Okay, welcome everyone. I think we'll get started with this session, High Impact Science, Novel Technologies and Approaches in Catheter Ablation. Welcome. My name is Ben Steinberg from Denver, Colorado. I'm joined by my co-chair, Dr. Mehta from Michigan, and first we'd like to welcome you and remind you that if you haven't already, the HRS 2025 app can be downloaded and that's where you can submit questions online for us to post to the speakers. So I believe there is at least one microphone here to pose questions. As you see from the program, we'll have a speaker followed by commentary for two minutes. There isn't a lot of Q&A time, which we hope to get to, although if speakers went over, we may move on to the next speaker. So thank you all for attending and I'll turn it over to Dr. Mehta. Good morning everyone. Thank you so much for being here. Let's get started with Dr. Musa Mansoor. He'll talk to us about the impact of linear ablation and persistent atrial fibrillation on outcomes using a dual energy, dual footprint ablation catheter analysis from the SPHERE persistent AFib clinical trial. He joins us from Boston. Thank you very much for the introduction and thank you all for attending this presentation. I'm presenting this data on behalf of my co-investigators for this SPHERE AF study and these are Dr. Teigen, Sharma, Kiel, Neer, Nuzel, Kotsner, Osorio, Natale, Montonakates, Hamel, Amin, Doshi, Siddiqui, Sirkvinik, Van Braak, Tarakji, Antwerp, and Vivek Reddy. So as a background for our study, pulmonary vein isolation for atrial fibrillation has been yielding unsatisfying results for persistent atrial fibrillation. Having said that, there's no proven benefit for any adjunctive ablation therapy for persistent atrial fibrillation. The wide footprint nine millimeter dual energy catheter, the lattice tip catheter, has the potential to create contiguous and durable lesion which could increase ablation success. So the study we are presenting today is a sub-analysis of the SPHERE AF study. SPHERE AF is, just as a reminder, it was published a few months ago. It is a randomized study for patients with persistent atrial fibrillation, randomizing them to ablation with the SPHERE catheter versus standard commercial RF catheter. And the primary results were non-inferiority in primary safety and efficacy endpoints. So the objective of this current analysis was to assess the impact of linear ablation strategy on acute and 12-month outcome in persistent atrial fibrillation. And the linear ablation that were performed in the study consisted of the following. Persistent atrial roof line, posterior wall ablation, and the floor line to ablate the posterior wall, mitral isthmus ablation, and caveotrous cuspid isthmus ablation. This is a distribution of how often these ablations were performed. The green column is SPHERE 9 group, the RF is a purple column. The LA roof and the posterior wall was done in 96% of the patients in the SPHERE 9 group compared to 67% in the control group. CTI line, 55% in the SPHERE group versus 67% in the RF group. Mitral isthmus line, 36% in SPHERE 9 and 12% in the RF group. Here is the acute success of these lesions. For the roof and the posterior wall in the SPHERE group, 100% success, RF group also 100% success. CTI line in the SPHERE 9, 100%, RF group 100% success. For the mitral isthmus line, all patients had acute success with the SPHERE 9 group. In the RF, there was only one patient where this line could not be performed. This slide illustrates the ablation time. So the total ablation time is shown in the first column here. The green bar is the SPHERE group, the control is purple. And the procedure was significantly shorter with the SPHERE 9 group. And all these columns, bars represent the time for individual ablation lines. As you see across, the ablation with SPHERE 9 for all these individual components of the procedure, were shorter with the SPHERE 9 compared to the control procedure. Similarly to the total ablation time, this is energy delivery time. The difference is much bigger now because for folks here who have used this catheter, the ablation duration is very short, like four seconds per application. This translated into a significant difference in the total ablation time delivered. Seven minutes for ablation compared to 30 minutes overall. And these are all the individual components of the procedure showing significantly shorter ablation with the SPHERE 9 catheter. So as you all know, the SPHERE 9 catheter is a dual energy catheter. So it can be used for RF and PF. And in this slide, I'm showing what the energy used for those in the SPHERE 9 group, which energy was used for each of those individual lines. So for the PVI, the majority of the lesions were done with radiofrequency ablation. The roof line, mostly, I'm sorry, I said radiofrequency is pulse field ablation. So pulse field is green and RF in red. For the roof line, mostly pulse field ablation. Floor line, mostly pulse field ablation. CTI line, mostly RF ablation because of the concerns of coronary vasospasm. And this is one of the advantages of this procedure. You can toggle between RF and PF. Mitral isthmus line, mostly pulse field ablation. Anterior mitral isthmus line, mostly more RF because you don't have to worry about the esophagus when you're ablating in the anterior left atrium. So this is the chronic primary efficacy success for patients receiving each of these lines. So if you look at all cohorts of both groups, there was a trend toward improved outcome when patients underwent PVI versus PVI plus anything. And when the patients got all those three lines, the success rate was better. Again, this was a small number of, when you divide the study, small number of patients. So this study was not powered to show this. But you see a trend toward improved outcome. You see the same trend with the Sphere 9 group. And there was no difference in the RF group when you do additional lines. So in conclusion, the Sphere 9 catheter can be used efficiently to achieve PVI as well as adjunctive linear ablations. The transpired ablation time and energy delivery time were shorter for each lesions with Sphere 9 catheter compared to a traditional small tip RF catheter. Acute success with Sphere 9 was 100% with no non-study device used to achieve block. So all of them were done with an investigational device. Adjunctive ablations in Sphere 9 resulted in a trend towards increased effectiveness versus PVI alone. And we believe that these findings are hypothesis generating to further evaluate adjunctive lesion sets versus PVI with the Sphere 9 group and a larger randomized clinical study. And thank you for your attention. We will now invite commentary from Dr. DeWalter on this study. Ladies and gentlemen, first let me congratulate Dr. Mansoor for successfully conducting such a trial. Can we start my? You should be able to click when you start it. Start. Okay. But let me give you a few critical comments and perspectives on that presented data. And first of all, I think you mentioned, Dr. Mansoor, that the PVI plus procedures didn't show any proven benefits. And that's why I'm a little bit asking when you come with a new concept and you compare it to a gold standard, which is a proven effective therapy, non-inferiority is, I think, fine. But if you bring something new and the standard is not really effective, as you said, I would love to see some form of superiority. So that's maybe one of my first points. And you have to also answer the question, how comes and how is the relevant difference among groups and the amount of LAA roof and posterior wall ablation effective clinical outcome? We have significant differences here in a randomized trial, which brings, I think, a relevant bias into the result concerning the different technology. And another point is, and I think this needs some explanation, you need 68 applications for PVI isolation as the mean number of application, which is 70 applications per vein when I'm correct, which is a high number of applications. And did you check for hemolysis, renal function when you add 68 applications and add some more for substrate modification? Let me come to the chronic effectiveness success. And to me, I've always the question when I see trials about persistent AF, the question is, is the concept of targeting extra PV sites wrong? Or is the execution of a correct concept erroneous? So we get no persistent lines of conduction block. And I think looking to the, well, variety in group sizes, like six only PVI in that group, but only three patients who have received everything in addition to the PVI isolation in the RF group. We have a lot of inhomogenities in the group, so I think we cannot answer this fundamental question. But I think it would be nice to comment why do we have those disbalance in the treatment groups. To summarize and to come to the end, I think the big point is this fast procedure times, which is really impressing, but I agree the trend towards a better outcome in PVI with additional lesions requires more prospective data. Thank you for your attention. Thank you. Thank you both our speakers. I think in the interest of time, we'll move on. We don't see any burning questions either. So our next presentation will be by Dr. John Hummel, rehabilitation in patients with documented isolated veins using a tailored approach to our electrogram dispersion, the restart trial. So, Dr. Mehta, Dr. Steinberg, on behalf of the investigators for the RESTART trial, I have my pleasure to present reablation in patients with documented isolated veins using a tailored approach targeting electrocranial dispersion. So, if you look at historical outcomes of redoablation in patients with durable PVI, freedom from any atrial arrhythmia is a little disturbing with freedom ranging from 29 to 52% with an average of 39%. There is no consensus for the ablative approach in these patients. We recently published in Nature Medicine the tailored to F trial which in persistent AFib patients randomized the cohort to either pulmonary vein isolation or pulmonary vein isolation plus an AI-assisted spatial temporal dispersion mapping. And the tailored arm had a superior freedom from atrial fibrillation as well as from atrial fibrillation in AT after 1.2 procedures per patient and after one procedure per patient and persistent AF lasting greater than six months. So, the question arose, could this approach be applied to these patients with durable PVI and recurrent AFib? Now, spatial temporal dispersion mapping aims to target anatomically clustered regions of greater than or equal to three bipoles with activation spanning over the AF cycle length suggesting localized re-entrant conduction. So, 213 patients were consented in this trial, 29 investigators at 20 sites, four countries and it was an interventional single arm prospective non-randomized trial of tailored ablation of AI-detected spatial temporal dispersion for the treatment of symptomatic AF recurrences and people with durable PVI isolation. Twelve-month follow-up was undertaken with visits at 3, 6 and 12 months and at each visit, patient underwent a 12-liter EKG as well as a minimum of a 24-hour Holter monitor but you can see here 76% of the monitoring was more extensive including 26% of patients who were monitored via their implantable device. Quality of life scores were obtained as well as clinical symptoms. Study design, we included patients with previous ablation of paroxysmal persistent and long-standing persistent AF with documented symptomatic AF recurrences within the last 12 months. We excluded people with excessive obesity, excessive left atrial dilatation and a severe heart failure. The main endpoints were freedom from AF at 12 months, AFAT at 12 months and AFAT burden reduction as well as quality of life improvement scores and a safety composite endpoint at 12 months. So eligible patients underwent assessment for durable PVI isolation. If they had reconnection to the pulmonary veins, they were withdrawn. If they did not, if they did have durable PVI isolation, then they underwent a tailored mapping approach and index procedure. They were allowed a repeat procedure and then the 12-month follow-up ensued. In terms of workflow, biatrial, AI assisted, high density dispersion maps were obtained in AFib and dispersion ablation aimed to achieve AF termination or regularization with elimination of all dispersion areas and connection to anatomic barriers. For those that had induced AFib, reinduction attempts were required. So in terms of results, the study population was 213 patients and at the index procedure, PV reconnection was the main reason we lost patients. In 80 patients with PV reconnection, non-disability of AFib was the other largest group. We had 96 undergo a successful index procedure and then at three-month follow-up, six-month follow-up, there was some minor attrition but giving us 84 total patients with 12-month follow-up and we have four patients sitting out there nearing the end of their follow-up window. I want to point out here, in terms of the study patient characteristics, half the patients had significant obesity and sleep apnea and roughly half the patients had two or more ablations with one patient having four prior ablations. The mean duration of their history of AFib was eight years so this is a pretty recalcitrant group of AFib patients. The procedure characteristics and safety events, the procedure duration was 149 minutes. Keep in mind, these were RF procedures. And interestingly, as expected, 96% of the patients had dispersion sites in the left atrium but 59% also had dispersion sites in the right atrium. Conversion to sinus rhythm was achieved in 47% of the patients. You can see here the safety profile was very reasonable with one pericardial effusion and one TIA and other things such as vascular complications we would expect with ablation. These are the results from AFib after a single procedure was 87% and in freedom from AFAT after a single procedure was 69%. When we look at patients without any class one or three anerythmic drugs on board, freedom from AF was similar at 87% and 74%. 14% of patients had their drugs briefly held at the time of the case and then continued on them afterwards and 30% had some drug reintroduction at some point in the ensuing 12 months. Interestingly, patients for which AF was terminated during the index procedure had freedom from AF at a year of 96% and freedom from AFAT of 80%. The overall AF effect on quality of life scores rose dramatically by 20 points and were sustained through 12 months and their general quality of life scores also were statistically significantly improved and persisted. So in conclusion, there is no consensus for the ablation approach in this complex population with recurrent AF despite durable PVI. Past clinical trials of different strategies of ablation have yielded arrhythmia-free rates of only 30% to 50% and AI-guided dispersion ablation thus offers a promising approach for these patients with freedom from AF after a single procedure of 87%, AFAT after one procedure of 69% with improvement of quality of life and a safe procedure profile. I wanna thank you for the invitation to present this and all the investigators for the trial. Thank you. Thank you, Dr. Hummel. We'd like to invite Dr. Garg up from Loma Linda to provide commentary on the study. Good morning, everyone. Thank you, Program Chairs, for the invitation. It's an honor to be here. And I congratulate Dr. Hummel and the entire team for the successful completion of the trial. So we all know, pulmonary vein isolation remains the holy grail for AF ablation. However, the ideal ablation strategy beyond PVI remains unknown. Let's go back again to tailored AF, published this year and presented last year. It was a randomized one-to-one study comparing a tailored approach, that is PVI plus AI-guided EGM ablation versus anatomical-based approach, which is PVI plus any lines at operator discretion. Freedom from AF was significantly higher in the tailored arm, both in terms of one year in per protocol and intention-to-treat analysis. If you look at the secondary efficacy endpoints, it narrowly missed statistical significance. Let's compare the results to restart trial just presented right now. Exactly similar results. 88% last year, 87% in the restart trial. So was the freedom from ATF slightly higher, 71% or 69% as compared to 60%. In fact, the rates for AF termination and sinusoidal conversion between the two trials were exactly similar. What does exactly this mean? Let's compare to STAR-AF1 and STAR-AF2, published 15 years ago. Results were 74%. And if you compare the freedom from AF between STAR-AF1 and STAR-AF2, striking difference, 74% versus 51%. Again, pointing towards the fact that there's a lot of interoperative variability, which is not there in restart trial, suggestive that it's an AI-guided model, better notation for the EGMs. And again, STAR-AF was a complex CAFE ablation rather than an AI-guided EGM dispersion ablation. Reproducible results, as we can see here, ease of use and rapid learning curve. But there are few unanswered questions in the current trial. 40% of the patients in the current study had paroxysmal AF, and therefore, would the clinical outcomes matter depending upon the AF burden for paroxysmal AF, as well as AF subtypes. At the bottom, what you see is a graph from STAR-AF. If you notice here, PBI plus CAFE ablation in the paroxysmal arm was no different as compared to PBI alone in the paroxysmal AF ablation, versus a significantly higher freedom from AF episodes in the persistent group. The comparison analysis between the AF termination and the sinusoidal conversion remains unknown and needs further investigation. Would pulse-filled ablation make a significant difference or maybe produce better results? And therefore, we need a comparison between a PF and a thermal-based approach. And what's the impact on the mechanical LA function? Clearly, we see that there's a dispersion both in the LA and the RA. Would extent of ablation impact the mechanical LA function? We all know pulse-filled ablation can actually cause acute LA stunning. But over the period of long haul, the compliance, the booster function, and the reservoir function of the left retirement does improve. So would that approach be a better option? And lastly, is it time for us to modify our clinical outcomes from looking into sinusoidal conversion to AT conversion? Because we all know AT is a simplified rhythm and organized rhythm, much more easier to ablate. Nonetheless, I think Dr. Hummel and the entire team provides a mechanistic endpoint into AF and it paves a path for a tailored approach to be considered in future for AF ablation. Thank you very much. Thank you. Thank you very much, Dr. Garg. We will move on to the next presentation on initial clinical experience using the TactiFlex Duo system, safety and acute efficacy by Dr. Sheth from Medical University of Graz. Thank you. So dear colleagues, on behalf of all the co-investigators and among these very sophisticated studies that we've seen, I'd like to present the preliminary results of the FocalFlex approval study. Here are my disclosures. A little bit of background. What you see here is a central illustration of a review. We, with Julian Jun as first author, published in Europace a year ago showing the evolution of PFA. And you've all been part of this journey, starting, most of us starting out with the pentaspline catheter, but the field has evolved. And to show you how much this field has evolved, you see the graph we had in there, 50K PFA ablations a year ago. Now we are talking about well above 300K PFA ablations worldwide. And it had also evolved in a way that we are entering the era of dual energy solid tip catheters among the M.A.T.E.R.I.U.M. One of those is the TactiFlex Duo system based on the tactical platform allowing 4F ablation. It adds deliberately of monopolar biophasic PFA ablation in a nominal and a low waveform. And I'll get back to that. It's embedded in the N-site system allowing for automarks and contact force indicators. And preliminary work, animal work, indicated that single applications, with a single application, depth, lesion depths above five millimeters can be reached and the growth increases with repeated applications up to 10 plus millimeters. The system has two waveforms, a so-called nominal waveform, four seconds per application. It's supposed to be optimized for GA. And the low waveform monopolar biophasic 2.1K volts, up nine seconds per application, so a bit longer, optimized for deep sedation. Again, I'll get back to that. Now the FocalFlex approval study, 25 sites worldwide, 147 symptomatic paroxysmal AF subjects, primary endpoints, seven days safety, and six months freedom from AFAT recurrence. And the patients are followed up for a total of 12 months. Now please keep in mind that the last patient was included four months ago. So all I can present you today is early procedural and safety data of the FocalFlex study. Some procedural details, the typical paroxysmal patients you may have in your lab, 62 years of age, BMI of 28, CHA2S2-RAS score close to two, fairly normal left atrial size. A little bit about the procedural workflow. Pre-procedure, a voltage map was mandatory. The PVI could be done with either PFA or the combination of PFA and RF. Why the combination? Because PFA was mandatory on the posterior wall of the left atrium. RF was mandatory for the CTI and for all areas presumed to be close to coronary arteries. And the PVI plus strategy was allowed at the operator's discretion. Now again, two settings, nominal or low. We were aiming for four millimeter interlesion distance. And please keep in mind that also a remap was mandatory, plus a 20 minute waiting period, plus entrance and exit block pacing, so a very diligent protocol. Here's just one of the 21 cases that we performed at our center. You see here the ablation starting close to the right superior pulmonary vein and the color-coded tags indicating the PF applications being done. It was mandatory to reach a contact force of above five grams, and it was advised to go above 10 grams. Some procedural characteristics, total PV ablation time, 43 minutes. You see the left atrial dwell time. For the total procedure time of 109 minutes, please keep in mind that that includes the 20 minute waiting period and the pre and post procedural maps. I think decent fluoroscopy time. And what strikes out is that for all, if you look at all the patients, that 91% of cases, for the PVI at least, were done with PFA only. And the graph on the right indicates that for most of the pulmonary vein ablations, it was PFA only, whereas for the extra-pulmonary ablation, also in 63% of all cases, it was PFA only, and in 25%, it was a combination of PFA and RF for the remainder. It was RF ablation only for extra-pulmonary vein ablation. But again, 91% of all cases, PVI only done with PFA. Sedation, at our center, certainly all patients done in deep sedation and on the same day discharge protocol. Overall in the study, 35% of patients done in deep sedation, and at a later conference, there will be a sub-analysis on that. Ablation targets, 80% PVI only, 20% PVI plus, and for the waveform, and I told you I'll come back to that, whereas the low waveform is optimized for deep sedation, at least in the operator's hand, it wasn't deemed necessary, so most of the operators stuck to the nominal only, higher voltage applications, also in the deep sedation cases. You see on the graph on the right, the targets outside the pulmonary veins, again, RF only for the CTI, and then posterior wall roofline, done largely with PFA. Acute effectiveness per vein and per patient, 99% PVI isolation rate, and first pass isolation rate, 94% on a per vein basis, and 90% on a per patient basis. This is the acute safety result. The primary safety event rate was 1.4%, based on one cardiac tamponade and one transient ischemic attack. Of note, there were two more patients, not part of the primary safety endpoint, but I can't talk about it because both patients occurred at our center with the wide circumferential ablation approach that we try to employ in our patients. We had two patients where we inadvertently blocked the roof as part of a PVI only strategy, so that's a signal that needs to be further looked at. In conclusion, the first results from the FocalFlex study of a dual-mode PFA ablation system demonstrate a decent acute safety and effectiveness of the system for ablation of symptomatic paroxysmal atrial fibrillation, and a longer-term follow-up will be presented at further conferences. At the end, I'd like to thank all FocalFlex centers and investigators, both in Europe and Australia. Thank you very much. Thank you. Okay, hi everybody, thanks for the invite to be here. Congrats to the investigators on the FocalFlex study. So I have no disclosures. So this FocalFlex study, as we just heard, about 150 patients with proximal atrial fibrillation utilized a novel dual system modality system that integrates both PFA and RF. And this allows for more of a tailored focal ablation rather than wide area ablation. And this was also a force-sensing catheter too, so that may enhance lesion precision, may lead to better outcomes durability-wise too. Integrates with Insight, it can support both general anesthesia and conscious sedation. But importantly, what this prelim study shows is that there's very high acute success, nearly 100% and very high first pass isolation of 90% too. Safety profile is promising, 1.4%. As mentioned, this was driven by pericardial effusion and a TIA. But there are some limitations. This is a single arm, non-randomized trial or study. It lacks a comparator arm, so how it compares to other systems on the market is still unknown. We only have short-term data. The long-term data is still needed to really define long-term results from this. And there was pretty significant protocol variability too. There was, as I mentioned, with the sedation requirements and with the lesion sets that varied from site to site or patient to patient too. And with any new system, there's always a learning curve. Whether or not that may influence outcomes is unknown. And real-world data is still needed too. So as we look forward, long-term data, of course, will be crucial to assess durability, sustain efficacy. Comparative trials against RF modalities, other PFA modalities on the system will really help define its clinical positioning. There's potential to expand to persistent AFib, other strategies beyond PVI. How it performs in the ventricle is still unknown. Impact on collaterals too, so how much hemolysis it causes, whether or not that may lead to renal failure, how it impacts the LA function too is still unknown. And with a dual modality system that can leverage both PFA and RF, the appropriate role of both with regard to lesion sets is undefined too. With that, thank you all. Thank you. We can break, we're doing very well on time, so we'll have a quick question that was from the audience. It's for Dr. Hummel. Have the Volta maps ever been examined for reproducibility, so has AFib been mapped if the individual was asking this, but I haven't used the Volta, I've used the Ablicon. So when I remap, I guess when I map, before I ablate and then I remap, it's consistent. So did you notice that in the workshop? Well, I can tell you this. I've used both the Ablicon and the Volta system. If you're doing an ablation, you don't have termination, you remap with the Volta, it is reproducible, the location, and it's always a lack of effective ablation. So from my own personal experience, I can tell you that much. So it is, in the individual case, it is. Right. But in terms of people that have had a Volta-guided ablation and then had recurrent AFib, whether the exact locations align, I'm not sure. Thank you. Okay. I think we're going to move on. Next, we'll invite Dr. Patel up to discuss pulse-field ablation of the mitral isthmus, transmurality and autonomic effects validated with vein-of-martial recordings. Okay. Thank you for the opportunity to be here today. I'm very excited to present our results to you regarding pulse field ablation on the mitral isthmus. As a new technology, we wanted to investigate the ability of pulse field ablation to create durable transmural lesions on the posteromitral isthmus. From the era of radiofrequency ablation, we know that mitral isthmus tissue thickness, coronary flow, adipose and epicardial connections are barriers to mitral block. We also know that ethanol and the vein of Marshall improve rates of mitral block, and in addition, improves ablation outcomes in patients with persistent atrial fibrillation. This has been demonstrated in two randomized trials, the VENUS trial on the right, led by Miguel Valderraban and colleagues at Houston Methodist, and the PROMPT-A-Fib trial. The vein of Marshall harbors parasympathetic innervation that contributes to the maintenance of A-Fib. Thus, ethanol not only aids ablation via mitral block, but also confers benefit via autonomic innervation of the vein of Marshall. In the panel below, we see that pre-ethanol high-frequency stimulation from a vein of Marshall catheter not only induces A-Fib, but a parasympathetic response. Post-ethanol, this response is attenuated. In contrast to radiofrequency ablation, PFA is noted to have myocardial-specific effects with neural sparing. In the panel below, in an animal model, PFA was performed directly over the phrenic nerve. And four weeks post-procedure, you can see there's no changes macroscopically or microscopically in nerve function. So in this context, we wanted to ask two questions. One, can PFA create transmural lesions on the posterior mitral isthmus? And two, does PFA have acute effects on autonomic function? And we felt that the vein of Marshall was a great way to study these hypotheses, given A, our ability to cannulate it and record electrograms from it. And in addition, we can perform high-frequency stimulation from it to test its autonomic function. The experimental design was as follows. First, we placed a two-french octopolar catheter in the vein of Marshall. We then performed high-frequency stimulation from the distal electrode to assess for a parasympathetic response. We then did pulmonary vein and posterior wall isolation and then mitral isthmus ablation with one of three commercially available systems. We then paced from the appendage and the distal vein of Marshall catheter to assess for mitral block. And again, we did high-frequency stimulation to assess for a parasympathetic response. We then infused ethanol from distal to proximal fashion. And we again did differential pacing and high-frequency stimulation. We studied a total of 40 patients with a mean age of 71 years, a slight male predominance, and a mean ethanol volume of 7 cc's. 15 patients underwent ablation with FaraPulse, 16 with the Fara, and 9 with PulseSelect. Our results are as follows. With respect to mitral block, PFA alone as a sole modality was able to obtain mitral block 27% of the time. 49% of patients required PFA plus ethanol in the vein of Marshall. An additional 24% of patients required coronary sinus ablation to obtain mitral block. With respect to high-frequency stimulation, 17 patients had an initial parasympathetic response to high-frequency stimulation prior to PFA. Post-PFA, only one patient lost that response. And after ethanol, all patients demonstrated autonomic denervation and did not have a parasympathetic response. I'd like to show you some representative examples. This first patient, we were able to obtain mitral block with PFA alone. You can see that prior to ablation, there were robust electrograms in the vein of Marshall catheter. PFA is then applied. And post-ablation, there's absence of electrograms. And more importantly, the electrograms remain absent over time. They're temporally sustained. When we then paste from the appendage, we see a proximal-to-distant pattern on the coronary sinus catheter and no capture from the vein of Marshall catheter. In a second example, you can see we're performing PFA with the pentaspline catheter directly over the vein of Marshall catheter. This is a visualization of that catheter on the mapping system. And post-PFA, this is a bipolar voltage map. Again, you can see initially, there are robust electrograms on the vein of Marshall. Post-ablation, these electrograms attenuate. However, after 15 minutes, there's reemergence of the electrograms, and mitral block is not present, although not shown here. We then administer ethanol, and now you can see there's complete absence of electrograms. And when we paste from the appendage, we have a proximal-to-distal block pattern on the coronary sinus catheter. In a third patient, again, you can see there's attenuation of the VOM electrograms, but they are still present. When we paste from the appendage in this patient, initially, both the coronary sinus and the vein of Marshall are activated in a proximal-to-distal fashion, which is consistent with block. However, after 15 minutes, the block pattern was lost, and ethanol was delivered. Finally, in a fourth example, we have what we call pseudoblock, or endocardial-epicardial dissociation. In this example, in the middle panel, when we paste from the appendage, you can see that there's initially a coronary sinus block pattern on the catheter from proximal-to-distal. However, when we look at the vein of Marshall activation, it's distal-to-proximal, which is consistent with the epicardial connection. In the right-hand panel, we then paste the distal vein of Marshall, and we can see that the vein of Marshall is activated again, distal-to-proximal, and the coronary center catheter has fusion. Thus, in this example, while we have unidirectional block on the coronary sinus endocardially in one direction, we do not have epicardial block. The relevance of this is that without a vein of Marshall catheter, there's no way to distinguish whether you truly have transmural block or just endocardial block, and if you just go off the coronary sinus activation pattern, you could be misled. Again, in a subset of patients, we directly perform PFA within the coronary sinus. These patients already underwent endocardial ablation and ethanol and still do not have block, and this is consistent with our data and data from the Bordeaux group that shows that their coronary sinus, the left atrial connections, which need to be disrupted with ablation in the CS, and at times, CS disconnection is necessary to obtain mitral block. Now I want to move to high-frequency stimulation. In this panel, prior to PFA, you can see the patient is in sinus rhythm. High-frequency stimulation creates direct local capture, induction of atrial fibrillation, and a parasympathetic response. Post-PFA, you can see that there is an ongoing parasympathetic response to high-frequency stimulation, and then ethanol is delivered, and now you see there's no longer any direct atrial capture, no parasympathetic response, and no induction of atrial fibrillation. So to conclude, PFA, independent of the ablation system used, does not consistently lead to mitral isthmus block. Certainly this may change as waveforms are optimized, as the technology progresses. There's a lot of interest in the synergistic effects of sequential PFA and RFA, but at the current time, we feel there's an ongoing role for ethanol in the vein of Marshall to obtain durable mitral isthmus block. In our experience, complete and sustained loss of vein of Marshall electrograms over time is consistent with block. When these electrograms recur, we tend to see the block patterns lost. Pseudoblock, or endocardial-epicardial dissociation, is only revealed with vein of Marshall electrograms and differential pacing. Without electrograms in the vein of Marshall, a coronary sinus pattern alone may suggest block even though it is not present. At times, coronary sinus ablation is required to disrupt coronary sinus left atrial connections. And finally, PFA does not affect the parasympathetic response to high-frequency stimulation, whereas ethanol abolishes autonomic innervation to the vein of Marshall. Thank you. Thank you, Dr. Patel. We'll next invite Dr. Raja Gopalan up to provide commentary. Thank you, Dr. Patel, for giving a very elegant presentation. I have no disclosures pertaining to this talk. So PFA and lateral mitalismus is the new kid on the block to see for, especially for mitral flutters. The authors have shown that it's important to consider mitalismus as a three-dimensional structure and not just a two-dimensional structure and with endocardial and epicardial connections. PFA, in the study, has been shown, similar to RF, has pitfalls in the lateral mitalismus. There is a need for CS ablation with or without ethanol infusion in nearly 25% of the patients. And the authors have also shown the importance of vein of Marshall electrograms and pacing in confirming the true block across the isthmus. And in real world, I feel this is grossly underutilized and differentiating between true block and pseudoblock. In regards to the study data, it raises a lot more questions than just answers. We all agree that there's limitations to lateral mitalismus ablation requiring multimodality ablation. The group here from San Diego, Jonathan Sue et al., have shown in their meta-analysis in radiofrequency ablation that an antiremital isthmus ablation has better outcomes compared to the lateral mitalismus ablation because of the effect of CS. The authors have also rightfully pointed out the impact of autonomic modulation in this region, which is lacking with PFA. Whether that creates a difference in persistent atrial fibrillation patients is to be seen, and we need large-scale data to assess this. Also another important thing that has been raised by the authors, which is the durability of this lesion set, with PFA, we are not sure what the long-term durability is, and we certainly don't have follow-up maps in a lot of the studies, and they're small size to make that determination. Last but not least, the catheter design and waveform have to be looked into, too, because there needs to be a catheter that needs to go into the CS and do additional ablation, so this is something to be studied, too. Thank you. Thank you, Dr. Rajagopalan. Moving on to our last study, novel ultra-low temperature cryoablation system for ablation of ventricular arrhythmias, a multi-center experience, by Dr. Carl Heinskamp. Okay, Dr. Mitter, Dr. Steinberg, ladies and gentlemen. So I'm replacing Professor Tilts, who yesterday late made a live ablation demonstrating the efficacy of Volt. And it was 9 o'clock in Germany, so it's difficult if it's 9 o'clock in Germany to be next day here in San Diego. So he was asking me to take that presentation over, which I do on behalf of all the investigators of this interesting study and interesting technology. So these are the disclosures. So ultra-low temperature cryoablation is using near-critical nitrogen refrigerant near its boiling temperature of minus 196 degrees Celsius. Lesions can be titrated from 4 to 10 millimeter in depth and can penetrate also chronic scar, which has been demonstrated experimentally. Transmural contiguous and durable lesion in preclinical animal models have been demonstrated. And the question comes up whether the size of lesion that can be made using this technology should and can improve outcome in VT ablation, where we still are struggling with. So the first publication was done in 2024, the CryoCure VT study. And that study demonstrated, as you probably know, it's a multi-center trial in nine centers across multiple centers in different countries. Total of 64 patients were included with ischemic or non-ischemic cardiomyopathy. And as you can see, 60% of people were free from any VT and 81% of the people were free from ICD shocks. So as shown in this example, if you make a direct comparison between the cryo-balloon technology, you can see that cryo-balloon technology requires pressurized liquid nitrous oxide, which is going from the tank of the console into the balloon. And it's creating an interface temperature of minus 60 to minus 40 degrees with a tissue temperature around minus 15 to plus 15 degrees Celsius. Now in contrast, using the Adagio medical ULTC technology, let me go back. As you can see here, it's using liquid nitrogen, which is delivered from the console and then also goes back into the console, but it's reaching temperatures, as you can see, of the tissue between minus 40 to minus 60 degrees. So it's a much and significantly lower temperature as what we are used to see if we are using the cryo-balloon. So as you can see here, this is the catheter that is used. It's a nine French catheter. It has a 15 millimeter, 1.5 centimeter ablation element and eight electrons on this element, which is used for recording purposes. Now our study was done in seven tertiary ablation centers, and the aim again was to evaluate the safety and efficacy of this novel ULTC system in patients undergoing both catheter ablation for ventricular tachycardia or ventricular PVCs. Now to make a long story short, as you can see here, patients were done in deep sedation. Transseptal cheese was done using the 10 French Zupka, which was nicely fitting for the nine French catheter, as I talked about. For mapping, either the BioSense catheter system or the Abrainsat system was used, and as you can see then, the energy was delivered via the V-class catheter and was titrated according to the recommendations that are shown here to you. So for a lesion depth of 4.5 centimeter, one freeze and thorough freeze application was done for one minute, and the maximum, as you can see here, would be for a lesion depth of 13 millimeters that you would require a freezing time of five minutes. So this is the patient populations, rather young patient population, mean age is 65. The ejection fraction was low at 35%, and as you can see, 59% of the people were in heart failure due to ischemic cardiomyopathy or dilated cardiomyopathy. 50% of the people had an ICD implanted, and most importantly, 40% of our patients had previous VT, PVSC ablations, which failed. Now the mean procedure time was 150 minutes, fluid time 12 minutes, the freezing time was 30 minutes, and the mean freeze temperature was minus 161 degrees. The number of freeze cycles were eight plus minus six, induction of VT, as I will show you in a minute, was in 88% of the people performed and done, and the number of induced VTs were two plus minus two. So this is an example of a patient with an ischemic ventricular tachycardia. As you can see, there's a substrate mapping, and in this particular patient at this region, we could see this very late potentials, and in some of these leads, you can see even later potentials, and this is the map that has been obtained with the same high frequency catheter after the freezing of this entire regions over here, and what is really different from a lesion formation using a radio frequency count in this type of population, that you can really eliminate all the potentials. Sometimes using radio frequency, we know that we can lower the potential, we can make it smaller, but here you really clean everything up using this ultra-low cryo-temperature device. Now this is an example of a patient with non-ischemic ventricular tachycardia. On the left side, you see the endocardial map, and on the right side, the epicardial map. Now the endocardial substrate in this particular patient was extremely small, if existing at all, but as you can see, there was a large substrate epicardially at the antireceptor region, at the apical region, and then we did something which I think is quite interesting. As you can see here, this is recording that has been obtained from this epicardial catheter, and this is the recording that comes from the ablation catheter that sits endocardially. Only endocardial applications were done in this particular study. Now I just would like to take your attention to the fact that there is a very high frequency potential at the end of the QS complex, like a lava potential, and if we start freezing from the endocardial site, you can easily appreciate that that high frequency potential totally disappears after a couple of seconds, almost one minute, and it stays away until the application is done and finished. Now we don't know whether that means that we reach really the epicardial site. You could also have, of course, block inside of the tissue, but at least, as you can see here, you see again this high frequency potential. Now we restart the movie, and it's interesting to see that you can affect at least the epicardial surface by an endocardial application. Now here I just want to show you, because I've discussed this already, that in all of the patients, almost in all of the patients, substrate mapping was performed, and then in some of the patients, either pace mapping, activation mapping, or entrainment mapping. Now these are the acute results that I'm going to present today. So VT induction was performed in 39 of the 42 patients, was sustained ventricular tachycardia. In 34 out of the 39 patients, VT was inusible, with a mean number of 2 plus minus 2. The cycle length was 360 milliseconds. Now after the application, non-inusibility was tested in 32 out of the 39 patients, and the VT became non-inusible in 59 percent, still was inusible in 41 percent. However, the clinical VT could not be in use in 7 out of these patients, so in total, the acute success rate adds to 81 percent. In 6 of the 13 patients, the clinical VT could still be in use. The success rate for PVCs was 88 percent. In 2 patients, the investigator felt that he should do additional radiofrequency lesion in one case for the right cusp, and in one case for RVOT. So there were four complications, one total AV block with spasmodic amputation in a patient with parahysion PVCs, one TAA, one pericardial effusion not requiring intervention, and two groin bleedings without any further interventions. Now the limitation of the study, of course, it's observational. Its initial experience in all of the investigators, they started their experience during that study with a limited number of patients, a mixed cohort with PVCs and VT ischemic disease and non-ischemic disease, and today we are only presenting the acute results. So in conclusion, Mr. Chairman, ladies and gentlemen, UTLC may provide increased lesion deaths and scar penetration and thereby improve outcomes in VT and PVC ablation. This multicenter acute study of ultra-low temperature cryoplation of either VT and or PVCs in both ischemic and non-ischemic patients, and keep in mind, almost 40 percent of patients were reduced, were safe, and effective with an 81 percent success. The clinical follow-up is ongoing. Follow-up data and larger patient cohorts as well as randomized trials, of course, are needed to assess long-term outcomes, and the design of the V-class catheter needs to be further improved. It's a rather stiff catheter, but the new design will be available very soon. Thank you very much for your attention. Thank you, Dr. Heinz-Koch. I think we'd like to have an invited commentary from Dr. Smith-Vasevala from Loyola. Thank you. I don't want exclosures. This is a thank you for your contribution. I think that all of us that take care of VT, we realize that we need better solutions and better answers to controlling and management this VT. I think this is a, obviously, the limitation, as I said, is a single-arm study, and it's not been compared to the currently available technologies such as RF. So we still need to understand that a bit. I think this study, what it really emphasizes is patient selection, so who's the right patient for this? And one of the things I do want to mention is that, and the strategy that we use at Loyola is VT induction. The question is, can these results be applied to patients who have broad substrate and you have not induced VT? Because these are long lesions that you're doing, three minutes, five minutes long, and if you have extensive substrate, how much is that going to add to the procedure time, et cetera? Having said that, I think that this is something that is well-needed. I think that it also points to the fact that wall thickness assessment is going to be very important with this, because I know a tool that presented some data where there was a pseudoaneurysm in a thin myocardium. The question is, how is that going to be done accurately? Do we do that with ice mapping? Do we do that with pre-upfront CT mapping? Do we do that with TEE? And I think so, the wall thickness assessment is going to be very important in applying this technology. I think that what's provocative is, can this be combined with PFA? If you think about Ohm's law, which is V equals IR, and you say, well, if you give cryo, it's going to significantly increase the impedance in that region. Are you going to then create a large voltage electrical field that is going to drive into that myocardium? And I think that this is something that is very provocative, and I think that would be very interesting for us to learn. Epicardial VT ablation, and endoepi, I think that there's non-ischemic substrates. The problem here, again, is the same thing as wall thickness. There are patients who have one millimeter wall thickness and ischemic infarcts. The question is, can you apply a technology such as this in a one millimeter thin myocardium? And the same is true if you have non-ischemic VT, where you have four, five, six millimeter or even eight millimeter thick myocardium. Is this going to work? So I know that there's been a lot of animal studies and a lot of case reports for this, but I agree that there's a huge need for applying this technology for randomized trials. I'm very fascinated with the work. I'm really excited to what this is going to show in the future. Thank you.

catheter ablation

atrial fibrillation

SPHERE dual energy catheter

AI-assisted mapping

TactiFlex Duo system

PFA and RF ablation

mitral isthmus block

ultra-low temperature cryoablation

ventricular arrhythmia

novel technologies