Well, I think the whole EP world has been consumed by the PFA mania. While we celebrate the success of this new energy form, there are a few things that I think we tend to conveniently ignore or forget or not have the desire to talk about, and this is exactly what this particular abstract is going to do. So historical, conventional thermal energies like the radiofrequency and cryoablation were very effective, and they actually helped us revolutionize the field of electrophysiology, catheter ablation in a big way, and we always had this Achilles' heel of collateral damage in the form of pulmonary vein stenosis or phrenic neopalsy, atrial-fascial fistula, the much-dreaded complication. And this remained a fundamental foundational limitation to how aggressively one could use these energy forms, and the quest to find an energy source that is safer, equally or more efficacious has continued, and this is where the pulse-field ablation or electroporative ablation really came into the forefront. So fundamentally, electroporation is done by creating a high-voltage electrical field delivered at a certain pulse duration, poking holes inside a cell that would enable the contents of the cell to basically come out of it, and depending on the amount of irreversible electroporation you create, you have a permanent damage to the tissue without destroying the tissue scaffolding. And that foundationally helped us to create this new, exciting energy form that I think has been embraced, and we have clearly seen, based on several thousands of patient data that has come out so far, the old problems of the world, which is the atrial-fascial injury, PV stenosis, phrenic neoparalysis, have essentially been sort of forgotten about and eliminated for the most part. We haven't seen these things come back up. But then new technologies or new things always bring to the table new problems, right? This is something that we kind of have been seeing here and there in some reports, and I mean, you have several major breakthrough papers that have come in this space evaluating different types of catheters, different types of technologies, really pushing the field forwards, and in the last three years, every meeting that you go to, there is nothing but pulse-field ablation that has engulfed our lives in many ways. So the current PFA systems, I mean, you have the PulseSelect that got an approval about a year ago, and then FaroPulse, and now the Aferosphere-9, and then the VariPulse, which was sort of the circular ablated PFA catheter from J&J. All of these catheters have made their way slowly into the marketplace, and everybody has a market share of varying degree and varying performance, varying adaptation in the real world. But all these things do have certain collateral effects, and these collateral effects could be catheter-specific, because every one of these catheter designs are uniquely different. They have specific energy variables that one has to take into consideration. And then patient-specific variables, how old they are, how frail are they, are there pre-existing anemias, renal dysfunction, cardiomyopathies that we don't know about. And then the procedure-specific variables, which is whether you had a contact with the tissue or a number of applications, periprocedural hydration. All of these really play a role in determining, to say, the degree of hemolysis or associated renal dysfunction or cardiac dysfunction. Is that serious enough for us to be worried about? This is where the Nemesis PFA registry comes into place, where we aim to assist the myocardial injury, red blood cell integrity, renal function, left atrial function, and the generalized collateral effects of PFA. So changes in the pre- and post-high-sensitive cardiac troponin levels, the N-terminal pro-brain nitroderitic peptide, hemoglobin levels, in some cases plasma-free hemoglobin, LDH, haptoglobin, reticulocyte count, and serine creatinine were systematically measured. We also looked at the left atrial parameters, and this particular sub-analysis is still ongoing based on institutional protocols. Based on characteristics, we looked at a total of 871 patients, of which 98 patients had the conventional radiofrequency ablation, and the remainder of the 773 patients actually had some form of PFA ablation. And the baseline characteristics were not that different. I mean, they are the usual routine AFib patients that you would come across. The intraprocedural strategies were contingent upon the operator, and that's the reason why we call this a real-life experience. And as you see here, a large contingent of these patients actually had post-revol ablation. Again, these are centers that do pretty aggressive ablation. I mean, there is no two ways about it, right? And the number of applications, as you see here, 39 minutes of RF ablation versus an average of 75 to 70 applications of the PFA. That's actually a pretty large number compared to average applications that you see elsewhere. So changes by energy source. What you see here is the level of the high-sensitivity myocardial injury, or the troponin relays, is dramatically different or higher in patients who underwent PFA ablation compared to the RFA, as it is very clearly evident on the top-left bar graph. And then you have the drop in hemoglobin is also pretty significant in the PFA group than it is with RFA. The change in creatinine, albeit looks smaller, but when you really look at the kind of numbers that you're looking at, it was also statistically significant. And the hemolytic effects of the PFA energy was very much reflected by the significant increase in the LEH levels. And even though these numbers were drawn within the first eight hours or so, it's interesting to actually see some of the haptoglobin levels actually coming down. Usually haptoglobin takes a day or two for it to really come down, but it's interesting to actually see that the haptoglobin level's coming down. The impact of number of applications. The more applications you give, higher is the amount of myocardial necrosis, or I would say the so-called, you don't know if you want to call it necrosis or not, but the troponin level are significantly higher when the number of applications go up. That increase is dramatically different. Similarly, the drop in hemoglobin levels or increase in LDH levels is also contingent on an increasing number of applications that go in these patients. Then how does each individual PFA system compare against each other? Pulse-select versus Fara-pulse versus Fara, right? When you really look at it, the myocardial troponin levels that are released in these patients ranges anywhere from 8,000 to 25, in some cases even 50,000 units of high-sensitive myocardial troponins. And how do you really put all these pieces of information, right, and what does this really signify in terms of the overall long-term effects on the patient's myocardium and overall atrial function is something that is yet to be determined. When you have a significant amount of hemoglobinuria or hemolysis, the resultant hemoglobinuria can cause nephrotoxic acute renal failures, right? And such number of cases are also significantly higher, and this used to be a lot more of a problem in the early stages of the experience than during the later stages. Coronary vasospasm was also more commonly noted in patients who had an RFA, in PFA than it was in RFA. So here are some of the complications, ST segment elevation, early parts of the learning curve once we started giving them nitroglycerin, I think this has significantly improved. Similarly, patients who developed renal dysfunction were also significantly higher in these groups. The other procedure-related complications are very comparable, and there was no significant individual differences in groin complications, vascular complications, or pericardial effusions and things like that. So these large-profile single-shot catheters or large-profile focal catheters can actually cause a significant amount of hemolysis, increased risk of acute renal injury, and a significant amount of myocardial injury, as it is reflected by a dramatic increase in the amount of myocardial high-sensitive troponin levels, and also a drop in atrial function, significant drop in atrial function, which is, I think, very interesting. What we got to reckon with is the effects of PFA are highly parameter-dependent. That means the electrode geometry, electrode counts, spacing, contact, electric field strength, and the field that it creates, the size of the field, the burst frequency, pulse duration, pulse count, pulse amplitude, polarity, target cell proximity, et cetera, et cetera, et cetera. And in this interesting race towards creating the most unique, the largest, and the biggest, and the most destructive catheter actually really is something that we need to explore. So the key takeaways, be aware of these side effects, and be watchful, and we don't know what this myocardial injury means. There needs to be further study, so there needs to be more of a regulatory process to really understand these type of effects on any new technologies that come in. Thank you very much. And you can actually pull this paper from Jack E. Peay today. Thank you, D.J., and now to introduce my co-chair, Dr. Atul Verma, to provide the commentary on the Nemesis PFA trial. Hi, D.J., and first of all, congratulations on a wonderful publication. I think it's always good when you've been partying all night, drunk on PFA, that eventually the hangover has to come about. And I'm not gonna summarize what D.J. basically said, but everything is really on this slide. So the question, though, is I think we need a little bit of caution when interpreting these results. Is PFA really killing more cells as evidenced by the troponin leakage? And there's no doubt that if you use a large form catheter and you're applying all over the atrium versus drawing thin, narrow lines, yeah, there's gonna be a difference in the amount of cardiac tissue that is being killed. So there is a workflow issue here where large catheters, multiple applications will kill more tissue. However, you also have to understand that troponin can move through porated membranes. And so we know that in addition to the irreversibly electroporated cells, there are a lot of reversibly electroporated cells that are also leaking troponin, but those cells are not necessarily going to die. So we're not necessarily killing the entire myocardium. The other important thing on the hemolytic side is that LDH levels can be elevated from myocardial damage and are therefore not specific for hemolysis. Plasma-free hemoglobin is really the gold standard measure that we have right now for hemolysis, and I know that you collected some of that, DJ, and that's gonna be in his paper. If you haven't guessed, I was reviewer one, DJ. LA function is a difficult topic. You know, a reversibly electroporated tissue will also be stunned and inactive for a period of many hours or even a couple of days. So when you do the speckle tracking echo, the atrial function may look a lot worse than it may look a few months down the road. And then finally, you know, the PFA time and the number of PFA lesions and the number of extra PV lesions that were done in the PFA group were substantially higher than the RFA group. And so, you know, when we talk about myocardial damage and workflow, we have to think about what we're ablating. So that's all I have to say. Thank you very much, but congratulations, DJ. We'll go ahead and likely have time for two questions. I have one for both of you. If it's a big catheter versus small catheter issue, the cryo-balloon troponin release is very close to the RF and it is independent of the technology and it tends to ablate more. And so to me, that tends to align that this may be more destructive therapy or is that overthinking this a little bit because the cryo-balloon, our two other thermal technologies were very close. I think what we are not sure at this point in time is the larger the catheter is, bigger is the electromagnetic field it creates. And so the amount of the cumulative reversible or irreversible electroporative effects on the myocardial cells is significantly higher. And to Atul's point, when you bring down the size of that catheter, then the amount of electric field is going to be smaller and the amount of injury is also going to be relatively smaller. So what does it mean to have this large non-reversible electroporative effects on the myocardial cell? What are its impacts in the long term and how does the tissue really recover and heal I think are yet to be largely explored in the longer term. I think this is insightful. I think there are data that have shown in the past and limited series that some of the MRI findings, the initial delayed hyper enhancement that you would see in the first 24 hours may actually improve and get better when you re-image them over the next few weeks. But microscopically, does the injury really go away? Okay, yeah, let's go ahead and move on to Stan. All right, so to introduce the next session, it's Christopher Chung from Sunnybrook Hospital in Toronto, Prospective Evaluation of Asymptomatic Cerebral Emboli After Pulse Field Ablation of Atrial Fibrillation, PACE-AF. Great, well thank you very much for the introduction and for the invitation to speak today. I'm excited to share with you the results of our PACE-AF study, Prospective Evaluation of Asymptomatic Cerebral Emboli After Pulse Field Ablation for Atrial Fibrillation. These are my disclosures. we know that certainly asymptomatic cerebral emboli is a phenomenon that can occur in patients undergoing atrial fibrillation ablation. This has been well studied in the radiofrequency literature and this is an example of one study that was published a couple years ago that showed that even depending on the type of radiofrequency, high power versus standard power, you can have embolism rates approaching up to 40% when you use high power short duration. Similarly, there have also, however, there have been randomized and non-randomized trials in the PFA space that have reported asymptomatic cerebral embolism rates that approach 10%. That being said, we've also seen some recent studies using new PFA catheters that have either paused due to concerns regarding cerebral embolism or potentially related to ischemic stroke. And so our study sought to evaluate the incidence of asymptomatic cerebral emboli after a PFA ablation and its subsequent impacts on neurological outcomes. So our objective was to evaluate what is the true incidence of asymptomatic cerebral emboli detected on brain MRI after a catheter ablation for AF using PFA technology. And this is our study schema. So we primarily, we screened and enrolled patients consecutively that were undergoing an AF ablation with PFA at a single center, tertiary academic center in Canada between, sorry, between October 2024 and April 2025. We performed a baseline neurological assessment including Montreal Cognitive Assessment MOCA score, Lawton-Brody IADL, as well as a quality of life assessment using the EQ5D5L quality of life questionnaire. And then we performed the AF ablation using PFA. Brain MRI was performed in all patients within 72 hours of the procedure. And then we also did a three-month follow-up which is ongoing. And the three-month follow-up includes a repeat and neurological assessment using the MOCA score, Lawton-Brody IADL, as well as an 88 dementia screening questionnaire, as well as a follow-up quality of life assessment using the EQ5D5L. So here we enrolled all patients that were eligible which included anyone 18 years or older that were undergoing a de novo catheter ablation for AF using pulse field ablation technology. We excluded patients that had a prior history of cerebrovascular disease or stroke and excluded those that had a known history of cardiac thrombus or those that were expected to have an increased risk of periprocedural stroke. Now for our ablation procedure, the PFA procedure was performed using a multi-electrode catheter, the Medtronic Pulse Select. Ablation was performed with support of intracardiac echocardiography to rule out any left atrial thrombus prior to transeptal as well as with electrode time tomical mapping in all cases. And in all cases, we performed a heparin bolus that was administered prior to transeptal and then therapeutic ACT, anti-activated clotting time monitoring throughout the left atrial dual time targeting in ACT of greater than 300 seconds. So now jumping to our results. So far, we've enrolled 35 patients in this PACE-AF study. Among these patients, the median age was 63 years with an intracortial range of 55 to 71. Approximately one third of patients were female, 29%, and the median BMI was 27.2. You can see the medical comorbidities there, 37% with hypertension, 23 with diabetes, 20 with coronary disease, 14% with a history of cardiomyopathy, and 20% with sleep apnea. And the median CHADS-VASc score was one with a intracortial range of zero to two. All patients were on anticoagulant at baseline and typically had their anticoagulant held on the morning of procedure. And the anticoagulants used were epixivan in 43%, edoxivan in 34%, rivaroxivan in 23%. And the LV ejection fraction was 61% as a median, and the left atrial diameter was 37.5. And then on the right here, you can see our breakdown. Approximately three quarters of these patients were paroxysmal atrial fibrillation patients and one quarter were persistent. Our ablation parameters are as follows. Among the 35 patients, the median number of PF deliveries was 68 with an interquartile range of 56 to 99. The total ablation time, which we defined as the time from the first PF delivery to the last PF delivery was 48 minutes. And the left atrial dwell time was a median of 66 minutes. And our total procedure time was 88 minutes with an interquartile range of 75 to 107. And as I mentioned, all patients received a heparin bolus prior to transeptal, and the initial bolus was typically around 11,500 units. And then the total heparin administered was 13,350. And then again, clotting time or ACTs were monitored throughout the left atrial dwell with the first ACT being typically measured in the therapeutic range with a median of 329 seconds. So for our outcomes, first off, there were no clinical strokes and no TIAs that occurred during this study. Now, our long-term neurological outcomes and the quality of life questionnaires are still pending as only less than half of patients have reached the three-month follow-up time point. And so brain MRI was performed in 32 out of 35 patients. So three patients declined the brain MRI at the MRI visit. And out of those 32 patients, one patient had it outside of the 72-hour window. So 31 patients had a brain MRI within the 72-hour window. And we identified asymptomatic cerebral emboli in 11 out of 32 patients, which corresponds to about 34%, as illustrated in the graphic here. Now, we did perform some univariate predictors for the asymptomatic cerebral emboli. You can see here age was statistically significant with an odds ratio of 1.09 and a p-value of 0.04. And we also looked for other univariate predictors, including persistent AFib, Chad's VASc score, ablations, total ablations delivered, total ablation time, total LA dwell time, first ACT and lowest ACT levels, and those were not significantly associated with the ACE events. We did run a single multivariable analysis, accounting for both age and persistent AFib. And you can see here that, interestingly, that these two were statistically significant and highly so. So age was statistically significant with an odds ratio of 1.19 and a p-value of 0.015, and persistent AFib with an odds ratio of 27 and a p-value of 0.035. So to conclude, our real-world experience with pulse-field ablation demonstrates that the asymptomatic cerebral embolism rate seems to occur in 34% of patients. Now the etiology and ultimately the clinical significance of these ACE events still remain unclear. That being said, this does represent the largest prospective registry to date on ACE with pulse-field ablation, and the combined events in this study outnumber the total events in the prior randomized and non-randomized studies. That being said, we did find that there was a potential signal towards increasing age and persistent AFib to be at a greater risk for cerebral emboli, but this, of course, has a caveat that this was a small study and that we may be underpowered to do this multivariable analysis. I think in summary, I think these patients likely will require some form of long-term follow-up from a neurological perspective, and that in general, our future studies that are looking at AFib ablation should have a systematic ascertainment for these types of cerebral embolism events. So thank you very much for your attention. I want to thank also the patients and families that participated in this study. And now I'd like to introduce Luigi DiBiasi from Albert Einstein College of Medicine to give the commentary on this. Thank you, Atul, and thank you, Jared. These are my disclosure, and the slides are coming. So let's comment on this trial. These are my disclosure. First of all, congratulations, Dr. Jung and all the PCAF investigators for completing this prospective evaluation trial that sought to evaluate the incidence of ACE after PFA and its subsequent impact on neurological outcomes. The fast diffusion of PFA energy source require a very careful analysis of all possible consequences. And PFA was performed in this trial using a multi-electrode character, a Pulse-Select Medtronic that's shown here. Now, during the presentation, I have to make some comment, and not only congratulations. So no mention was about was anticoagulation uninterrupted or interrupted or minimally interrupted. We all know with warfarin that uninterrupted anticoagulation is the way to go to eliminate TIA and stroke. This was our seminal work that was followed with the randomized trial on warfarin. And then we have a lot of trial with NOAC that has replaced warfarin. We know that uninterrupted anticoagulation is the way to go to eliminate clinical strokes. We electrophysiologists, differently from intervention, also want to look in the brain to make our life more complicated. And with interrupted anticoagulation, we start reporting these lesions. And these are silent cerebral finding, or ACE, described with many energy sources, including phase RF, with interrupted anticoagulation. We perform an uninterrupted anticoagulation trial where in group one were on uninterrupted warfarin. Group two, people were not compliant and they were off warfarin. And we went down to 2%. And in that trial, in 2014, we find out that subtherapeutic INR, more than three ACT below 300, and no heparin bolus prior to transceptal were predicting this ACE. So I only saw some value below 300 in your table, and I think that matters. By doing this, with the precursor of PULSELECT, the PVAP call, Dr. Verma was able to reduce the incidence to 1.7%, which is very similar to the 2% that we found in our trial. So randomized control trial demonstrated that uninterrupted anticoagulation is key. It's unclear if it was used here. It's unclear how the sheet management was done. It's unclear the number of consecutive ACT below 300. It's unclear what's the clinical meaning of this ACE. The MRI was not reported to be done with flare or without flare. That's also very important to understand the clinical relevance, and was done only after the placebo. But apart from this comment that then needed to be made, congratulations for your work. Thank you. Congratulations as well. We'll open this up for discussion. I think aligned with the fact that asymptomatic may be a misnomer, just because we don't use the probes to really test these events. And that's aligned with a number of the questions. Are you seeing any cognitive changes off baseline? And also when cognition is considered, you're going to have to look multiple years. And what's the duration, if you're seeing, for cognitive testing you're planning to perform in these patients? Thanks, Jared. That's a great question. I think when I talk to the stroke neurologist, they say all brain matter is important. So any loss of brain matter is important. Certainly for this study, we've restricted it to three months, but I think the main, as you highlight, that we need to do long-term follow-up. And it may not be within three months, but it may be in the range of years. So the thought is that early, many of these repeated insults potentially put someone at greater risk for developing degenerative disease down the line, whether it be Alzheimer's or vascular dementia. And so that's perhaps something that we need to look into. And was uninterrupted antivoagulation utilized for this trial, or? So it was held on the morning of procedure. You know, one question. You need to explain what type of imaging protocol you used to look at this. Was this DWI? Was this DWI plus FLIR? The big differences in terms of the way you report this. Yes, and that's a great question, Dr. Verma. So this was with DWI with FLIR, and all these lesions were picked up on DWI. I think the additional caveat is that we used a specific Siemens protocol called Resolve, which actually results in higher spatial resolution. So there's a possibility that the higher spatial resolution may actually, in fact, pick up more events. Yeah, and the slice cut as well is absolutely critical. And then the other point here, which is to some of the questions that are popping up here, is that it's not just pulse field ablation that can cause silent cerebral emboli. There are a lot of workflow issues. This is definitely way higher than anything that's been reported. Pulse-selected actually in the Pulse-AF trial do a systematic MRI study, and this is way higher. Part of it is the definition of the imaging protocol. But can you explain how you controlled all the other aspects of your ablation procedure? That's a great question, Dr. Verma, I think. So in general, this was done by a limited number of operators that have very standardized workflows. So certainly I think that opens the can of worms that we need to potentially do a more randomized study to assess this, to ensure that workflows are the same. But for the least purpose of the study, the investigators that performed the ablations certainly had very standardized workflows. Why the incidence rate was so much higher than the other studies still remains in question. I think part of it is that this, I think, is a real-world application, so perhaps the patients that are enrolled in more of a real-world study are different than those that are seen in a rigorously performed randomized or non-randomized study. So perhaps these patients have a higher burden of medical comorbidities comparatively. There certainly is an aspect that perhaps the imaging protocol is different, as you just mentioned. So perhaps with this different protocol with the resolved slicing, we can get higher resolution and maybe pick up more of these events. I think this really just serves as an impetus to show that we need more prospective monitoring, and perhaps in a randomized study that compares different types of modalities, different types of catheters, different types of energy modalities, with that standardized work to show what is actually the safest for preventing these ACE events. Great. Wait, go with one question and then one quick question. Thank you very much. Congratulations, great work. Gunjan Shukla from Westchester Health Network. It's clearly higher incidence of ACE with this. Do you think that this, all of your patient had a pre-imaging too? Because many persistent AFib patients would have a pre-existing ACE. You may not know about it. So if you are just doing imaging afterwards, it could include all the pre-stroke patient, or ACE patient may have. Thank you. Yep, that's a great question as well. So in this study, we did not have pre-imaging, so these were all post-imaging. That being said, the division-weighted DWI sequences typically show acute infarcts, so they're pretty specific for that. But you're right that we can't say that that specific event occurred during the ablation itself. It could have been that the patient went in and out of persistent AFib days before the procedure, and that's why they had an acute DWI lesion. So we can't say specifically unless we did a pre-MRI, for example, very closely before the ablation. But that being said, the DWI is pretty specific for an acute infarct. All right, thank you very much. We'll move on. Thank you very much for doing that and informing us. Let's... Thank you. Thank you. Let's go ahead and move on to our next topic. This is the role of post-ablation catheter remapping and pulse-filled ablation of atrial fibrillation and related atrial arrhythmias. We had the pleasure to hear from Dr. Alexander. He's from, and Dr., representing Dr. Mina Chung's group at Cleveland Clinic. Dr. Alexander. There we go. Thank you for the introduction, and thank you for inviting me to present today. My name is Alexander Izda from Cleveland Clinic Lerner College of Medicine, and today I have a privilege to present our work titled, The Role of Post-Ablation Catheter Remapping in Pulsed-Field Ablation of Atrial Fibrillation and Related Atrial Arrhythmias. Pulsed-field ablation, or PFA, is a promising new alternative to thermal ablations such as radiofrequency and cryoablation, with the unique ability to selectively target myocardium through irreversible electroporation that disrupts cell membrane permeability, leading to cardiomyocyte apoptosis and necrosis, while sparing other tissues. The need for electroanatomic mapping has been controversial with PFA. Mapping following first-pass isolation has the potential to identify residual conduction gaps. However, this comes with some potential downsides, such as prolonged procedures, increased risks due to catheter exchange, and also increased costs from extra catheter. With this in mind, we designed a study that would allow us to observe and evaluate trends in PFA use at Cleveland Clinic in the period from January to July 2024, to assess the yield of post-ablation remapping in PFA procedures, and characterize the distribution of gaps requiring additional ablation. And lastly, to evaluate whether post-ablation remapping influences arrhythmia recurrence. In a retrospective cohort study using patients undergoing AF ablation from January to July 2024, we focused on patients undergoing PFA ablation, while simultaneously identifying thermal ablations for comparisons. We utilized Cleveland Clinic EP procedure database to obtain information such as baseline demographics, past medical history, and ablation procedure details. Follow-up data were obtained from review of electronic medical records to identify arrhythmia recurrences and redo ablations. After this, we performed a descriptive analysis to evaluate patient characteristics and procedural characteristics, as well as logistic regression to analyze the association between remapping and AF recurrence within 180 days post-PFA procedure. Out of 695 patients undergoing intended atrial fibrillation ablation, 438 underwent PFA ablation, while 257 underwent thermal ablation. In our PFA patient pool, the mean age was about 68 years, and 68.5% of patients were male. Interestingly, 59, or 13.5%, of patients underwent prior ablation. It is also important to note here that the majority of patients, or 287, undergoing PFA had persistent AF, while 151, or 34.5%, had paroxysmal AF. Additionally, our mean procedure duration was about 128 minutes, with fluoroscopy time of 23.5 minutes. This slide shows the trends in thermal versus post-field ablation use since the availability of PFA in late January 2024. Since its release, PFA ablations have almost entirely replaced thermal ablations, with over 90% of ablation procedures being PFA towards the end of our study. Additionally, we noted an increase in total number of patients per month undergoing ablation from January to June. This slide shows the proportion of patients who underwent remapping after first-pass PVI. And what we see is that in PFA ablations, operators remapped close to 75% of the time. Additionally, we see that this number of remapping does slightly decrease across the study period, with largest percentages of remapping occurring in January and February, and lowest being in June. After observing a trend for remapping, we wanted to look more closely at how this corresponds to reablation following these remaps. What we saw was that nearly one-third, or 31%, of remaps led to additional lesion deliveries in PFA ablations. Additionally, we can see that following the FDA approval of commercially available PFA, there seems to be an increase in number of reablations up until April, after which the rate of reablation starts to trend downward. We next wanted to investigate what the most common locations were that received these additional ablations. And what we found was that the most common locations of additional lesion deliveries included left atrial roof and posterior wall, as well as left superior and right superior pulmonary veins. An important limitation here is that the reablation site classification was based solely on the procedure note documentation. So any mention of the site, any mention of the given anatomical location was included in this table, which may introduce some imprecision. Therefore, we have ongoing efforts that are focusing on reviewing electronatomic maps of these patients to get a more accurate characterization of specific sites of reablation. After this, we identified all of the patients with report of recurrence within 180 days and performed a logistic regression to observe the effect of remapping on AF recurrence. And if we look at the Table 1 and 2, we have two groups of 0 to 180 days post-procedure and 90 to 180, with difference being whether we included or not the blanking period. And if we focus on Table 2, although we did not find any significant effect between 0 to 180 days post-procedure, we did observe a protective trend in our 90 to 180 days post-procedure group. We analyzed the subgroup excluding atrial flutter, because in those cases, remapping would be affected by selection bias, as patient with atrial flutter will almost always have gotten remapped. And once again, as I stated previously, we saw no significant difference in AF recurrence within these patients with remapping. In summary, PFA ablation has quickly replaced thermal ablation at our institution in 2024, and post-ablation electronatomic remapping was performed in majority of PFA cases, with 31% of those that were remapped receiving additional ablation lesions. Most common sites of persistent conduction were identified to be left atrial roof and posterior wall, along with left and right superior pulmonary veins. Lastly, this study highlights the utility of post-ablation remapping, and underscores the need for further studies to assess its impact on long-term arrhythmia recurrence. Thank you. We'll now welcome to the stage Dr. Nagarakanti from Northern Arizona to provide the commentary regarding the trial. So I'm Randy Nagarkanti from Northern Arizona Health. I have nothing to disclose regarding this. However, I do have to, for full disclosure, we currently do not use the PFA. We still use the traditional RF and the cryo, and we still map pre and post during this ablation. I don't want to bore the audience with all this. They already spoke about there are different types of PFA. It was supposed to produce highly durable lesions and also improve the safety, especially in the esophagus. And as they already discussed before, there are different kinds of PFA catheters available with different energies and different footprints. And the PFA, as Dr. Alexander mentioned, is being increasingly used with a great uptake. That we have seen with prior energy catheters. However, we have been seeing more extensive use of the PFA in the posterior wall, other flutter ablations, which we haven't seen with prior energies where we were doing predominantly PVIs. And it will be interesting to see the real-world independent reports to reflect the use of PFA in a broad spectrum of proceduralists like low-volume centers like us as well as the high-volume centers. And as we have seen with the earlier study that Alexander presented, there is at least a significant amount of these patients had recurrent arrhythmias, and also there are still durable PVs that are... I mean, there is a lot of PV reconnection. And this was reported in the real-world studies such as Manifest-Re-Do, Euporia. And they also showed a significant difference in the safety. So this makes it important that we do map with the new energies that we are using. So I think the post-PFA mapping is helpful in understanding the contact along with the eyes. It does help us understand lesion tracking to identify the gaps. For example, here you can see in the right upper pulmonary vein. And as we always did with other energies, it will help us identify the entrance and exit into the pulmonary veins. And the post-ablation voltage map will help understand the inadvertent extensive substrate ablation that can sometimes result in creating isthmuses that can cause the flutters. And Alexander's study has excluded the flutters, but I think it's important to include the flutters to actually assess the success of these ablations using the novel energies. So I would like to conclude that PFA is increasingly being used, especially other than PV eyes into the posterior wall as well as other areas. I think it becomes important to use mapping to better understand, provide guidance, and improve the outcomes with these newer ablation technologies. In addition to mapping intermediate post-PFA, I think we need to have more medium-term and longer-term follow-up real mapping data, which is independent of industry, and I think it will be beneficial. Thank you for your attention. It's open for discussion. There's a comment from the audience that I share, and that's the post-mapping threshold is often 0.1 millivolts, and I think people are advocating perhaps that should even be more lowered. Have you looked at threshold for acquiring voltage after and how that influences incident of signal to go and remap? It's a great question. So unfortunately for our study, we relied on the procedure database where we just reviewed the procedure notes and characterized whether the patients were remapped or not remapped in general. So we did not have the power or time for this to evaluate that specifically, but that is a great question. Any other questions? Any other questions from the audience? By the way, Alexander's a medical student, so pretty impressive. Very impressive. Thank you very much. So our next presentation is on ultrasound-based renal sympathetic denervation as adjunctive upstream therapy during AFib ablation. The Ultra-HFib Study. William Wang from Mount Sinai Hospital is going to be presenting this study. Thank you. Thank you very much to the chairs. It's my privilege to present this research on behalf of my co-investigators at the Ultra-HFib Pilot Study. Sorry, these are disclosures. Of note, I'll be talking about off-label use of the ReCore Paradise Ultrasound Renal Denervation System, which has FDA approval for treatment of hypertension. During AFib ablation, adjunctive renal denervation, by virtue of its effect on the sympathetic nervous system and the renin-angiotensin-aldosterone axis has been shown to improve AFib control. Prior studies have primarily included patients with uncontrolled hypertension despite medications. In the Ultra-HFib Pilot, the effect of denervation using an ultrasound denervation catheter on rhythm outcomes was assessed in patients with treated hypertension, including those with controlled hypertension, undergoing AFib ablation. This was a prospective multicenter, single-blind, sham-controlled randomized trial funded by ReCore Medical. We included patients who were planned for their first ever AFib ablation procedure, whether it was paroxysmal or for persistent AFib. Prior to randomization, patients needed to have a technically successful AFib ablation and patients also needed to have a history of hypertension and either, number one, documented history of systolic blood pressure at least 160 or diastolic blood pressure at least 100, or number two, receiving at least one antihypertensive medication. Catheter ablation in paroxysmal AFib patients involved PV isolation plus or minus linear lesions for any documented or induced flutter. In non-paroxysmal AFib patients, PVI was performed followed by ablation of non-PV triggers, SVC isolation, linear lesions, or fractionated electrograms at operator discretion. After completion of the last ablation lesions, a renal angiogram was performed and based on the renal angiogram findings, if the anatomy was suitable for denervation, a one-to-one randomization was performed either to sham control consisting of discontinuing the procedure at that point or intervention consisting of denervation. This slide shows the Paradise Ultrasound Renal Denervation System. The six French cylindrical ultrasound transducer emits a circumferential ultrasound lesion to heat the tissue surrounding the vessel lumen. The lesions last for about seven seconds on average and the catheter is designed to deliver lesions to renal arteries three to eight millimeters in diameter. A low-pressure balloon surrounds the catheter and it's infused with sterile water to cool the catheter and prevent injury to the vessel lumen. Participants in the study were provided smartphone ECG monitors to perform weekly ECGs during months four to six after the ablation, then biweekly during months seven to 12 or for any symptoms. In addition, a one-week continuous ambulatory ECG monitor was performed at six months and 12 months post-ablation. Endpoints for the study included, number one, single procedure freedom from arrhythmia recurrence off any class one or three antiarrhythmics at 12 months. Number two, single procedure freedom from arrhythmia recurrence either on or off antiarrhythmics. Also procedural adverse events within 30 days post-procedure, between group differences to changes in quality of life by 12 months and between group differences to changes in systolic blood pressure at 12 months. This slide shows our enrollment flowchart. 180 patients were screened for eligibility. Of these, 107 were randomly assigned either to control or to intervention. Seven participants in the intervention group were excluded from the study post-randomization due to ineligible anatomy, and they were treated as screen failures. So all told, 100 patients were analyzed from the study, 52 in the control arm and 48 in the intervention arm. This slide shows the baseline characteristics as well as nominal p-values on the right. Average age was 66 and was similar between the two groups. Chad's VASC score was 2.9 and also similar. 85% of the participants had paroxysmal AFib overall, and a greater proportion of patients at baseline in the denervation group had paroxysmal AFib. Also, systolic blood pressure was 139 millimeters mercury in the sham control group versus 130 in the denervation group at baseline. LVEF was similar between the two groups. Left atrial diameter was slightly higher at 4.2 versus 3.9 in the denervation group. And participants were on an average of 2.1 antihypertensive medications at baseline. This slide shows arrhythmia-free survival Kaplan-Meier curves either on or off antiarrhythmics at one year. In the red is the denervation arm and in the blue is the sham control arm. The Kaplan-Meier survival estimates were 61% for the sham group and 80% for the denervation group. The p-value based on the log-rank test was 0.08. This slide shows the same two curves as before. In addition, in red and blue again are arrhythmia-free survival curves off any antiarrhythmic drugs at one year. The Kaplan-Meier estimate for arrhythmia-free survival off antiarrhythmics was 49% in the sham group versus 67% in the denervation group. The p-value for the log-rank test was 0.17. In a Cox regression model adjusted for age, sex, and persistent AFib, the hazard ratio for recurrent arrhythmia off antiarrhythmics with denervation was 0.65 with a 95% confidence interval of 0.32 to 1.31, p-value of 0.23. There was three procedure-related adverse events, two chest pain events, and one pseudoaneurysm, but there were no directly denervation-related adverse events including no hypotension. This slide shows some of the non-arrhythmia outcomes. The change in stolic blood pressure was greater in the sham group compared to the denervation group, probably due to the higher baselines to stolic blood pressure. Quality of life in terms of AFib score was similar in terms of the change by 12 months as well as the antihypertensive medication changes. Limitations of the study include the baseline imbalance in stolic blood pressure between the control group and the denervation group, which was due to chance. In addition, we cannot provide comprehensive measures of arrhythmia burden due to the lack of continuous arrhythmia monitoring. Also, we had small sample size, so we cannot provide precise effect sizes. In conclusion, our multicenter randomized sham-controlled pilot study of denervation as adjunctive therapy to catheter ablation demonstrated feasibility and safety of the intervention in a cohort of patients with relatively controlled hypertension. The efficacy data did not reach statistical significance, but is promising. And our results suggest that a fully powered trial is warranted to conclusively determine the impact of denervation on atrial arrhythmia recurrence following AFib ablation. Thank you very much. Thank you. All right, I'd now like to welcome Dr. Hakan Oral from the University of Michigan to give a commentary. Thanks so much, Atul. Atul, Jared, and Dr. Wang, you know, I first want to congratulate you all for this wonderful study. This is a very impactful study, and we have a lot to learn it from. The question we have indeed is whether we can do anything incremental, additional to catheter ablation, to improve the outcomes of catheter ablation for atrial fibrillation. Regardless of the technology, and regardless of the advances we have had over the last decade, the efficacy of catheter ablation has kind of plateaued. Now, we had a pulse-feed ablation. We all are super excited about it, and using and adopting it in our workflows, but its efficacy is not necessarily any better than that of cryo- or radiofrequency catheter ablation. So the fundamental issue probably is a lack of complete understanding of the mechanisms of atrial fibrillation. Therefore, this study is important, looking into autonomic innervation of the atria as a way to improve outcomes. There are animal studies and experimental models where renal innervation has been shown to reduce sympathetic innervation of the atria and reduce nerve sprouting. So rightfully, the authors and their predecessors thought of including renal innervation as an adjunct to catheter ablation. There have been two major randomized clinical trials preceding this study. One was ERIDICATE-AF study that demonstrated a potentially beneficial effect of renal innervation improving outcomes of catheter ablation. This was followed by SIMPLICITY-AF study, which did not show any benefit. Both of these studies were limited by their sample size calculations and the power needed to have to show a difference. The current study was carefully conducted. It used a novel ultrasound-based model to perform renal innervation. And as an outcome, there was not necessarily a significant difference among patients who did and did not have renal denervation. As alluded by Dr. Wang, there were significant differences in demographics of the study patients. You know, renal denervation group had a higher proportion of patients with paroxysmal atrial fibrillation. Their left atrial size was smaller, and also their systolic blood pressure control was better. And more importantly, the study was not powered enough to show a significance. So if we put all together, there probably is a need to conduct a carefully planned and sufficiently powered study to answer this question once for all. The other question that comes into mind, as we have learned from prior studies, is that there could be a potential beneficial effect of ablation of ganglion plexi, which reduces the parasympathetic inputs. Whether including GP ablation in addition to renal denervation can improve the outcomes of catheter ablation still remains to be determined. I once again congratulate the authors for this carefully conducted study, and thank you for your attention. Thank you. We'll just go with one question from the audience. They noted the lack of response in blood pressure in the active group, maybe two parts. One is, is the dosing appropriate to get the actual metric you want to achieve? And number two, if it's not the blood pressure, what is it? That's a good question. The dose of the denervation intervention was similar to the type of intervention performed in prior studies in hypertensive populations. So we don't think it's the dose or the way the intervention was performed. It's interesting that the eradicate AF study, as well as a prior study from South Africa that used implantable loop recorders and showed a reduction in AFib in people just at risk for AFib who had denervation. They both showed that there was no change in blood pressure, yet there was still a reduction in AFib. So we think it has some non-BP-related mechanism based on sympathetic nervous system effects. Got it. All right. Well, thank you. We'll move on quickly due to lack of time. We'll welcome up Dr. Joseph Chan from Prince of Wales Hospital to discuss the acute long-term clinical outcome after pulse field ablation in proximity to the coronary arteries. Thank you for the kind introduction. And it will be my privilege to present the work of my hospital on the acute and long-term effect of PFA ablation on the coronary arteries. So the title of our study is the acute and long-term clinical outcome after PFA in proximity of human coronary arteries. So for background. So this is the early reports of six patients undergoing PFA in the CTI area and actually resulted in 2 out of 6, 33% of them have actually ST elevation in the inferior leads. And in this report, the patient was not given the preemptive TNG intravenously, which is recommended in the current practice. Even with the intravenous TNG, given a dose of a 2 milligram, in this case report, the patient actually undergone a PV ablation and then given a 2 milligram of intravenous TNG and then performed the CTI with the PFA cavities with 10 applications. And then this patient still developed ST elevation in the inferior leads, followed by non-sustained VT and then asystole. And then the coronary spasm was only relieved by another two doses of 2 milligram intravenous nitroglycerin before the patient become stable and the ST elevation actually resolved. And during the period of asystole, the patient actually need right ventricle pacing support. So this report from Vivek Reddy group actually showed severe coronary spasm happens quite very often if you apply PFA cavities in the proximity of coronary arteries, especially during the CTI ablation for atrial flutter. And the absence of ST changes was actually thought to be a reassuring after given nitroglycerin. But whether the coronary spasm actually translate into long-term coronary artery stenosis is actually unknown. So our group actually want to look into this and we perform this study with 19 patients undergoing atrial fibrillation ablation together with either CTI ablation or mitral isthmus ablation in 20 vessels. So 19 patients, one patient actually undergone not only CTI ablation but also mitral isthmus ablation. And serial coronary angiogram and optical coronary tomography, which actually able to give a high-definition study of the coronary artery at three months post ablation. So on the day of the ablation, the patient was planned for the CTI ablation or the mitral isthmus ablation after completion of the PVI ablation. And then intracoronary nitroglycerin was given as a bonus before the ablation and also throughout the ablation if needed. And then the coronary angiogram and also the OCT was performed before the ablation. And then ablation was performed with the fire pulse system over the CTI area of mitral isthmus area on average two to three application at each site and then two to four sites to create a linear block. And this serial coronary angiogram was checked for spasm after each PFA application at each site. And the OCT was repeated at the peak spasm time. And then all the patients was followed up with coronary angiogram and the OCT study at three months. So this is the ECG changes. And we noted that even with a mean dose of 800 microgram of intracoronary nitroglycerin, about 45 patients developed severe coronary spasm as defined by more than 70% narrowing of the coronary artery. And notably with this, five patients actually did not demonstrate ECG changes despite they have severe coronary spasm on the coronary angiogram. So these are some of the cases. So this patient developed moderate spasm with ECG changes with ST depression in the inferior leads. And this patient actually developed severe spasm as noted, but there was minimal ECG changes. So ECG without any ECG changes does not really mean the patient is not suffering from severe coronary spasm. And these are the results of the OCT findings at three months. On the left panel, there was a vascular wall area increase by a medium of 17.1%. So the OCT actually enabled us to study the vascular wall area, which with an increase may actually means that there may be intimal hyperplasia. On the right panel, because the vascular wall area can be subject to vascular tone changes, so we do a correction with the segment that did not have spasm to correct for the changes in the vascular tone. So with that correction, still there was a 10.1% of increase in vascular wall area noted at three months. So these are some of the OCT findings, and you can see this is the, at the left-hand side, this is the baseline OCT and the coronary angiogram, and showing the patient did not have any coronary artery disease, and then after the application of the PFA, you can see severe spasm, and then with, you know, decreasing the luminal area, and then increasing the vascular area as well, and then at three months, without the application of PFA, repeated OCT still showing an increase in the vascular wall area. So, and that result was actually reported in last year at APHRS, and today I'm going to report the long-term clinical follow-up of this study, so with a medium follow-up of 16 patients, for these 19 patients, none of these patients, even, you know, the three months OCT might show increase in vascular wall area, did not suffer from any acute clinical events, including angina, acute coronary syndrome, or the need of required revascularization. There was a recurrence of atrial arrhythmia in four patients, accounting about 21%, and there's some limitation of the study, so it is only a single center, small study, involving only 20 vessels, 90% are CTR, and 10% are mitral isthmus. Only three months imaging follow-up data was available, and it is not known if the lesion will progress or regress over time, unknown if the effect of the coronary vessel is catheter-specific or not. The reason we mention that is, you know, we know that with different catheters, different footprint of these PFA catheters, you know, the lesion size may be different, and then, as shown, this is not the one on the top, it's not the case included in the study, and it's done by pulse-select catheters, and you can show a very focal, you know, small segment of spasm only. So, in conclusion, ladies and gentlemen, so applying PFA near coronaries can cause severe spasm in about 45%, even with preemptive intracoronary TNG use. The absence of easy change does not preclude underlying severe spasm. Mild coronary stenosis at three months, median 10% reduction in coronary artery area was observed in a series of 20 vessels. After median follow-up of 16 months, none of these 19 patients developed clinical coronary events. A longer-term re-angio study should be done to evaluate if coronary lesion will progress or regress. So, the main findings of our study is available today in the JEC-EP. Thank you. Because of time, we won't take questions, but we'll conclude with Dr. Carruth to provide the commentary for this interesting study, and congratulations on doing that study. Thank you to the chairs and HRS for this opportunity to talk about this really very important study. These are my disclosures just waiting for the slides to get going. Okay so my comments really are going to involve some important highlights about the study which I think are worth repeating. Severe spasm is common with PF. It's a class effect. As long as you're in proximity to coronaries whether it's six or ten millimeters every catheter will have its own specification and that needs to be well studied. Remember absence of ST changes does not exclude spasm. Nitroglycerin intravenously or infracoronary can reduce severity but does not eliminate spasm. My commentary really is going to center around the publications by my colleagues Dr. Reddy and Dr. Malyshev who contrary to what this study showed and this study demonstrated that despite one milligram of intracoronary nitro which is a pretty good dose severe spasm was still seen but they define severe spasm as 70% or greater. What Dr. Reddy's publication demonstrated was with the three milligram two milligram two milligram peripheral administration severe spasm was eliminated. You only had moderate or mild spasm but the definition of severe spasm was greater than 90%. So these subtle differences are important but in general the fact that you can eliminate subtotal spasm which is likely the one that's going to cause the most severe ischemic effects is important. Remember nitroglycerin can be used to treat spasms so if you have a acute event during the case the way to treat that case would not be peripheral nitro but ideally intracoronary nitro with the support of alpha agonists. The authors demonstrate a median reduction of 10%. What we really need to know between catheters is the extent of this reduction. Is it a very focal area? Is it a very wide area? And that depends on the footprint of the catheter. It's reassuring that at 16 months in these 19 patients there were no clinical coronary events but this is a little bit different from the Malyshev study from our group that presented 11 month follow-up of 30 patients with no new coronary irregularities and I think it's important to understand that the WASP clinical experience is supportive of the fact that clinically coronary clinical severe coronary events are not common. Remember that thermal ablation does cause the same thing. It's been well described and the questions that we need to answer is what the natural history of a one-time insult that causes intimal hyperplasia is. We talked about the reassuring clinical data and what we need to do is OCT studies that look at radiofrequency catheters, particularly the modern catheters, keeping in mind that there is data to say that even when there is no spasm with radiofrequency you see the same changes that we see with PFA. Thank you. All right. Thanks for hanging in. We did go a little bit over time, but there were a lot of great presentations. No time for questions, but thank you very, very much for attending.

pulse-field ablation

PFA

medical procedures

radiofrequency

cryoablation

myocardial injury

renal dysfunction

Nemesis PFA

asymptomatic cerebral emboli

coronary arteries

standardized protocols