Welcome, everyone, to another episode of The Beat, a radio ablation overview. I'm Michael Lloyd, and on behalf of the Heart Rhythm Society, thank you for attending. You can call this radio ablation, SBRT, STAR, whatever you wanna call it. Today, we're gonna talk about noninvasive ablation of cardiac arrhythmias using energized particle beams, a super exciting topic, and I'm very pleased to introduce my colleague and coordinator of this program, Dr. Jason Jacobson at Westchester Medical Center. Jason. Thanks, Mike, for that introduction. Since the New England Journal publication by Kuklic, Robinson, and colleagues, noninvasive stereotactic arrhythmia radio ablation of ventricular tachycardia has captured the imagination of the EP community. And while still in its infancy, adoption of STAR is growing worldwide. As Mike mentioned, on this installment of The Beat, brought to you by the HRS Digital Education Committee, we'll be discussing this paradigm-shifting technique. Peter Postema from Amsterdam University will get us started with a review of the clinical data thus far. Peter. Thank you very much, gentlemen. Also for the invitation, it's a real pleasure to share with you this data. Let me see here. There we are. I think, yes, we're here. Thank you very much. So I will get this one smaller. There you go. So ladies and gentlemen, I will give you an overview of the clinical data and we'll have discussions thereafter at the end of the session, probably. Let me see. So for disclosures, funded by the Dutch Heart Foundation on this radio ablation topic. And another one, I believe in is therapy, but there's a few buts. It should be used with caution, should be used in trials, and we should optimize it further. And it might just stay a niche treatment, although we are all extremely excited. It doesn't compare at this moment to our conventional ablation therapies, but we'll talk about that further. So one of my colleagues, Joost Verhoef, radiation oncologist, talked about radio ablation as being like sex for teenagers. So there's more talk about it than people have actually done it. And I think, I always speculate the patients, I think there's about 200 or 300 patients treated worldwide at this moment, but we just don't know exactly, but it isn't a lot. And there's several excellent reviews on this data. Two suggestions, of course, from our own group, from Ray et al in Heart Rhythm 2020. And we just had a publication, I had a print in Heart Rhythm 2024 issue. So some initial notes, which I will repeat in the end of the slide. So the overview is discussing current and scarce clinical data. Probably there's a lot on the way. There's trials running, there's cases being reported, quite often, actually. Everything we know now is based on the data that is published. It's best investigated in ventricular tachycardia, ventricular fibrillation. And again, it should preferably be performed at clinical trials. And as to my opinion, please refrain from radiating atrial fibrillation. We have excellent techniques, they have an excellent prognosis, and there are case reports and even series out there, but I do think that radioblation at this moment should be held for malignant conditions. And if you are to start or think about starting radioblation, please do talk to investigators who have experience, contact your radiation oncologists, and know that these are nice and knowledgeable people. They will amaze you. They do talk a different language though. And there's opportunities to learn from each other on how to talk to each other about radiating, hitting a target, avoiding complications, et cetera. So when did it all start? Actually, it started not with a New England Journal paper, but much earlier. This is data from Japan. The first order is Dr. Amino. And they were investigating the consequences of radiation to the skin actually. And they found out that there was up-regulation of some proteins, namely connection, connection 43. And they were thinking about where connection 43 was most localized. And they discovered that this was the heart. So they actually ran a program, preclinical program on investigating radioblation on a model using rabbits, where they tried to get this connection 43 up-regulate. And this is strange, right? Up-regulation of a protein while giving a treatment. And actually they found out that if you give these rabbits myocardial infarctions, they will get fibrosis. And if you would radiate this infarction, they will get a change in the total connection 43 in these cardiomyocytes or in this area. And then they did this wonderful study where they had controls, they did program simulation. And in this myocardial infarction rabbits, they were able to induce ventricular tachycardias. But when they radiated this myocardial scar, they could not anymore induce tachycardia. So this was actually the first proof, preclinical proof of the efficacy, potential efficacy of radioblation. And then there were two case reports, 2014, 2017. Discussing cases where this actually has been performed. And in the meanwhile, Cukulich and Philip Cukulich and Cliff Robinson, with all the team at St. Louis Wash U University, they were gathering this famous series of five patients was published in the New England Journal of Medicine, 2017. And they showed us that when these five patients, they had a lot of events before treatment and they performed the treatment one time, 25 gray to the VT substrate. And within two months, two to three months, the VTs went away. And importantly, they stopped the enteric medication, amiodarone that is. And you do also see a slightly return of ventricular tachycardias in the end. But an amazing effect in patients who have been treated with high dose enteric drugs, multiple previous ablations and a high burden of VTs. So from these data, we perform a systematic review in 2019, look at the number of files that we investigated. And in the end, we only had 23 left, 13 discussing preclinical data, 10 discussing clinical data, and in 2019, only 41 patients were treated worldwide as published. Most of them were treated for VT, some for ventricular exocystoles that could not otherwise be managed and one for atrial fibrillation. And there's a lot of data in this sheet, but the low number of patients is the most important issue here. And also already at that moment, the data was quite promising. And that's the reduction of VT displayed in percentages per month. So there was a reduction of VT burden per month between 99.5 and 78% in the papers we discussed in which we were able to calculate a reduction in percentage per month. So this was 2019 published in 2020. And we redid this last year, 2023 published in 2024. And we now included only prospective trials. So again, a lot of data gathered, 1,861 hits. And finally, we only had 10 left with prospective trials discussing this new therapy. Again, I want to show you that number of trials and show you that number of patients is quite small still. So it's 82 patients. So in four years, we doubled the number of patients from 41 to 82. And that's all about it at this moment on prospective patients. The median follow-up is of course a little bit longer now. So we have between six and 22 months and all these data was evaluated. Of course, what you get with this kind of heterogenic data is that you have different reporting between the different papers. And, but we were able to deduce that there was a, that you could make categories with the amount of VT burden reduction. So most centers were able to reduce VT burden by more than 50%. Some up to 75, some even would, were able to reduce the burden with more than 95%. Also, we were able to get this data from the original authors to really try to make this data more homogeneous. So we had this original data and we were able to transfer that to a mostly similar pre and post-treatment follow-up period and including a blanking period, which was different indeed for quite some papers. But mostly is between one month and three months. And this is the plots you will get. So there's a 95% VT burden reduction and with a 0.61 and a confidence interval of 0.45 to 0.74, 75% 0.8 and 50% even 0.9. So you will be able to reduce with a fair amount of certainty, the amount of VTs when you use this technique. And these were all patients with previous VT ablations and high dose entry drugs. Of course, there's quite some notes. This is a niche category of patients. This is not patients with a first VT. Most of them had multiple VT ablations, also epicardial ablations. But of course, there's several caveats to this clinical data. For example, the target that should be recognized as accessible in one way, and it's quite difficult to get safe from experience to really get all this data together and try to really focus without any intimate relationship at that moment with your target, as we all have with VT ablations, to get this target offline and just treat. And of course, there will be inter-surfer and operator-dependent variability. And esteemed colleague, Yusha Tedro, will talk about this in a minute. And there are some rules, though, which we discussed in a paper in 2023. And one of the key notes is always attended to by Philip Kukulic, is the Goldilocks principle. If you delineate a target too small, you might miss it. And if you delineate too large, there's a likely higher risk for normal tissue injury. And of course, we are still learning. We don't know how it works. And of course, when we are better in knowing how it works, probably we can learn from that and optimize the treatment. Our esteemed colleague, Corrie Tesh-Chabron, will talk about that. And there's a lot of different ways to deliver cardiac radiotherapy, and that's the talk from Ms. Simpson. And of course, there's discussion on how to follow up and look at efficacy, and also on safety, which is important, and we'll show you in a minute. Because there's no such thing as a free lunch. We could miss the target, we could hit it or create something new, and we could do a lot of damage with this new radiation therapy. And this is an example of such damage, patient who died actually from a fistula between the pericardium and esophagus, with a target, which was in the backside of the heart, really basal, with the esophagus really close to the target, and it fistulated. This kind of complication can occur late after radiation. So between six months and a couple of years, you could get this type of complications. There's also a gastropericardial fistula, there's lung toxicity, there's pericardial effusion. There are things that can go wrong. So, again, I gave you a short and pretty speedy overview of the current and scarce clinical data. There is probably a lot on the way, which we don't know of yet. And there's also a clinical trial going on at this moment, led by the St. Louis team on randomization between radiotherapy versus a redo VT catheter ablation. That's gonna be exciting. They need large numbers. And if you're interested, please talk to them. Again, it's best investigated in VT, VF. And in my opinion, at this moment, we should save it to malignant conditions like VT and VF. And if you're interested in using this therapy, there must be centers around you who have experience and you could go in this together. There's a lot to learn. We always have, also in our own center, we learn with every case. And when we do twitch things, not only on the radiation oncology side, but also on the cardiology side, image integration, thinking about targets, and also pinpointing a target when you're doing your mapping and you think you will not be able to terminate VT. These are all things that you can learn by really upfront thinking about radioblation later on, possibly in the course of a patient. So, and a little thing to warm you up a little bit more. There's a symposium called Snowstorm, which is a combination of snow rat with St. Louis symposium on non-invasive radioblation and StopStorm, which is the European initiative, a large registry sponsored by the European Union on radioblation with 30 centers across Europe, and they combine in Snowstorm. It's in Amsterdam, right after the European Heart Rhythm Society meetings in London, the 2nd to the 4th of September. Most welcome to join us and please go to this website if you are able and join us in Amsterdam in September. So thank you very much. And I will happily give the floor back to our chairs. Thanks, Peter. That was a great overview and thank you for kind of outlining our agenda for today. So next we'll move on to Corey Chavron from the University of Pennsylvania, who will bring us through that preclinical literature that you alluded to. Great, thank you. It's wonderful to be with everyone. And Peter, thank you for that wonderful introduction to the literature. So I'm going to be discussing the preclinical data. And again, when we talk about SBRT, just to echo some of what Peter started with as well, we're really talking about ventricular tachycardia and would also caution on using it in the atrium at this time for sure. So just taking a step back for a moment, right? When we think about the VT arrhythmogenic substrate, we're generally thinking about structural and electrical remodeling that's occurred. So of course that means after an infarction or some other non ischemic cardiomyopathy, we have fibrosis and areas within scar that are healed and electrical remodeling with the loss and the lateralization of gap junctions connects in 43 as shown here. And so what does this result in? It really creates this arrhythmogenic substrate that's quite complex. We have fibrosis, survived myocardium, fat, all kind of intertwined with each other. And as all the clinical electrophysiologists who take care of these VT patients know, this can be really challenging in the EP laboratory. And just to show a little bit why, this is what when you do a ablation lesion in a normal heart, this is a pig, just to show you kind of some context, this is what we can create a normal tissue with a 40 watt lesion for about 80 seconds, good impedance drop 10 grams of contact at six and a half millimeter lesion, pretty good lesion, normal tissue. Corey, can I interrupt? These pictures are really good, but I'd like to see them zoomed in. We're seeing your... Oh, I'm so sorry. That's okay. We can see them, but I want to blur them. Perfect. Okay. Sorry about that, everyone. Okay. So this is the, just showing that arrhythmogenic substrate and then the limitations of ablation and scar. You can see here, first in normal tissue, this is a good size lesion. And what we can do with kind of conventional irrigated tip catheters in the ventricle today. And then when you're trying to ablate heterogeneous scar, you know, the quote unquote border zone, if you will, you can still create a reasonable size lesion. This is kind of showing a lesion created at the edge of the scar. So again, 40 watts, 90 second lesion, a pretty good size lesion still, you can kind of penetrate reasonably in the myocardium. And this is in a healed infarction. But what about more complex, dense scar? And this is where things get challenging. And I think why this therapy has come to be, and this is the challenge. When you have areas in this kind of, not sure if you can see my mouse here, but there's layers of adipose tissue and fat and dense fibrosis that actually prevents that lesion from extending deeper. And the lesion becomes wider, but the heat is not being transmitted deeper. And so if you're a reentrant circuit, a critical components involving kind of somewhere within this area of the tissue, you're really going to have a difficult time reaching that with RF therapy. And this, you know, these types of clinical challenges have been, you know, been around for a while. And that's why there's been a lot of investigation focused on alternative techniques, whether it's epicardial access in some cases, bipolar ablation, simultaneous unipolar, half normal saline, needle ablation, like Dr. Tedra's pioneered and others. So there's been a lot of focus on trying to create these adjunctive therapies to deal with these clinical challenges. And now radiation therapy has emerged as a more recent approach to that. And I think, again, also taking a step back, how did we get here? I want to talk about the genesis of what's being used currently in most centers, which is 25 gray photons. So most of this talk in terms of the preclinical literature is going to focus on photons, which is what most people are using, not proton therapy. So this is again, photons. And Peter showed that nice rabbit model showing the Connexin 43 upregulation in rabbits, but also the reason why 25 gray began was basically some interesting dose adjustment studies, which I'm going to show here. So this is one study shown again, this was in pulmonary vein atrial tissue, but really just important to show that there is a dose effect. So as you deliver higher doses, you get more intense compact fibrosis. So 25 gray was where we saw, at least in this study, there was some observation of some mild fibrosis seen, not severe, so you can create some fibrosis, but it's not an extreme effect. And of course, as you increase that dose, you have these other complications that become much more problematic. So 25 gray was thought, I think at the time, by many investigators, okay, we're creating some effect with radiation, some fibrosis, but maybe this is something we can get away with from a clinical perspective. Paul Zai and others showed also in a dose adjustment study, again, with photons, that with 25 gray, and this is again in a canine model where they deliver radiation to pulmonary veins that at chronic time points, I think they look three and six months, that you can create pulmonary vein isolation. So you can have an electrophysiologic in a tissue, in a histological effect with 25 gray that may be clinically meaningful for this type of therapy in patients. So just again, further data that 25 gray seems to be that potential spot for creating some fibrosis, some electrophysiologic effect, and that's why I think many have utilized this clinically. So fast forwarding, Peter showed this paper as well, Phil Kukulich and Cliff Robinson and the colleagues at Wash U, their paper in New England Journal in 2017. I think what's so puzzling about this and really got everyone interested in both the clinical potential therapy, but also the scientific effect, when we showed this data to our radiation oncologists and radiation biology experts, they said, well, if you're creating fibrosis, there's no way a month after treatment you're getting fibrosis. And so when it was perplexing and I think a really interesting scientific question to explore, and this has been shown in other studies as well, that there is this early effect as soon as in this, this is a paper specifically looking at patients with VT storm. Of course, all of these studies are confounded by a lot of challenges, but basically they also observed an early effect that can't and shouldn't be driven by fibrosis with this therapy. And trying to understand why that is, there is some, this is in mouse studies, some assessment of looking at what happens in the acute period. And really what was found in this paper, again, this is in mice and normal myocardium, so not abnormal infarcted or scarred myocardium, but you get this diffuse vacuolization, but there isn't an acute cellular necrotic or apoptosis seen. And so there's probably some level of tissue edema that's altering membrane, membrane alterations that's leading to this acute effect. That acute effect isn't driven by the presence of fibrosis. Another really compelling and interesting preclinical study done by the WashU group, this is Stacey Renschler's lab at WashU, took a look at the delivery of 25 gray to infarcted mice. I'm not going to go through this entire slide for the sake of time, but I think the most compelling part of this data was similar to what was observed in the rabbit study. They found an increase of connexin 43 or gap junction expression, and that resulted in a increase in conduction velocity. And interestingly, this was observed up to 42 weeks following radiation therapy. So there is this potential antiarrhythmic mechanism that's driven not by creating a fibrotic, ablation lesion, so to speak, but also increasing conduction speed and affecting the potential likelihood to develop reentry in that way as well. The recent study published, this was from the group at University of Pittsburgh, did a large animal study in pigs where they essentially infarcted a small group of pigs, four pigs, and they had a control group. And what they found in this small series was that when they remapped these hearts compared to, they didn't have any pre-radiation mapping, but in the animals that were infarcted but not radiated, you could see a kind of more heterogeneous patchy scar versus those that were radiated and more dense and homogeneous scar. And again, the hypothesis being here that they're ablating tissue and their histology seemed to have some anecdotal correlation to that data as well. Our experience, again, this is some data I'm going to show quickly from our lab, is a bit different than that group in Pittsburgh. So a small series of animals as well, but we mapped our animals and imaged them pre-radiation and post-radiation. And I'll just show you quickly what we found. So just showing in control pigs, you get a, again, large interoceptal scar, and that scar is still, of course, there after radiation therapy. But what we found here was myocardium, this is six weeks after radiation delivery. Myocardium was still thickened. There wasn't an extension of that scar. Scars weren't bigger at that six-week time point. Again, consistent with what we know to be true about the radiation biology at this time point. There shouldn't be really a lot of fibrosis at six weeks. We didn't see more fibrosis. We actually, surprisingly enough, saw an increase in the ejection fraction. So this is an animal that was infarcted without radiation. And then we did see increased ejection fraction after radiation. So still not sure why we're seeing that. Others have seen this in some emerging small animal data. So we're still trying to understand this mechanism, some more to come on that. In terms of the electrophysiologic effect, we still were able to induce VT in all the animals after radiation therapy. We were still able to find areas of slowing, significant slowing, and we were still able to induce and map these VTs coming from the scar. So from an induction perspective, there was no difference after radiation therapy in terms of the induction of arrhythmias. I'm just gonna fast forward for the sake of time. This is just showing, I'll show this image here. This is a pre-radiation voltage map and activation map during RV pacing and a post-radiation activation map and voltage map after radiation. You can see, again, no ablation was done in this animal. It's just after SBRT, six weeks. You actually, in this case, see some more slowing in this area. So the scar's a little different looking, that the chamber's actually thickened and hypercontractile. So that's why the voltage map looks a little different. But we actually tended to find potentially some more areas of slowing after radiation therapy. I'm just gonna skip some of these slides here. We did look at conduction velocity in the whole scar. We didn't find a significant difference between infarcted and radiation animals, interestingly enough, when looking at activation across the entire scar area. We may have to tease out this a little bit more in terms of looking in border zone activation conduction versus a dense scar. But in the entire scar as a binary assessment, we didn't see any difference in terms of conduction velocity. When we looked at Connexin, we actually saw the opposite of what others have reported. And again, we have some more ongoing work, at least in the pigs. Our finding was that there was a decrease in Connexin-43 expression after radiation therapy. So I'm just gonna summarize here. I think this probably, all of this data taken together raises more questions than I think provides really concrete information in terms of what this therapy is doing. I'll just say the radiation biology is incredibly complex. We don't know if there's a tissue response that's different in normal versus abnormal myocardium. Does infarcted chronic infarct tissue respond differently to SBRT than non-infarcted substrates? We don't know that answer. We do know there is a response that's been seen clinically, but that response has been heterogeneous in different groups. I think there's a lot of work that has to be done to try to understand more of why that is. Is that due to variation in the delivery techniques? One thing I've learned just from interacting with our radiation oncologists and radiation biologists is that 25 gray is not like 20 watts, right? 25 gray is different. And so in terms of one person's way or strategy for delivering 25 gray to a target is different than others. And so I think we have to kind of, again, like Peter said, speaking on that language, understand some of that more. Like many treatment modalities, we can have the potential to be good in terms of VT elimination. We have seen cases of some proarrhythmia or potential proarrhythmia as well. So this may also depend on the underlying, the response may depend and likely does depend on the underlying substrate characteristics. So a lot more to tease out there. And just generally the dose delivery techniques and time response of photons in the VT arrhythmogenic substrate definitely requires a lot more study and that's something we and many others are actively working on. So really look forward to seeing how this field continues to evolve. So I'll just end there. Thank you, everyone. Thanks, Corey. That was a great overview of a really complex topic and a complex set of literature. Next, Usha Tedro from Harvard and the Brigham will be discussing how to pick the ablation target. Usha. Thank you so much. Let me see if I can get this to work for us. If everyone can see that, okay, just give me a thumbs up, is that all right? Thanks so much for inviting me to participate in this. I was just listening to Corey's work in the context of what Peter had said at the beginning and rather than even Goldilocks, not too much, but not enough. It feels a little bit more like Alice in Wonderland where we don't really know even where we're going and where we're headed for some of the patients that we're treating. But I do have to say that I'm a bit of a believer in this therapy too. For the patients where I've seen it work, it definitely can work very well. So we just have to figure it out a little bit better. So I'm gonna talk to you a little bit about different ways to assess what the treatment volume ought to be. And I think that before we do that, we have to talk about a little bit about how we figure out what the treatment volume is for catheter ablation. So what do we do when we do a catheter ablation for say ischemic heart disease? So here's like a map of a patient with an apical infarct. We are interested in knowing the anatomy of the chamber of interest. We're interested in knowing where the scar region is located. We use typically voltage pacing late potentials to generate the substrate for the VT. But then we also use pacing to determine where the VT exit might be located and to help us pick out where we would wanna do our catheter ablation lesions. And I would sort of say that when we're trying to pick out our treatment volume for the SBRT patients, we might be doing something very similar. So here's a patient that was treated by my colleague, Paul Tsai. And you can see that this is a patient now, instead of looking at an electroanatomic map that we in EP are very comfortable looking at, we're looking at a CT image. And what you can see is a treatment volume here that involves scar tissue that's in the apex of the LV, just like what we were looking at in the electroanatomic map. Here, we're looking at it in a kind of a short axis view. And here we're looking at it in a sort of a sagittal type of view. And if we look at the VT morphology, we see that it's a left bundle VT with concordance throughout the precordium. It's positive in one and AVL and superiorly directed. So all of us would kind of think that it's probably exiting out of kind of the septal part of the apical aneurysm that this patient has. So in our mind, we're kind of localizing the VT in three dimensions. And then we're looking at the scar in three dimensions. And so the hope would be to try to select the part of the scar that's relevant to this VT morphology. The biggest challenge though, a lot of the time, we know in our heads kind of where we would want to treat. We'd even have done the ablation. We say, oh, I just wish it was a little deeper in this spot. And then you talk to your radiation oncologist, your radiation physicist, and figuring out where that spot really is in three dimensions on the CT scan is really the big question. Like how do we get ourselves all talking the same language, taking the imaging data that's available, all of the information that we got from the electroanatomic mapping, and how do we get us all oriented in the same place in space about the anatomic region that we want to target? And that's harder than you would think to make that happen. And I just stole some of the images from this great paper in EuroPace talking about the different considerations that we all have when we're treating these patients. And I'm not going to talk about the delivery part because I think we'll be talking about that in the next talk. But I think when you're trying to decide where to treat the patient, you want to use all the information that you might have available. Previous electroanatomic mapping, previous induced VT morphologies, other imaging that you might have that would suggest where the scar might be located, and then any opportunity you have to register the data together before bringing it into the radiation oncology conversation would be really, really helpful. I think that all these other considerations we can talk about a little bit more in the panel. Now, when we do catheter ablation, we're used to worrying about certain structures. We're usually used to worrying about the coronary arteries. We're used to worrying about the conduction system. And we can talk about how important those are. But the big thing in atrial fibrillation, we worry a lot about the esophagus. And as Peter was mentioning in the beginning, it's the GI tract in my experience that's been the biggest trouble in terms of establishing a safe treatment volume. And here you can see a patient whose heart is here. The intended treatment volume is down here, and you have loops of bowel and stomach that come very, very close to where you're planning to deliver your treatment. And that two years even later after you deliver this treatment could cause trouble for the patient. So it's very, very important to think about all the structures that might be near the heart where you're planning to treat. So what can we use? I think Phil Kuklis talks about the Rosetta Stone. What's gonna be the Rosetta Stone to help us communicate between the electrophysiologist and the radiation oncology radiation physics team. One of the techniques that's been used is the AHA 17 segment model. And a lot of folks will be familiar with this. It basically divides up the left ventricle into a bunch of different segments. It shows how the relationship of the septum with the right ventricle should be expected to be. And then you take these same segments and think about them from the base to the apex, the most basal segments and the middle segments and the apical segments. And I'll show you that here. If you take, it requires adjusting your CT views a little bit. You need some help from a great cardiac CT team to help you get the right views. But here the idea is that you can arrange your left ventricle in such an orientation that you can see where the right ventricular insertion is and then try to draw where you think the edges of these segments would be. And then if you look at more of a coronal sagittal type of view, then you can divide the left ventricle into the segments that you see here. And similarly, you can also use the axial views to look at all these different structures. I'll have to tell you personally, my big problem is that so many of the non ischemics involve the outflow tract of the left ventricle, which is really not well represented in the 17 segment model. So I always feel like when you have these VTs that are tucked up right by the aortic valve, that this kind of model maybe doesn't represent those so well. So this is actually, I was, hate presenting someone's data to themselves when they're in the conference with me, but this is some of Peter's very nice data looking at inter-observer variability regarding target location. And this is in the top, they're looking at the spinal canal, which like doesn't move around very much. Everyone agrees where it is. And if you take 10 people and have them draw where they think it is, everyone agrees where it is. The problem is when you look at both the interventricular septum and the lateral wall, if you're trying to draw one of those segments of the 17 segment model and you take 10 people and ask them to draw them into a CT scan that looks like this for planning, you end up with very high inter-observer variability when you compare the intended treatment targets. And so this is something we have to talk about a little bit more. There's a potential solution that I'll talk about when I show you what we've been doing for our patients, but it's something we have to keep in mind because we're used to in catheter ablation, we're like, I put my catheter there. We all agree it's gonna go there and the ablation at least goes somewhere near there unless something happens before it's delivered. So that's really a big problem for this technique. I wanted to show you the workflow that was used in the ENCOR VT trial. Peter showed that in his meta-analysis, it was one of the big trials that was done. And the workflow that was used for that is they determined the anatomic scar using imaging, either they could even use nuclear imaging at times, but they also used MRI. And then they used the ECGI during VT to determine where the VT exit was located. And that would help them to determine the proximate fibrotic area to the VT of interest. And so based on that, they would develop a plan for treatment and then position the patient, align the patient and treat them. ECGI, for those of you that don't know, involves a multiple electrode vest that calculates body surface potentials and then projects that onto a CT image of the epicardial surface of the LV. It can be helpful for general localization of VT exits. It's also been shown to show cardiac activation during bundle branch blocks. You can identify that a bundle branch block is present, but tracking the entire VT circuit is challenging with ECGI, but it can show you the exit just as they were using for this. So what do we use in our group when we're doing it outside of a clinical trial? This is the InHeart software, but there's also the ADAS software, like anything that allows you to bring the electroanatomic mapping and the imaging studies together. So these techniques, you can either use CT imaging, you can use MRI, you can even bring in PET information and register them together and then do your electroanatomic mapping on top of that. So the reason I like this is we have all these fiducial points like the coronaries, we have the leads from the defibrillator wires, and we have the coronary vein structures. We can tag wall thinning areas. We can also identify areas of fibrosis. So we use a lot of contrast enhanced CT with delayed imaging to identify some of these scar areas because we've been able to get in the patients with defibrillator implants, we've been able to get a little bit better imaging of some of the substrate in those particular patients. So we can maybe reconstruct some of the fibrosis areas. I think this type of patient that I'm showing here is the most confusing for me because it's basically a ring-like scar that goes almost all the way around the left ventricle and it really challenges us. You know, in the patients that have ischemic cardiomyopathy, we feel like we know where the scar is, we know where all of the stuff we're interested in seeing might be, but for the non-ischemics, we're not exactly sure what part of the LV to target when the scar is circumferential like this. But then when we do our ablation procedures, like with that information, we can have the fibrosis and the electroanatomic mapping acquired together so that they're preregistered. So it at least takes that part of the error out of the mapping. And then we have a workflow where we basically have the cardiac CT, we do the rendering of the scar and we do target surface delineation with transmural expansion with the help of our radiation oncology and radiation physics colleagues. And then they construct the treatment volume on the basis of that. So we usually get together on one big call with a bunch of electrophysiologists, the radiation physicists, the radiation oncologists. And when we were developing this technique, we did it in collaboration with the Lyric Institute and the InHeart group. What we'll do is we'll have the important electroanatomic information, the imaging at the same time, we will all review where the mapping was done during the failed VT that happened before, and we'll decide what part of the substrate do we want to target. And then we'll use the reconstruction to also reconstruct the esophagus and the GI tract. So we can look at what the proximity of the intended target is to some of these critical structures that we don't want to injure with the radiation treatment. And this is just preliminary data. This is under review currently, but this is a similar inter-observer variability study done with this technique. And we've got reasonably good agreement between 10 electrophysiologists looking at some of these treatment volumes, but there are certainly types of anatomies where the inter-observer agreement is not as good as this. And I'll just show you an example of a patient that we treated who had an inferior wall scar. I'll go through it kind of quickly to save time. There's inferior wall thinning. They had a VT that has a right bundle configuration with a transition at the mid-ventricle RS configuration in one and ABL, and sort of at the mid-ventricle in two, three and ABF. We found that he had a very large inferior scar on the imaging, and we were able to target certain parts of the scar. The ideal spot that we wanted to target here was too close to the GI tract, so we were able to modify our target so it's not so close to either the esophagus or the stomach. And with that type of targeting, we were really able to reduce the number of VT episodes that this patient had very significantly. Our overall experience looks just like the Encore VT series where there was a significant reduction in VT episodes in our overall population. We noticed that there were some patients that were non-responders, and as was alluded to, there are a couple of patients that appeared to have more VT after treatment, and we don't know if that's an effect of the therapy or if that's the patient's underlying disease. The non-responders tended to be people whose treatment volumes for us were very, very near the GI tract, and we probably peeled back our treatment volume to avoid complications. The other thing that we saw in our series, and maybe we can talk about this in the panel, is that there were a number of patients that had adjunctive catheter ablation after SVRT was delivered. We saw very slow VTs in some of the patients that were actually much easier to ablate than they were before SVRT delivery, and this is one of the cases that we published a couple years ago. In your case, this is a patient with an apical septal infarct scar who we had peeled back the treatment volume to avoid the Hispokingy system. We can also talk about whether that's necessary or not, but what happened is he went into incessant, very slow VT and just had this very isolated channel, just basal to the area that was treated, and required just a couple ablation lesions to interrupt, and then he was VT-free after that. So just to summarize, the cardiac radio ablation can leverage existing technology for non-invasive therapy of VT. You want to use your EP data, ECG imaging studies, whatever you have available to help you make your target. Anatomical constraints are very, very important, and VT can occur post-therapy, but in my experience, has been easier to control after treatment. Thank you so much. Great, thank you, Usha. That was a really nice introduction to how to target. And to complete our talks for today, before we get to our question and answer and panel, we have Pamela Sampson from Washington University who will discuss planning and delivery of therapy. Pam. It seems Dr. Jacobson is frozen, so I'll introduce Dr. Pam Sampson, who made it. Hey. Target selection. Thank you. Sorry about that. Thank you. Can you guys hear me okay? Can you hear me okay? Okay, thank you. Thank you. I'll go ahead and share my screen now. Great. One second. All right. So thank you for this opportunity to present today. I am a radiation oncologist. My specialty is thoracic radiation oncology. Oh, goodness. Can you see okay? We don't see slides. It says it's coming. Yeah. I am at a convention center for a different meeting currently, so... It just says it's loading. It's trying. We're used to this in electrophysiology. Okay. Thank you for your graciousness. All right. Okay. Can you see it now? Okay. Thank you. I apologize. Thank you for this opportunity to talk with the HRS community today. I always appreciate it, and I always learn something when I'm here as well. My disclosures are listed here. Oh, goodness. Yeah, we're not actually seeing your slides, I think. Okay. Would it be possible, is there a backup option if I'm having trouble? I believe we have your slides. We can on the backend, I think. Progress through them. Just tell us when you want to switch slides. Okay. Okay. Let me stop share, because that is not going well. I apologize for that. Give us a second to- Yep, yep. My apologies. That's okay. Yeah, it seemed like it was freezing for some reason. All right, let's see. Hang on. I thought they were up for a second, but they disappeared. Let me just, wait, hang on one sec. I think everybody's internet is a little slow today. Might be some holdover from last week. There we go. Let's move forward to the next presentation. I think we're a little sluggish. Ah, frozen too. Give it a sec. So maybe it wasn't just my internet. I don't think so. I think everyone's just slowing down. Yeah, apparently we haven't recovered from last week's worldwide issues, I suppose. Would it be OK if I asked a question while this is kind of being uploaded? I just had a question for you, because we've been also doing SBRT clinically for a couple of years. I've run into some major logistical issues with respect to timing of the treatment planning and delivery, especially around the time of the patient's initial presentation. On average, for us, they'll come in for an ablation. I'll realize there's more that needs to be done, and I can't do it with catheters. And then I've been keeping them hospitalized to facilitate the payment issues and all that stuff. What's the workflow been like for you? Yeah, so that can be variable. These cases certainly take priority at our center, especially for inpatients. But from the time of CT simulation to treatment delivery, it's usually at least a five-day workflow. Because it, first of all, takes the coordination of the EP and the radiation oncologist to sit down and delineate the target together. And we use a similar format to what Dr. Tedra described of like a Zoom conference to really hone in on that target together. Once that is finalized, I then have to make what I call the motion envelope and the margins to encompass that target volume, no matter where the target is during the patient's cardiac cycle or during their breathing cycle. We also contour out all the organs at risk, as was described. Once I have signed off on all those additional structures between dosimetry, medical physics, and QA, that's at least typically a three- to four-day process. So I would say even with people working after hours on these cases, it is usually a minimum of a four- to five-day turnaround. If the target has to be modified or a replan generated for any reason, that will add on additional days, unfortunately. Yeah, I could add to that. But for us, it's a bit like that, too, where it's almost two weeks kind of lag time from the moment you decide you want to do it to get everything ready and able to deliver the therapy. So we haven't been able to do any of the VT storm kind of patients immediately. And I've usually been able to, with a number of antiarrhythmic drugs, bridge them to an outpatient situation. So then you do send them home many times and then bring them back as outpatients? Yeah, almost everyone. I don't think we've done any inpatients, actually. OK, yeah. And we've done both. Well, I suppose if the slides are not going to load, I could just do a conversation. Because what I'm seeing is that my slides are still not loading, either through myself or through the backup slides with Sarah. I see Usha's slides. And slowly moving forward, I think we're trying to get. That's a little quicker. Yep, keep going. I was going to say, I'm happy to have just an ad hoc conversation, too. I can basically present them verbally, as well. I think we're getting there. As soon as we get to your slide, I think we can start. All right. Yay, thank you, thank you. So I'll be closing today with just our perspective on what goes into treatment planning. And first, I wanted to back up for just a minute of why we use SBRT and what does that really mean to us. Because it's only one of the tools we have in our toolbox as a radiation oncologist. Next slide. This is the standard workflow we're all familiar with now, the shared participation of both the electrophysiologist and the radiation oncologist. So I'll be talking about the portion that goes from the CT simulation through the delivery itself. Next slide. But why SBRT? So what is really unique about this treatment modality is the focus nature of it. And when we use this technique, it automatically implies that there is going to be a very steep dose fall off between the high dose radiation and the low dose radiation. And we have been using this type of treatment in radiation oncology for almost two decades now. And we have been using it pretty much ubiquitously throughout the body, the brain, spine tumors, lung, liver, prostate, pancreas. So we have more than two decades worth of experience in treating critical structures to very, very, very high doses while trying to protect structures around it. And I show here two such cases. Like when we do spine SBRT, we have to literally carve dose around the spinal cord to avoid toxicity there. And in the brain, we're giving ablative doses to small brain tumors or brain metastases while working to functionally protect the healthy brain tissue that is around it. So we don't just use this for heart. We don't just use this for lung. We use it throughout the body. And it's this property where we use multiple, multiple beams that individually are very, very weak. But where they converge on a single spot or a single small area is where we get our ablative dose. So that's why SBRT was initially used in this regard to cardiac radioablation rather than some of the other approaches you may have seen or heard about for other types of malignancies. Next slide. And there's a few ways to deliver SBRT. And I just want to quickly talk about the advantages and disadvantages of each of those approaches. So the most common way that SBRT is delivered and as well as for cardiac radioablation is with photon-based therapies on a linear accelerator. So this is what we conventionally call x-ray therapy. And this is the majority of types of treatments we do across the country for malignancies. And some advantages of photon-based therapy that we are able to use fluoroscopy and gait moving targets. So we're able to assess the target motion, the cardiac motion, the respiratory motion immediately before we deliver the treatment. And that's always a very good gut check, especially when we're only using a single treatment for radiation. Again, photon-based therapy, we're able to get very, very conformal distributions with rapid dose fall off. It has documented safety for patients that have pacemakers and ICDs. And there is good access and availability of these machines both nationally and internationally. So when we're talking about scalability of providing this type of cardiac radioablation to lower resource areas, the technology is already in those clinics. They don't necessarily have to purchase any special equipment. The disadvantages, however, is that there can be a low-dose radiation bath. So as those individual weak beams of X-rays converge, as they get closer and closer to the target, you are eventually going to start to have a low dose of radiation, then a medium dose of radiation, and then the high dose of radiation within the target itself. Next slide. Another way to deliver SBRT would be with proton-based therapies. And that is either a machine called a synchrotron or a cyclosynchrotron. And the advantages of proton therapy is that there is virtually no exit dose. And now with more modern proton machines called pencil beam proton therapy, there's also a decrease in proximal dose distribution as well. So literally, the proton travels into the prescribed depth. It deposits its dose, and it's gone. So there's very little collateral damage. So clinically, the most common scenarios we use proton therapy for are things like pediatric tumors, re-treatments, where we're really trying to decrease integral dose to growing tissues, developing tissues, tissues that have seen radiation before. However, there are some disadvantages with proton therapy. The biggest thing is that because it's depositing its dose at a very specific depth, there can be some setup uncertainty when the volume of a target changes. And for patients with class 3, class 4 heart failure and the cardiac volume can change depending on their fluid status, this does make us a little nervous in that regard. Additionally, with proton therapy, there's a higher neutron dose. And that is known to potentially interfere with pacemaker and ICD functioning. However, probably the biggest limitation to proton being used for cardiac radioablation right now is the lack of access nationally and internationally. Even within the United States, there may be 200, 300, 400 miles in between individual proton centers. They're almost exclusively located at NCI-designated cancer institutions. Not all cancer centers have a proton machine. In fact, the minority do. And then internationally, the prevalence of proton machines is even less. Next slide. But let's talk about, now let's move to how we would plan a patient. The CT simulation is going to be very similar whether or not we're using a photon or proton therapy. So when the patient comes to our department for their, quote, planning scan or CT simulation, what does it look like? So basically, the patient is supine. We make them a custom immobilization device where you see this cushion behind them, kind of like a memory foam cushion, so that their body positioning on the day of treatment is very similar to that of when they were simulated. And we use a small paddle with abdominal compression to kind of limit the chest wall excursion. We do ask that the patient be NPO for four hours prior to the CT simulation, as well as the treatment day, to decrease the stomach volume and help the stomach be a little bit further away from the heart, especially for those inferior targets. We get both free breathing images and a 40 CT to capture both cardiac and lung motion. So what I'll see is I'll see a free breathing average CT that averages all of the cardiac and lung motion together. But then we will take individual pictures or CT scans during each of the cardiac cycles, during each of the breathing phases, so I can make a movie to see how far up the target's going to move, how far down the target's going to move. Usually supine is the motion we see the most. We don't see so much lateral or anterior posterior motion. Regardless of the patient's creatinine, we do use IV contrast just because it's so invaluable in helping us see the septum, helping us really get accurate left ventricular contours to use our mapping software on. And then images are bent according to the breathing phase and imported into our treatment planning software with the 17-segment model, so that basically each patient's left ventricle has their own 17-segment model projected onto their anatomy. And there's several both in-house and recently commercialized products that now do this. Next slide. So creating the target volume. So the very first thing we'll do is create the clinical target volume. And once this target is imported from the treatment planning software, I will sit down and manually correct this or adjust this. And this is what I'll do on the Zoom also with our electrophysiologist. And what we wanna make sure of first is that this target volume is encompassing the full thickness of the myocardium, because this is one of the purported benefits of radiation is that I can send those X-rays wherever I need them to go. So I want to make sure we're hitting the full thickness of the myocardium. I will pull the target contour away from any blood pool that it may have accidentally included. I'll confirm the target with the electrophysiologist and together we may make minor adjustments to that target with their guidance. So I know Dr. Cheddar mentioned earlier that often the 17-segment model doesn't appropriately sometimes get towards the aortic root and it may miss that area. And I found in my experience sitting down during these Zoom meetings, that's a common place where they'll have me bump out the target to include. Next slide. Once we have that clinical target volume, the next thing I'll do is I will copy that structure and make a new structure called the internal target volume or the ITV. And what this volume is, is this is the motion envelope you will hear us talk about. So I will scroll through each of the cardiac phases, each of the bend respiratory phases, and I will basically adjust that contour so that no matter where that person is in their breathing cycle, the target is always included. So you can see in the top image here, if I were to only use the CTV to treat this patient, there would be a portion of the breathing cycle where the target, that inferior portion is clearly outside of the target volume. So what the green structure, the ITV will do is that is the motion envelope. So no matter where the person is in their breathing cycle, their cardiac cycle, that target is being hit. However, I do not make any further edits to the blood pool because at this point now it's representing the cardiac motion, not the blood pool itself. Next slide. Finally, the last margin we will put on there is the planning target volume or the PTV. And this is a three millimeter isometric expansion. So just expansion the same in all directions of the ITV to account for any minor setup uncertainties on the day of treatment, also for any minor patient movement that they may have during the course of treatment. I will usually check the total volume of the target once that PTV volume is complete, because we do have some data to suggest that when volumes are under 200 cc's, they tend to have better outcomes. It's not necessarily a riskier treatment. We just know that when the volumes become over 200 cc's, we're usually dealing with a very nasty scar that we don't necessarily see improved survival for or improved outcomes with this treatment. So it's not so much that we would stop the treatment or abandon the treatment if it was a large target. We would just make sure everyone is kind of clear that this is going to be a more challenging case, that the EP knows that, that the patient knows that. So it's one final gut check of what this case is going to look like. Next slide. But before I send the case off for treatment planning with our dosimetrists and our medical physicists, like I said, we will contour those organs at risk, and they are just as important as the target. And our group has previously published on what dose constraints and dose objectives we use to design these treatments. So it then becomes an optimization process with our treatment planning of how can we maintain target coverage while minimizing dose to the esophagus to the stomach below. So this will be kind of our typical contours of the great vessels, the esophagus, the lungs. We also look at the dose to the non-target heart tissue as well. Next slide. Treatment planning considerations I always take into account when designing these treatments. So the most common organs at risk that can limit coverage are certainly the stomach, the large bowel, where the splenic flexure is, and the esophagus. And what we'll typically do, because these are, these luminal structures can all have day-to-day, even hour-to-hour variability in their position because they're GI organs, is we will usually not only, not usually, we will always not only contour that structure itself, but we will add a safety margin to those as well. Again, a three-millimeter expansion to the stomach, to the esophagus, to literally allow some wiggle room of those GI structures. We do have strict dose limits for the luminal organs, the spinal cord, and the ICD. Every ICD has a dose limitation, and we will always work to make sure that we're under that. Next slide. The most common cardiac radioablation treatment plan type today that we use, and this is true across centers, is what's called a volumetric modulated ARC therapy. And basically all that means is it is a treatment plan where, like I said, we're using multiple individually weak beams, but where they come together is where we get our concentrated dose. And what you can see in this figure on the left is that not only will we use those ARCs or half ARCs of therapy where the machine will rotate around the patient and deliver those small, small beams of radiation, we can vary the intensity of each one of those beams. So here, the longer red lines indicate where we're using that angle a little bit more because maybe it's a really good angle where we can deliver a little bit more dose and not hit the esophagus, not hit the stomach. And then there's some areas where we're still trying to hit it, but we're backing off. We're putting on the brake a little bit because maybe that's an angle where we are getting close to the stomach or the esophagus. So you'll see us really weight these angles differently. So different angles, different weighting. We will even ARC them differently to, again, so the same areas just not getting hit over and over and over again. And it's because of that technology that we are able to develop these really conformal plans that you see on the right side. Next slide. So when I have the treatment plan that's been optimized by our dosimetrist and our medical physicist, and I sit down to do the final review before signing off for treatment, I'm looking at several things. So I'm looking at, does the target meet our planning goals? And typically what that means is, does my PTV, is 95% of the dose hovering 95% of the target? That's kind of like our golden rule for a successful treatment plan. Are the organs at risk meeting the dose constraints? And again, we have hard stops for things like the spinal cord, the esophagus, the stomach. For things like the non-target heart and the lung, those constraints aren't as strict, but we will keep an eye to make sure they're being optimized on. If dose is being carved out significantly from a target, would it benefit from being replanned or trying a different approach? So again, that's something that may mean that there may be a treatment delay of one or two days. Like the red on told you, oh, we're shooting for next Tuesday, but it turns out we're kicking the plan back to be re-optimized. That could be why, is because one of these two things is not happening. We're not meeting the planning objective or the organs at risk are being exceeded. But ideally what I'll see is a plan like I've shown here, and this is just one I did a couple of weeks ago, where the esophagus is contoured in orange. There's that margin around it to account for any GI day-to-day variability in the magenta. And what you see are the isodose lines of the 20 gray, 25 gray, and higher. They are bowing away very nicely from the esophagus. And you'll actually see that high dose radiation is actually concentrated well above the 25 gray. Prescription dose is actually concentrated within the target itself. And that is very, very common for these SBRT plans, that the interior of the target actually goes significantly higher than the prescription dose. And that is fine. That's a very common aspect of, again, these beams converging together and making intentional hot spots. So again, I'll look at it not only in the axial plane, but I'll look at it in the sagittal views and the coronal views to really make sure that these organs are being carved out correctly. And then finally, what will happen is another limitation to maybe delivering treatment as quickly as possible is we do QA each treatment, meaning we do a mock delivery of that treatment to a phantom the night before to make sure that the machine and the treatment plan is delivering exactly the dose and type of plan we have ordered it to. Next slide. The patient preparation tips that I will do independently of the electrophysiologist is I will see them before their treatment that day. I'll review their expected experience that they're not going to feel anything with the radiation. They're not going to feel any heat or warmth or zaps or dizziness. I'll answer any new questions or concerns they've thought of since the last time we talked. You know, a lot of people have had radiation therapy, a lot of family members, friends for other reasons, and they'll come to me with new questions of, am I going to throw up? Am I going to get sunburned? And we talk through those concerns on the day of. Every now and then I'll have somebody that's nervous enough I have to give them a little anxiolytic that day, which is fine. For the ICD management, we do interrogate the ICD both immediately pre and post treatment to make sure that everything's in good working order before and after. We do not change any settings on the ICD or the pacemaker. We do not put it into safe mode or anything like that. This is not MRI. And the chance of SBRT somehow causing an inappropriate shock is just not there. And in fact, if the patient does go into VT, we want the device to work. We don't want somebody having, you know, a VT storm in our department without their device working. Other common questions we get, we have had a patient go into VT and get shocked during the CT simulation procedure. Basically afterwards, we confirmed that they were stable post-shock, and then just proceeded with the rest of the simulation. We have treated patients actively in VT, but no one to date has been shocked on the table. But if that were to happen, we would handle it the exact same way. We are able to pause the treatment once it started. So we can just hit the stop button, go in, assess the patient, and if the patient is feeling okay after a little while, we can resume. If for some reason the patient was so ill or felt so poorly that they did not think they could continue treatment that day, again, we can simply pause and deliver the rest of the prescribed radiation dose at a different time. Doesn't matter if they were a quarter way through it, halfway through it. We can simply parlay the rest of that treatment into a different day. And we do not have to put in arterial lines or anything like that. Basically, we have a dynamap in the room. We have a crash cart at the machine for good luck that we've knock on wood never had to use. But unless they're an inpatient and have other monitoring devices on them, we do not do anything special. Next slide. This is for an outpatient. This is what it would look like. They basically check in at the treatment machine. We confirm their name, date of birth, and organ we are treating. We get them set up on the treatment table. This is what a linear accelerator would look like. Again, he's got his custom cushion that was created at the time of CT simulation. We do a clearance check, making sure that when the machine rotates around him, it's not going to hit his cushion or his abdominal compression paddle or anything like that. We get those CT images and that fluoroscopy before we beam on the radiation oncologist is present at the machine to confirm that alignment. And then we deliver the treatment. If we're not doing a breath hold or a gated treatment, typically it's about a six minute radiation length of treatment. Total time in the room is about 25 minutes on average, I would say. Again, with most of that time being the setup that you see going on in the top half of this image and the confirmation imaging before treatment. Next slide. Post-treatment, like I said, we'll interrogate the ICD before they leave. If the target was close to the stomach or the GE junction, I will consider or prescribe three months of either a PPI or a H2 blocker. Anticoagulation is determined for the electrophysiologist, but for the rest of the day, they may resume their activities. If they drive, they're allowed to drive. They can go back to their normal PO intake. We do like it when they follow up with both the rate with the electrophysiologist, obviously, but also the radiation oncology personnel, because we do want to assess for RT-specific side effects, pericarditis, chest wall myositis, gastritis, or very rarely has been described in a few series, gastric ulceration. Next slide. I think it's my last one, is the next slide. Yep. So, just conclusions. I think for people that are interested in starting this workflow and having this treatment option at their hospital, what you want to make sure of is that you have a dedicated radiation oncology team that does high volume SBRT cases. So, the very first couple slides I presented were, you know, I talked about the history and tradition of doing this in other disease sites. You want to make sure that your center has been doing that for a while, and they have a dedicated physics team, dosimetry team, that regularly handles SBRT cases and specializes in SBRT cases, because so much of the workflow for cardiac radioablation has directly evolved from that process, especially with lung SBRT in particular, because they would know how to handle the motion management. And again, I can always speak to having close collaboration between the radiation oncologist and the EP during target delineation, and it's not over once the segments are chosen. I'm always going to run it by you, make sure this looks like what you want it to look like, and if your catheter could go to all these places, is this where you would want it to go? All right. Thank you. Thank you, Dr. Sampson, for offering that perspective from the radiation oncology realm. It is a team sport. And speaking of team, we have panelists and lots of questions. Our expert panel also today includes Elena Arbelo from the Hospital Clinic de Barcelona, Natasha de Groot from Erasmus University, and Dr. Wendy Zhao from the University of Colorado Anschutz campus. Thank you, panel. We have a lot of questions, a lot of texted questions. Please enter them through the Q&A if you do, and we will either try to type answers, which has been done by Usha and Corey, thank you, or bring them up live. Jason, do you want to kick this off? Sure. So there were a couple of questions that were asked online and actually have already been answered. I don't know if we want to rehash those for the audience, but maybe we can just kind of stick to our questions. I do have a question to start off, and we were talking about organs at risk. And when we do epicardial ablation, we're often very concerned about the phrenic nerve. So no real talk about that. Is it really resistant to radiation damage? Yeah. So to date, we've done over 70 patients now at WashU, and with over four years of follow-up, we have not seen any phrenic nerve injuries or paralysis or anything like that. Nerves, because they're such a differentiated structure, they're no longer dividing or anything like that. Actually, nerves are some of the most radio-resistant structures in the body. So that historically has not been an issue for us. Dr. de Groot, we have a lot of anecdotal, retrospective patient series. In your mind, the ideal trial, the ideal next trial that should be done is what? Well, that's an intriguing question. If I summarize now what I've heard from the speakers, I would say we have treatment modality with a promising clinical outcome, namely the reduction of the VT burden, but we have problems there that we don't know the effect on the short and the long term. What also worried me is that Peter actually mentioned that even after years, you might have complications. So, yeah, of course, the randomized clinical trials is always the best way to, to evaluate treatment. But I think we have to start with a standardized protocol. How are we going to, what is our methodology? Is it the same for all centers? How are we going to do the follow up and actually what should we do during the follow up? So that would be, I think, the points to start with. Actually I was gonna, I was gonna mention the same thing as Natasha had just mentioned. We've only spoken briefly on the complications of this therapy and the, when these complications may occur. Some of them may be in the early phases, but some very severe ones may occur even beyond the year or two years follow up. So could the panelists or the speakers expand a little bit on how you would do the follow up in these cases and to continue on Natasha's suggestion, what kind of protocol would you propose for a study to evaluate this therapy? Or Elena, perhaps we should also add like, what is the ideal study population to start with? Yeah, a lot of questions. Yeah. For the start we have 60 years and older. Are you going to include also younger patients? So I would like to hear that also from the speakers. Any thoughts? I could just, yeah, so there's a lot of questions at once, of course, which is very much acceptable in this kind of new, exciting, but unresolved field. So to start with the last one, there's young patients treated and you should have a very good imagination of their life expectancy. So if this is a 25 year old, I would rather not treat them unless they have a real reduced life expectancy. There has been patients treated that had a life expectancy of six months, but they were in continuous VT. So those patients could be treated as well. In my practice, our youngest patients was like 57 or so, severe heart failure ischemic. And the oldest one was 80 something, which also complicates my VT ablations, of course, with tortuosity and fragility, et cetera. And these, I didn't talk about the mortality rates of these patients, but about a third of these patients are still going to die during follow-up, not especially because of the radiation complications, but due to their heart failure, fragility, vascular complications, we have lymph amputations for other reasons, people get cerebrovascular accidents, et cetera. So the mortality rate in this population is still high. And actually, when you talk to these patients, many of them don't mind dying. They just want to get rid of the shocks and the numerous hospitalizations, et cetera. That's their goal. But that should also be one of the, maybe it should be, have a place in the discussion of these patients. As to follow-up, we have quite strict follow-up rules in our center. We did this with the Stop Storm Consortium in Europe. It is a three-year period. We have landmarks every now and then, and in general, in our trials, we'll have a direct follow-up in one week, one month, three months, six months, nine months, 12 months, and thereafter every six months. And these six months follow-up include echo, CT, lung function, lab. So it's quite a rigorous follow-up. Patients can have some difficulties with traveling, et cetera, but also the lung to CT and the late complications should probably be follow-up quite extensively. And after three years, we get to one year. I'd like to hear what the panel thinks about some of the disparate results between different centers and in the literature. Wendy, what do you make of some of these differences and how we can try to use that experience to push this forward? Great question. I mean, I think that the disparity in results also speaks to the heterogeneity of patients in general, as well as the challenges in trying to design a clinical trial that would compare this type of therapy to the standard therapy. And in fact, just focusing on radiofrequency ablation of VT, there have been challenges in designing trials. So on the balance, I actually think that they're somewhat consistent in terms of the results, you know, in that there's a reduction in VT burden, even considering the wide heterogeneity of substrates. You know, I think it's clear that there is at least an acute effect. And then, you know, when recurrences are seen, they may be seen sometime later. But that overall, even though that there's an improvement, it's not a cure. You know, so I think that's an important aspect to consider too, especially when we're talking about how to follow these patients. I mean, you know, very rarely are we going to do a VT ablation and not continue to follow them. So I think that that's probably where we'll continue to capture some of the complications. But knowing the potential of risk, especially if ablation has, you know, SBRT or STAR has had to be applied in regions of potential anatomic sensitivity, we're probably going to need to be more vigilant about looking and screening for those types of complications moving forward for the growing number of patients that we're now offering this to. And Wendy, I also noticed that in some of the papers, people are referred for ventricular ectopy. Would you do an ablation in this way for ventricular ectopy? That's a great question. I personally am not doing that. I think that SBRT is a very effective tool when you can identify substrate. And unless we're talking about a very large area or a defined area of scar from which there may be arrhythmogenic foci originating within that scar, I would say I have not personally done any SBR treatments for patients with refractory PVCs in the absence of structural heart disease. Also, I think I treat it or I think of it in the same line that Peter had mentioned about treating AFib. Since we're on the topic of patient population, one thing we struggle with is LVAD patients, non ischemics who no longer have epicardial access. The question of should they have ICDs in general aside, does any of the panel or any of the speakers have experience treating these types of patients? We have done a handful of LVAD cases as a bridge to transplant to help them basically stay alive until a transplant would become available. From a radiation planning perspective, it did not present any challenges for us, but I understand how it can from a patient selection standpoint for y'all. May I ask Pamela one question? We've heard from other speakers that 25 gray is not the same depending on the patient or the substrate. How would you tailor it and would you tailor according to the different VT origins and then would it make sense to play with the fractionation so you have less toxicity and you can give- Yeah. That's a great point. It actually speaks to two things. 25 gray, as of right now, the way cardiac radio ablation is done among radiation oncologists, 25 gray is not the same from center to center to center. What I mean by that is even though we write 25 gray in our orders, the way we plan that 25 gray is very different. For example, I showed you some examples in my plan where we go very hot. We go to 35 gray to the target itself and 25 gray to the margin. Other centers, they will do a much more homogeneous plan without those hot spots. Their 25 gray is closer to 25 gray where washing plans are much hotter. There's that difference between centers. It is good to know, I think, what your center is doing. How are they planned? Are they homogeneous? Do they have hot spots? Are they running those plans hotter? Are they running them colder? Because that could also affect your outcomes as well. I think that's good for EPs to be aware of. Also the margins your RADOCs are using because those, again, may not be the same from center to center. What you're talking about, though, is a very hot topic of debate in radiation oncology is should we be dialing up or dialing down the dose depending on the substrate, depending on the size of the target? Should we be doing one fraction or should we be taking that dose and chopping it among five fractions? For example, when I treat brain metastases, if they're small, we will treat those in a single fraction. If they're large, I will take that similar dose and I will distribute it among more fractions to hit it multiple times. That is something we just do not have an answer for right now. As you know, the 25 gray dose came from very important preclinical studies at Harvard, at Mayo, and we extrapolated that to this clinical scenario. Obviously, that was done in healthy animal hearts. Should we be doing a totally different dose and fractionation for VT scar substrates? We don't know yet. It's an active area of research and debate in our community as well. I'd like to hear people's predictions about the evolution of this therapy and where we'll be in the next five, 10, how many years, and at what point, if ever, will this become standard or maybe even first-line therapy? Let's hear from Wendy what she thinks. Maybe we'll go through the panel and then maybe we'll get a final word from the radiation on. I mean, my prediction about this is that it will become more commonly used. It's hard to envision it as more than a bailout strategy, at least at this point. However, if we get better at, let's say, cardiac gating, because Dr. Sampson described a very methodological approach for trying to adjust for the movement of the heart, but if we could actually gate to the heart and be more precise about the delivery, and perhaps if the, is it photon beam therapy, proton beam therapy, the one that's more targeted, if that could become more widely available, I think it actually could really change the way in which we approach these types of patients. I think there's a lot of time that has to elapse before we get to that point. But I think that the early experience shows a great deal of promise. There was a question from the online audience about how patients recover, and the recovery is like easy peasy, I mean, you know, compared to standard catheter ablation. So from a patient satisfaction standpoint, I think it would be huge if we could be more effective in all the other means. Natasha, what do you think? Well, actually, the majority, I agree with Wendy. I think the only major problem we also have to solve is that we need to be able to identify what we want to ablate non-invasively with high accuracy, and it will also determine like how much volume of tissue do we need to ablate, or do we need to target, sorry. So I think if that can overcome, it will be a promising future therapy. Elena, your thoughts? So I have to be a little bit more cautious, I think. I do see this as a very interesting alternative, but I don't think in the near future it will gain a more prominent position. We still need to understand how it works. It seems that it reduces the VT burden, but it doesn't abolish it 100%. The long-term duration of the efficacy, it's also questionable, and we have some severe and long-term complications that we have to take into account. So I'm going to take the more conservative standpoint in the panel, I think. All right. Since I think we're running a little over, which for technical reasons I think is good, let's give the final word to the side that's delivering the therapy. What do you think? Where are we going with this? What's the timeline? So I think I speak for most of us where we say we're cautiously optimistic, and that hopefully this treatment expands in a way to include more patients from treatment rather than taking patients away from a gold standard. So what I mean by that is increasing accessibility to patients that maybe don't have the option of high-quality EP care, or, you know, because a lot of this could be done virtually. Like I could virtually simulate, plan, and deliver this treatment hundreds of miles away. So I would love to see maybe implementation of that in 5 to 10 years from now. The other thing I'm really interested in is could this be used as a preconditioning procedure? You know, we've noticed a similar experience at WashU where future ablations, our EPs are also noticing that they go more smoothly, that they're quicker, and they're technically easier, in cases they didn't expect it to be. And again, that's anecdotal at a few centers right now, but I think that deserves to be studied. I think that's their signal there that could speak to, rather than either or, actually a combined approach between our fields. Great, well, thank you. I'd like to thank all of our speakers. I'd like to thank our panelists and, you know, my co-moderator, Mike Lloyd. On behalf of the HRS Digital Education Committee, I'd like to thank everybody who tuned in today. And remember, this will be also available online for everybody to re-review. I think, obviously, there's so much more to discuss on this topic, and certainly an exciting future ahead, I think, for radiotherapy, STAR, SABR, SBRT, CRA, whatever your favorite acronym might be. Again, thank you, everybody.

Dr. Pam Sampson

radioablation therapy

cardiac arrhythmias

target selection

imaging modalities

specialist collaboration

ventricular tachycardia

VT storm patients

treatment variability

research dosing

long-term outcomes

future advancements

refractory ventricular arrhythmias

patient selection