This is Heart Rhythm TV. I'm Daniel Alyesh. And I'm Nashwa Abdulsalam. And we are very excited for late-breaking science session one clinical trials and registries. A lot of great science coming our way. And let's start off with the PULSAR IDE trial, a large spherical array catheter. We're gonna learn the results at one year. Another single-shot catheter in our armament for PFA. And we'll shift gears to a conduction system pacing with the iCLASS study, which is an international collaboration comparing Luff-Bulder branch area pacing to CRT in patients with EF less than 50%. So the question is does capturing the conduction system really lead to better syncretin outcomes? We'll find out more. Yeah I think I love building data in that question. I mean I think we're building towards randomized trials and this is very important. The next is the OMNI-IRE study, middle footprint PFA catheter. You know we're trying to figure out now that we have the single-shot catheters, what is in the space of middle footprint? What can we learn? What can we learn? And next up is a sub analysis of the OPTION trial. We know through the OPTION trial that left atrial appendage closure is non-inferior to anticoagulation post AFib ablation. This sub analysis is going to see if it actually affects outcomes and recurrence of AFib. And I'm excited to know more about that. You know the OPTION trial added so much to our evidence base. Now understanding the critical question of recurrence of AFib will be huge in this data set. So and now your Late Breaking Science. All right. Good morning ladies and gentlemen. Welcome to the 2025 iteration of the annual Heart Rhythm Society meeting. So we're really excited to have you all here. It's going to be a great one hour with a lot of exciting new data from various facets as our anchors for the HRSTV pointed out. It spans from ablation to conduction system pacing through left atrial appendage closure. So with that we have our first late breaking clinical trial called a multi electrode spherical array pulse field ablation system to treat paroxysmal atrial fibrillation. One year outcomes of the pulse RIDE trial by Dr. Vivek Reddy from Mount Sinai Fooster Heart Hospital. Vivek. Thank you very much. Okay. Get your seats. Get comfortable. Okay. Fantastic. So I'm really pleased to be able to present this on behalf of my colleagues who are listed here. These are the one year outcomes for the pivotal pulse RIDE trial. These are my disclosures. Importantly I'll be discussing an investigational device that does not have regulatory approval in the United States. And these are some of the other disclosures for some of my colleagues. So with that where are we and what do we need. So we do have pulse field ablation technology that gives us some degree of functional tissue selectivity. What we want is controlled ablation so that the energy goes just into the tissue that we want to ablate. Ideally we have a relatively simple procedure and we have durable PBI in the first in human studies. But so far this is not really translated in subsequent multi-center studies or clinical practice. So what we really want is scalable durability so that operators even when they initially start using technologies you get good durability. We have somewhat limited mapping integration which is improving now often times requiring an additional mapping catheter. But we want is fully integrated solutions. So this is a technology that tries to achieve this. It's an all-in-one system composed of both the ablation catheter and the system. It allows you to map target the tissue and treat the tissue. Here's the catheter itself. It's a 30 millimeter heparin coated catheter. Not that much different in size from other large focal large one shot catheters. 122 electrodes and can deliver bipolar biphasic pulses. Importantly they're directional. They're coated on the other side so it goes just into the target tissue. It has a thermal contact sensing that I'll speak to and you can select the electrodes that you want to target. So after you manipulate the catheter and create the map you identify where you have contact, select the electrodes that you want to deliver energy from, ablate and then you can remap if you want. Contact sensing is one of the key aspects of this system. There's a somewhat real-time flow map that actually measures the cooling of electrodes. When you're touching tissue it actually cools relatively slowly compared to when you're not touching tissue. Then once you feel it in a good location you do a contact scan which takes about 10 seconds or so which measures warming of tissue when delivering a very low energy current. This is the trial itself. Adults who are intolerant or failed one class 1 or class 3 antibiotic drug who had paroxysmal atrial fibrillation. The trial actually also includes persistent patients. We haven't enrolled yet in that phase of the study. So what we're going to talk about today are the paroxysmal patients. These are some of the key exclusion criteria. You're all familiar with this. I'll just point out BMI greater than 40 patients were excluded if they had a pre-existing device, reduced ejection fraction, LA diameter greater than 55 millimeters, prior ablation procedure or a planned LA procedure, and hypertrophic cardiomyopathy. So the primary endpoint is sort of a composite of things we're used to including AF recurrence exceeding 30 seconds, failure of the procedure, cardioversion, etc. The primary safety endpoint, all the usual things that we care about, and a number of other endpoints. This is a non-randomized study, single-arm study conducted at 12 sites, 19 operators in the US, Canada, and the EU. A total of 183 patients were enrolled, including lead-in subjects in the pivotal, and there was a 12-month follow-up. So overall, again, 183 patients, 19 were the roll-ins and 164 pivotal, and you noticed only two patients were lost to follow-up. The follow-up included ECG monitoring, including trans-telephonics weekly and for symptoms, as well as 24-hour holters at 6 and 12 months, and 12 ADCGs. And compliance overall was quite reasonable, you see here. Who are the patients that were enrolled? You see the mean age was 65, consistent with the paroxysmal population. 60% were male. The BMI was a mean of 28. The left atrial dimension was not enlarged at 3.8. It was somewhat preserved ejection fraction. The CHAZ VASc was 2.1, and the majority of the patients did not have heart failure history. So if we look at the procedure parameters, here's what you see. The overall procedure time was an hour and a half. Of course, this is a clinical trial, so there was a number of mapping, other protocol-related activities. If you look at left atrial catheter dwell time, it was about an hour. And if you look at the transpart ablation time from first to last application, it was 25 minutes. And again, remember, except for one operator, the rest of the operators were using this technology for the very first time. The fluoroscopy usage you see there at nine minutes, and now let's look at the procedure. Oh, I'm sorry. Now let's look at what the outcomes were. First thing you notice, the number of applications to achieve PBI was right around one. The actual mean was 1.2 applications per pulmonary vein, so it really is a single-shot technology. Primary safety outcome, you don't oftentimes see this many zeros, so it's quite impressive. The one safety event that did occur was a patient with a hemorrhagic stroke. So the overall device-related primary adverse event rate was 0%, and the primary adverse event rate as defined by the safety endpoint was 0.6%. What about effectiveness? I think this is one of the most interesting aspects of the technology of the trial, I should say, which is an overall 12-month primary effectiveness of 78%, which is, I have to say, quite remarkable. You don't typically see this in FDA trials that are multi-center, so I think this is very impressive. Why is that? How is the success so good? And I think it's related to this. The PBI durability, because we had a few patients, about 10 patients that underwent repeat ablation procedures, but the durability that was seen here was 95%. Again, remember, this is a multi-center study, so it's pretty impressive, and these are the redo patients, the patients that theoretically could be enriched for recurrences. And I should note, this 95% may actually even be an underestimate. The last two veins, we're still trying to understand, it may even be higher, but the point is it's excellent durability. So with that, I think I want to conclude a couple of points. Number one, safety was excellent. Again, first time that the majority of these operators had used this technology, with the device-related primary adverse event rate of 0%, a safety event rate of 0.6%. Effectiveness, again, this is very impressive, I think. It's 78% for a FDA clinical trial, with all of the follow-up and the monitoring that is associated with these trials. And importantly, this is a relatively efficient procedure. The transplant ablation time was 25 minutes, with applications of about one application per vein. Again, I also want to note, in subsequent work, we believe this transplant ablation time will actually be down to about 10 minutes, when you remove all of the protocol- related activities associated with this technology. And last, and certainly not least, is I think we have a technology that has scalable durability, and I'm very excited about this. There were relatively few patients who had repeat procedures, which is, of course, we're a victim of our success here, but in those patients, the durability was quite high. So I think with that, I'm going to conclude that, you know, I think the 78% is probably approaching what we can actually achieve with good PVI in a paroxysmal population. And I think that, because I think we have non-PV triggers and other points, and I think it'll be very interesting to see what the outcomes are with this technology in a persistent population, where PVI alone, we still don't know what the success is going to be in a persistent population. We may be able to find out. Thank you very much. Since Dr. Mansoor is stuck in another room next door, so I'll probably provide the commentary for Dr. Reddy's presentation. So it's actually very exciting. When I first looked at the trial and the size of the catheter, I thought, wow, I mean, this is really, this must be really difficult to maneuver, and maybe contact would be an issue. But then it's quite contrary that the fact that it is a bigger catheter looks like it really provides you fantastic contact with the tissue. And the number of applications per vein is only a positive 1.2. I think that's very impressive. And without doing a cable tractors for distance ablation, you still had a pretty high success rate arrhythmia freedom at the end of 12 months, which I think is also pretty impressive. So when you really look at the other three major randomized control trials, prior ID studies for PAFs, you have the ADVENT, ADMIRE, and PULSOR, of which ADVENT was a randomized and the other all are single arm studies. The cohort size is slightly smaller, but I think for what needed to be done in a single arm study, I think 150 was actually plenty there. And the primary safety endpoints of 0.7 is very impressive. Despite the catheter being large, I was very impressed to see that there are not many vascular complications that you would have anticipated, not any major transeptal related or left atrial perforation related stuff. And I was also surprised to see for when I was looking at the way the catheter unfolds itself or deploys itself, there are a lot of parts to it. And I'm impressed that the catheter actually did not have any malfunctions despite all of these complexities, at least that are perceived in that. And the primary safety endpoint of 0.7 is again super impressive. That could be related to the fact that a lot of the operators in this study are experienced operators that are very well-faciled in the a-fib ablation procedures. The primary efficacy endpoint of the 77.8% I think is also very good to see. I mean they actually outperformed a lot of the existing trials at this point in time in that whole number. So the follow-up using trans-telephonic monitors and ambulatory monitoring, this seems to be pretty standard for most of these clinical studies that we have embarked on. So it's good to conclude that I think PULSAR is a relatively well-designed and well-executed IDE study with excellent primary safety efficacy endpoints. And then the future adoption of the technology will primarily depend upon the ease of use and what arrhythmia is it that we are targeting. So here we go. We have one more tool in the armamentarium to tackle atrial fibrillation. With that, we'll open up a discussion. So feel free to send in your questions through the app so that we can actually spend some time on discussing the PULSAR study. So a quick question. Actually, congratulations. Excellent, exciting study, exciting results. You know, the one question, you know, nine minutes of fluoro is obviously not a lot, you know, but is there the combination capability to some kind of mapping system that might even further reduce that? And then do you have any data on AFib burden? Yeah, great question. So to the first, it is, it actually is, there is a mapping system. There is some localization. So as you sweep the catheter around, you create the geometry. So in terms of the fluoro exposure, we've actually done cases with zero fluoro. So it can be done and certainly, now again, this is the first in human experience for many operators here, so in the trial that is, so people were using fluoro appropriately. So with regards to, now I forgot the second question. Oh yeah, AFib burden. No, I wish we did. I mean, we're going to do an analysis of AF burden using intermittent monitoring, but it's a, you know, it's a relatively, it's not a dense amount of information. So I think that is information that we need. That is, do this study with implantable loop recorders and you'd certainly like to see that with like the next part of the study, which is the persistent population. Let me just make one last comment, which is on the, which is something that all of us, I think, see when we first see the device, especially on fluoro. You see this big, what looks like a big dangerous thing potentially, but when you think about it, the size of the device is actually 30 millimeters. It's well, just within what we see with other balloon technologies. I think the major difference actually, I was thinking about this, is that this is fluoroscopically highly visible. That's the major difference between this and other large sort of one-shot technologies. So, and I think that's why the safety is what it is. The device is technically complex because it makes the procedure easy. You put it wherever you are, wherever you're touching, those electrodes you choose to avoid from. So one question that came up, Vivek, is the catheter size being what it is, how many times did you inadvertently isolate the posterior wall? Well, it's a good question. I don't have a real answer to that because to really answer that question, you'd have to remap the patients, right, and really understand where that is. Having said that, look, part of the advantage is you can see electrograms also. So you can tailor where exactly you want to do the ablation. But, so that's the potential flexibility. The answer to the question, we'll have to see. So you don't have to do, so you don't have to endure the unnecessary leakage of the lesion sets onto the posterior wall if you chose not to? Well, these are bipolar lesions, so you don't have too much lateral spread. So, yeah. Perfect. Thank you. Our next presentation is going to be delivered by Dr. Marius Deitschaber, and it is entitled Safety, Efficacy, and PVI Durability of a Contact Force Sensing Large-Tip Focal Pulse Field Ablation Catheter Integrated with 3D Mapping to Treat Paroxysmal Atrial Fibrillation First in Human Omni-IRE Three-Month Results. Mr. Chairman, ladies and gentlemen, it's an honor to present for the first time the results of the Omni-IRE study on behalf of the co-authors listed on this slide. This paper is available in the simultaneous publication with Jack Clinical Electrophysiology, and I will show you the link in the QR code at the end of the presentation. These are the disclosures of all the authors of the paper in the study. The objective of the Omni-IRE three-month study was to evaluate the safety, the acute efficacy, and the PVI durability using a contact force sensing large tip focal PIV catheter integrated with mapping to treat paroxysmal atrial fibrillation with PVI only. It was an interventional prospective single arm study in 13 centers in Europe and Canada. Patient populations comprised of patients between 18 and 75 years old, all diagnosed with symptomatic paroxysmal atrial fibrillation. The procedure was done with the omnibus catheter, which will be referred to as the investigational catheter throughout my talk, and we applied point by point, sphere by sphere ablation until the achievement of adenosine proof, isoproteranol proof, pulmonary vein isolation confirmed with mapping with commercially available catheters. The primary endpoint was evaluated in 136 patients. It was acute effectiveness, being patients with proof pulmonary vein isolation at the end of the procedure, and it was a preset performance goal of 90%, and it was the primary adverse events. All primary events we care for within seven days, tamponade up to one month, and then that's fistula PV stenosis up to three months. There was a preset performance goal of 12%. Very interesting for the study was a subset analysis, group of patients, 31 patients who underwent extra safety analysis and PVI durability analysis. Safety analysis was neurological assessment, including brain MRI, pre-procedure discharge and one month, esophageal endoscopy within 72 hours, and an angiography of the pulmonary veins pre-procedure and at three months. The same patients were also invited for invasive remapping at a pre-specified date of 75 days plus or minus 15. This is the study ablation system. It's the omnipulse catheter. It's the investigational catheter. As you can see, the catheter at its tip ends with six splines equipped with two electrodes in a stacked position. And these six splines, they form a mini basket that behaves as a smooth, atraumatic, compressible tip with a width of 12 millimeter. The catheter itself is a 7.5 French bidirectional catheter. It was inserted via a steerable sheet, a 10 French outer sheet diameter. It has the typical contact force sensing, spring-based sensor, and it has a magnetic location sensor, which allows it to be integrated with the mapping system. Centrally, you have the integrated reference electrode and the irrigation pore. So overall, you see a large tip catheter, spring-based force sensing, and it is connected via a generator, which is called the true pulse generator, to deliver biphasic, bipolar pulsed field ablation only, no radiofrequency. During the procedure, we do not use intracardiac echo except for the centers from Canada. The procedure typically is performed, started with mapping with the investigational catheter, so you create a 3D map, and then you encircle the pulmonary veins, typically at the LAPV junction or slightly wider, and you do it sphere by sphere. One application, one tag, consists of a series of pulses, minimum three, maximum 12. On average, it's around 12 grouped pulses per application. How do we apply and what are the criteria? We targeted an intertag distance of less than six millimeters on the anterior wall and nine millimeters for the posterior wall. In the beginning, we allowed nine millimeters for all walls, but after seeing the first 28 patients, we optimized the workflow to six millimeters anterior. The PF index we use is designed by the preclinical work by Dibiase, showing that the lesion depth depends on the number of applications, the number of pulses, and the contact force. So we strive for 400 on the posterior wall and 550 on the anterior wall, and we target a certain contact force value to be sure that we reach that index value. During the ablation, there is a 40 mL per minute irrigation. If adenosine-induced reconnection, then touch-up ablations were allowed. 188 patients were enrolled. There was a roll-in phase that will be discussed in the main paper, which will be then the 12-months paper in a few more months, but this three-month study focused on safety and acute effectiveness. It was evaluated in 136 patients, and then the 31 patients that underwent the extra investigations. Patients were 59 years old, predominantly male patients, low TsVASC score, and normal-sized atria with hypertension being the most prevalent comorbidity. The procedural time was 105 minutes. Don't forget it includes mapping at baseline and also mapping at the end of the procedure. The dwell time for the catheter was 70 minutes. The ablation duration was 46 minutes. The mapping time at baseline was 9 minutes. Fluoroscopy was 5 minutes. The PF ablation time was 175 seconds. The number of applications, 61, and mapping was done with the investigational catheter. The acute effectiveness being adenosine proof as a paternal proof isolation was achieved in 100% of the patients, so we did meet the primary endpoint of acute procedural success. The primary adverse event rates was 3%, so we did meet the primary safety endpoint. Looking at the complications, three patients had a vascular complication, which is procedure-related but not catheter-related. There was one pericarditis, which is procedure-related, possibly, probably related to the catheter, but overall a good safety profile and zero of the typical primary adverse events that were all scanned for. The additional safety analysis in the subset of patients was as follows. The MRI brain showed a silent cerebral lesion in one out of 30 patients. It was a 3-millimeter lesion, the cerebellum, and it was not present at one month's follow-up. In that patient, there were five catheter exchanges throughout the procedure. One of the patients that underwent endoscopy showed thermal injury at the esophagus. And third, looking at the imaging of the pulmonary veins, zero out of 24% showed PV narrowing more than 70%, and by the way, 0% more than 50%, et cetera. Finally, and this is the most interesting part of the study because this is multicenter. This is in a pre-specified population. It's the PVI durability data. It was done at 81 days after the procedure. It was performed in 29 patients, and the strength of this study is that it combines the mapping of the first procedure with the mapping at repeat, so we can really judge whether the veins are isolated at those sites where we did ablate. And we observed that on a vein level, PVI durability was 85%, and in the last patient group with the optimized workflow, which was the largest group, it was 89%. Looking carefully at the spatial distribution of the reconnections, it was observed that it was more on the right veins and more at the carina anterior or posterior. This is how I put the data on PVI durability in perspective. It's in the manuscript. It's in the paper. I think this is another device that provides excellent durability, again, in a pre-specified mandatory repeat situation. In conclusion, the omniaia demonstrates the safety and acute effectiveness of this large tip catheter. The primary effectiveness endpoint was met with 100% isolation. The primary safety endpoint was met with 3% primary adverse events, promising safety profile, and high PVI durability. This study itself is ongoing, and we will present the 12-month data later, and the U.S. IDA study is currently enrolling patients. I thank you for your attention. Great. Nice presentation. Now we'll have our commentary by Dr. Jared Bunch. It's great to be here. And thank you to HRS, the Organizing Committee. These are disclosures that are relevant. First, I want to say congratulations. Trials are hard to perform. They're hard to execute. They take commitment, and we're grateful for the contributions for those that do these trials. In the spirit of conversation, I want to talk about the fact that all trials have strengths and weaknesses, and then I want to talk specifically about three things I like about this trial and three things I don't like. First, and number one, remapping was performed in a subset of patients. I think this is critical, and this is the only way we're really going to move technologies forward is by remapping and looking specifically at what we're doing, because we really can't say we're completing our objective without verifying pulmonary vein isolation, which is the cornerstone of AFib ablation. Now, one of the challenges I think that I'd have liked to have seen, this is a company-sponsored trial that has a very nice, multipolar, closely-spaced electrogram catheter, and that was a missed opportunity to map with a more high-resolution catheter, but nonetheless, I think that's a great strength. A return to force makes sense. Contact to force are important to deliver electrical energy, and blood resistivity is approximately 100 ohm per centimeter, where it's about 1,000 in tissue. We've known that for multiple years, so going back to good contact I think is critical when we think about electrical force, and I think next, bigger and quicker isn't always better. I love the idea of a smaller shaft, smaller tool, one that may be more nimble, and one that will minimize risk of iatrogenic transeptal defects, but also access complications. Now, let's move on to the three things that I don't necessarily like. One is dosing energy without long-term dosing data is a problem, and this is the Daviasiv trial, and you can see the tremendous scatter looking at the ablation index, the amount of applications in this graph, and segregating actual dosing from this is very hard, and the contact data is also that way, and this was an acute spline model. We need long-term models, multiple dosing parameters, and because of that, you have to learn as you go, and this trial, they learned as they go, but we have to ask ourselves, should we be doing that in human trials, or should we be much more focused on preclinical trials and long-term animal trials? Number X, we cannot forget the patient and what they want. Acute effectiveness is good, but long-term, we have to know, do we improve their symptoms, their atrial fibrous side effects? Do they have a low burden? Do they have low healthcare needs? And I'm hopeful that will come in the 12-month trial. And finally, single-arm trials are appropriate for established technology, like radiofrequency ablation, with the same technology, the same energy, we can expect a similar performance across different catheters. We can likely shorten those trial designs, compare towards existing technology, and then use long-term registries to look for rare side effects. But pulse-filled ablation catheters are not the same. They deliver proprietary waveforms. They have different foot plates. They deliver a different electrical force, and we can't say that these are apple-to-apple comparisons, and I really think with regulatory bodies, if you're here, we have to start doing longer-term comparative trials. We have, in Dr. Reddy's Nemesis PFA trial, highlighted this. These do not perform the same. They do not have similar outcomes, and we have to compare them against one another to really understand their place amongst our tools that we have available. Thank you very much. I think Dr. Bunch really brings out several important factors that are, I mean, some of the limitations of any trial that we do. What is interesting about this is, Dr. Deitch, was there a specific reason why you guys chose to do an MRI scan in these patients, or is it just a sub-study that the FDA wanted? Because you don't see this being done in pretty much all the clinical trials. You don't see this being done in pretty much all the catheters that are being studied now, right? So if we look at asymptomatic cerebral embolizations, it happens in a vast majority of cases. So why was this particular study needed to have an MRI? I think this study, in particular, does not need the MRI. I think it's the opposite. I think we should have done it in all the prior studies as well, because now we go sometimes from surprise to surprise when reading MRI brain data, like the other paper published today or yesterday on MRI brain. So I think it should be part of a subset population, and it's very interesting to include it in all the trials when presenting a new catheter. So where do you see the smaller footprint or medium footprint catheters fit in the electrophysiology space? Like when we're essentially taking the physiology out of electrophysiology, and we've become electroanatomists in our ablation techniques, you think this, in a way, brings it back where you can still preserve some of the elegance involved in substrate mapping and understanding and not doing sort of a shoot-at-sight left atrial ablation procedures? Yeah. I don't see this catheter for PVI only at this point in time. That's my only personal experience. Although we tested it as a PVI only device, I think the next set of studies should focus on how this catheter could be of value in the beyond PVI patients. Because with the mapping, which is its main strength, and because of its versatility, second strength, it would be ideal to do either patient-specific ablation, whether it's low voltage, whether it's lines, whether it's patient-specific atrial tachycardias. It could also help patient to make anatomical lines beyond being patient-specific. So I see it in the PVI plus as an important tool. So we'll move on to the next trial in light of the time limitations we have. The next late-breaking clinical trial will be presented by Dr. Pugal Vijaraman from Geisinger Heart Institute. He's going to talk to us about the left bundle branch area pacing compared to the biventricular pacing in candidates for cardiac resynchronization therapy with ejection fraction less than 50%. Results from the international collaborative LBBAP study I-class. Dr. Vijaraman. Thank you, DJ. Thank you, Dr. Russo. I want to thank Heart Rhythm Society for this opportunity to present our registry results. The study is left bundle branch area pacing compared to biventricular pacing in candidates for cardiac resynchronization therapy. The LV ejection fraction less than or equal to 50%. And this is the results from the international collaborative left bundle branch area pacing study group. These are the various investigators and the study centers. And these are my disclosures. Cardiac resynchronization therapy is a guideline-recommended therapy. In patients with heart failure, severely reduced LV function. And also those with mildly reduced LV function, they have left bundle branch block or indication for ventricular pacing in the presence of guideline-directed medical therapy. Conduction system pacing, especially the left bundle branch area pacing, has been shown to be a safe, physiologic, and effective alternative to biventricular pacing. We previously reported the results of our registry in two separate populations, one with less than 35 percent and those with 36 to 50 percent. While these studies showed that left frontal branch area pacing or conduction system pacing and along with histone pacing, there was significant heterogeneity between the groups. And so we wanted to combine these results, and the objective of this study was to compare the overall clinical outcomes between left frontal branch area pacing and biventricular pacing among all patients, LV ejection fraction less than 50 percent undergoing cardiac resynchronization therapy, and performed a very strict propensity score match analysis in this population to overcome the differences that we showed in the previous studies. This was a non-randomized retrospective observational cohort study. Enrollment period was from January 2018 to June 2023, and patients should have had at least six-month follow-up and ended at December 2023, and included patients who underwent successful CRT utilizing left frontal branch area pacing or biventricular pacing. And as mentioned before, the LV ejection fraction had to be less than or equal to 50 percent. Past two to four heart failure symptoms, cures duration of more than 130 milliseconds, or anticipated or ongoing ventricular pacing more than 40 percent. We excluded patients who had failed prior CRT or had prior CRT device or generated change. The choice of CRT was at the discretion of the operator or the institute. Biventricular pacing was performed targeting the mid to basal posterolateral wall, as expected, with those with long QLV, and also utilized quadripolar leads whenever possible. And left frontal branch area pacing was considered successful with the deep septal lead placement that paced morphology with a QR pattern. In the absence of that, at least you should demonstrate transition with any of these following factors, demonstrating left frontal branch potential, showing peak R-wave times in lead V6 with less than 90 milliseconds, or you can demonstrate program stimulation to capture differential capture of the two tissues, myocardium and the conduction system. And the primary endpoint was to assess the composite endpoint of time to death or heart failure hospitalization. Individual endpoints of all-cause mortality or heart failure hospitalization were chosen as the secondary endpoints. Comparison between the two groups were accomplished using usual statistical methods, but we performed propensity score matching to match participants from bi-V pacing and left frontal branch area pacing group in a one-to-one fashion, using nearest neighbor matching with a caliper of 0.001, suggesting very high strict criteria and used in a multivariate logistic model. Kaplan-Meier survival curves were obtained with differences assessed with log-rank test. So the baseline characteristic of the combined group, we had overall 2,579 patients with bi-ventricular pacing in 1,118 patients and left frontal branch area pacing in 1,461 patients. And you could see that there is differences in the age, the sex, a presence of hypertension, the type of cardiomyopathy that was predominantly non-ischemic cardiomyopathy in the left frontal branch area pacing favoring better outcome in that group, and the LV ejection fraction was higher in the left frontal branch area pacing group. When we did one-to-one matching, we ended up with 1,560 patients, 780 patients in each group, perfectly matched in all aspects, age, sex, hypertension, type of cardiomyopathy, ejection fraction, and the range of ejection fraction in the various group less than 30, 30 to 40, and 40 to 50%. Overall, again, in the baseline group, there was significant difference in the base and QRS, the presence of frontal branch block, medications, but when matched, we had perfect match in terms of having similar QRS duration and indications and underlying frontal branch block and medications are all well-matched, suggesting a robust model because we have several ongoing clinical trials, randomized trials to assess the effectiveness of this population. So the procedural characters, you can see the procedure duration, fluoroscopy duration was similar, the type of devices used were slightly different in the left frontal branch area pacing. We used more single and dual chamber devices and less defibrillator implants in this, but overall, you can see the capture thresholds are lower with left frontal branch area pacing, and while the baseline QRS duration was similar, the pace QRS duration was significantly narrower. The complications, slightly higher incidence of complications in the biventricular pacing group. The primary endpoint of time to death heart failure hospitalization was significantly reduced with a 19% relative risk reduction in the left frontal branch area pacing group and reaching statistical significance. And the individual endpoint of heart failure hospitalization was significantly decreased and the overall endpoint was driven by primarily heart failure hospitalization decreased. There was a 37% relative risk reduction. There was no difference in all-cause mortality between the two groups. If you're looking at echocardiographic outcomes, there was significantly greater improvement in LV ejection fraction in the left frontal branch area pacing group. The change in LV ejection fraction was about 9% in the biventricular group and 12% in the left frontal branch area pacing group. Similarly, there was significantly greater incidence of echocardiographic response, a change in EF by more than 5% or hyper-response change in EF by more than 15% was greater in the left frontal branch area pacing group. We have shown this in another propensity score match analysis of the reduced EF patients only, EF less than 35%, the arrhythmic events were similar translation in this population, overall incidence of non-sustained ventricular arrhythmias, sustained VT, ICD shocks or nuance in atrial fibrillation were all significantly lower in the patient with left frontal branch area pacing. Of course, this is a retrospective non-randomized observational study associated with all of its limitations. And this is only an on-treatment analysis, not an intention-to-treat analysis. And there may have been a significant selection bias, population bias, as this was a multi-center international registry, and the centers that perform left frontal branch area pacing had extensive experience in this technique and may need to be translated into other centers which may not have as much of an experience. In conclusion, ladies and gentlemen, left frontal branch area pacing was associated with significant reduction in the primary composite endpoint of depth of heart failure hospitalization in patients with LV ejection fraction less than 50% requiring cardiac resynchronization therapy. And left frontal branch area pacing was associated with significant reduction in heart failure hospitalization compared to PIV pacing. And with greater improvement in LV ejection fraction and a reduction in arrhythmic events. I want to thank all of my participating and collaborating investigators. Thank you very much. So now we have a commentary by Dr. Rajesh Kabra. Good afternoon, everyone. Thanks to Dr. Vijay Raman for spearheading this field of conduction system pacing and showing such fascinating results. So I'm just going to go through the strengths, limitations, and future directions based on the results of the study. So if we look at the patient population here, it was a large study. International institutions, over 2,579 patients with a good follow-up of up to five years. These were all appropriate BIV candidates with EF of 32% average. Average QRS duration of 156 milliseconds with left bundle branch block in 52%. These patients were all on appropriate guideline-directed medical therapy for heart failure, 84% were on beta blockers, 45% on ACE inhibitors and ARBs, and 31% on R9. The primary CRT indications were present in 71%, and AV nodal ablation and AV block were present in 17%. 68% had ICD implant, while 32% had pacemaker implant. The investigators, they used strict criteria, and they were all experts in left bundle branch area pacing. Ventricular pacing was achieved in 96% during the follow-ups. QRS shortened significantly to 136 milliseconds more with left bundle compared to biventricular pacing. And as Dr. Vijayaraman summarized, compared to BIV pacing, left bundle branch area pacing was associated with decreased procedural complications, decreased composite of heart failure hospitalization and mortality, decreased heart failure hospitalization with trend towards decreased mortality, higher improvement in ejection fraction, higher rate of echo response and hyper response, and decreased arrhythmia burden, non-sustained VT, sustained VT, VF, and new-onset AFib. So what are some of the limitations of this study? So as, again, Dr. Vijayaraman mentioned, this was a non-randomized retrospective observational cohort study, which has inherent selection bias and population bias. So if you look at the demographics closely, compared to left bundle branch area pacing, BIV pacing group had lower percent of females, lower percent of non-ischemic cardiomyopathy, lower EF, higher percentage of patients with EF less than 30%, and lower percent of patients with EF 41% to 40%. So we know BIV pacing has better outcomes in females, non-ischemic cardiomyopathy. So that's something which we have to keep in mind. And all these were centers with high experience in bundle branch area pacing. So in conclusion, this current retrospective cohort study demonstrates superiority of left bundle branch area pacing compared to BIV pacing in CRT-eligible population. However, the clinical outcomes of BIV pacing versus left bundle branch area pacing need to be studied in large prospective randomized clinical studies, some of which are ongoing and will be crucial to establish the superiority of conduction system pacing. Long-term data regarding performance of left bundle branch area pacing leads, their extractability is still needed. Improvement in implantation techniques with better tools to achieve successful left bundle branch area pacing lead placement, as well as device algorithms specific for conduction system pacing are needed. So for now, an individualized approach to CRT implant strategy with BIV or left bundle branch area pacing, according to patient's characteristics and operator experience, needs to be undertaken to achieve good clinical outcomes. Thank you very much. Thank you. Thank you for the excellent presentations. And we have a couple of questions. Let me just start out with, you know, we talk a lot now about experience with left bundle area pacing. And I wonder, you know, the experience with putting BIV leads in good positions, do we know where those leads were and where they, you know, or, you know, a lot of times that might be just quick, more quickly aborted and someone puts a left bundle area pacing lead. Do we have any information on where the positions actually were in the final BIV? So the BIV, we had in the original studies, we have looked at where the leads were located, a majority of them in post or lateral locations. I would say about 75%, and very few in the anterior locations or really posterior locations. So they were all well done. We had looked at QLV in a subpopulation in the initial less than 35% group, and they were all well above 120 milliseconds on average. So these are all well done BIV pacing. And you could see that compared to the older study results the average year of improvement is 10 percent. Yeah congratulations to your colleagues two quick questions first. Did you do any sub analysis of different subgroups to understand who if it's true across all patient populations or for example is scheming patients versus non ischemic and second did you look at left bundle area versus left bundle. Yeah great questions. I think we've looked at the various factors obviously the greater benefit in the non ischemic population is coming population the difference are minimal regarding the second question greater benefit with connection system versus by the in both groups but the difference was greater even in the non ischemic population in the non ischemic population left one branch area pacing perform even better. So compared to by the basic ischemic population they were not so much difference regarding the second one. That's a million dollar question and the challenge is that left bundle capture confirmation has various challenges we are learning and even an experienced hands identifying true left one branch capture in left one branch block. We have lots of criteria we've developed some of them are primarily in Braddock area population when you start applying them to cardiomyopathy population we know we fall quite short and I know there are a few papers out there that suggest that fear will be septal pacing and your outcomes are not as good and by we may be even better than that. But clearly if you have left one capture those patients do better. I did not want to do that analysis in this large population even though we have because I don't have confidence in the criteria that we currently use to be absolutely able to tell you that we had left one branch capture or we don't have left one branch capture. So we need to refine our criteria help our colleagues understand when we have capture because it takes multiple steps. No one single criteria helps and it's it's a really truly understanding the physiology to help you make that judgment and we are finding that it's harder and harder to make those adjudication on an individual electrogram or on one single criteria and the right bundles more dramatic effect or did you like it. Hopefully Valentina could Tifa and rot tongue will present the results soon. I know the his CRT study is nearing completion 120 patients we are very close. Hopefully we'll they'll give us a result from the next HRS. Great. Thank you so much. That was terrific. Our last presentation today is atrial fibrillation recurrence after left atrial appendage occlusion in patients undergoing atrial fibrillation ablation. Lessons learned from the option trial presented by Dr. Arwa Eunice dear esteemed panel dear colleagues on behalf of Dr. Wesley and on behalf of the option trial investigators. I would like to thank you all for giving me the opportunity to present our study. Today we will discuss the impact of Watchman implantation on atrial fibrillation outcomes lessons from the option trial as we all know the left atrial appendage is a sophisticated and complex structure that has been shown to have pro arithmogenic properties in patients with persistent AFib. Studies have shown that the left atrial appendage can lead to the patho pathology pathophysiology the progression and the maintenance of atrial fibrillation. The option trial has demonstrated great safety and efficacy of left atrial appendage closure in patients undergoing AFib ablation. However whether the additional catheter manipulation within the appendage and the implantation of a device would compromise AFib ablation outcomes or influence AFib recurrence remains unclear. In addition the impact of AFib recurrence in this unique high risk population on clinical outcomes is also unclear. In our study we included all patients that were enrolled in the option trial. The option trial included and randomized 1600 patients that were randomized to two arms ablation plus Watchman or ablation plus continuation of oral anticoagulation without a device in each arm. There were two separate arms sequential and concomitant based on the timing of randomization from the catheter ablation. The study followed the patients for 36 months. In our study the primary endpoint was AFib recurrence as predefined and pre specified in the protocol of the option trial. AFib recurrence was defined as patients requiring newly prescribed or increased dose of anti arrhythmic medications the need for cardioversion or the need to undergo repeated ablation. All other safety and efficacy endpoints were similar to the option trial option primary efficacy was a composite of death stroke or systemic embolism and option primary safety was non procedural major or clinically relevant non major bleeding. Here are the results at 36 months of follow up. AFib recurrence was noted in 52 percent of the patients. When we look at the baseline characteristics as expected we see that patients with AFib recurrence were more likely to have persistent atrial fibrillation at the baseline. They were also more likely to have cardiomyopathy and aortic valve regurgitation. When we try to identify predictors of AFib recurrence in these patients then after a step wise multivariable regression analysis we see that only two factors were able to predict AFib recurrence. AFib onset greater than one year and persistent atrial fibrillation at baseline. The main primary finding of AFib recurrence occurred at a cumulative incidence of almost 52 percent which was and did not differ significantly between the two arms with a P value of zero point zero eight for the overall comparison. When we look further into the events we see that the main AFib recurrence was captured as the need for cardioversion followed by repeated AFib ablation and change in medications all did not differ significantly between the two arms. When we look into the Watchman as we said earlier we have two groups. We have a concomitant group and then we have a sequential group and then when we look whether a concomitant procedure of a Watchman implantation would affect AFib outcomes then the results were very similar. We see that the cumulative incidence of AFib was very very similar to the cumulative incidence of AFib irrespective of the timing of Watchman implantation and this happened despite having more patients with persistent AFib in the Watchman concomitant. So again despite 55 percent versus 42 percent yet the AFib recurrence rate was similar in both arms. Does it matter to have AFib or not in these high risk patients. There was a trend toward increased events of the primary efficacy that did not reach statistical significance. Patients with AFib recurrence were more likely to meet the primary endpoint. There was no difference in all other endpoints. When we look at the interaction between AFib recurrence and the treatment arm we can see that for the primary efficacy endpoint there was no significant difference whether patients had or did not have AFib recurrence whether patients were in the Watchman FLEX arm or in the AWACS arm. For the primary safety endpoint as presented already in the option trial we see that in patients without atrial fibrillation recurrence those with Watchman had better outcomes than those without the Watchman. However when we look at the P value for interaction between treatment arm and the endpoint all P values were insignificant. Our study has some limitations. The major limitations is the lack of continuous monitoring for AFib which reflects the real world practice. However this may affect the overall rate of AFib but should not affect our conclusions since the study was randomized and the lack of continuous monitoring was similar in both arms. Similarly with PFA PFA was not used. However it is unlikely from our current experience that this energy modality will affect these findings. In conclusion among high risk patients undergoing catheter ablation for AFib concomitant or sequential lift atrial appendage closure with a Watchman device does not affect AFib ablation rhythm outcomes. There was a trend toward a higher incidence of adverse events in patients with AFib recurrence compared to those without the overall rates of FLEX in patients with AFib plate stroke or systemic embolism where low with Watchman FLEX and the oral anticoagulation irrespective of AFib development. With that I would like to thank the option investigators. Thank Dr. Wasney again and thank you all for listening. Great presentation. We have a commentary by Rodney Dr. Rodney Horton. Thank you panel. Thank you for inviting me to participate in this. I think mine was originally a different presenter. So first of all as I think Dr. Bunch had mentioned doing these big trials they're hard. I mean these are there's a lot of commitment and I tip my hat to the primary investigators that were involved in the option trial in general as well as with the sub selection. So these are monumental facts and also I'll mention that I think the option trials had a bigger clinical effect than I was honestly expecting since it was published and made public. I do have a few comments. I think I'm going to start with Dr. I do have a few comments though. It's my job. You know you're captivating a study hypothesis with a long follow up for AFib recurrence data. The you're looking at the recurrence of AFib in population of patients with a watchman versus a popular population of patients with anticoagulation. But you're missing one kind of important point and that is if you have a watchman in the appendage is it harder to address that after the watchman is implanted than if you had an open appendage in the event that the appendage was a source of the trigger and that's not really addressed there because there you know it's kind of apples and oranges there a potential confounding factor that led to the negative results could be related to you know was it concomitant versus sequential were these randomly done were these preferred were these higher risk patients that were done at the same time that could potentially have impacted the results. And finally we have to always say this wouldn't be interesting if we could look at this and sort of sub select looking at AFib type. OK you're looking at persistent you know all AFib isn't created equally so if some patients have paroxysmal AFib and in those patients closing the appendage may have may make a clinical impact but probably isn't going to affect whether or not there they have a recurrence when their veins are indeed isolated. I'm not even going to address the PFA issue because that was brought up in the presentation and would would it be useful to actually look at the patients that had an isolated appendage if it was already isolated proven to be isolated was that a was that an influencer on whether they would have a late recurrence and B if it did require re isolation how much more difficult that was if there was a device in there and so safety endpoints beyond a year would also be useful. So those are just my thoughts on this. I think it was a very interesting and intriguing study. It's it almost raises as many questions as it answers. So thank you. Thank you Dr. Unfortunately we are run out of time and the organizers have already reminded me that we need to wrap this up. So I once again want to thank you all for being here. The presenters will be around so if you have any further questions you can talk to them off the podium. I want to thank my co-chair Dr. Andrea Rousseau and the participants in this little breaking clinical trial session for wonderful information. Enjoy the rest of the meeting. Thank you.

Heart Rhythm Society 2025

PULSAR IDE trial

pulse field ablation

paroxysmal atrial fibrillation

OMNI-IRE study

iCLASS study

left bundle branch pacing

OPTION trial

Watchman device

cardiac electrophysiology