All right, we'll go ahead and get started. Good afternoon, everyone, and welcome to this session on Meet the Trialists, which is really for you, this session, by the way, because we had the late-breaking clinical trial sessions and we asked a lot of questions. Now it's your turn to ask the questions. I'm Sana Al-Khatib. I'm an electrophysiologist at Duke University, and I'm the program chair for HRS 2025. Thank you so much for being here. And the format is we're going to ask each PI of each trial to give us an overview, a brief overview of the trial, and really we want to devote most of the time to questions. And so with this background, I'm going to invite Dr. Frederic Sacher to the podium to give a quick overview of the CT-guided ablation for ventricular tachycardia trial, or the in-your-heart multicenter randomized clinical trial. Thank you. Thank you very much, dear Sana, dear colleagues. It's my pleasure to present two slides to just sum up this study on behalf of the co-investigators. So basically, the in-your-heart studies was to evaluate the interest of computed CT-guided CT-guided ablation for ventricular tachycardia. It is an institutional multicentric prospective single-blind randomized clinical trial funded by the EITS, which is an organism for European Union with the role of innovation in health. So there were 14 clinical sites that were participating. 11 of them were naive to the procedure, and we included 113 patients. And basically, what we find in the CT-guided group compared to the conventional VT ablation without imaging, we had a reduction of procedure duration by 90% in intention to treat, and a reduction of 28% when the protocol was followed without increased procedural risk with a one-year probability-free rate of 76.8% versus 67.3, but this was not significant. And the protocol cost was reduced by 10% in the CT-guided group. And just to open the discussion, there was potential next steps in improving imaging, improving ablation tools, and also maybe modeling based on the images to be probably more specific based on modeling of the scar and how to identify better the area responsible for sustaining VTs. Thank you. Thank you very much. I'd love to invite you guys to walk up to any microphone to ask your questions as people try to do that. I would like to ask a couple of other questions. I know I asked you quite a few questions earlier, but so we talked about the sample size calculation. We talked about how many people you would need to enroll in a trial where you look at harder endpoints. If you have your pick of what primary endpoint to look at, I mean, of course, we talked about VT recurrence. What endpoint would you pick? Yeah, so I think it makes sense to get at least a reduction in VT burden, but definitely VT recurrence would be great. And this is something we are thinking about, especially with new ablation tool, as we think this new ablation tool combined with imaging can be a very good combo to improve that dramatically. So this is something we are thinking about, and that could make sense to get other endpoints such as absence of VT recurrence, but also reduction in burden of VT. Indeed, and then if we again go back to the characteristics of the patients who were enrolled in the trial, we talked about the low enrollment of women. Could you comment on that? What efforts did you guys implement in the trial to try to enrich enrollment with women? And then the other question I want to ask is quite a few patients actually presented with a VT storm. So could you comment on why you ended up with so many people? It was that intentional? Do you feel like the site investigators were biased toward enrolling more of those patients? What are your thoughts on that? Yeah, that's a very good point. So concerning women, the thing is, so far it may change, but as you see in the population, they had infarct in average 15 years ahead of the ablation procedure. So fortunately for women, they are less subject to mucolar infarction at that time at least. It may compensate with risk factors and things like that. But in any ischemic cardiomyopathy VT studies, this is the rough percentage of men and women. So one thing would be to go in non-ischemic cardiomyopathy and that would be a more, I mean, better representation of female. But I'm not sure it's a bad thing that we don't have much female for them at least, meaning that they didn't have VT or ischemic cardiomyopathy at least. And concerning the arrhythmic storm, it probably reflects the way, and in some centers it's still not clear when to go to VT ablation maybe, and probably they are waiting a bit too long to go to VT ablation. And that's another problem. It has to be democratized. And this was the idea also of this strategy, having a simplified and standardized workflow to be able to spread this kind of procedure to more centers and not just to some specific highly experienced centers. Any other questions from anyone? Please go ahead. Thank you for sharing with us this beautiful study. I have two questions. So one is the procedural cost, which is reduced in the CT arm. What yields that in which extent? Is it because of the CT? Is it because of reduced time of procedure and so on? Yeah, so that's a very good point. So there was two main factors that driven this reduction of cost. One is the use and the absence of use of high-density mapping catheter or less use of high-density mapping catheter as a CT-guided group. That was one. And the other was the reduction of duration, of procedural duration, yes. Okay. I have a second one. So if we look at the future, you were talking about new technologies and new catheters for VT ablation. Do you think that this would change anything in the result or maybe push more towards better outcomes? One, and this, again, related to the cost, maybe you would lose eventually the advantage of cost. Yeah. So that's a very good point. I truly think that new tools, and we are working with these new tools, not in a randomized control trial, but in daily practice now. And especially the large footprint would be a very nice combo with imaging, because imaging can tell you where to go, and the large footprint will get the job done much faster and probably going deeper with repetition, more durable lesion, at least this is the hope we have. So I truly think that using these new tools will help a lot and increase even efficacy and probably to answer the previous question of the number of patient. I think we would need much less patient if we have to use these kind of tools. I think this is my guess. Thank you. Great. Thank you so much. We'll go ahead and move on to the next presenter, Dr. Varun Sundaram, who is from Cleveland VA Medical Center, and he's going to give us a quick overview of the TRANSFORM-AF trial targeting metabolic therapy with GLP-1 receptor agonism for secondary prevention in atrial fibrillation. Thank you. I'll be briefly presenting the results of the role of GLP-1 receptor agonism in the secondary prevention of atrial fibrillation. As you all know, this is the results of the ADVENT trial, which compared pulse field ablation with thermal ablation techniques in patients with refractory AF. But what is quite important to note is 30% of these patients experienced primary outcome within a year of follow-up. And even more important is the residual risk of atrial fibrillation demonstrated a cumulative increase over time, and possibly reflecting substrate remodeling that persists despite initial procedural success. And this is quite important because most of the patients who undergo AF ablation are likely to live for at least two decades, because the average age of AF ablation is 60 in the United States. And this shows a very high odds of getting a repeat ablation procedure during their lifetime. So it's a multi-center pharmacopedemiological study, and I'll explain why you had to do so. This is a very complicated slide, but you had to explain the methodology in detail. So this is how the base cohort of the study included those patients with diabetes, atrial fibrillation, and a body mass index of greater than 30, and identified those with new initiation of GLP-1 receptor agonist. And we had to compare it to a group of sulfonylurea or DPP-4-inhibitor, which had a neutral cardiovascular safety and efficacy profile. And after including patients with active atrial fibrillation, where we introduced something which is very similar to the pre-randomization run-in phase to identify those with active AF, we had around 2,500 patients with well-phenotyped AF and body mass index of greater than 30 on GLP-1 receptor agonist, which is a treatment group and the comparative group. So during immediate follow-up of 3.2 years, we had around 320 AF-related events. This is excluding all-cause mortality. And what we observed was a 13% reduction in the primary outcome, which was time-to-first hospitalization with a primary diagnosis of AF. AF-related procedures are all-cause mortality in favor of GLP-1 receptor agonist. And what we observed was also a heterogeneity of treatment effect in favor of GLP-1 in those patients with increasing BMI, showing by that what we mean is a greater effect of GLP-1 receptor agonist in those with increasing body mass index. So overall, the study, we all know that there's a significant residual risk of AF post-ablation, especially in patients with suboptimally controlled cardiometabolic risk factors. This nationwide epidemiological study from 170 VA Medical Center showed that the use of GLP-1 is associated with a reduction in the residual risk of AF-related events at diabetes management doses. These were diabetes management doses. But what was interesting is we observed this even at modest weight loss only. There's an incremental 4% weight loss because these are diabetes management doses, signifying there could be possibly pleiotropic effect of GLP-1 receptor agonist. And with weight loss doses, you likely could possibly have a greater effect, as was observed in HFPAF, patients with HFPAF. And these should be viewed as hypothesis-generating findings. But the feasibility of an RCT right now to have modifying a risk factor as obesity and randomizing them to control group and having a long-term follow-up, because modifying risk factor is going to take a time. Without GLP-1, with no reliable crossovers during long-term follow-up, it's going to be highly challenging. So thank you very much. Yeah. Yeah, thank you very much, and congratulations on the completion of the study. While we wait for others to ask questions, I'd like to ask you, what do you think the mechanism is? Is it actually causing this just based on weight loss, those kind of things? Or is there a direct effect, do you think, on the burden of arrhythmia and AFib recurrence? So that's a great question. I believe there's multiple plausible reasons. One is weight loss. And largely, what we understand is we can try to extrapolate from what we've observed a lot studied in HFPAF, where one, it's weight loss mediated. But then the other one thing, regardless of weight loss, what has been observed with GLP-1 is a change in visceral adiposity and epicardial adiposity, which is another mechanism which is possibly explained in patients, which is likely to be one of the possible reasons. And we did perform mediation analysis, so it's just beyond weight loss, too. So we can't exactly say what it is. We can hypostolate from HFPAF that is probably visceral adiposity or epicardial adiposity. And that is dose-related. That's a dose-response relationship. So with higher weight loss doses, or with tercipedite, where the weight loss is higher, we may experience a greater effect. That's excellent, actually. So let me ask you the next question, is how would you implement those results in clinical practice? Do we need to be using these medications in similar patients going forward? So again, I will emphasize the limitation of the study, one, because it's not immune to residual confounding because of the non-randomized nature. But I think we'll have to have a Bayesian approach to this, because as I mentioned, the feasibility of RCT now to randomize thousands of patients, body mass index of greater than 30 with no GLP-1, for a longer period of time, we may have missed the boat at this point of time. So is to look at a Bayesian approach of historical evidence in this area, largely from the Adelaide group of pressure centers looking at modification of risk factor modification and subsequent reduction outcomes, using the evidence from HFPAF, where we know that significant part of patients with persistent AF have subclinical HFPAF. And we have mechanisms to calculate the probability of HFPAF in these patients with persistent AF, and use obesity as an indication, at least among all patients who are undergoing AF ablation to prescribe. So we may not, unfortunately, have a firm randomized evidence in this space, and there's no ongoing randomized trials going on in this area. So anyone who is going, we should probably use obesity, and who especially have HFPAF, as an indication to prescribe GLP-1, starting with patients who are going for ablation. Got it. Thank you. Any questions from the panel? Congratulations for this beautiful study. I think it puts a bit, you know, AF into perspective for us as interventional cardiologists, electrophysiologists, like we're taking a bit into account the whole phenomena of disease evolution, chronicity and stuff. So thank you for that. Now if I have to imagine a randomized trial, to evolve what you were just saying, it will be more than challenging. Of course, number of patients to treat, and all this, but also ethically, how would you select an obese patient, maybe with diabetes, and without giving him the drugs that we know is helping him? So it's a bit challenging. How would you address this? So we've been working on the funding aspects of it. So it is extremely challenging now, with GLP-1 receptor agonist widely being approved to, especially as you know, unlike AF ablation, modifying the risk factor, and to see a change in outcome, it's going to be years of drug exposure. It's not going to be quick. So to actually have years of no drug exposure of GLP-1, when we know that there's no clinical echo poise, so we can only randomize when there is clinical uncertainty, that there's no clinical uncertainty in terms of obesity, it is in terms of AF, to not randomize is going to be, I think, extremely challenging. And even if we do, during long-term follow-up, to do it without reliable crossover is going to be very challenging, in our opinion. And we've been asked this question even while applying for funding. So we convinced NIH to fund this, because of some of the limitations which we had, yeah. So congratulations. We, at the Cleveland Clinic, we're doing a randomized study, looking at GLP-1 agonists. The enrollment rate has been really good. It's a randomized control trial, two arms. One is getting the drug terzapetide, the other one is getting placebo. It's a different study. It's not secondary prevention. It's primary prevention. It's not secondary prevention in patients with AFib. But I think secondary prevention would be even more ethical, more challenging. I have a question about, you know, BMI and AFib has shown a U-shape relationship. Is there a point where you think, okay, that's up from this BMI, it's not going to matter? We're not going to help these patients? Or do you still think that there is a role of GLP agonists, even in markedly obese patients? So most of the studies looking at the relationship of the U-shaped relationship in terms of relationship between BMI and AF is the limitation because part of this is the extremes of BMI is very difficult to quantify in an epidemiological study because of the selection bias in epidemiological studies where we end up excluding significant part of patients at the extremes of BMI and limited follow-up. So the relationship is not as clear as what I would argue. So in this, we have patients of BMI of up to north of 45, and we still saw kind of an interaction effect, even the group which I said was BMI of greater than 40. So I'll not be able to say what would be a cutoff, but at least in the patients, a significant part of patients you would see if not the BMI of 45, you could argue that even in, and this is extrapolating studies from obesity and HEPA, you could still see an effect size, yes. That's very encouraging. Let me ask one other question since we have a couple of minutes. Can we talk about cost, especially if we're going to start implementing this in clinical practice? What are your thoughts about cost effectiveness, analyses, the need for those, and will patients really afford them? Yeah. So that's a great question. So that is one of the serious issues as the previous FDA commissioner on day one was actually mentioning about this, the cost regarding GLP-1 receptor agonist being exorbitantly high here as opposed to outside United States. So whereas in Europe and in certain aspects of England, the cost is quite different. So it is something which is going to be, it's going to be at this point of time still prohibitive because most of these studies, it's quite prohibitive, especially with weight loss doses. It's more, it's more expensive weight loss doses, but we believe that it's highly likely to change shortly because the overall cost effectiveness, especially the average age of ablation in the United States from the National Ablation Registry is around 60, and the life expectancy has been exceeding to 85. So we have most of these patients going to live for two and a half decades. And we know that within just one year of follow-up in the advent trial, you had 30% of them experiencing the primary outcome. So in a lifetime, most of them are going to have second, third, and advent trial was paroxysmal AF, not even persistent AF. So while cost-effective studies are to come, but with healthcare policy changes, this would probably be a much more logical approach for suboptimal, especially cardiometabolic risk factors are quite suboptimally controlled. So it's, at this point of time, it's prohibitive. So but I think we have to wait it out. Indeed. Thank you so much. And so our third presenter is Dr. Derek Chu, and he's going to share with us the results of the MAP-IT CRT trial. Thank you, Dr. Al-Khatib. So yes, there's also the MAPIT CRT trial. So this was a randomized prospective trial where we compared an MRI model-based approach to CRT lead placement in both the RV and LV leads compared to standard of care. So in people with indications for CRT, symptomatic heart failure, ejection fraction less than 35, and QRS duration greater than 120 milliseconds, we enrolled 210 patients and randomized them to this model-guided versus standard of care approach, primary outcome being change in ejection fraction greater than 5% at six months when we measured the ejection fraction at baseline with MAGA and compared it to an ejection fraction also with MAGA at six months. So this was enrolled, we enrolled patients between September 2014 to May 2020 from seven Canadian sites with follow-up through to December 2022. Secondary endpoints, as follows on the slide, quality of life questionnaires, as well as clinical endpoints, all-cause death, heart failure hospitalization, and ventricular arrhythmias. So in terms of what the MRI-guided model was, well, we used 40-phenomics, which incorporated deformation analysis to be able to identify the areas of latest mechanical activation, and we also used scar analysis, quantitative and qualitative, to figure out regions of the heart on this mesh diagram with latest mechanical delay and areas of minimal scar burden. So based on those two characteristics, plus figuring out how to maximize the distance between the LV and RV lead, this model recommended two positions, plan A and plan B, for the operator to be able to guide their LV and RV leads during their implant procedure. For those who are randomized to the MRI-guided approach. And what we found, so here's the baseline characteristics. On average, the median age was 69 years, 31% female, with half being ischemic etiology. The ejection fraction was 28% on median. These were left bundle branch block asterisk stress criteria with a QRS duration of 162. And what we found in the MAPIT trial is that using this MRI-guided model, there was a greater proportion of people who had their injection fraction improved. So there were greater CRT responders by our definition of CRT response. 66% had an injection fraction increase of 5% or greater at six months compared to 52% of the standard of care arm. No difference in secondary endpoints or quality of life measures. Thank you. Great. Well, thank you so much. Let me ask you, how should we implement those results in clinical practice? And then the second question is, are you planning to follow this with a larger randomized clinical trial? And if so, what lessons did you actually learn from this study that will help you design and conduct a better trial? Great question. So I guess maybe I'll jump into your second question first. So some of the challenges of this trial was just a very, very slow enrollment. Lessons learned were at the time, especially during this trial in Canada, the availability of finding enrolling sites with availability of both MRI and nuclear cardiology to do the MUGAs and CMRs was a bit challenging. So what we found, this was an MRI-based trial, so all the centers that we had approached and engaged, great cardiac MRI programs, they're at the expense of nuclear cardiology. So with our endpoints, we actually wanted to measure ejection fraction and LVN systolic volume, but some of the centers didn't actually have the MUGA imaging that we needed, rather than the spec they had planar. So I think that was a challenge of the times. Now I think if we were to do this trial again, there would be a more uniform availability of imaging. The challenge I would say now is with the ADVENTA-LUF bundle branch block, our conduction system pacing, I think enrolling would be even more challenging, as I think the motivation to enroll in CRT trials without conduction system pacing is a lot less. In terms of the large MRIs, I think one step between a potential large randomized trial is because the trial took so long, we haven't actually assessed long-term outcomes of this cohort, so that's one thing that we're going to go back and actually see what the heart failure hospitalizations and mortality outcomes are like after this extended period of time. You bring up an excellent point that I'd love to ask you, although this is not related to this trial, but this is such an important debate now in the EP world. Do you think that conduction system pacing is going to replace biventricular pacing? That's a loaded question. So I think, so this is just my personal opinion. So conduction system pacing, loss of promise, very exciting, very optimistic, of course waiting for randomized controlled trial evidence, left versus left will be really important when the trials do come out in several years' time. I think all these approaches will still have a role. If we can get selective or non-selective level capture, great, but what about people with distal conduction disease, where we never actually do narrow the QRS, we need to fall back on the tried and true approaches of LV epicardial, or sorry, SCS lead placement. So I think there will be a role, and who knows, it could just be a combination of both approaches, like LOTC or T for example, but no, I do think there would be, there still is a role, and I do think the nice part with conduction system pacing is that I believe that it'll make resynchronization much more accessible to people, and the implementation gap of people not getting referred for a CRT, I think that barrier will be less, so overall I think both approaches still have a role. Thank you so much for saying this, because the concern, at least in the US, is that a lot of practices have shifted completely toward placing, conduction system pacing, and as you said, there are still great and important groups of patients that we see in clinical practice who would benefit from biventricular pacing, and LOTC-RT as you mentioned, and the concern is that without doing enough biventricular pacing, like the newer generations of EP fellows are not getting trained in how to implant CS leads, and I think that is a concern. Absolutely, that'll be an interesting thing to figure out in the future, how to train the next generation, well, and this is the concern too, I guess, not just in the device space, but the ablation space as well, with PFA, you know, right now we're at a good time where people are experiencing RF and PFA, but in five years, there will be a generation that doesn't have the RF volume. Great, well thank you so much. All right, so our, I'm sorry that my co-chair, Dr. DJ Lakhiredi, is in a different session, he was supposed to be here by now, but I'll go ahead and introduce the next, oh, there he is, there he is, excellent. You want me to introduce him so that you can catch your breath, okay. To give him a chance to catch his breath. I am delighted to introduce the next speaker, Dr. Arwa Yunus from the Cleveland Clinic, he's gonna tell us about AFib recurrence after left atrial appendage occlusion in patients undergoing AFib ablation, that refers to lessons from the option trial. Thank you, Dr. Al-Khatib, thank you, dear panel, thank you everyone for being here. Can I have my slides, please? So click on that, and then once it pops up on the top, yeah, start. Okay, excellent. Still loading. Okay, so I left all slides, and I'm happy to discuss any slides that you wanna focus on. Can you speak up a little bit, if you don't mind? Sure, sorry about that. Thank you, of course, no problem. We all know that the left atrial appendage structure is a fascinating but very complex structure that not only plays a significant role in thrombus formation, but also in the pathophysiology, the progression, and the maintenance of AFib. The option trial was a positive trial, however, whether left atrial appendage closure implantation in a concomitant procedure would somehow compromise AFib ablation outcomes is something that we felt during the enrollment. Many physicians would say, I don't wanna, I'm afraid to compromise my AFib ablation by adding a device and manipulating now within the appendage an area where we know that is highly arrhythmogenic, we just, we now have sinus, we don't wanna do this. So this was a pre-specified analysis that tested the AFib recurrence, and if we go and look at, we used all patients and intention to treat, and then when we look at the results in terms of AFib recurrence, AFib recurrence in the option trial was captured as clinically AFib recurrence, meaning the need for cardioversion, the need for repeated ablation, and then increasing or new prescription of antiarrhythmic medication. So we are, we're focusing only on clinically reported AFib events. The AFib recurrence at three years did not differ significantly between the two arms with a great separation that happened actually early on, and then after that, maintained with no difference. Importantly, when we look at the real question, concomitant versus sequential Watchman implantation should actually answer that, because now we have within the Watchman arm, we have two arms, we have a concomitant arm, and we have a sequential arm, and if we wanna see whether implantation of a Watchman would affect somehow AFib ablation outcomes, then looking at these two groups might answer that as well. So when we looked at this, we saw that there was no difference between concomitant and sequential despite having significantly more patients with persistent AFib in the concomitant group, so these results were reassuring. We have other, all other findings were similar. Safety endpoints, efficacy endpoints, death, stroke were low and were similar in both groups. Limitations, we have lack of continuous monitoring for AFib, but this lack of continuous monitoring for AFib was in both groups, so it should not affect our conclusion. It may affect the rate of AFib recurrence, but it shouldn't affect the conclusion. No PFA was used, but again, this may affect the rate, should not affect the conclusion. Overall, the option trial was criticized for the low event rate of stroke and systemic embolism, which may affected also our results, because now we have even subgroup analysis. So in conclusion, among patients undergoing AFib ablation, concomitant or sequential Watchman implantation does not appear to affect AFib ablation rhythm outcomes. There was a trend toward a higher incidence of adverse events in patients with AFib recurrence compared to those without. Thank you. Dr. Yunus, it was a nice presentation. If I were to summarize this, you basically looked at patients who had an appendage occluder and those patients who were just kept on oral anticoagulation and then looked at the overall incidence of arrhythmia. So it's not surprising to see that the presence of an occluder didn't really increase or decrease the risk of arrhythmia recurrences in this patient. That's a fair comment to make, right? So how did the trial account for those patients who had recurrences of arrhythmia? Was your strategy a little bit different? I mean, especially when you have an appendage occluder, were you more aggressive going after the appendage isolation? What percentage of patients had appendage isolation subsequently, and did it impact any of the outcomes in any form or fashion? I think that's an amazing question that we are now looking into it, but I can tell you the pre-finding. And I can also tell you what we found in the literature. As you mentioned, implantation of a Watchman doesn't mean electrical isolation, obviously. And then when you take these patients back into the lab, and we saw it mainly with the surgical ligation, then oftentimes you find rotors and you find things that you don't want to find on the appendage. And now you have a Watchman device, so what do you do? In the option trial, patients were not taken into the lab before the blanking period. So even if you have a redo, they would wait. The endothelialization allowed somehow safer procedure. But prior studies, we still don't know our results. We will look into it. But from prior studies elsewhere, I know a study from Nebraska and a study from Missouri 2017, 2019, when they went back and did ablations in patients with a Watchman device, this resulted in increased risk of stroke, increased device leak, and more recurrence. So that's a very fair point to say. We might see now good results, but what happens when they have AFib recurrence? Yeah, I think that debate will continue, right? As the push towards concomitant procedures increases, then what's the give and what's the take, right? I mean, obviously, the argument one can make is early stopping of oral anticoagulation safely, but then if patients do come back for arrhythmia recurrences, and now you may have non-pulmonary venous targets, i.e., left atrial appendage may be an important contributor, and in those cases, then how do we really manage an appendage-based trigger? I think it would be an interesting discussion to follow through. Yeah. From the limited cases that I was involved in recently, mainly with Dr. Kanj and Dr. Mwazni, it was easier to ablate now with the furropulse than how it was with the focal point RF catheter. I think maybe if we are deep enough, even if we still have some activity, it's going to be dissociated activity similar to the veins, and if you can isolate the os of the appendage, then you might get away with it, but as you mentioned, I think we need more. Can I ask you a quick question? Is there a plan to have a follow-up trial to this trial, and if so, I'm sure the intent is to use PFA, that's what we're doing anyway, but then what would you do differently in the trial if there is a follow-up trial? I think what I would do differently is first findings of remapping, and then success rate of, and then findings of also Watchmans. How many leaks do you have after you do the ablations? Now you're going to have, it's a more challenging ablation procedure that can compromise your prior successful Watchman implantation, so I think there are many questions. I'm not aware of anything that we are doing now with the option. Any questions from the audience? I have a quick question. So congratulations. Thank you. Just it's a question on the methodology, so because maybe I missed it. So my understanding is the primary trial was a non-inferiority design. Yeah. And then there was a pre-specified analysis. So is this still a non-inferiority or a superiority design, and that probably would have affected the statistical power of what you're looking at to look at arrhythmia records? That's an excellent point. This is also non-inferiority. This was captured. This is also non-inferiority. This was captured. And the non-inferiority margin? The P value in this Kaplan-Meier is a true P value that you can get from a Kaplan-Meier. Okay. So all safety endpoints, and afib recurrence was one of them, in the option trial were non-inferiority. Oh, okay. And what was the non-inferiority acceptable margin, which was? I think it was 0.04 in the option trial. So this is, you're much better. Okay. But it's a fair point. The good thing is you are way overpowered, seems to be, because you have so many events. 2% of the patients had afib recurrence within three years. So I think power issue, I think we are powered to test for afib recurrence. Yes, no? One question. So with the watchman flicks, you're having less leaks. And then when the leak happens, it depends, I think, on the severity of the leak. Most leaks that we see, we don't do anything with it besides continue monitoring, and you will be surprised to see that more than 60 to 70% of these leaks are sealed by one year. So even if you see a leak at three months, oftentimes we continue the anticoagulation, and then when we follow them at one year, the leak is non-significant. It is extreme rare, at least from our experience at the Cleveland Clinic, that we would need to implant a plug or a device to cover the leak, depending on how big the leak is. Great. Great. Thank you very much. Thank you. All right, the next trial is Dr. Mattas-Deitschever's study. No, it's not him. And that's okay. Let's see. Maybe that is not the one. It's the study, but it's not him. I will be presenting on his behalf. I'm Alexandre Almorad. Okay. If you don't mind, just go ahead and introduce yourself. Yes, I'll do that. Sure. I'm Alexandre Almarad, one of the co-investigator of the Omni-IRE study. I'm based in New Zealand, Brussels, and I'm here to report on the Omni-IRE three months result first in human study. So these are my disclosures. So this study, so to evaluate the safety and efficacy and PVI durability of the omnibus scatter when performing PVI in AF patients, it was performed across 13 centers, including 21 operators across Europe and Canada. The outcome, the endpoints evaluated here were acute effectiveness and safety, of course, profile, and a subset of patients underwent an extra protocol, including a safety protocol, including MRI, PV stenosis evaluation, and endoscopy. Another subset of patients went through a three-month mandated remap to assess PVI durability. This is the scatter, it's a basket scatter delivering PF energy in bipolar biphasic fashion. It's worth to say that this scatter is contact force enabled. I will skip this. So we enrolled 136 patients, and acute effectiveness was met in 100% of the patients with first pass isolation with adenosine proof PVI. For the safety profile, we are reporting 3% of adverse event, mainly groin and vascular access bleeding. One pericarditis most probably related to the scatter itself. No major adverse events, so no neurovascular, no deaths. Regarding the subset of patients who went the extra safety analysis, we report one patient out of 30 having one silent cerebral lesion, which was asymptomatic and self-resolving after one month. It's interesting to note that this patient underwent several catheter exchange during the procedure. We can discuss this later. From a PVI durability perspective, 29 patients underwent a mandated remap regardless to any recurrence, AF recurrence, and we report 89% PVI durability. Interestingly, most of the reconnections were on the right side, on the right PVs. Yes, I will go later. So the omni-IRE study showed that the omnipulse catheter is effective and safe to perform PVI. It has a promising safety profile and high PV durability. Yeah, that's it. Thank you. Any questions from the audience? So in your opinion, where do you think this catheter would fit in the workflow? This is kind of an interesting technology that's not like a large single shot, but it's not a focal tip, but it's somewhere in between. So how do you see this catheter really anticipate this being utilized? So I think that this catheter will fit between the single shot, most probably for permanent vein isolation only, and the more complex procedures like persistent or re-dos where you intend to do a bit more than PVI in a safe fashion. I think that if you want to perform lines, it's a good catheter because the footprint is big enough to do linear lesion with few applications, but it's also big enough to do area ablation like posterior wall. If you want to do ablate a bit more in a bigger area, I think that this catheter could fit in. The contact force, I think the contact force is an added value. If you compare it to other catheters, for example, the lattice tip where you don't have contact force, I think it could help there to achieve good lesions. Even if the lattice tip is doing a great job. Remind me again, this was not RF compatible, right? It was PF only or was it dual energy? It was and it is still not. Okay. All right. So you can turn on the RF if you want to. No, it is still not. It's still not RF. I don't know if this will come, but it is a single PF energy bipolar biphasic. Okay. So it's PFA only energy catheter. Yeah, exactly. Gotcha. Interestingly about your first question, so where it would fit is that, so when we look at the data to do a PVI, you need around 20 applications, which is at the end, if you do a complete set, you'll have like 35 applications. And this is roughly the number of applications that you would do with a single shot catheter like the pentaspline or the variables, for example. So it's around also 16 to 17 applications. Even if it's a single shot, I mean, you still do the same number of applications. Any other questions from the panel here, the audience? All right. This is it. Thank you very much. I think the next one is going to be presented by Dr. Vivek Reddy, Trial Submittee on the Multi-Electrodes Spherical Array Pulse-Field Ablation System to Treat Paroxysmal Atrial Fibrillation One-Year Outcomes of Pulse RID. Okay. Okay. Let's stretch a little bit. So I think I have about two minutes, right? Yeah. Yeah. Is this time taken away from my two minutes? Okay. Well, only if you didn't have that many conflicts. I know. I think a lot of these are repeats, by the way. I don't, it's not all real. You're doing it on purpose. It's true. Okay. So the PulseR trial was a FDA clinical trial that, and these are my colleagues who participate in the trial. So this is a multi-center trial conducted in the U.S., a few sites in Europe, and Canada. These are my own disclosures, and this device does not have regulatory approval in the United States. So let me just describe the device really quickly, and I'll show the data. So the system includes both the ablation catheter, here's the tip of the catheter, here's the handle of the catheter, as well as a mapping system. So these are all fully integrated. It's a completely integrated system. And the idea is you can put the catheter in the chamber, manipulate it around, create an anatomy, then push it up against the tissue, identify which electrodes are touching the tissue. There are different contact sensing strategies. It's actually really clever. There's a relatively quick contact sensing called flow mapping, so as you're touching the tissue, it's constantly looking at the temperature of each electrode. There's a thermocouple in every single one of these 102 electrodes that goes around. And so during the flow mapping, it's looking for a drop in the temperature. So if you're touching blood, it drops very quickly. If you're touching tissue, it doesn't drop as quickly. It gives you a general idea if you're touching. Then once you feel like you're in a good position, then you turn on the contact map. There it injects a very small amount of current into the tissue and looks to see elevation of the temperature, just one or two degree elevation. Because again, if you're touching tissue, you'll get an elevation. If it's touching blood, there'll be no elevation because the blood is flowing fast quickly. In any event, the point is, regardless of the approach to the vein, once you push up against it, some electrodes are going to be touching. Those are the ones you select to deliver energy and you can deliver pulse field energy. By the way, this system was initially designed as an RF system. So you can also deliver RF energy, interestingly. Though that's not what we did in this trial. And then of course, you treat. If you want, you can remap afterwards. The most interesting thing here is the safety profile was quite remarkable. You can see that of the 164 patients that were enrolled in this trial, and this is a single arm trial, paroxysmal AF patients, sort of a typical regulatory approval trial. We see none of the major safety events, except we did see one hemorrhagic stroke, which can occur. So there were no device-related adverse events. There was a 0.6% rate of primary adverse safety events, as defined by the study. On the effectiveness side, we see the 12-month effectiveness is 78%. And this is where all the patients had reached the follow-up, one-year follow-up point. I think it's really interesting, I think, to think about that success rate, which I would argue is quite high for a multicenter FDA trial with all the monitoring that's required in these FDA trials. There were only 10 patients that underwent redo procedures, which is a relatively small percent, 6% of the patients. But when we looked at those patients that had redo procedures, at least 95% of the veins were durably isolated. So again, this is not a protocol-driven remapping. This is clinical-driven remapping, potentially enriching for patients that have recurrences, I'm sorry, that have reconnected veins because of recurrences. But in effect, the durability was extremely high in this population. So the primary safety was quite good. Primary effectiveness, we just discussed. We didn't really discuss the workflow efficiencies, but the transplant elevation time was 25 minutes. And that includes some of the analyses that we wanted that probably wouldn't be used in clinical practice. We believe that this will take about 10, 12 minutes to isolate all the veins in regular practice. And it really is pretty much a single shot. You put it in the location, and then it delivers the energy, then you go on to the next vein. And I would argue this is one of the few catheters that seems to be demonstrating scalable durability. What I mean by that is it is durability, but it's durability in the setting of multiple operators across multiple centers, the majority of whom had never touched this catheter before the clinical trial. Only one operator had. So this is a very good durability. And I think that the 78% is approaching what we can achieve in terms of success in paroxysmal patients with durable PV isolation alone. Thanks. So Vivek, I mean that catheter looks pretty dramatic. And also when you really look at that contact points, it kind of looks really non-circular that it's all over the place. After you deliver the lesion and then when you remap it, what does that line of lesions look like? Does it look this jaggedy, geographically isolated area? Or does it look kind of cleaner? Yeah, I think part of the jaggedness is simply because each of these 122 electrodes, it's either yes contact or no non-contact, right? So in reality, what happens is part of it's touching tissue and part of it's not touching tissue. In reality, when you look at the, and I wish I had a map here, a post-ablation map, it actually looks very similar to all the other maps. Let me make a comment. I mean, the catheter does look, I forgot the word you used, but let's use the word dramatic. Okay, is that what you said? Yeah. It does look dramatic. And I've been thinking a lot about this. You know, the catheter is 30 millimeters in diameter. That's not that different than the cryo balloon, which was whatever, 28 millimeters? I can't remember anymore. But in most of these other devices, I think the major difference here is that this is fluoroscopically not translucent. You know, with most of other devices, you look on fluoro and you see something, you don't see the balloon, et cetera. This, you see the whole thing and it's there, you know? And I think that's the main difference. I also do want to point out, I mean, the safety was extraordinary here. Remember, only one operator had used this catheter before the study. Everybody else's learning curve is right there. So I think that while initially it looks, oh my gosh, it looks big and look at this thing on the end, there's a lot of technology in here. But the reason there's a lot of technology is that the procedure is easy. You go in, you push it up against where the vein is, and then some electrodes are going to be touching and you just select them and ablate. So, and by the way, this is a paroxysmal trial just doing PVI, but we have done in the first human experience, European experience, we've done posterior wall ablation, we've done mitralismus ablation, we've done CTI ablation. So all of these can be done. I kept talking about the durability of those other lesion sets. We still don't have that data yet. But the fact is, it does appear to be a relatively versatile tool. Yeah, it almost feels like it comes from a sci-fi movie when it unfolds itself with all the little rotations and the petals unveiling themselves. They don't get caught up on thrombus issues and stuff like that. So these are actually heparin coated, and no, we haven't had any of these issues. We actually did do brain MRIs in the post-EU, that was the European study. I will say, it probably won't fit very well in the coronary sinus. I don't know. Can I ask a couple of questions? Yes. Congratulations, by the way, on the completion of this study, and thank you for presenting it. Two quick questions. So the first one regarding safety, I agree. I mean, the safety results are amazing. But I also suspect that all the operators in this trial were highly experienced operators. So could you comment on that? And then the second question I have is, what's the next phase in relation to this catheter? Yeah, good points. Look, you're absolutely right. These are going to be operators that have a lot of experience, and that is certainly, I won't call it a limitation, that's the reality of it. There's a second aspect, by the way. These are FDA clinical trials, and you've seen the inclusion-exclusion criteria. This is not your general paroxysmal population. Let's be clear. You're excluding hypertrophs. You're excluding patients who have a number of things. So I think once it gets into clinical practice and we see this, the post-approval studies are going to be very important. Talking about which, I know that this has all been submitted to the FDA, so I don't know what the timeline is, but I expect approval before the end of the year, certainly, and hopefully before that. Now, this is a paroxysmal cohort. The company I know is considering – not considering. They are going to do a persistent cohort. What they're considering is whether or not to make it a randomized study, whether or not to use implantable loop recorders, which I hope that they do because I think that's information we all want to see. So these are things that they're deciding. It's a relatively small company, and, yeah, I don't know how long it will take them to make these decisions, but that's in the plan. We have two more minutes. If any, please go ahead. Well, I think anybody that can do the procedure should be able to do the procedure, certainly. I mean, I have no problem with that. I mean, I think if you're – I'm not sure if you're an electrophysiologist now, but if you want to start doing microclips, I have no problem with that either. So I think the question becomes do you have the clinical expertise and the technical expertise? The technical expertise is probably easier, but there's also clinical expertise questions, right? And, you know, what happens when the patient goes into an atypical flutter during the procedure? What happens – and these are things that require some electrophysiologic knowledge. Having said that, I think we all envision a future in, let's say, five years, seven years. I don't know what the timeline is where you probably don't need EP expertise. You can probably just move it around, and the AI algorithm in the device is going to tell you this is the flutter, this is where you oblate. And you add some robotics, and it will do it itself. So all we need to do is get access. So anyway. So one thing I would actually add is that the Heart Rhythm Society is seriously considering putting a document together regarding the training requirements that should be met before people can do these procedures. I'm just saying that we're definitely looking at that seriously. Go ahead, please. Can you repeat the question? Yeah. The question was, do we have any atypical flutter? Actually, I'm not saying anything about that here. We did not – so, again, we didn't have that many recurrences, but the recurrences so far – it is a combination of flutters and fibs, so there may have been a couple of atypical flutters, but the majority of the recurrences were atrial fibrillation. Oh, during the procedure? No, no, no. I mean, maybe there was one or two. There were some typical flutters. If patients had typical flutter, then one in this study had to use an RF catheter. When we did this study, we actually hadn't done the work on using this catheter to do CTIs and S-lines yet. In the persistent study, which is going to happen, the plan is to use this catheter not just for PVI, but also for CTI if needed, and potentially also other left atrial lesion sets, including posterior wall ablation, voltage abatement, if there's some data supporting that, as well as some not supporting it, as well as micro isthmus lines. So all these things – I mean, the hard part is if you ask five electrophysiologists what the study design should be, what should you randomize, you're going to get 10 different answers. So we have to coalesce and come to something that's practical. What do you think the cost of this type of catheter would be? Well, I don't know what the cost is, but I know how much the hospital is willing to pay for it. That's what I know. I mean, look, the one good thing is that – this is complex, by the way, but these are all printed electrodes, so I don't know anything about cost of goods sold. But my understanding is they feel like they can create it for a price, that they can sell it at a level that we pay for it, and that they can make some money. So we'll see. May I ask the last question? Yeah, go ahead. Just for the 1.2 – thank you. Just the 1.2 application per vein, so it's roughly like five applications per patient. And where was it? Do you know? Was it like mostly the carina, mostly the roof? Was there a pattern where you had to do an extra application? Yeah, I don't have that data. You know, the main reason typically for doing an extra application was during the application, if for some reason the patient moved, the device moved, whatever, that's usually the reason why people deliver an extra one. You know, the veins get isolated on the very first lesion. The question is trying to get durability. Great. Well, thank you guys very much. Thank you all.

clinical trials

ventricular tachycardia

atrial fibrillation

GLP-1 receptor agonists

CT-guided ablation

female representation

MRI model-based CRT

Watchman device

catheter technology

electrophysiological interventions