Good morning. Thank you for joining us for Adagio's FULCRUM-VT KOL Investor Event. Before we get started, I want to remind everyone that this call is being recorded. Some of you may have seen the late-breaking panel presentation and our press release yesterday on FULCRUM-VT, our 209-patient pivotal study for monomorphic ventricular tachycardia. We feel very fortunate to have had the results of FULCRUM-VT at HRS, and we look forward to sharing the study results with you today. I will moderate today's session, but the key contributors will be Doctors Atul Verma and Dr. William Stevenson, along with our Medical Director, Dr. Matthew Hakimi. In terms of logistics, Dr. Verma will kick things off by walking you through the presentation of the FULCRUM-VT results, which will be on your screen and which is also available on the IR portion of the Adagio website.
Dr. Stevenson and Dr. Hakimi will join Dr. Verma in a discussion of the results, their experiences with Adagio's ultra-low temperature ablation, and how they see the technology playing out in the broader treatment of VT. We will open up the call to take questions for the doctors. If you would like to ask a question, you can either raise your hand on screen to ask a question live, or you can write in questions on the Q&A prompt in the Zoom. I would like to kick things off with a brief introduction of our doctors, all of whom are incredibly accomplished. We're fortunate to have their time and expertise today. Dr. Verma is a Professor of Medicine and Cardiac Electrophysiologist at McGill University in Montreal, Canada, and serves as Director of Cardiology at the McGill University Health Centre and for McGill Division of Cardiology.
His research focuses on interventional solutions for arrhythmias, including catheter ablation. Active participation in multiple clinical trials evaluating new ablation technologies. He also leads a translational laboratory evaluating emerging ablation technologies. We are honored to have Dr. Verma as the PI in our FULCRUM-VT trial. Dr. Stevenson is a Professor in the division of cardiovascular medicine at Vanderbilt University Medical Center. He specializes in the management of cardiac arrhythmias and prevention of sudden cardiac death. His research focuses on the treatment of complex heart rhythm disorders and catheter ablation. Dr. Stevenson's methods of cardiac mapping, incorporating pacing technologies to guide catheter ablation, are widely used. Dr. Stevenson is past president of the Cardiac Electrophysiology Society and is the founding editor of Circulation: Arrhythmia and Electrophysiology of the American Heart Association.
We were so lucky to have Dr. Stevenson as the PI at Vanderbilt and as the highest enroller in our FULCRUM-VT study. Dr. Hakimi splits his time between being our Medical Director at Adagio and practicing medicine as a cardiac electrophysiologist. Dr. Hakimi earned his medical degree from UCLA School of Medicine and completed his fellowship in electrophysiology at the Weill Cornell Medical Center in New York. He joined Adagio as a consultant in 2021. Then as Medical Director in 2024, he has been instrumental in our FULCRUM-VT clinical trial and in contributing his physician perspective to product development while also practicing two days a week at Cedars-Sinai Medical Center in Los Angeles. Before I hand it over to Dr. Verma, I'd like to remind you of our forward-looking statement disclaimer, which I'll let you take a moment to read.
With that, it is my pleasure to hand it over to Dr. Atul Verma.
Hi, everyone. First of all, thank you very much for the opportunity to be here, and it is with a lot of pride on behalf of all of the co-investigators of the FULCRUM-VT trial that I am going to walk you through the results. As you probably know, this was presented as a late-breaker trial at the Heart Rhythm Scientific Sessions conference yesterday. I must say that the feedback that we have received so far has been overwhelmingly positive. I will walk you through this. Next slide. These are my relevant disclosures for all of you to read just for a moment. Okay, next slide. Many of you may know or may not know that VT ablation has been a challenge for many, many years. I think that we have realized that for several reasons.
One is that sometimes the critical circuits of the VT are not just on the surface of the ventricle, but are actually located down deeper within the ventricular wall or even on the surface of the outer ventricular surface, which we call the epicardium. Up until this point, the tools that we have had simply haven't had enough depth or penetration in this thick ventricular tissue in order to eliminate all of these potential circuits. As you know, up until this point in time, the standard of care for most VT ablation was performed with radiofrequency. Although it gave us some effectiveness, we were still lacking a lot in our ability to tackle the problem of VT. There is a lot of VT out there in the world. I think we could be doing a lot more VT ablation, the tools have held us back.
Now, of course, PFA has come over the horizon in the last few years, and everyone is saying that PFA is going to solve all of our problems. In fact, PFA is still very, very limited in the ventricle. We are still not seeing systems getting enough depth. Use of PFA in the ventricle is still very much an open question. We need to be able to tackle a wide variety of different VT, not only in people who have had a previous heart attack, like ischemic cardiomyopathy, but also those with other forms of heart disease, which we put into a basket called non-ischemic cardiomyopathy. Next slide. Ultra-low temperature ablation is one of these potential tools specifically purpose-built for endocardial ventricular ablations. The catheter is a deflectable catheter.
It's a nine French catheter, so it's not nearly as big as some of the PFA catheters that we're using. It has eight electrodes, which can record electrograms as well as are allowed pacing. And most importantly, there's absolutely no irrigation. One of the problems that we used to have with irrigated RF is these procedures would go for a long period of time, and these patients with very poor heart function would get fluid overloaded and often end up in heart failure. This was a major problem and complication of prior VT ablations. And you can see here that depending on how long you freeze the tissue, you can easily get tissue depths that will satisfy any need within the left ventricle. Some parts of the left ventricle, which are very scarred, can be very thin.
Maybe they're only about 4-6 millimeters, but there are other parts of the ventricle, like the septum, which can be 12-15 millimeters thick, and you can see we can easily get to those depths. Next slide. In addition to that, a lot of these VTs are occurring in scarred ventricular tissue. And one of the other limitations of radiofrequency, and we all knew this, is that radiofrequency had a limited ability to penetrate into that scar. So even if the wall thickness wasn't that thick, we still had problems penetrating down to the tissue, which was actually responsible for creating the VT circuit. But one of the nice things about ultra-low temperature ablation is we get the depth regardless of the presence of scars.
ULTA is able to penetrate the scar, and I know that some people in the PFA world say that only PFA is capable of this. Well, they're wrong. Actually, ULTA does this very well also. Next slide. So what was the FULCRUM-VT trial? Well, the FULCRUM-VT trial was actually the very first IDE trial of a purpose-built VT ablation catheter. This was a bit of a big deal. It's a single arm study. It's not a randomized study. 209 patients. Some of these patients were in an early feasibility phase, 20 patients specifically. And then in the pivotal enrollment phase, we enrolled 189 patients. Now, importantly, we only allowed endocardial access. The whole purpose of having a catheter that can go deep is to avoid the need of having to go around the epicardium.
Although many operators will say that, "Oh, we have no problem going into the epicardium to do ablation," it's actually very challenging. It's rife with complications. And while there may be a handful of people around the world who are really good at doing this, for the vast majority of electrophysiologists, it's either not feasible or they just don't have the skills to be able to do it. This was a mixed population of ischemic cardiomyopathy and non-ischemic cardiomyopathy. These were sick patients, as I will show you in the design, and some of these patients even had a prior VT ablation. This was a redo ablation, which is even a trickier population. The primary endpoint were protocol-defined major adverse events. So what are these? The FDA and Adagio basically talked and negotiated as to what a list of major adverse events by protocol should be.
However, we will show you all of the serious adverse events of the trial. We will also acute non-inducibility of a VT at the time of ablation and freedom from any sustained VT or appropriate ICD intervention without AAD escalation, or if there was AAD escalation was counted in the endpoint. This was a very broad endpoint. Next slide. In terms of the patient demographics, let me show you a few key features. Number one, the trial included almost one-third of non-ischemic cardiomyopathy patients. This is unusual. A lot of previous trials either included a very small proportion of non-ischemics or didn't include any non-ischemics at all. This trial was designed to look at both of these populations. You can see that the ejection fraction was only 35%. Going back to my point, these were sick patients. These were not easy, straightforward patients to deal with.
70% of the patients came in on amiodarone. For those of you who are not familiar with amiodarone, this is our biggest gun for antiarrhythmic drugs, but it's also one of our most toxic drugs. The fact that 70% of the patients came in on amiodarone is a big deal. It means they were sick, they were having arrhythmic events, and patients absolutely hate being on amiodarone. Next slide. Okay. Let's look at the procedural characteristics, and I think a couple of things I want to point out here. You don't need a lot of lesions in each patient with this catheter. This catheter is capable of delivering very nice, large lesions. You can see here that we were only delivering about 11 or 12 lesions per patient.
Contrast this with radiofrequency, where we often end up delivering 80 to 100 lesions in order to get the desired effect. That's why this was such a time-efficient ablation because if you look at the freeze time, it was only 47 minutes. The ablation time was only 54 minutes. Maybe, Janelle, if you can, yeah, build that slide. Yeah. Those two arrows are pointing out that this was less than an hour of ablation time, which is a huge paradigm shift for VT ablation and shows a lot of efficiency in the ablation. Now, you might say, "Well, what was all the other time spent on?" We have to map during VT, so about an hour of time was spent on mapping. You have to prep the patient. You have to make sure the patient's stable, et cetera.
When it came down to ablation and catheter dwell time, very time efficient. The other thing is, if we look at where we delivered these lesions, it was pretty much everywhere in the heart between the ischemic and non-ischemic. There isn't any limitation about where we can deliver therapy in the heart. Most importantly, when we're thinking about PFA, we've now seen several reports of PFA causing ventricular fibrillation or damaging leads or ICDs or pacemakers. With ultra-low temperature ablation, this is not an issue. There were no induced VFs, no meaningful effect on the performance of ICDs, pacemakers, or leads. Next slide. Okay, I want to highlight this primary safety event because this is something that we were very proud of. If we look at the primary safety endpoint, 2.4%.
You can go back into the VT literature and look at as many VT ablation trials as you want. This is one of the lowest safety endpoint rates in the VT literature and is a huge step forward. Those were the protocol-defined safety events, and you can see the major adverse events listed below. We've also listed all of the serious adverse events for transparency, and you can see that in the table on the right. These are adverse events that were adjudicated as not related to the device. They were related to the procedure. Remember, these are sick patients. I'll go back to that statement that I made earlier. We expect that these patients are going to have some complications.
In contrast to previous reports where complication rates have ranged anywhere from about 12%-20%, here we had a primary safety endpoint of 2.4%, and more inclusively, the safety endpoint was 8%. Again, for a very sick and challenging population, this is a major step forward in terms of safety. Next slide. In terms of eliminating VTs at the end of the procedure, the results were very good. In total, we had 302 targeted VTs, and of those, 296, or 98%, were non-inducible by the end of the procedure. What that means is, at the beginning of the procedure, we stimulate the patient's heart. We see how many VTs they're having. Is it just one, two, or three, et cetera. After we're done the ablation, we re-stimulate the heart to see if we got rid of them.
Again, 98% is an excellent result. Next slide. What is the primary chronic effectiveness? This is the freedom from any VT recurrence or any VT-causing ICD therapy or any antiarrhythmic drug escalation. This is a very broad endpoint. I make that point because unlike the AF ablation literature where we have very well-defined endpoints, we don't have very well-defined endpoints or standards of reporting for VT ablation. When you go back and you look in the VT ablation literature, the success rates can be all over the place. Some are reporting success rates of 40%, some are reporting success rates of 85%. The thing is, you need to look at the population of patients that were enrolled. Was it a patient population that was sick and already had VT, or was it a relatively well population that didn't even have VT before?
Are they measuring time to any VT recurrence, or are they just measuring time to VT storm or VT-causing therapies? There's a whole lot of heterogeneity out there, and I'm going to make the point later, you have to make sure you're comparing results apples- to- apples and not apples to oranges. The primary effectiveness endpoint, and you can see in full transparency all of the different events that happened on the right side in the table, was 59%. If we look at ischemic and non-ischemic cardiomyopathy, usually the non-ischemics have a much worse outcome because of their challenging substrates. Here we see that the success rate was exactly the same in both populations. The primary effect is performance goal set by the FDA was met. Next slide.
If we look at some other secondary endpoints, freedom from any ICD therapy, we see it was about 62%. Again, exactly the same in the non-ischemics versus the ischemic. If we look at freedom from ICD shock, it was an impressive 84%. Again, the same in ischemic and non-ischemic. Next slide. If we look at this VT burden plot, what we see by the bar graphs, the red bars represent how much VT these patients were having before their ablation, and the blue bars represent how much VT was after the ablation. You can clearly see these patients were having a lot of VT before their ablation. This was not a well population. Their pre-ablation median was three episodes of VT, and post-ablation, the median was zero for episodes of VT.
You can see that ICD shocks were reduced by over 80% in both the ischemic and non-ischemic. Next slide. Now, this is something that is usually not talked about in VT ablation trials. We talk about antiarrhythmic drug use in AF ablation trials. We almost never talk about it in VT ablation trials. Yet it's so important because amiodarone is the most commonly used drug in this population. Amiodarone is very toxic. More than 15%-20% of patients who are on amiodarone will end up having a serious side effect from this drug. We need to talk about it. What's really impressive is that at six months, 72% of the patients were either able to come off their amiodarone or were on a reduced dose of amiodarone.
A lot of these patients were not even on antiarrhythmic drugs by the time of their last follow-up, which is also a very important point. In many other VT ablation trials, many of the patients remain on full-dose drugs throughout follow-up. Next slide. Payers and hospital systems are very interested in 30-day readmission rates after a procedure. It's not just payers and insurance companies. Frankly, patients don't like coming into hospital within 30 days, and doctors don't like their patients coming into hospital within a month of the procedure. We can see here that the readmission rates were very, very low in this otherwise sick patient population, 1.9% for VT-related admissions, 1.3% for heart failure-related admissions. Remember I said there's no irrigation for this catheter, so we're not seeing the type of fluid overload that we used to see for our patients, and all-cause was 8%.
Next slide. The next step is to expand the FULCRUM-VT trial with the second-generation catheter. What is the second-generation catheter? Well, first of all, it's smaller. It can fit through any standard 8.5 French sheath that is available on the market. The stiffness profile is a little bit improved, so the catheter is softer. The curves are a little bit tighter. The ablation element length is a little bit smaller without sacrificing tissue depth. Most importantly, the freeze time is going down. Even though we saw very time-efficient ablations in this trial, those numbers are going to get even better because now what you were able to do with a four-minute freeze, you can do with a one-minute freeze. That's a 75% reduction in ablation time. Next slide.
In conclusion, I'll end up there and say that this was the first IDE for a purpose-built ventricular catheter. It was endocardial ablation. Only one-third of the patients were challenging non-ischemic patients. 2.4% is a very good primary safety event rate, 59% freedom from a very broad endpoint, including any VT recurrence or antiarrhythmic drug escalation, 84% freedom from ICD shock, equivalent outcomes in ischemic and non-ischemic cardiomyopathy. The median burden reduced from three to zero post-ablation, and 72% of patients were free from or on reduced dose of amiodarone. Again, when you're looking back at the literature, it's very important to compare apples to apples and not apples to oranges.
Yeah. Thanks so much, Dr. Verma. Before I open the call for questions, I'd love to ask the doctors to share your perspectives on these data. Dr. Stevenson is the top enroller in the U.S., and somebody who's had the opportunity to use our device in many different VTs, including a recent compassionate use case. Maybe you could share some of your perspectives on our results. More specifically, not only what are the most important data points here clinically, but maybe also put a finer point on your own experience with ultra-low and what matters most when you're treating your patients.
Yeah. Thank you very much, Debbie. I'm really delighted that there's more of a focus emerging on the treatment of ventricular arrhythmias. For such a long time, everything has been atrial fibrillation in the EP world. Of people that receive a defibrillator, of which there are a lot in the U.S., about 40% of them will have an episode of spontaneous VT within the next two years. Once they have that episode, about 50% of them will have a therapy from their defibrillator, often a shock, within the subsequent two years. There really is a need for this therapy. What we've been doing so far is radiofrequency ablation.
As Atul shared with you, the big limitation that we have with that is these VTs often involve three-dimensional reentry circuits where portions of the circuit are deep in the ventricular myocardium, and it's challenging for us to adequately ablate those with radiofrequency current. In fact, in our lab, the way that we've been approaching that with RF is often 90-second to three-minute RF applications, not very different from a long freeze, trying to get that depth. The availability of this catheter, we were very interested in, and we've been very pleased with it in our patients. It's very stable. When you freeze, the catheter sticks to the tissue. In some of these kind of harder to reach places where you're struggling a bit to get the catheter in position, once you get it there and freeze, it is stuck. We knew that would happen.
We didn't realize how much we would like it when that happened. We've taken an approach to the ventricle transseptal, kind of what's referred to as an anterograde approach. We've been able to maneuver pretty much everywhere in the ventricle that we felt we needed to get to, and we think that's going to be even easier with the next generation catheter. You don't get any ectopy or any induced arrhythmias during the application. The patient is very stable. There's no fluid load. My impression is that we are making deep lesions and that that's borne out by the pretty impressive efficacy, particularly in the non-ischemic cardiomyopathy patients. We've kind of focused a little bit on our experience with a particularly difficult part of the heart, which is the periaortic region up by the aortic valve at the top of the heart.
That's a common location for VTs in non-ischemic cardiomyopathies. It tends to be thick. We all recognize that's an area where when you see VTs coming from there, you know it could be a long day in the lab, and at the end of the day, you still might have inducible VT. We've been very impressed with the use of this catheter in that region, and I think that is part of why you're seeing the efficacy for the non-ischemic cardiomyopathy patients being similar to the ischemic cardiomyopathy patients. The ischemic folks are more likely to have subendocardial substrate that we know we're going to be able to get. That's not so much the case with the non-ischemics. Then finally, I would just say that I've been very pleased with the safety of the device.
I think, as Atul mentioned, the lack of need for irrigation, the stability of the catheter during the application. We've been very pleased with the safety, and of course, that's critical for us going forward.
Great. Thank you. Before I open it up, maybe just for the panel to discuss, how do you anticipate that these results will affect the use of ultra-low temperature outside of the trial and in adoption sort of beyond the trial sites more broadly?
I can make a quick comment here. I think it's really nice to see the safety and efficacy of the catheter and the ablation itself, but I also think about all the ancillary and very procedural efficiencies that this brings. It's a painless ablation. The need for general anesthesia is very, very low, and the cases have been done with conscious sedation. Also the lack for irrigation, and as we saw, the data on the hospitalization for these patients post-procedure is quite low. All those things, I think, are factors that are needed to, I hate to use this term, but democratize VT ablation and make it possible for VT ablation to be used in not necessarily only tertiary care medical centers, but more in capable community medical centers with capable operators.
I think those things are going to be factors that doctors really want to see before they feel comfortable taking on a VT ablation and knowing that the chances of them having to have CT surgery for backup because they might need to go epicardial is very low. The patient is not experiencing any pain. They can usually go home the same day. The chances of them having to need to be in the hospital post-procedure or even have to come back within 30 days is quite low. Those advantages, I think about in terms of the effect of this ablation technology and the trial as a whole.
Yeah. Maybe I'll make a quick point on that because we didn't even mention the sedation strategies in the results. As you know, there are parts of the world, like most of Europe, where general anesthesia is just not available. Even putting these patients on general anesthesia can be a big deal. Some of these patients have very fragile hemodynamic states. They're sick patients. They have low EFs. Once you put them on general anesthesia, you have to use a lot of blood pressure supporting medications, et cetera. It can take time for those patients to recover after the procedure as a result of that. The fact that you don't necessarily have to use GA, whereas some of the emerging PF alternatives for ventricular tachycardia almost necessitate GA, that's a big deal.
I'll also say that just feedback that I've had from colleagues after the presentation, there was a lot of VT related stuff presented at this meeting. We saw some preliminary results for some pulsed field ablation in the V. We also saw an experience from the Cleveland Clinic, on their experiences with the lattice-tip catheter in the V. A couple of colleagues said ultra-low temperature ablation actually looks like the best option for them of all the options that were presented. These were people who were not part of the trial. They've never held the catheter before. They've never done a procedure. Just as an outsider looking in, they were like, "That was the best of the bunch.
That's great to hear. Okay, we will now open up the call to questions. We'd like to take advantage of this time we have with the doctors, so we ask that all questions be directed towards our panel and their insights. We'll start by taking some live questions from the group, then I can mix in some questions that have been written in on the Q&A prompt if we have time. Once again, if you'd like to ask a live question, please raise your hand, and once we call on you'll see a prompt that you must accept in order to open up your line. First question looks like it's from Frank. Frank, we will open up your line. If you could just introduce yourself and make sure you are unmuted, please.
Great. Thank you both very much. Great presentation. I'm Frank Takkinen with Lake Street Capital Markets. I was hoping to follow up really on the question that Debbie just asked about more real-world use. Once this is in an approved capacity, is there a subsegment of specific VT patients that you will use this on? Is it all patients? Is there still a subset of patients that you might elect to just use RF? Then if you think about extending that to include the next gen, how does that change once the next gen is available?
Yeah, I can comment. Actually, if you look at all of our ventricular arrhythmia ablation cases, half of them are PVCs. Of those, most of them are up in the outflow tract, in that area that I kind of mentioned as also being a hotspot for VT that's difficult. We've had some off-label use, integral compassionate use with the technology for PVCs in a papillary muscle patient. I think that this would likely be our first line device for the left ventricular outflow tract. That's a large number of patients as well. I think that there will be that sort of off-label use is likely to occur as happens in the electrophysiology world with just about every device we've ever had.
We would definitely use it for that area in the non-ischemics, in the VT patients, in anybody with an area where we're concerned about getting depth. We also have a little bit of experience with it in two patients in arrhythmogenic right ventricular cardiomyopathy, where often the substrate is epicardial with those, so you have to go to the epicardium. We've had two patients where we were successful from the endocardium after not being able to fix the problem elsewhere. We're anticipating that this may reduce the need for epicardial ablation as well. I think the patients where we'll think about it as maybe not being the best option is the patient with a huge anterior wall scar where you've got a broad area and it's all subendocardial substrate. There you might want something where you very quickly kind of just are sweeping across.
You might still do RF or PF for those. Those patients are dwindling in numbers as the treatment of acute myocardial infarction now is so most centers get the patient reperfused relatively quickly. We don't see those folks very often.
Yeah. Maybe from my perspective, I'm practicing in Canada, we're very cost-constrained. We have to be very careful about the tool we pick at the very beginning of the case, because after that we don't have the option of pulling another tool. For me, I really like the idea of using this catheter first line for almost any VT because if it's a very superficial substrate, you can do very short freezes. You don't need the depth, no problem. If halfway into the case you realize, "Uh-oh. I didn't intend that there would now be a mid myocardial substrate, guess what? I found it." Now suddenly I have the option of doing a longer freeze and penetrating deeper. That's what I like about the titrate ability of this. If I have something very superficial, quick 30-second freeze and I'm done.
If I run into trouble during the case, I can suddenly go much deeper.
I think titrate ability is really important, especially as we talk about getting into the space of being able to go deeper. I think having a technology that can preserve healthy tissue and really target the depth that we want to achieve, also keep a surface area coverage that's wide enough, and in a way making each ablation more efficient than going point by point. I think it's really important. I'm glad Dr. Stevenson mentioned ARVC. That's a patient population that traditionally, or really most of the time we know we have to go epicardial, and to be able to get it without going epicardial and risking the coronary arteries, that's significant. I think there was data on dual-energy presented at HRS that was not successful in ARVC.
This is very helpful to see that it's been used in this trial and also in compassionate use cases with ULTA.
Great. Thanks so much. I think our next question is from Matt O'Brien.
Hey, can you hear me okay?
Yep.
Excellent. Thanks so much for the time this morning. It's Matt O'Brien from Piper Sandler. First question, I have two. The first one was just, I think Dr. Verma you started to talk a little bit about the comparison of ULTA versus PFA. We saw some data over the weekend of a little bit better efficacy and a feasibility study there. Can you just maybe compare or contrast ULTA versus PFA? I heard the commentary on anesthesia, but just other benefits of ULTA versus PFA, especially in terms of duration of procedure.
Yeah. I personally would be very hesitant to call the early feasibility dual-energy results better. That was a very small experience in a very small number of highly selected patients. Their result was still in the low mid 60 range, and their endpoint was different as well. I would just be a little hesitant to make that direct comparison. I think number one is that it is clear with that particular system which was reported, that they don't yet have an optimized PF formula for the V, and they don't have an optimized RF formula for the B. Neither of their energies is optimized for the ventricle, number one. Number two, Pasquale Santangeli reported their experience from the Cleveland Clinic, which was actually larger than this EFS study.
While they had some very good results with this other technology, they also had a lot of unanticipated results. For example, they completely destroyed an ICD that was in place. When they were pulling out the catheter, they noticed char in a couple of cases on the catheter, steam pops on the catheter. Perhaps even a little bit more concerning when they put it in the epicardium, they were pulling out the catheter, seeing fat and other tissues caught into the lattice of the catheter. I think remember this system was originally designed for the atrium, and it works well in the atrium. Now suddenly we're putting it in the ventricle with the assumption that it'll work just as well, and there won't be any issues, and everything will be fine.
Pasquale is a super operator at a super center in Cleveland Clinic coming from UPenn, and I found the experience he presented to be very informative.
I can comment on that as well. One of the other things that was noted in the Cleveland Clinic experience is that they had several cases of entrapment of the device within the chordal apparatus of both the mitral valve and the tricuspid valve. They were able to manipulate the catheter and get it out in each case. I'm also aware of a case in Europe where it was quite a big to-do to get the catheter unencumbered from the chordal apparatus. I worry a little bit about that. One of the other appeal of PF is that it's very quick. It's very quick to deliver an individual lesion. Actually, if you look in that SPHERE trial, they applied with the dual-energy, they applied RF lesions and PF lesions. They gave 27 RF applications and 70 PF applications. It's a lot of repeated applications.
One of the concerns that I have in the ventricle is that when you give a pulse field ablation, it has a relatively broad area of effect where you lose your electrical signals from the myocardium over a broad area, you know that some of that is going to come back. Right now, we don't have a way of telling what's going to come back. That's one of the things that drives this repeated application. People are doing, with the dual-energy ones, an RF application and then repeated PF applications, we don't really know how many PF applications should be delivered, we don't have a way of assessing what's going to heal and come back. That's going to make people do a little bit more maybe than what you need to do.
Even with that large number of applications, the efficacy was kind of similar to what we were seeing with RF. There's that aspect as well. There's also the coronary spasm aspect, particularly up around the base of the heart. We're a little worried that there may be something there, that you may be getting coronary injury even that doesn't result in spasm, that may later become a concern. You may have seen there was a presentation that looked at a mortality signal from the AF ablation population. In Europe, it appears that there's a sudden death or a possible arrhythmic death signal occurring late after the patient has left the hospital since centers switched from cryo and RF to PF. There's some thought that that could be a sign that we need to be worried about inadvertent coronary injury.
This is pretty preliminary, it's still a very, very low incidence, it is a little bit worrisome. There's a lot with PF we don't understand that we need to.
Just to tack on to William Stevenson point, I fully agree with everything Bill just said. If you look at that EFS study procedural time, it was long. It was really long. Everyone says PF is so efficient, it's going to make everything faster, yet the procedure time was quite long in that experience.
I appreciate that feedback. The follow-up question is kind of along the lines of that as far as procedural time. I think with Gen 2, you mentioned a 75% reduction in ablation time, which is already fairly low. I think we're going to be able to get under three hours with Gen 2. Is that the magic number, I don't know what the better term is to use, to see broader adoption for VT ablation? Is it sub three hours? Does it need to be even faster than that? How do we think about workflow in terms of being able to, with PFA and atrial fibrillation, you can do five cases in a day if you wanted to. VT ablation, do you need to get to two hours so you can do three or four in a day before you see rapid adoption, or no?
Thank you so much.
Maybe I'll take that because I'm the less expert operator than William Stevenson. Time and efficiency is important. First of all, I'm going to actually take that not from the doctor's perspective, but from the patient's perspective. Right? These patients are sick. It's hard for them to be on a table for an extended period of time in the lying down state. They often have heart failure and other comorbidities. The faster you can get the procedure done, the better it is for your patient in terms of safety. Efficiency is important from a patient safety point of view. Yes, from a doctor point of view, it's also important too, because we don't want to be stuck doing a procedure that's going to take three, four, five hours. We would rather have something that's a little bit more predictable.
I come from a time where AF ablations used to take five hours, I can't believe where that's gone now. VT ablations used to take a whole day, I can't believe even now where we've gone to that point. I think, if we can get it to a two-hour predictable procedure, that's great for doctors, but I think more importantly, it's great for patients too.
Great. Thank you. Our next question is from Josh Jennings.
Hi, good morning. Thanks for the time, congratulations to the investigators and the Adagio team on the FULCRUM-VT results. I was hoping to just touch on the primary chronic effectiveness result, freedom from any VT recurrence or AAD escalation. Dr. Verma, you've talked about if we look apples to apples, cross-trial comparisons are always challenging and maybe not academic. Can you just level set us, especially considering that the non-ischemic patients that were included, how impressive is this primary chronic effectiveness result, and how will it resonate within the EP community that focuses on VT ablation?
Well, look, I'm biased. I think it's quite impressive. I think that for including non-ischemics in the population, this was an impressive result. Some people will look at other small studies, like for example, the FIELD medical study, which was published earlier this year. Basically, a single or dual center experience, which was reporting about 80% success. Again, look carefully at what they were measuring as success. That was driven by ICD therapies and mostly ICD shocks. If you actually look carefully, you'll see that there was still quite a bit of ATP going on in the patients after ablation. How big was that study? Only 16 patients made it to their six-month follow-up. We're talking such a small number of patients, I don't even know what you can make of that number.
I'm not in any way criticizing Vivek or his skills or trashing a competitor. I'm just saying that from a clinical trial perspective, when you're comparing one trial result and it says, "Look, we got 80," another trial result and says, "Oh look, we got 60," it's just really important to look at what the endpoint they were measuring it on, how many ischemic or non-ischemic they had, because the non-ischemic are tougher, then also how many patients were in the trial. How many centers were involved? If it's one center with 16 patients, that's very different than over 20 centers with 209 patients. The previous person asking the question was saying, "How can this be broadened out to the greater population?" I think when you have a large experience, that really tells you how that's going to translate in the bigger EP population.
Yeah.
Thanks, Atul.
Sorry, go ahead, Dr. Stevenson.
No, I was just going to totally agree with Dr. Verma. Our center, of course, has an interest in VT, approximately half of our patients with sustained VT coming for ablation are the non-ischemic cardiomyopathy patients. This is a really encouraging finding.
Thank you. A similar question, just wanted to focus on the 84% freedom from ICD shock or defibrillation, post-ablation. I think it's, in terms of patient satisfaction, quality of life improvement, that seems to be a fantastic result as well. Maybe help level set and help us understand how important that metric is. Thanks for taking the questions, and congrats again.
Maybe I'll take that, and then maybe Dr. Stevenson or Hakimi want to follow up. Shocks are the worst things for patients with defibrillators. They are very uncomfortable to the patient. Many patients will develop anxiety after they get a shock because they're worried about when the next shock will come back. Some even describe it as a post-traumatic stress disorder. Patients don't like shocks. On the one hand, yes, they're saving their lives. On the other hand, it's very frightening. It's very scary. Shocks also damage the heart. One or two or three shocks is not going to damage the heart, but for patients who are getting repetitive shocks over time, there can be a negative effect, and studies have shown that mortality is actually higher in these patients.
Shocks are the worst thing, and if you can get rid of shocks and a patient just has one anti-tachycardia pacing event, and they don't feel anything, the VT comes and goes, it's gone, that's a huge difference-maker, I think.
Absolutely. I would not underestimate the PTSD part. I would have said most of them get PTSD once somebody's had a shock or a couple of shocks. The quality of life measures right after a shock go way down, and then they gradually recover as, I guess it's kind of like childbirth. The further the patient gets away from it, you forget how difficult it was, I'm told. Shocks are like that. For people who receive a shock, it is a big negative quality of life impact. In trials, it's sometimes difficult to measure because if you do a quality of life assessment at baseline and then six months later, well, if they had a shock at one month or two month, their quality of life during that phase was very low, and then it gradually recovers by six.
The ones that have a shock at five months, they'll have a low quality of life. It's a tough thing to study in trials.
Great. Thank you. Our next question is from Marie Thibault. Marie?
Thank you so much for doing this with us and putting all the clinical details into context for us. This is Marie Thibault from BTIG. I'll just keep it to one quick one. I think, Dr. Verma, you mentioned, some of your colleagues, peers, outsiders were saying that ultra-low looks like the best option out there. It feels like over the last few years, PFA has sort of swallowed the world. I'm just wondering what your EP colleagues, in terms of their bandwidth, have. Do they have the bandwidth to take on new technologies? Is there still an eagerness to adopt new technologies at this phase of PFA adoption?
Yeah. A great question. Never underestimate the ability of an EP to want new toys. Every EP wants everything. To a certain extent, this geography, Europe, Canada, will be a little bit more limited in what we can afford. The U.S., China, their markets may be a little bit broader in what they can afford. I think right now what we're seeing is an openness in the EP community to adopt any new technology that works, and that is safe, and that is time efficient. Whether it's PFA, ultra-low temperature ablation, radiofrequency, whatever it is, as long as it can demonstrate efficiency, safety, and efficacy, I think people's minds are very, very open.
One of the nice things about this system is the catheter manipulation and maneuverability is the same as what we've been doing for decades with our radiofrequency ablation catheters. There's nothing new to learn about the catheter manipulation and getting it to different spots in the ventricle. Then once you're there, when you turn on the freeze, as we mentioned, it sticks. It'd be very easy for anybody who's doing standard old RF ablation to use this technology.
Great. We're going to squeeze in one last question from Stephanie. Stephanie, your line is open. You just need to unmute, yep.
Hi, Stephanie Algazi from Bank of America. Thanks for taking the question and doing this. It's been really helpful. Appreciate the positive insights on the trial results. I just wanted to ask if there were any questions from the results that came up that you want to see answered or further investigated in next steps of the trial or other trials. Thanks again.
Yeah. Well, we all are very anxious to see the next generation catheter that Atul mentioned, that's going to allow for single freeze, shorter duration, catheters a little bit softer. That's really, I think, the next thing that we would like to see. Of course, we want to continue to get more experience with patients in other populations, and we're very interested in exploring further the ARVC population, and some of the epicardial substrates that we've not been able to attack from the endocardium. You're right, there are lots of nuanced EP sorts of questions.
Great. Well, thank you everyone for your questions, I particularly want to thank the doctors, Dr. Verma, Stevenson, and Hakimi. We at Adagio are incredibly grateful for your support and your partnership, we're really excited for what's ahead. Thank you for spending the time with us today, thanks for everyone who joined the call. Have a great day.
Thank you.