomes for our patients. Dr. Natale is currently the executive medical director of Texas Cardiac Arrhythmia Institute in Austin, Texas, United States. In addition, he's an internationally acclaimed academician, clinician, and a passionate researcher at the Institute. Thank you for joining us, Dr. Natale. And our second speaker is Dr. Amin Alamad. Dr. Alamad completed his undergraduate studies in bioengineering at Syracuse University in New York and went on to complete training towards his EP fellowship at Pubbs University's School of Medicine in Boston. He joined the faculty at the Stanford University School of Medicine for an additional 10 years before he joined Texas Cardiac Arrhythmia. Dr. Alamad was the recipient of several excellence awards in teaching. In addition, he's an avid researcher, author, and co-editor of several books in the field of EP. He's an international speaker. He currently serves on several editorial boards, including Heart Rhythm Journal and the Journal of Interventional Cardiac EP, and also social media editor for the Journal of Circulation Arrhythmia and EP. In addition to private practice with Texas Cardiac Arrhythmia, Dr. Alamad continues to be actively involved in a large number of research grants and trials with a special interest in development of new technologies. I know that was a mouthful, a lot of introduction, but these are the esteemed speakers. I couldn't shorten those intros. With that, I am honored to invite my co-chair, Dr. Sanders, to take the platform, and he's joining us from Australia. Thank you, Tamarisa, Dr. Tamarisa. I want to add my welcome to this first live webinar from HRS, and it's an esteemed group of speakers. It's my pleasure to introduce to you the panelists that we have for this session. We have three panelists who are going to help us with the discussion. We first have Dr. Melanie Gunawodner, who is from St. George Hospital in Hamburg and has recently had a tremendous amount of work that she's published in the area of pulse field ablation, and so we're looking forward to hearing on her experience and her input into the discussion. Similarly, Dr. Boris Schmidt, a good friend who's from Frankfurt, again, recently has a large experience in the clinical utility of PFA, and we're looking forward to hearing his experience. And finally, Dr. Javier Sanchez, who's from the Texas Cardiac Arrhythmia Group, and again, with a large exposure to the PFA technology, and we look forward to the discussion that we can stimulate from the speakers today. With that, I'd like to introduce Michael Lloyd, who's the co-chair of the Digital Education Committee at HRS, and Mike, I'd like you to introduce the social media team. Thank you. Thank you, Prash. Welcome, and I'm excited to be a part of this first-in-its-kind event. I'd like to thank and welcome our social media influencers, Dr. Mihak Dande, Dr. Clint Thurber, and Dr. Murdad Emami for keeping us current and relevant. And with that, I'll hand it over. Thank you, Michael. So just a request to the audience, please use the chat box for Q&A, and with that, we'll hand over the platform to Dr. Amin Allamad, who will give us an overview on electroporation animals to humans. Okay, thank you so much, Prash and Kamala, for the great introduction and for allowing me to share with you and participate in this. I think this is really an area that's very exciting. First and foremost, I want to acknowledge a few people who've been kind enough to share some of their slides and some of their insights, both Jacob and Kamala. So the concept of electroporation is not a new one. In fact, many years ago, when ablation was first starting, when we were doing DC ablation, this was a little before my time, in the mid 80s, applying high energy to try to ablate tissue, there was some electroporation that was ongoing with those types of ablations. But there was also barotrauma going, and this really did not take off very much. There was issues related to flash arcing, which, of course, is not ideal for anything that we're doing in the heart. But that concept of being able to destroy tissue in that way has existed. It's not a new concept, necessarily. Now, so what is electroporation? Well, essentially, it's delivering these ultra short, fairly high voltage electrical impulses to the tissue. And in doing that, it changes the electrical field across the cell membrane and creates these nanoscale pores. Essentially, it porates or opens up the tissue. Now, you can have it either permanent electroporation, which results in cell death, or reversible electroporation, which has utility, for example, to create permeability of the membrane, which allows you to insert things into the tissue, for example, gene therapy or so forth. This is an example for up here. You can see this is a catheter that may deliver electroporation. And you can see here you're delivering a pulse train, and that pulse train is what essentially changes the electric field. In this bottom video that you're seeing here, you can see that as you deliver a pulse train, it porates the cell. So if you have a fluorescent dye, that fluorescent dye can now enter the cell rapidly. So this is all occurring in a matter of just a few seconds. But like everything else, when you have this kind of technology, we need to understand it a little better and understand how it works. And so this diagram is a little bit helpful in that you can see there's an electric field that you can generate based on the voltage that you're giving as well as the pulse width. And there's some other determinants that I'll go through in some detail with you. But as you do that, as you modulate how high of a field you create, you can go from reversible electroporation, which again, the application is to allow something to enter the cells and then have it be reversible so those cells don't die, to irreversible electroporation at a higher amount of energy, to thermal ablation, which is what we're trying to avoid because of the problems with thermal ablation. The good news with this in a lot of ways is that there's tissue selectivity. And so, for example, you can look here and see in this graph how different it is between the myocardium and the nerve. So to electroporate a nerve cell requires a substantially higher electrical field than the myocardium. And that's really important because what that tells you is that you can be fairly tissue specific with this kind of technology. The other important thing about this is that if it's killing myocardial cells or ablating myocardial cells, you may still be able to keep the tissue scaffolding in place. And that may end up being fairly important as well. You can keep the structural integrity. That's very different than thermal burns. It's worth talking about this for a little bit. And so up in this upper corner, you can see the difference of different types of catheters. There's monopolar ablation, which would mean ablation from one of these poles to a surface patch that's considered monopolar or unipolar. Bipolar ablation would be ablating from one pole to the other. And so you can deliver electroporation, either monopolar or bipolar. Now, the other thing you can do is deliver these pulses that you see. They can also be monophasic, meaning they're all either above the line or below the line, either a positive voltage or a negative voltage. Or they can be biphasic, as you see here in the diagram, where some of these pulses are positive and some of these pulses are negative. You can vary the amplitude of the pulse. You can vary from hundreds to thousands of volts. And so you can see here in this lower diagram, there's the A, B, C. The A is the amplitude of the pulse. The pulse width is the B. The time between the two pulses is C. So all of this can be modulated. And if you get into even more detail, you can see that the actual pulse, the rise time, the amount of ringing, the type of decay that occurs, all of this can be changed. So you can modulate all this. And what I'm really trying to tell you with this is that there's so many different iterations of this. In other words, you can have a device that delivers a certain type of pulses and a different device that delivers a different type of pulses. Whether the number of devices in a train is different, the number of pulses in a train is different, the voltage may be different, the pulse width may be different. All of these things are things that can be modulated and changed. Therefore, all of these devices are essentially very different devices from the perspective of the basic engineering of the device. Now, they're all supposed to do the same thing, but they can be very different. It's also worth mentioning that the device is really tailored to the delivery system. So your delivery system is tested with that pulse train. You can't necessarily add a new pulse train to a different delivery system without testing it. These are just some of the things that may be modulated. And of course, as I mentioned, the different types of devices will have different recipes, if you will, for their particular electroporation. And now, when we perform electroporation, we're essentially performing what we now call pulse field ablation or pulse field electroporation. In other words, you're giving some pulses, and that creates an electric field, and that creates the electroporation. These are some of the different catheters that are out there at the current time. These are either in development or have undergone clinical studies. And I think Dr. Natale will mention some of these and potentially talk about some of the results related to them. I'm really going to focus a little bit more on some of the animal work and some of the safety aspects of these more than that. Here's an example of this device. This, I believe, is the Boston Scientific device. You can see here in the panel, the pulmonary vein potential. And with delivery of these pulses, the pulmonary vein potential goes away. Now, it's probably one of the most important messages with electroporation is that the electrical effect is greater than the cellular effect, meaning that you may see diminution or elimination of the electrogram before you actually reach cell death. And that can fool us a little bit, because when the electrogram is gone, it doesn't mean that you're done, in other words. Now, it's been tested pretty extensively for safety. This is a really elegant experiment that was done by Jacob Kruth and the group at Mount Sinai, where they essentially tried for a worst-case scenario. They actually took a esophageal deviation device, pushed the esophagus up against the inferior vena cava in animals, delivered radiofrequency, and delivered biphasic PFA. And they were aggressive with this in order to try to see as much damage as they could. And in the animals, all four of the animals that they tested in this particular study developed mucosal problems, whereas zero of the animals studied with electroporation developed that. That's very encouraging from the perspective of it's possible that the field doesn't go that far or that the tissue type is different enough that it's not selective to esophageal tissue type. This is another example of what you will see with electroporation. You'll see that the vessels are well-preserved. There's no significant damage to the vessels. You'll see that the nerves also, particular areas that we worry about, like the phrenic nerve, are damaged. And you can see that the lesion demarcation is really quite beautiful. It's really nice and clean. If you try to get pulmonary vein stenosis with the device, you can test this versus RF with PFA, essentially zero pulmonary vein stenosis being shown. This is a summary slide of the Medtronic device, all of the different types of testing they've done. Just looking here at the pulmonary vein stenosis, you can see if you deliver irrigated RF in an animal model, you can clearly get pulmonary vein stenosis with fairly aggressive pulse field ablation. You don't see that. You will not see thermal effects. You will not see any other significant effects. So it appears to be fairly safe. If you look at how well the lesions look, they're fairly well demarcated, and you can see here really nice fibrous tissue that develops when you look at this histologically with the arterioles looking fantastic. Here's another example. This is in an animal, right atrial appendage. You can see how clearly demarcated the lesion is, and you're able to deliver some pretty big lesions with this. An example of radiofrequency versus PFA and the kinds of things we've seen for years with radiofrequency where you can see within the lesion areas of hemorrhage and thrombosis, whereas with PFA, it's fairly homogeneous fibrosis and the blood vessels remain patent. Here you can see that the arteriole becomes remodeled, the wall becomes thickened, whereas here really looks completely normal. And then lastly, you can get lipogranulomatous inflammation with RF where you would not see that with PFA. Pulse field ablation directed essentially right on top of the nerve really does not seem to affect the nerve again, primarily because the threshold for damage for the nerve is substantially higher than the threshold for damage for the heart. There's a couple other new catheters that are in development. This particular catheter can deliver both RF and PFA. And so you can modulate what you want to do, which is interesting because, for example, if you want to deliver radiofrequency in certain parts of the heart, you can. And if you want to deliver PFA in other parts of the heart, for example, the posterior wall, you can do that. And again, the types of lesions you're seeing here are pretty impressive. You can see with RF, the typical kinds of things you'll see the necrosis, the hemorrhage, whereas with PFA, really nice, clean fibrosis. This is just a video of that particular catheter and how you can within really a matter of just a second or so deliver this pulse and then move the catheter on. A lattice ablation catheter, a larger ablation catheter is also in development. This one can be placed within the pulmonary vein and ablate pretty quickly as well. And all of these essentially have iterations of the same thing where you'll be able to place the catheter in the thoracic vein that you're interested in or the pulmonary vein you're interested in, rotate, ablate, rotate, ablate, and so forth. The last thing, this is kind of an interesting slide. There is some signal that perhaps being close to a coronary artery might pose some risk, although I think we're still trying to understand this a little bit more and a little bit better in terms of how close do you need to be. Of course, a lot of these studies are worst case scenario studies and whether there's ways to mitigate that type of risk. So I'll summarize a little bit with electroporation. The electric field is what determines the lesion. The catheter tip and pulse design are unique. Every catheter tip and pulse design have been married together so that it's optimized. Contact is important. You don't have to have a lot of force, but you do have to have contact. And then repetition of dose is important. It turns out that just because the signal disappears, it doesn't mean that you've created a lesion. Limitations of the lesion creation, the electrical effect is greater than cell death effect, meaning, again, the electrical effect, you lose the signals quickly, but that doesn't mean that you have created cell death. And that means there's a recipe for doing this, which we're learning with part of these clinical studies. Durability assessment is difficult. Acute assessment is difficult in the sense that once the signal is gone, it may not return. And if there is, if it does return, it may return later. So one of the things we need to learn about this is overall durability. You will not have any steam pops char. The lesions are fairly quick. High quality or strong contact is not needed. You do need contact though. It does not appear that because there's no char, you won't have diminution of energy delivery and it may be easier to ablate intercavitary structures. Some of the things we don't know, can you control the seat lesion size, shape and direction? Can we titrate this to effect? That's not entirely clear. How can you tell when a lesion is complete? Again, because you lose the electrical signal, the electrical information, you may not be able to necessarily know. Are we at risk for inadvertent ablation areas that are important like the sinus node, AV node? What's the risk of coronary spasm? Is there any risk of phrenic nerve injury in humans? And then what about parahysian type work that we have to do? Will this be too easy? Are the catheters going to just create a lot of ablation? How is it gonna work in scarred myocardium? And then what if there's metal objects around like ICD stents and we're very close to them with our delivery, what will the effect be on these objects? And then lastly, in the ventricle, will there be induction of arrhythmias? So with this, I'd like to thank you for your attention and I will stop sharing my screen. And I know Dr. Natale will move on to discuss some of the more clinical issues with this and some of the experience with humans. Wow, thank you very much, Dr. Alamai. That was fantastic preclinical overview. And with that background, next is Dr. Natale speaking on the types of PFA, its clinical experience and some of the clinical nuances. Dr. Natale. Okay, can you hear me? We can hear you. Great. So great introduction, I mean, this is my disclosure. So Amin already talked about the biophysics. The one thing that I want to mention is this. Amin said that. So in the device that we're using today that we're going to mention, those parameters that Amin mentioned, the waveform, the peak voltage are all different. And those have a significant, they can have some impact on the outcome. And this is something that we learn in the initial clinical experience. Some of the feature are known to us and some are not. For example, the duration of the train, some of the variable that Amin mentioned, they are not necessarily known to us. What we know is the peak voltage, which as I mentioned is different in some of the technology that we use, but really the detail of the waveform that is used to deliver are not necessarily known to us at this point. And certainly that's something that's going to change once all those devices are going to be FDA approved. And so, but those are clearly important variable as it is important, the design of the catheter. So, and this is something that Amin mentioned. Also, and I'll show you some clinical data, monophasic and biphasic do generate different type of lesion. If you use a single point catheter, we kind of learn that the biphasic lesion are very superficial where monophasic are deeper. And the same probably is true when you use single short catheter with multiple electrodes. Those are three of the four, I'll show you a picture of three of the four catheters that are now undergoing FDA ID trial. The A and B already have finished enrollment and they are very close to the one-year follow-up. C just finished enrollment the last month. So now I have to go through the one-year follow-up required by the FDA. Whereas the B catheter in B is very close to the end of the one-year follow-up that I think it should be close to around January, February next year. Whereas with the catheter in A, the end of the one-year follow-up should be around May. And then hopefully after the submission, they will become available to us. The catheter in A was tested in a randomized, a large randomized study in paroxysmal patient. And a single arm persistent study should start in US soon. The catheter in B was a single arm in both paroxysmal and persistent. Whereas the catheter in C was a randomized study in persistent, randomized to RF contact force. And Amin showed this before. This is kind of the difference in the footprint of the area that we cover between the single point that we're used to today in this catheter. And this is an example. So this is sort of a single point, but with a larger footprint. And one things we learn, I think this is very relevant for us, not too much for all the operator, but clearly with this PFA, we need to really sort of stack up lesion on top of each other. Otherwise, even if the electrogram disappear, otherwise those are all area of potential reconnection and recurrence. So what you see here is that as we move, those lesion are really on top of each other. We don't have to worry about as with radiofrequency energy, that if we're close to the software stacking up lesion, it can be actually dangerous. This is something actually we tell people don't stack up lesion when you're close to the software because you don't give time to cool. So you increase the chance of a social problem. With this catheter, there is no issue. And we actually, in some of the early human tests in Europe, we actually measured the temperature in the software. We've done some endoscopy and we never saw any issue. So Amin already mentioned that. I think the safety of this device, Amin show you some animal, then I'll show you some human result. But the safety, it's really, I think, something that make this technology very exciting. Many of the issue that we dealt with in the last 20 year are gonna go away once this become available to us. And I think this is exciting from a safety point of view, especially for the patient. Amin already showed you, so I'm not gonna spend time. This is actually, that was an animal. This is actually inpatient. It's an MRI study showing that when you look at late enhancement and compare cryo to radiofrequency and PFA, both the cryo and the radiofrequency show some enhancement around the esophagus, which is not instead visible inpatient undergoing electroporation ablation. This is another catheter that also just finish last month enrollment in a USID, a single arm non-randomizing paroxysmal. This is actually the name, the study that I was part of in Europe that I think now is very close to getting CE market. And this is some example of deletion. It's kind of a loop, large catheter that was slightly redesigned. I don't know who of you were involved when this catheter was used with radiofrequency energy. That approach was abandoned because of some cases of esophageal fistula in Europe. Obviously with PFA, we don't have to worry about that. So this is, Amin mentioned this. I wanna show, look at the electrogram. Gone with a single application. That does not means, that does not means that the lesion is done and you can move away. We learn that, and this is actually part of the protocol, that we need to apply multiple lesion. And I think one of the things that Amin mentioned that contact is important. We don't have to have good contact, but we need to be in contact. And the way we now overcome the inability to know contact, especially with a single short catheter is to try to deliver more lesion and to rotate the catheter, reposition around the area of interest. And this is a study that we did, and we've done many of these in Europe with early human testing, showing that the amount of esophageal temperature increase as we deliver in front of the esophagus is really dismal. And in fact, we've never seen any issue so far. Amin already showed this is in animal. I'll show the same in patient. This is from Vivek, showing that the dimension of the pulmonary vein before and after the ablation remain unchanged overall. So also in clinical study, this has shown to be safe. All the FDA, they have sub-study to look at this issue. And also another one that I'll mention later, which is the potential risk of asymptomatic stroke. And as you see in this early report of Vivek, that the complication rate are more related to the procedure rather than to the ablation. So there is no pulmonary vein stenosis, there is no esophageal systole, there is no pericarditis, which actually we tend to see with RF, especially after extensive ablation in at least 20, 25% of the patient. So those are all things that are going to go away. Obviously, stroke are possible because you have still catheter inside the cardiac chamber. I think in U.S. where uninterrupted procedure is more popular, that would become less likely. But also we need to remember that some of these catheter have large sheath. So managing those sheath in term of potential air embolism is important from the point of view of embolic event. Obviously, vascular access is a procedural problem, but for those of you, and I think this is becoming standard everywhere in the world, that use vascular access guided by ultrasound, I think this is going to become also a rare issue. This is some early experience from Vivek showing what Amin mentioned inpatient, how important is the wafer in the way you deliver amni. So clearly monophasic was not a good option because they had a reconnection rate similar, maybe even worse than current, actually for sure worse than current radiofrequency energy technology. But once they moved to biphasic and optimized the biphasic, look at the reconnection with a single procedure went up to the upper 80 and 90%. So this is certainly encouraging results. One of the things that I wanted to mention in our experience with high power short duration after we optimize the recipe, the most common area of reconnection is the area where we deliver on tissue facing the software. We see 91% of the reconnection that we see in our lab are in those area facing the software. So clearly, and the variable that sort of is different because the power is kept the same is the duration because of this temperature increase, the duration in those area is five point something second versus more than 10 in the other. So all of this is going to go away with the pulse field abrasion. In fact, this is a recent paper from Vivek showing posterior wall isolation that was durable in nearly 95% of the patient with a single procedure. So those are all exciting things for our field because certainly we make this procedure less operator dependent and also less dependent on the variable that where they affected the RF because of the proximity of the software, for example. This is the early human experience that is on the publication with the Aferacat that I mean, show you, and I showed you before this is the lattice mesh. And what you see here is similar to what I show you with the Farapulse where the waveform affected the persistence of the lesion and as there was optimized, that improved. So you see that with the Pulse-1 that there was a 50% reconnection around the PB and then with Pulse-2 became 87. And then with the Pulse-3, which is the one that we're using now during, with the use now in the study in US, it was 97%. So clearly the waveform is extremely important by keeping the design of the catheter the same. Sorry. The same is true for linear region. You see that all linear lesion and the roof line are improved from a 63 with Pulse-1, 200% with the Pulse-3 in the roof. And overall with all the other linear lesion which include also the mitral, we're around 91%. So very encouraging data that are going to be relevant. This is the success rate. Success rate, I think we have to measure this in the real world because those are all procedure done by experienced operator. Also, there is some patient selection to potentially can affect the outcome, but clearly you see that both in paroxysmal and persistent very similar results, so they're certainly encouraging. And this is instead with the Medtronic device that probably would be the first to obtain FDA approval in US. This is the result from the feasibility that were published. So there is no patient outcome. It's more about the lesion duration, procedure of duration. And you see that those number are certainly on the shorter side than what we're used to currently with the current technology. I mean, mentioned about SVC, this is an example of SVC delivery without affecting Frenninger function. Another things that I want to mention is that with some of the technology we use, especially with cryo and the balloon and some of the other balloon technology, we learned that the chronic effect, although the acute effect looks more antral, but we learned that the chronic effect is actually really an osteoisolation. This is very different than what we see, obviously with RF and with pulse field ablation, you see that the chronic lesion are more antral. So I think that the effect around the border is actually more permanent than acute, as we have seen clearly with cryo and in general with the balloon technology. This is actually a case of a PFA application in the persistent lesion of urea acava that our group and other have published as an important target when present. So a patient with a persistent lesion of urea acava, if you don't target that anatomical variation, those people usually tend not to do well. And here you see a case where the PFA catheter was delivered in the persistent lesion of urea acava and ablated to treat this patient. Here you see, again, a series from Boris, actually is on this with the complication that, as I mentioned, they are mostly procedural related, so confirming the safety of this approach. And again, from Boris, a learning curve that is achieved in about 20, 25 cases and then remains stable over time. So clearly we are talking about very quick learning curve with good chronic efficacy so far. This is a large registry that was published recently in Europe, first author Vivek, but many contributed to this, is 1,700 patient, showing again that the complication, obviously, are mostly procedurally related. So you see that the vascular complication, pericardial effusion and stroke, TIA, all the stuff that we worry about with the radiofrequencies of a GL fistula, PV stenosis, a frenal nerve paralysis, they are not there. There is some case of transient frenal nerve, but so far it seems most of these were recovered pretty quickly. So we're dealing with complication that are more procedurally related. As I mentioned before, for those who use an interrupted stroke, a TIA become less of an issue. And I think pericardial tamponade also, for the U.S. center, they use intracardiac echoguided transeptal are less likely to happen. The source of tamponade these days are the transeptal axis, a steampop. With the intracardiac echo, that become less of an issue. Issue, obviously, with PFA, there is no steampop. So I think this procedure can become extremely safe from the patient perspective. One issue, obviously, is embolic event. Obviously, I already mentioned that one reason could be the fact that you're doing a procedure stopping the blood thinner. Another one could be with large sheath, large air embolism. But one problem that we've seen with RF, and we have been investigating with also PFA, is what we call micro bubble generated by the energy delivery that are detected, as you see here, with transclinical dopper during the procedure. This is an example of such cases. So we just finished a study in Europe with the group in Brussels. And I think you will see probably some abstract related to that. I think the result are reassuring. So, although we'll continue to expand this series, we look at comparing in the study RF cryo and PFA and look at the MRI. So I think it would be an interesting study to in terms of looking at the result. But I can tell you that so far this does not seems to be an issue. The amount of micro bubbles that we see with PFA can be different from the different device and the way from the user. So this is important. But so far doesn't seems to be a major issue. This is the experience that the team in Austin and you see here compared to a match control with RF. So clearly, if you look at the PFA time and this is not just the pulmonary vein we have done a procedure wall. So we go from nine to 60 minutes. That's certainly impressive even in our lab. Amin mentioned about this issue. This is a case of a spasm during ablation along the mitral isthmus. And here you see again the same during ablation with the flower cap along the right side, the right isthmus. DIVEC has done a study that just came out. I think the implication are important. So you look at this, the coronary spasm after PV and posterior wall versus application in the right atrial isthmus. I'm gonna go through this quickly because I wanna show you. So here, you know, a picture of the spasm. Here you see the catheter in the right isthmus. And let's go to here. So what they saw is they never saw spasm during PV ablation and posterior wall ablation. So what we do for a typical procedure is safe. When ablation was done in the cavity of the isthmus, there was, if you see here, there was spasm in five of the patient where energy was delivered without administration of nitroglycerin and it was severe. However, and this is important, in none of these patients spasm was associated with the ECG manifestation. So there was no ST elevation, okay? But when nitroglycerin was administered, then there was no evidence of severe spasm. Most of the spasm were mild and in one case, moderate. So this is something I think we have to learn and understand a little better. But overall, the fact that with a pre-administration of nitroglycerin, that can be reduced. And also the fact that it was subclinical because without doing the angiogram, actually there was no ST elevation, also reassuring. So, but I'll show you a case that was, this is actually a case from one of our ex-fellows that now is in Europe. So this is a UCPFA application. And then you start seeing a little bit of ST elevation in the inferior lid. And then more ST elevation with some PVC, then more ST elevation by germinal PVC, and then eventually the patient went to EF. By the time, then very quickly it was cardioverted and you see that right after cardioversion, the ST is sort of normalized. And by the time the intervention came and did the angiogram, the coronary artery are completely normal. You see that the RCA, and here you see the LAD, they're completely normal. So clearly this is a spasm. This is not the type of effect that we see with RF, where there is a narrowing that actually need to be dilated when you deliver RF close to a coronary artery. This is really the effect of a coronary spasm that very quickly resolve spontaneously. So I'll stop here saying that the adoption of this new non-thermal energy for RF ablation pulse filabration has the potential to significantly reduce procedural duration, improve lesion durability, although here we are the caveat of the design of the system and the waveform use. But, and more importantly for our field, they completely eliminate the risk of collateral tissue damage. Obviously, as Amin mentioned, the efficacy could change based on the device design and the waveform used to deliver the energy. Thank you very much. Thank you, Andrei. I'm going to remind everyone to post their questions in the Q&A section so that we can post this to the speakers. And I want to now bring out the panelists to kind of get their view on the presentations, but also from their own experiences using these techniques. Boris, you've got a large experience from Europe. Would you like to make some comment on this? Yeah, thank you, Prash. Hello, everybody. So to give you a perspective, we have used the Ferropulse system in a clinical setting. And in the past approximately 18 months, we've treated close to 500 patients using that system. What did we see? So we can basically confirm what the two speakers have presented. So it certainly speeded up our procedures, accelerated our procedures. So we have observed skin-to-skin procedure times as low as 20 minutes sometimes. So the average procedure time is below 40 minutes in our lab with, I think, eight operators having used the system. So that's certainly a factor that will have a major impact in the field. In terms of safety, I can also confirm what the speaker said. We haven't seen any issues with the esophagus. We haven't seen a major side effects except for transient phrenic nerve palsies. Maybe we can discuss the mechanism later on. So when delivering energy to the right veins, we sometimes see a weakening of the right hemidiaphragm, which usually resolves within seconds, sometimes minutes. And we haven't seen a patient leaving the table with a weak contraction of the right hemidiaphragm. So certainly a functional problem. And I think there's also bench data confirming that there's no structural harm to the nerve. What else? We have also published our data on remapping in patients with repeat procedures. So patients coming back with various types of arrhythmias after an index PVI using this PFA system. And what we see is an enormous durability of the lesion. So in 91% of the remap veins, the veins were completely isolated. That is, for us, it's a major step forward. So whenever you are targeting a region, obviously the lesions remain durable. And I think Andrea also referred to this other system, the AFERA system and showed some data on durability of also linear lesions that seem to be very durable too. So that's really great. What else? The spasm, maybe the spasm. Yeah, that is certainly one thing that deserves further exploration. We actually had one case of spasm after ablation of the right superior pulmonary vein. So this is a little bit in contrast to what Vivek and coworkers published. So it might happen rarely. Maybe it's a completely different mechanism. I don't know. It's not a mechanism that is related to distance, but maybe to a massive release or increase in vagal tone because we're working on the GPs, right? So that is at least a mechanism that is well-known in the field of interventional cardiology. And yeah, I'd like to hear your opinion on that, whether this particular side effect of this energy may limit its applicability to certain regions in the heart. Especially Andrea likes to address more than just the PV region, especially in persistent AF patients. And that may be a limitation. I don't know. It could be an interesting point of discussion. Great. Melanie, can I switch over to you because you published probably the first case on the spasms. So it's kind of an important prelude to some of the discussion we're going to have. So do you want to talk about your experience and particularly maybe enhance on the spasm side as well? Of course, sure. Thank you very much. So yeah, it's true. We were, I think the first ones who observed it and we were kind of surprised because obviously the first moment we didn't think it was a spasm, right? Because we were told that there was no collateral damage. So we thought it's air embolism because of the big sheet. And it's also something you need to know also when talking about silent thumb embolisms and everything that the sheet is very large and that you need to manage your air. So that was our first thought. We thought there was air, so we waited for a bit but then we realized that ST elevations that presented in a patient didn't disappear. So we got curious and we waited like nothing happened. And so, yeah, we did an angiogram on the patient and we saw the spasm and then we applied nitro and it disappeared completely. And I agree with Boris. I think so far, all the data that has been published and the workup that Vivek Reddy has done on the topic shows that they don't seem to be so harmful. Like they disappear quickly with nitro. But I think still we are talking about a really new energy source that we have not that much experience of, for example, compared to RF, where so many of hundreds of thousands of patients have been treated. And now we have a small number of patients and we've seen it in a few of them. And also, I think it was really impressive what Dr. Natala presented where the patient went into ventricular fibrillation. And I think this is harmful for a patient. So maybe the spasm itself isn't, but what it can cause, asystole and VF. And this is something electrophysiologists that use that technology need to know. And at the moment we're using it at high center and experience centers, but it's a technology that's supposed to be easy and that we wanna bring in the broad field of electrophysiologists. So I think this is really something that we need to consider and think a little bit about before moving forward. Great. Dr. Sanchez, would you like to make some comments about your experience as well? You're on mute, so please unmute yourself first. Perfect. Yes, my experience has been very limited, but I'm certainly very excited watching the field. I wanted to ask Dr. Smith, in your lab, since you have it available for all cases, are you doing it for all cases with PFA? Yeah, that's a good question. No, actually, no. First of all, I never believed in monopolies, so I wanna keep a little bit of variability in the lab, but that's not a scientific answer, of course. I don't think that currently there's data that shows that PFA, let's say, is superior in terms of long-term outcome. Certainly it accelerates the procedure and et cetera, but I don't think that all thermal energy forms or devices should be abandoned immediately until we see those results, if they come. The second thing, of course, is that we also are talking about economical constraints. So this is a new technology, and it's certainly more expensive for us, in Germany at least, so we also need to consider these points, and that's why we still do ablation with thermal energy sources. Yeah, I wanna mention exactly what Boris said is very important. I wanna explain this, because I think the people in the US, they don't necessarily understand the difference. In Europe, the DRG is different in every country. Germany has the best DRG in Europe for ablation. Like here, for example, in Italy, the DRG varied between 3,500 euro, 3,500 and 5,500 euro. So this device in US are now sold for $8,000. I think in euros is way less than that, but even if it's 4,000 euro, that's very close to the entire DRG value. So I think that is gonna be something that is gonna sort of slow, beside what obviously Boris said about, we need to understand better with long-term results if really there is a big difference, but just the economic of this new technology, I think it sort of slow down moving to 100% use of PFA, because that kind of pretty much, at least I can tell you in Italy, it would break the bank in most center, because the DRG is that the hospital get paid is lower than the actual cost right now, the device. So I think that's an important consideration. Camilla. Yeah, no, great points. I'm just learning along with everyone else. So a couple of questions, probably I'll give this to Boris. What do you think about contact force and mapping and utilization with PFA? And this is from one of the audience. There's no discussion on the various PFA solutions providing contact sensing capability and can you comment on various vendors with regards to that? I think what Mia and Amin mentioned, the contact is important and the way we overcome that problem is by delivering more than one. I would say in our lab, more than one or twice or three times, all the device require at least two application in the same position. We usually tend to do more and move the counter in different position. So right now, that's all we have. The next generation, many company are already working about surrogate of contact or actual contact information in the next generation device. So this is gonna change, but probably it will take another couple of years before we see it. Right now, the best we can do is to just do more application. One thing that we have been exploring is using imaging. So using eyes, for example, to actually make sure that we are in a good position that could help. But that's a potential limitation, especially with the single-shot device that have multiple electrodes to actually control contact across the entire system. Cutting is difficult. And so the best way we can do is to try to reapply in different positions so that we cover the therapy well. Melanie, I see your hand up. So comments, please. Yes, thank you very much. I just wanted to add something. I think it's a really interesting point with the eyes because what we've seen when we started using PFA is that we found acute reconnections and it was in a superior range. And I think Boris also published it in his remapping data in Europace. And we didn't find anything about this in the early experience. And maybe that's because eyes was used. This is one of the explanations I have in the US trials. And in Germany, it's not reimbursed. We don't use it. And the device tends to turn posteriorly because it's an over-the-via device. And also you have to make sure that the catheter is self-centered. And you can't, like, if you open it up too wide or press it too much, you might not get the proper and homogenous electrical field. So I think this is a really interesting point. And I also agree. I think we need some image integration maybe if we don't have eyes. That's just my comment. Thanks. Amin, you want to make a comment? Yeah, I agree completely with the comment about eyes. We were utilizing eyes extensively during some of the clinical studies that we did to make sure we had good contact. And I agree with Andrea that, you know, it doesn't seem to be a penalty for sort of, you know, doing a little bit more in particular in areas that are critical like the pulmonary veins. I think that one of the other answers may come in the future with the integration with mapping systems. I think the technology will exist where once you have full integration of these systems with mapping systems, the proximity of the catheter to the tissue might be detectable and might have some help. The last thing I want to say is I think that the efficacy safety thing are two sides of the same coin. It's like what Andrea showed us that when we look at our recurrences, they're next to the esophagus. We're unable to deliver. It's not that the risk of esophageal fistula is so high. It's just that you can't deliver good therapy there because you're limited by your fear of that. And you can't find that sweet spot. You blight too much, you have a fistula, you blight too little, you get ineffective. How do you find the right spot? And so I think this is one of the big potentials for this. And of course we need to understand the durability of this therapy. Yeah, I wanted to add to what Tamim mentioned about the integration with the mapping because actually the varipool system come integrated with the three-dimensional mapping system. And actually we see the lesion on the three-dimensional map so that we can actually decide if there is an area where we don't see overlapping of the dots and deliver more energy. So the three-dimensional mapping is another way. It's not going to give us contact, it doesn't now, but at least we can look at the lesion deployment and make sure that they overlap and they cover properly that area. And there are cases where we have done additional, just based on what we've seen on the two-dimensional mapping system. Boris, you had a question. Yeah, it's more a comment than a question. Just let's say specifically adding on the question towards contact force. I think the point is made, the importance of contact force with PFA is certainly much less than with RF. It's more about proximity. So you need to be close to tissue because the electrical field will be unchanged. It would always be the same regardless of the tissue that is nearby or not. And if you're close enough, you will be transmural. And I think there's nice work done by Hiroshi with the point catheter and the Galaxy system, PFA system, that shows that if you have contact force of 10 grams, that is certainly, well, or if you go beyond 10 grams, let's put it this way, you won't get additional depths to your lesion, at least when you do point ablation. And that's, I totally agree with everybody that integration into a 3D mapping could help, but as of now, at least using the PFA system, Ferropulse, the 3D mapping integration is still not perfect because usually when you deliver energy, the whole map disappears and you don't see anything for, let's say, seconds. And you need to wait until everything is recalibrated and you can see your catheter back. And I think that's a little better done with the Ferro system, as far as I saw from the life case at Rio, right? And also with the J&J, you actually see that in real time, so you kind of see the overlapping of the lesion. So yeah, otherwise with the Ferropulse right now, that's a problem, yeah. Especially if you use the ABL system, everything kind of goes beyond. So we have a question about really workflow. Now, how are people doing these cases? Is it under conscious sedation? Is it under general anesthetic? I mean, I think this is kind of important questions as people start to use this. Do you each want to make a comment on that? Andre? There will be probably a difference between, I know I've been done cases in Europe, anesthesia is more relaxed. In US, so far we've done all cases under general anesthesia. I think it's kind of more an expectation here from the patient. They don't want to feel anything. So that even those little muscle twitch that they're going to feel if they're awake, I think you're going to be a problem in our patient population. But I think in Europe, bodies can talk about their protocol. They've done this even with the RF, so I'm sure that they are doing many of these cases without right bodies. Yeah, right, right. So we are in the luxury situation in Germany that we ourselves can apply propofol. And so we don't need the anesthetist in the room. It's not a legal issue as it is in other countries, even in Europe. So yeah, and it works. I mean, even with deep sedation, usually applying between let's say 30 and 40 milligrams of propofol per hour and adding some analgetics like fentanyl, that works. And you can do the procedures without, let's say, bad memories of the patient to do the procedure. It's not very different from thermal energy procedures. Melanie, are you doing anything different there? Oh, we use the same cooking recipe as for Schmidt. So it works. What you have to know when you use it is that the patient might be moving a bit more. This is something you need to consider. And also they cough after ablation of the left superior vein. So also something you need to consider because you kind of have to wait. It's not really getting better with more sedation. So the patient's coughing and you would think you need to apply deeper sedation, but I think it's just the effect of the ablation and you have to wait a moment for it to disappear. And then on the right side, while you ablate, you can have phrenic nerve capture. So there's a lot of movement going on, which you're not used to in the beginning, but after a little learning curve, it's usually fine. And the patients, we talk to all of them, they don't remember. And I think that Carsten Eben presented at a German conference, also patients described less chest pains and pericarditis-like symptoms and things because it's so sensitive to the myocardium. Yeah, so far we haven't. Actually, that's a good comment because we pre-treat all our RF patients with Colchicine. And then, you know, if they don't have a problem, we stop it after. And they want to have some chest discomfort, we continue. With PFA, we haven't done that and patients don't feel anything the next day. So it certainly, that's another added benefit to this technology. Great, I know we talked about the atrial tissue. Any experience in ventricular tissue and PFA amongst any of the panelists? I have done a few cases in Europe with the single point catheter. I think we need more experience. I think the nice things about this technology is that I think we mentioned that multiple application of the same site increase the depth. And I've seen lesion that go from nine to 16 millimeter in my ventricular myocardium in, you know, this is all preclinical testing. So I think that's exciting because that means that we don't need to go in the epicardium anymore and maybe do a better job with mid-myocardial scar with this approach without using, you know, bipolar or, you know, all this other sort of technology. But I mean, that's something that is going to happen for sure. That's actually fantastic comment, Andrea. And I'm also really, I was surprised to see the depths of those lesions, but I'm a little worried to be honest with you about the width. If you look at the animal data that Eli Hunter and his group published, I mean, those lesions are up to 2.5 centimeters wide. And if you're working in a human ventricle that is not enlarged, you could damage a lot of the surrounding tissue. Are you, would you, are you afraid of this? No, this is Boris. That's a very good comment. I think we're going to have to be very sort of selective the way we apply this. Part of that is probably device dependent because it was with the lattice catheter, but I think, you know, you're, that's something that totally we're going to have to be aware when we do. So if you're in the middle of a scarifying, when you're at the border, you have to certainly worry about that. Absolutely. Dr. Sanchez, you know, Javier, you know, you're a master ablationist. I mean, you ablate like a very high volume operator. As in someone standing outside, what do you think of the PFA, just the future, when compared to the RF and the cryo? Just comments. I think that what Dr. Smith was saying, that not using it for everybody, that the expense is going to be something that limits, that you cannot do, at least it doesn't seem like it's easy to do an AVN or deablation in the same procedure, or to go after an atrial tachycardia in the same procedure with the same equipment, that I don't think radiofrequency is going to go. We keep emphasizing the idea that the procedure is faster, but like Andrea was saying, we already do the cases in an hour, for a paroxysmal normal heart, an hour and 90 minutes. In terms of safety, the idea that one doesn't have to worry about the esophagus, that for sure would be nice. Like Amin alluded to, it's really not a common problem. As a matter of fact, we've gone now several years without seeing it, but the worry is constant. We're still a week later when the temperature gets, the patient gets a little bit of fever. So I think if the price is right, it's certainly going to be used. I don't think radiofrequency is going to go away, but it for sure is very exciting. I've been reading lately also, I wanted to see what the other panel is, the idea that it doesn't seem to affect the autonomic system as much. I take that as a positive, right? So I'm curious to see if you think that that would change the success rate from the ablation. That's a good point, yeah. I think we still have to understand a little better if more extensive might be different. I think we're done maybe a little more than other, and we've seen some change at least for a few days, not as long as you see with RF, but I'm not a big supporter of the additive effect of gangrene. In fact, most of the surgeons that we know in our area that actually do a good job, they completely abandon ablating the gangrene during surgical procedure. We did a study when I was in Cleveland with a tool, that the tool probably is showing that even if you suppress all the gangrene with RF, the patients still have recurrence. So I'm not sort of worried about this effect at all. I have to say that to me, the safety is, I want to mention this because with amine, we did a case with amine coming from a different state that had two previous procedure, and this young woman had stenosis of two veins. One was completely occluded, they could not dilate it. The other one was dilated, and when we did the procedure with ice, we saw that the stent was sticking out in the left atrium that much. So this is a young woman that's life has changed because of this. Even if it's rare, in our end, it's not happened. Those are things that I think are going to go away, and I think there will be a great things for both us as doctor, as you said, the phone call a few weeks after with the fever, and for the patients more importantly. So even if it's rare, those are things that affect people life forever, and I think it's going to be great that they're going to be gone. Yeah, I may mention about that case. That case, unfortunate lady, that complication would not exist if they had used PFA, if it was available. But the flip side of that is also that young lady ended up having an SVC trigger, which was not recognized. And so even with PFA, we still have to be electrophysiologists. It's not just fast ablate and get out. I think we still have to give this some thought and continue to understand what we're doing, and it's not just fast ablation and leave. So I think all of those, and like Javier said, I mean, if you have an atrial attack, you're going to chase it, so. Andrea, can I ask you a question? So you've presented multiple different catheter types here. Are they all going to be equal in what they achieve, unlikely? Now, in terms of coronary spasm, you know, we're kind of being told that's generic to the energy, but could it be partly the catheter as well? You've used most of these, so. Yeah, I think the answer to the efficacy is no. We learn that every catheter have sort of different issue. Some of them has to do with the peak voltage and some of that with the catheter design. So I think people are going to learn about different efficacy with different catheter that relate to the design of the catheter, but also to the waveform, both in terms of peak voltage and other characteristics. In terms of spasma, you know, I have to say that both in the case I've done in Europe and in US, we've been kind of limited because we're all sort of either early in humans or we're kind of sticking. So I never use those catheter in the sort of unusual era. But I have to say, we did the linear lesion, as you have seen, including the right atrial isthmus, and we haven't seen it. But said that, remember that Vivek was doing angiogram, but none of those patients in Vivek's study show ST elevation, despite if you look at the coronary angiogram, it was a remarkable spasma. So I don't know if the jury's out. And, you know, I think now we all feel that is probably pulse field ablation in general, you know, the electroporation in general that can do that, but we need to learn. But so with other system, we deliver in the same area, but we haven't seen, but we were not doing angiogram. So I don't know if I can completely say that, you know, it's going to be less of an issue. Okay. Thalani, I think your hand is up. Yes, thank you. Just a comment on this, because we are talking about different catheters and waveforms. And if it's true that different waveforms pretend patients from maybe an adverse outcome or a safety issue, I think it would be necessary for us doctors to actually understand what the recipe is. Dr. Ahmad showed it very nicely how we can incorporate different parameters in the generator to create it. And now we're having this magic tool that is fast and easy to apply, but there's different things out there. There will be more things coming. And I think it is interesting for us to understand more about what is the difference between those waveforms and what does it do to our patients. Boris, I think you wanted to add something to it. Yeah, thanks. I would love to pose a question to the other panelists and speakers. So the one device that was presented and allows toggling between PFA and RF energy. And I just wanted to hear your perspective on why would I use RF or in which scenarios did you toggle? Do you like that feature or is it just because it's there? You use it. What are the clinical scenarios to apply that? Yeah, so I'll start answering because I've used it. So when we started using in Europe, it was RF in the anterior segment and PFA in the posterior that are facing the solar. Then we moved to just totally PFA because that's where the field was moving. I think one thing that we have seen with RF, you know, I show you the linear lesion. They're both remarkable, but with RF clearly in the area that are problematic with the single point, we achieve really almost 100% permanent block. So I think that's an option that can become valuable in certain patients like hypertrophic cardiomyopathy where clearly that area is way thicker than the average patient and maybe most of the PFA might not be enough. I think we need to learn about this. So I think, I don't know for sure, but I think that there will be some specific patient where that option can become valuable in the situation where the tissue is unusually thicker. So that, but you know, that's a speculation right now, yeah. Eleni. Yes, I, oh, sorry. I have a question in regards to this. So Dr. Natala, do you think this is because you would actually need more PFA at those thicker tissues and we're not delivering enough? And there's some regression of the lesion because we have a zone of maybe only not irreversible but reversible electroporation. And this is something we also don't know yet which like the size of the lesion is going to end up. Yeah, so if you look at it, yeah, this is exactly. So if you look at the, most of the PFA we're using in the atrium, they have sort of a depth that is about five millimeter. Five millimeter is probably okay for most patient but there are cases, and the reason why I mentioned hypertrophic cardiomyopathy those are people where certainly that can go beyond that especially in the area of the isthmus. We've seen in some time the amount of the appendages. So they are exceptional case where the tissue is going to be thicker. And some of these device are calibrated to achieve a depth that doesn't necessarily reach that sort of exceptional thickness. Obviously as this device evolve, we mentioned in the ventricle lesion that goes nine millimeter to even 16, I've seen that can be a new point, but I'm talking about the current device that we're using now could have that limitation. Yeah. Boris, anything to add to that or you ask the question. So Michael, any other questions for the panelists? I know they spend so much time with us. I really like the point of the varying pulse waveforms and duty cycles, how that's the great mystery of this technology. And until we are enlightened as to what variables can change, I think for me, that's gonna really accelerate it. I would like to ask everybody, how different is one versus the other? Is there any sense? I know these are proprietary, but how different are these waveforms? Michael, right now, what we know is the peak voltage and it is different in the technology. The waveform is a mystery because we're totally blind. So that's the part that I think we eventually, we would like to know because I think it's important for us to understand how they impact. Certainly the peak voltage we have experienced can be a factor. And that's certainly different from the technology we've been using, but it's not just that. So, and the waveform right now is totally obscure to us. That was a wonderful session. And I think we are getting close to, we went more than 75 minutes. So I appreciate everyone's time. Thank you, everyone. Incredible faculty for your time and expert comments and our social media influencers. You don't know that they're sharing everything on LinkedIn and Twitter. And our audience, thank you for joining us. I know it's in the middle of the day here in United States and elsewhere, the time is not perfect, but appreciate that. And HRS leadership and the staff, thank you for your support and happy holidays, everyone. Thank you. Thank you, bye. Thank you very much. Bye-bye. Thank you, everyone and attendees. Just a reminder, please do complete your evaluation and claim your credit for attending this webinar. If anyone needs any help, you can reach out to our CME team at cme.hrsonline.org. Thank you all very much for your time today on behalf of HRS.

pulse field ablation

PFA

background

studies

animals

humans

practical applications

catheters

waveform

contact

ablation

safety