We should get started. All right. Well, good afternoon, everyone. It's my pleasure to welcome you to San Diego and Heart Rhythm 2025, the 46th annual meeting of the Heart Rhythm Society. We just ask to remind you, if you haven't already done so, please download the HRS 2025 mobile app from the App Store. This is how you can participate in the live Q&A questions during this session. You can scan the QR code on the screen to access the Q&A. And then, when using the mobile app, please log in with your HRS credentials. My name's Ammar Killu. I'm one of the cardiac electrophysiologists at Mayo Clinic Rochester. And I'll be Jacob Schrobeck. I'm co-chairing. I'm from Cleveland Clinic. So we have four wonderful talks today. Dr. Siontas will be going second. He has to leave for a conflicting session. So we'll take some questions after his talk. But otherwise, we'll reserve them for the end. The first talk is by Dr. Peter Pajko from ICOM in Czech Republic. He's going to be talking to us about when not to take a patient with frequent PVCs to the EP lab. Dear gentlemen, dear chairman, ladies and gentlemen, first, I would like to thank the organizers for inviting me. And these are my disclosures. An important disclosure is that I do perform ablation of PVCs for 15 years now. So I believe I'm biased. So if you look at the guidelines, you will find that the ablation has become a kind of first-line therapy for many different locations of PVCs. But if you consider this, it's not that easy to implement, because PVCs are very common. This is just one of the recent studies that look at that. And if you take a kind of cut-off value of 5%, you find that in the 9% of patients, which makes a lot of work to do. And maybe not a good idea to insert all the resources there. So this is an analogy that I kind of found kind of appropriate. So if you're working with the fluids or PVCs, there are some that are very easy to get. And there's something we call the low-hanging fruits. This is not the topic of my talk, but we're supposed to talk about those that are very hard to get. But there's also other things to consider. So there might be some that are very high added value, so they really matter. But there are also some that are very low added value, so they are unworthy of the action. So generally, I divided this into the three groups, some that are impossible to ablate, really not worth doing it, and some that may be risky, difficult, and some may be unworthy to effort. So which are the unfeasible to ablate? Actually, we failed to ablate those, so maybe you will. But I hope to show you some cases. So this was a 40-year-old female with very frequent symptomatic PVC. And we tried three times on papillary muscles. We failed. Generally, if you look at it, it's a lot of PVCs with this kind of morphology, which allowed a post-traumatological papillary muscle, but other things going on. And only then we did the genetic testing and realized this is something that is outside of our realm. That was Anderson-Tuttle syndrome. So this is obviously a genetic disease, which comes also with some morphologic changes. We don't usually ask our patients to show their toes in the ambulatory. Maybe we should, because if it's like this and we don't think about it, it can be very difficult to ablate. And actually, this is one of the recent reports that look at this. And generally, all the reported cases so far show that it's really impossible to successfully ablate. And this is something for pharmacotherapy and antiretroviral therapy. This is another example, a patient with a very narrow PVCs, funny axis on the P-wave, but the very narrow PVC is coupled by gemini. And this is something coming from conduction system. And it turned out to be a sodium channel disease, so full multifocal ectopic-Parkinson-related premature contractions, which is a disease that every normal beat is followed by ectopy from the conduction system. To ablate it, you actually have to wipe up all the conduction system in the heart, which is probably not a good idea to do. And the way to do it is to use antiretroviral therapy. Hydroquinidine is quite effective for this. We have several patients that this was effective and worked. Another disease, this is due to the exercise VF with some ectopy prior. Obviously, this is CPVT. Can you ablate CPVT? Well, I thought before this presentation, it's not found some serious in the literature coming from the places when they do not have a flaconide for treatment. So I believe it's much better to give a flaconide for those patients with CPVT. If you're not allowed or it's not available, you can try ablation. If some moderate outcome, you're probably not able to ablate all the extra systems, but maybe prevent some of the polymorphic BTs to somehow alleviate the disease. What about the structural heart disease? So far, this was a primary electric diseases, but there might be some structural heart disease that might be due to genetic mutations. The most common one is the mutation in titin gene. And so if you, this is a recent paper that look at this. And if you look at for the PVC patients, which are eight of them, the complete abolition of PVCs in this was only in 13% of patients. So a bit futile outcome. And mostly, they originate from the LV summit. Generally, it shows, again, that this is quite difficult. Although in the long term, there seems to be some effect, but because of the low number of patients, it's difficult to know what's the reason. And why we fail in these patients? Probably because if we want to be successful, we probably have to ablate all the sites. And that's not possible because the genetic problem is in every single myocardial cell. So this is a study that look at the strategies that focus only the prevalent PVC or just try to ablate all the morphologies. If you succeed, the outcome is generally better. So the other group, which I will only touch, is the end stage heart failure. These are some ice images. If you have a failing heart at this stage, I believe the PVCs are very common, but the ablation probably won't stop the progression of the disease. And this is something probably even VT is not a good idea. And there is also other kind of a lot of different scenarios of irreversible causes. This is, for example, end stage heart failure of ephedra on toxicity. A lot of ectopies coming from different parts, probably also not a good idea to ablate. So these were really known to go because you probably only waste your resources. The other part is that some locations might be risky or difficult to do. And because the PVCs can come out from anywhere, we know from ECG quite well that there would be some areas that would be more easy, more difficult. There might be some risky ones. I have no time to really go more into the kind of detail here. But for example, if you have an ECG that looks like this, that the morphology is very similar during the sinus retinum and the PVC, it's probably prohesion. And just to show that there might some be tricks how to do this. But it's still worth trying because you can be successful for many of those. It's very difficult to predict from the ECG the failure. But this is what we used. It's cut the tear under the septal leaflet for this one. We published on this some years ago. And it was replicated by some other studies. Generally, from the ECG, it's very difficult to know who to kind of defer from the ablation. This is just a recent example. It was a patient who had a mechanical atrial, sorry, aortic and mitral valve and had a discontinuous bigeminy. Should we try? There might be two scenarios. Either it's easy accessible from above the valve or from the CS. And or it would be very difficult because we require alkalization of this summit area. We try. And the signal was not particularly interesting. This is the location. This is the ice image of the aortic mechanical valve. And this is the formal right cusp. And to surprise, just was very easy and long-hanging fluid. It's just when you start to ablate, it's immediately gone. So I believe from the ECG or from the scenario, it's sometimes difficult to say it's going to be difficult or easy. This was supposed to be difficult. Turned out to be quite easy. We went in 45 minutes. We were finished with this procedure. So this is sometimes you're lucky. Obviously, we do remember more difficult cases. And the last one goes into this PVCs that might be not a boarded effort. Because they generally, if you can do it, I mean, you don't gain much. And you just endanger the patient with the risk of ablation procedure, with risk of silent brain injury and things that are associated with, especially with left-sided access. So generally, why we don't treat all the PVC patients? Because we have data, for example, like this from Canadian experience of 100 patients with symptomatic PVCs. Some burden, but then they look at them over time. And no treatment, no drugs, no ablation. In 44% over some time, they all disappeared. Because it just was generated by something. And only a few of them developed something which is probably PVC-induced cardiomyopathy. So we use this kind of threshold of burden. This is the study already 15 years ago that set the 80% sensitivity specificity for PVC burden of 24%. Obviously, we know also that one halter is not good enough. Because there are some patients who have a very stable PVC burden. So this was a two weeks monitoring. And they just calculated the minimum maximum average. And over two weeks, you can find patients that have like a 0% and 30% over this. If you're just unlucky and just take one of those days, you may be puzzled what it really means. Let me finish just showing some other parameters that, if I can make it forward. So there are a lot in the literature, a lot of factors that look at the parameters that should predict the significance of PVCs. It's not about the burden. It's also the kind of coupling interval, whether they're interpolated, whether there's epicardial origin, broad QRSs, non-sustainability, surprisingly asymptomatic course of it. Again, there's no time to go into the detail. But this might help you to prioritize and select those that are endangered with the risk of cardiomyopathy. So let me conclude that I believe ablation therapy is very effective for most of the PVCs that are there, considering, obviously, that the original causes have been ruled out. I mean, for those patients with genetic mutations, if you know, you better think twice. If you don't know, you better think of genetic mutation as a cause of this. And obviously, it's still out whether the ablation of something in frequent PVCs should be done. And it's worth it. Or you should reserve these capacities for patients with AFib or VTs or something, which probably is more meaningful for the patient. Thank you for attention. All right. Just as a reminder to the audience, we're going to be taking questions at the end of the session, with the exception of the next talk, because our speaker will have to leave. So please save your other questions for the rest of the session. So it's my pleasure to introduce Dr. Konstantinos Tsiontis from Mayo Clinic. Thank you. Yes, so we heard about PVC ablation. And I feel, generally speaking, it's easier to say no to PVC ablation for the reasons that were mentioned, as opposed to VT ablation, especially when a patient is having recurrent episodes and ICD shocks and a lot of symptoms. But we will review some of the scenarios and some of the situations where this makes sense. But there's a lot of subjectivity. And take everything that I'm going to say with a grain of salt. It's obviously a lot of different things that you account in these complex patients to make those decisions. There is obvious, easy, low-hanging fruit in the contraindications to VT ablation. So if you have a mobile LV thrombus, you wouldn't do a conventional endocardial ablation. Reversible causes of VT or VF, if you have an uncorrected coagulopathy, active infection or sepsis, those are patients you would usually defer an ablation. But then there's some relative contraindications. And those would be patients with prohibitive procedural risk without an exit strategy, and patients who are too high risk with a life expectancy, typically of less than three to six months, where the issues of futility and risk come up. It becomes difficult to know when it is too late to ablate those patients. And again, there's a lot of factors that will go into those decisions in the conversation with the patient. We do know that early ablation makes sense, and even prophylactic ablation, based on a lot of clinical trials. We haven't, however, defined this end of the spectrum of the timing and the indication for VT ablation. When it is too late, what's the risk and benefit in this very late stage, post-second line, post-third line ablation? What is the definition of futility? And for every patient, that might be a little different. The other thing to remember is that in these trials, high-risk patients, patients with end-stage heart failure, New York Heart Association class IV, were typically excluded. If you look even at the most recent example in VANISH-II, there's a handful of New York Heart Association class IV patients. So we don't have a lot of data from clinical trials to tell us what to do with those patients who we're left with, often, some of the most challenging scenarios in clinical practice. This is data from Mayo VT ablation patients, and there is an early mortality rate in the first 30 days of about 5%. And overall, that will be 0.4% of procedure-related mortality in the first 30 days. When you try to break down those patients who died in the first 30 days, heart failure, end-stage heart failure, accounts for the majority of those. It's about one in three deaths in the first 30 days are because of heart failure, and the minority are actually procedure-related. So it's clear that there are some patients in that mix of patients that we ablated that were not going to do well because they had near-end-stage heart failure at the time they were ablated, and maybe the procedure had something to do with it, but typically not. So we can do a better job about identifying those patients and understanding that spectrum of futility before we take patients to the lab. So we'll review a few clinical scenarios, and this is not a complete list. It's just some representative scenarios that we see in clinical practice, and I will start with a relatively easy one. This is the scenario for active inflammation, inflammatory cardiomyopathies, and sarcoidosis, and other such conditions. We know that taking those patients for ablation at the time of active inflammation is probably not a best idea, except if you're dealing with VT storm, a patient that you cannot get out of VT in the ICU, and you have to do what you have to do. But ideally, you want to delay. We don't deny these ablations. We want to delay those ablations until the inflammation has been treated, has resolved, and patients can come back in a more steady state for VT ablation with better long-term outcomes. Another scenario is the young patient with advanced cardiomyopathy, recurrent VT, and previous ablations. And the main example that comes to mind is a genetic cardiomyopathy. Some of those were mentioned already for the PVC side of things. And I will mention, for example, laminopathy patients. So this is multi-center experience with very experienced operators, some of the best VT ablators that are out there. Patients were followed for seven months after VT ablation in the setting of laminopathy. And almost everyone had a VT recurrence. 83% had recurrence after multiple procedures. Half of them ended up with an LVAD or a heart transplant. And one in four of them died within seven months of immediate follow-up. So these are patients who are not going to do well after ablation. So keep that in mind when you consider the risk and benefit and end point of the procedure for these patients. Another illustrative example, 35-year-old female with PLN, phospholambin cardiomyopathy, one of the most malignant phenotypes in the genetic cardiomyopathies, in the arrhythmogenic cardiomyopathies, especially LV dominant. EF is 25%, but not a lot of heart failure, but a very malignant family history of early sudden death. The typical low-voltage electrocardiogram extensive delayed enhancement, and this is the VT phenotype, almost ventricular flutter with multiple shocks, and this is despite amiodarone. So this is a patient who's not going to do really well with multiple ablations and should be considered for the definite treatment for this disease, which is transplant. So these patients have diminishing returns with repeated ablation attempts. You often will need to consider continued antiarrhythmics, including amiodarone, unfortunately, or other non-ablative treatments for VT control, whether that's a sympathectomy or something else. Importantly, these are generally good candidates for transplant. They have no major non-cardiac comorbidities for the most part. These are young people, and we do have improving organ availability. Transplant care is improving. The outcomes of post-transplant survival are better. So these patients, we typically, in our practice at least, we will, concomitantly with a VT management, we'll also have them see advanced heart failure for an early conversation about that process and what that might entail, for them to be familiar and to quickly proceed to transplant advanced therapies if the clinical scenario mandates that. And then the final scenario that I will talk about is probably the most common that falls within the spectrum of risk and futilities. Advanced heart failure, usually older patients with recurrent VT and not being able to be considered for a transplant or an LVAD. So LVAD and transplant non-candidates. We have good scores to tell us and inform us about the periprocedural risk of decompensation, hemodynamic decompensation and mortality. And you may consider hemodynamic support for those patients, whether that's an impella or ECMO at the time or periprocedurally. But you also want to keep in mind that the outcomes of these patients who require upfront or even more so bailout MCS, mechanical support, are not very good. And we know that from IVTCC. We know that from first in human experiences with impella that these patients don't do well. It's exactly the reason that they require MCS that they don't do well. It's not the mechanical support itself. It's the fact that they're really sick and they generally won't do well. And not from a VT standpoint alone, but more so from heart failure standpoint. So we often think about nothing to lose and nothing to gain. And most of the time, there's nothing to lose in these patients. We give it the best shot. But if there's also nothing to gain, I think it's a good reason not to take these patients to the EP lab. We think about candidacy for periprocedural mechanical support for those patients, whether that's upfront or bailout. We define expectations and endpoints of the ablation procedure. And sometimes, these ablations may be a bridge to defining the goals of care. We take these patients, recognizing that they won't do very well long term. But it might be time for them to consider palliation and hospice. This is an example of such a patient, 82-year-old, with very significant comorbidities and end-stage cardiomyopathy, who was stuck in the hospital with this recurrent incessant slow VT. So we took this patient to the lab to eliminate this VT and allow this patient to leave the hospital, spend some more time with family, and define their goals of care and settle their affairs. And did well from the ablation standpoint, but passed away, as expected, a few months later. So if we say no to ablation, what is next? Then, of course, everyone will be continued or on an escalated antiarrhythmics. I think we'll hear a little more about those options for medical treatment in the rest of the session. Denervation is a reasonable option, especially for rapid VT and VF, SBRT, and other combinations of these approaches. If the patient is a candidate for advanced therapies, then, ideally, we expedite that evaluation. We proceed to the path and consider transplant or LVAD. If the patient is not a candidate for transplant or an LVAD, then that is a pathway to hospice and palliation. So in my mind, VT ablation should be a bridge to one of those four things. Quality of life improvement, long-term survival, potentially, heart transplant or LVAD, or palliation. If none of those four things are part of the picture that you see, then probably better not to take the patient to the AP lab because sometimes the best ablation is the one that you don't do. Thank you very much. the next couple of minutes just question Questions and answers so I invite everybody in the audience to submit their questions through the online system While we're waiting guy I'm curious about what you think about situations Specifically what you mentioned at the end about quality of life I can recall a handful of scenarios where we had patients who are either class four You know and hospitalized or patients with slamming myopathy Yeah, so clearly very poor candidates, and they undergo an ablation Which you know they have shocks afterwards they basically meet every endpoint in any trial You know as a failure yet If you ask them what quality of life they were able to leave the hospital and oftentimes these patients are hospital bound with lidocaine drip On is it an issue about how we study these extremely high-risk patients because mortality is really not a good endpoint for them Yeah And exactly that's the reason why these patients are not in the trials because they would you know the issue of Futility and equipoise is problematic at that point when survival is expected to three to six months but I think that makes a lot of sense as a patient that you have to If the goals of care is to get the patient out of the hospital and allow them to go home and spend some quality Time with family. I think that's a very appropriate utilization of a VT ablation Recognizing that it's a high-risk procedure and sometimes and the the downside of that is a severe complication that could be you know potentially Major problem for them. But yes, I think it's a it's a conversation with a patient the family and setting that expectation the setting that Goal of the ablation defining what the endpoint is Again if you have any questions, please submit them. So because it's very nicely done. I think we all have these success stories that keep us coming back for more but unfortunately The ones that often stick in our mind up because it may have been you know One of those that you wouldn't have expected to get such a good result and you you take that kind of case on again But may end up being futile as you mentioned You made a comment about SBRT and given your expertise and I just want to ask you a question so in terms of let's say someone who has Incessant VT and are not deemed to be a good candidate for catheter ablation What is the obviously SBRT takes a lot of planning? How do you reconcile that and then in terms of the timing of treatment effect? Yeah, is it something that you would expect to see within a few days a few weeks? How do you get them through that? Yeah, good question. So the In our opinion the timing of the effect of SBRT of radiation is not acute It takes at least a few days if not weeks and months and we definitely see Progression of the lesion over months even six to nine months. It's an apoptotic process There is some hypothesis that it could be an electrical remodeling that happens pretty quickly We haven't really seen that in our practice quite yet Peter has also quite a bit of experience with SBRT. So maybe he can chime in on that but we in our experience It's not an acute treatment for for VT storm or incessant VT I know of case reports that SBRT terminated incessant VF in patients on ECMO and with an LVAD But we haven't been utilizing it for acute treatment of storm for that reason We have a question from the audience about an implement Just want to back up you there because our experience is exactly the same for just the acute VT suppression It doesn't work that well. I would say it works horribly if you need some time to work for the radiotherapy to take Action and in generally what I saw is actually increasing the number of episodes after the radiotherapy sometimes because of the inflammation and things that may occur and so so for a Electrical storm, I believe is not the perfect solution by far Quick question from the audience, you know, you mentioned for inflammatory VTs you delay you don't defer. How long do you delay? Until the inflammation is gone. Ideally, you know, we'll treat these patients with a meal Load them up in a hospital let them go home and on immunosuppression and bring it back and repeat a PET scan typically in six Months, that's our usual time frame for reassessment If the inflammation is gone and they wish to get off the amyotron, which is usually the case Will we in amyotron offer them an ablation procedure? Thank you very much Okay So our next speaker is Dr. Andrew Epstein. He's going to be talking about recurrent VT or Frequent PVC's when to prefer escalation of antiarrhythmic drugs to ablation and dr. Epstein's from the University of Pennsylvania Thank you very much, it's a pleasure to be here whoops My charge is to actually follow up on these first two talks which have set the stage for me to discuss when to use drugs versus ablation in managing these patients. I have no disclosures. So why do we want to treat the PVCs and, to some extent, the VT? The VT is more of a problem, obviously, than PVCs usually. But we really have two things that are our goals. One is to make people live better, and the other is to help them to live longer. Certainly, symptoms negatively affect quality of life, including palpitations and fatigues. And for making people live longer, they can be treated for tachycardia-mediated cardiomyopathy, interference with biventricular pacing, and life-threatening ventricular arrhythmias, to be specific. My talk has to be framed from an evidence point of view, and there are at least two studies that have looked at the role of antiarrhythmic drugs versus ablation for treating ventricular arrhythmias. In this first one from the Mayo Clinic, it turns out that all medications that were used decreased the PVC burden. Beta blockers and calcium channel blockers were successful, almost surprisingly, and led to a 40% reduction in ectopy. Only amiodarone came close to achieving a 90% reduction in ectopy. But at the end of the day, the EF normalized, and 47% of patients undergoing ablation compared to only 21% treated with drugs. In a randomized trial from China with 330 patients with normal ejection fractions and RV afloatrach arrhythmias who were treated with metoprolol and propafenone, the elimination of PVCs was achieved in the 12% in the medical group versus 80% in the ablation group. So certainly ablation seems to win here. And in fact, complications or adverse effects occurred in 10% of the medical group, but 2% of the ablation group. So in that context, why should we be using drugs? When we look at the AHA, ACC, and HRS guidelines, they're all consistent in recommending drugs before ablation in virtually all disease entities. And rather than showing you each frame of these, just to review the substrates, ventricular arrhythmias in a structurally normal heart, afloatrach and annular arrhythmias, papillary muscle, interfascicular reentrant tachycardias, PVC-induced cardiomyopathy, and older patients with comorbidities all fall into this category. And in fact, the European guidelines and APHRS are consistent with this recommendation, and they have their list of arrhythmias for which drugs should be used first. Not to go through the entire list, but just to mention afloatrach tachycardias, non-afloatrach tachycardias, including those that are epicardial or parahysian, PVC-induced cardiomyopathy, and non-responders to CRT because of frequent arrhythmias. The U.S. guidelines have a caveat that two areas where people should be treated with ablation first are, number one, those with bundle branch reentry, which is curative with ablation, and second of all, people with structural heart disease who have failed endocardial ablation and require an epicardial approach. In the context of all of this, we can't forget the importance of shared decision-making, especially for PVCs, having the discussion with patients and their families about pros and cons of the approaches, what they want, what they feel comfortable with, is of paramount importance in choosing a therapeutic strategy. So what are some of the factors that will influence decision on how and if to treat? One is symptoms. How bothersome are they, and is there actually clinical correlation? And for those of you who read ambulatory monitors with diaries, I'm sure you're well experienced in seeing these monitors where people have 100 complaints and all of it correlates with sinus rhythm. There's also the imperative to treat. Certainly if somebody has LV dysfunction and frequent PVCs and they're in an area of the heart that we think that we can ablate, it would be nice or not nice, not only nice, but it can be life-saving to improve LV function. Are there enough PVCs to map? And we're going to come to this in just a moment. And what's the site of origin? This has been discussed already. Certainly if it's near the hiss, epicardial, septal, or in the summit, there are risks that are attendant, and multiple morphologies are problematic. And if there are too few to map or the site of origin is unfavorable, certainly antiarrhythmic drugs are especially reasonable. And then, as I said also, what does the patient want? For a young person who doesn't want to take drugs for the rest of their life, the option for cure is very desirable. This is just to remind us that we have to be very careful when we monitor. This is a patient who has a high burden of PVCs in the first half hour of monitoring, and then they go away. If you'd give a drug here, Ebola, you'd say, oh, this is a drug effect. But, in fact, this is spontaneous variation. This shows that for a group of 20 patients with 50% suppression in the first half hour, that suppression is continued in only five of 14 patients at one and a half hours. So to be reasonably certain that measuring a drug effect rather than spontaneous variation is going on, there has to be at least a 90% reduction in suppression of ventricular ectopy that is maintained for at least an hour. What about the use of 1Cs in the PVC-induced cardiomyopathy? I won't go through all the entry and exclusion criteria for this. This is our Penn experience with Matt Hyman and Dave Frankel being the primary authors. In 20 patients who were treated with flecainide or papafenone, you can see that the PVC burden decreased from 37% to 10%, and the EF increased from 37% to 49%. So 1C drugs can be used in people with structural heart disease, and we had no proarrhythmia. Why is this? And this comes up all the time. PVC-induced cardiomyopathy is different than the substrate that was addressed in CAST. There was no myocardial infarction in these people, often no scar, and most importantly, there's no ischemia, and these are reversible cardiomyopathies. This is from a sub-study in CAST where we showed that it was not the people who were on placebo with no ischemia, the people on active drug with no ischemia, placebo with ischemia, but the active drug interacted with ischemia. So it's the interaction of ischemia and a 1C drug that carries the mortality risk. So why should antiarrhythmic drugs be used especially first? First of all, they're effective, they're noninvasive, they're generally safe, their use is guideline given, patient choice plays a big role, and since neither antiarrhythmic drugs nor ablation are 100% effective, a stepwise approach is reasonable, and at the end of the day, ablation is always available. Thank you very much. Last but not least, it is my pleasure to introduce Dr. Melissa Robinson who's going to talk about BT as a terminal heart failure event. Can this be predicted? And she's coming from the Providence Heart Institute. I'd like to thank the organizers for putting this depressing topic on. It's always nice when the title of your talk has the word terminal in it, but I am married to a heart failure doctor, so I'm well versed in this. I think most of us have seen this slide, this sort of cyclical chicken and egg between heart failure and ventricular arrhythmias, and I think it's worth pointing out a couple of the ways in which they interact that may help us predict the individual patients who are really not going to do well in the context of heart failure and have BT. So there are those that have just a higher level of triggers in the setting of increased heart failure, neurohormonal activation, metabolic dysregulation, which has become a sort of hot topic in heart failure, if anything can be a hot topic in heart failure. Here's my little diss to my husband's field. But also, dyssynchronous myocardium in the setting of ventricular tachycardia, interesting concept of mechanical or bioenergetic uncoupling, sort of an interesting phrase that I haven't said too often before this talk, and then again metabolic shifts that may lead to deleterious effects in the heart. I guess getting that out of the way, we are in a whole new era for heart failure, and that is something that's difficult. I know the prior talk in talking about BT, that's difficult for those of us who trained a decade or more ago, a decade and a half ago, when it was really just beta blockers and ACE inhibitors if the blood pressure allowed it. So our concepts of heart failure really need to change and be more updated. This new class of drugs, the sodium channel, sodium glucose transporter inhibitors, really potentially could have an effect on ventricular arrhythmias. This hasn't seemed to pan out yet, and it may be a dose effect. It may be individual agents. But there is a positive effect on atrial arrhythmias. It may be that in the ventricle there's too much scar at that point that they're on these medicines, they're too late, or we need a longer time horizon. But I do think there's sort of an interesting signal there. But stepping back, so can we predict this? What is the crystal ball just in general for these patients? So which patients with heart failure will have ventricular arrhythmias? So if we're going to predict it, we just need to sort of be looking in the correct group of patients. Most of our modeling in EP has been predicting who's going to benefit from an ICD, so who within a population of heart failure patients has a high enough risk to warrant that SICD. And we've moved into a new era for that as well. So this is a nice study where they did deep learning and took various categories such as the MRI characteristics 12 lead characteristics the medications that they're on and put them into a fancy computer. That's how I understand this and spit out the probability of this patient having ventricular arrhythmia and that moves us beyond our standard ejection fraction cutoffs. Another aspect of this in CMR is to look at not just the extent of LG but the dispersion. So patients that have a higher degree of dispersion of LG even if they have lower LG are at a much higher risk of having a malignant ventricular arrhythmia. So I think that one of the fields that we can leverage to really help us understand our patients better is in imaging what changes precede the development of ventricular arrhythmias in these patients. So what physiologic parameters can we find. And we have a ton of data in these patients right. We have tons and tons of remote monitoring data in patients with implanted devices. So can we get better at predicting this. This is a really interesting study collaborators a little cut off on my screen but hopefully not up there. Perfect. From the University of Chicago and they took data from the impact trial which is a CRT multiple site CRT trial and they looked at all the usual suspects for logistic regression but also put in just that huge amount of data into a neural network to get more refined characteristics and then they compared the two. So the sort of standard multivariate predictors that we would not be so surprised at if they'd had increased V to V sequence events so increasing PVC is if they had an increased need for both ventricular or atrial pacing decrease sinus conduction decrease shock lead impedance which we've also seen so all those kind of make sense to us. But if you fed it into the computer they could do much more sophisticated analysis and these are called shaft values which are sort of additive characteristics. So if you take that particular variable and add it to the model how much better will the model be how much more predictive can it be. And you can see there's lots more factors and the other thing that was really interesting about this is that the neural networks the artificial intelligence networks were able to trend out things like a rise and a fall in a parameter. So sort of another way in which the computers are smarter than us so we need sort of binary cut offs. OK you know if the sinus rate falls below this or the heart rate variability falls below this number then they're at higher risk but the computers can really look at more nuanced things like rises and falls over the course of a day how that changes day to day and some of those can be as predictive as finding something 30 and 60 days ahead of a terminal ventricular event. Not all these were terminal in this study but particularly interesting certainly human dynamics are part of this and this was discussed to some extent in the VT talk. But again they're sort of more nuanced predictors and I think you really do have to partner with the heart failure side. So it's not just ejection fraction obviously but indices of cardiac output both non invasive and sometimes invasive with a right heart catheterization that can help you understand those patients that are at risk and then functional parameters even six minute walks sort of non sophisticated things like that which patients will not survive their ventricular arrhythmia. So we're trying to predict who's going to have the VT and then who's not going to get through it. And this is actually a harder one. There really isn't as much data. We have a lot of non fatal events but we do know old data. This is Scott have Jeannie pool published this many many years ago now showing that shocks for anything shocks for both appropriate and inappropriate arrhythmias are inappropriate shocks will increase mortality. But the question is really why this is a more recent set of data from the made at trials. It was made at one two and made it CRT all grouped together and showing the same thing if they had an appropriate shock much more increase risk of mortality. I think one of the things that's hard in these trials is we often aren't looking at the type of arrhythmia they get really lumped when they're on those bigger scales. So it would make sense to us sort of by first principles that patients that have ventricular fibrillation that's not necessarily driven by ischemia or not driven by ischemia that we can revascularize or patients who have polymorphic VT or much faster VTs that those patients might have worse outcomes with those arrhythmias. And that same made it trial did show that so much stronger association with increased mortality in the red. If your VT was above 200 beats a minute but they're kind of lumping both that fast VT and VF other things from that study that pan that showed up here are failed ATP followed by a shock and that may have something to do with the size of the circuit or the conduction velocity through the scar sort of electrophysiologic parameters that may make that VT less likely to be terminated with ATP. So we do know that patients have the events. What is the mode of death in those patients and remember Scott half was a shock only trial. So if we're just focused here on the ICD arm of this so 20 percent of total mortality was due to the tacky arrhythmia so sudden death in immediate proximity to that VT episode and we see that in the in the graph here. What about in the post VT patient post VT ablation patient rather. So this is a conglomerate study really nice nine centers lots of patients referred for VT ablation and they're looking at survival based on ejection fraction as well as whether or not they recurred and you see a very strong trend there for the patients that had a lower EF and no sorry an early recurrence and you can see that panning out over time. So in conclusion it's more than just pump failure that's going to predict who's going to have ventricular arrhythmias in the setting of heart failure. Certainly there's an autonomic component of this there arrhythmia characteristics and we need to be looking at those post VT ablation patients even closer. So what I would say in conclusion is I don't know if they can be predicted but we've never been closer than we are right now. So thank you. Thank you to all the all the presenters for those very interesting talks. I think an hypothesis generating let's say I can remind all the audience that you can submit your questions in the in the online system. Actually since this is fresh in my mind I'm going to ask Dr. Robinson one thing a lot of you showed a very very vast amount of different predictors of death and you know I'm sure a lot of these are nonspecific markers. What do you think about the importance of teasing out what's specific because ultimately the question is what are we going to do about it. Right. It's not about you know it's good to counsel the patient on their prognosis but you want to actually help them. And you know oftentimes this is in the context of implanting a primary prevention ICD if it's in a more advanced setting and maybe you can even talk about prophylactic VT ablation which is a whole nother question. But at the end of the day you need to make a clinical decision. How often would you make a clinical decision just based on nonspecific markers of all cost mortality. Yeah I mean I think currently never. Right. I don't think we're seeing heart rate variability change or sinus rate change or an increase in ventricular pacing and thinking we need to intervene in terms of acting on the arrhythmia substrate. But but these factors could be a target in an integrated heart failure practice and those could be patients that are brought in for evaluation and then most of this is honestly moving into the patient's hands. You can't imagine a world in which like the defibrillator is looking at numerous factors and then you get an alert on your phone that says you might die in the next 30 days. Like I don't think that's going to happen but I don't think it's far fetched for them to for it to be a marker for the patient to increase diuretic see somebody to have their medications adjusted something. So it's more than just human dynamics but we don't have a lot of good targets. Right. Question for you Dr. Epstein so you nicely showed the effect of class 1 C agents in patients with PVC mediated cardiomyopathy. Do you get an MRI in patients before if you suspect they have it or do you go based on the echo and your suspicion. It I knew this question was going to come up and what I've got that had that one slide that is how is it different from cast that there's no scar. I think there's scar and there's scar in the MR data is mixed in that how much scar is important. I think most of these people yes we do get it. And certainly if somebody's got 20 percent scar that's very different than somebody who's got that you know a little you know 2 percent that's right by the mitral annulus scar by itself would not trouble me because remember in the placebo arm and in in cast their scar there but they didn't have increased mortality. So I think the chance for reversibility is the thing that you want to bank on non ischemic cardiomyopathy these are in large part reversible. Just look at the results that we get with SGLT 2 inhibitors and and the new therapies for heart failure. It's remarkable how much better these people get. I showed the study to like it's not scar is not just scar right. So the distribution of scar and that dispersion you can get a lot of question for I guess all the panelists especially Dr. Pico Dr. Epstein since you talked about VT PVCs what do you think about initiating therapy versus monitoring for patients who get ATP respiratory disease. patients who get ATP responsive VT. They feel OK to get a few runs here and there. It upsets more the device clinic than the patient. How do you manage those. No no I just didn't understand. I think he's saying if they're if they're having ATP but not shocks when do we escalate therapy. You know ATP in and of itself are slower VTs has not been shown to be associated with mortality. So I do offer it because it has been associated with an increased risk of VT storm sort of the indirect middle ground. But I don't offer it to everybody. If they're an isolated event in a single day we talk to them about it and but kind of usually generally sit on it lower a lower threshold for ablating patients if they've got a distinct substrate like ischemia ischemic VTs I think are more likely to come to the lab if they're not in terrible heart failure. But that's my practice. Generally reflect that I mean if it's just one single episode here and there it probably doesn't matter. But on the other hand if it's a person my VT and it's probably easy to get you should discuss with the patient because the procedure could be quite short and be quite low risky and it's a more morphic VT. This is something we are very good at. If it's a non ischemic epicardial substrate and ITP works fine and it's a very few episodes I believe that's also a different story. Yeah. And like we're in heart rhythm 2025 I'm hoping that heart rhythm 2026 is all about PFA and the ventricle right. And so maybe the risk balance will change for us. I think it's important as well to ensure there's no reversible cause for the for the episode right. So we can be pretty aggressive sometimes taking someone to the lab but often it may be they didn't take their medication or there was you know electrolyte abnormalities you were talking about being able to predict episodes. I think electrolytes is an important thing that you could probably glean a lot of information from the device tracings or wearable ECGs you know what does it correlate with. So I think it will be an evolving field but often one isolated episode as you said I agree I wouldn't overreact to it. But you need to watch them closely I think. Peter can I ask a question. So the MEPS patients that you've described the multiple ectopic Purkinje I know I've missed that syndrome like certainly in the past because it wasn't described yet. But do you are you genetic are you doing genetic testing and more of your PVC patients than you were in the past or how do you approach generally if you if you know up front you wouldn't send them into the lab but you sometimes don't know and they somehow be a referral patient that had the ones that I showed that one had a tree ablation which were unsuccessful. The other one with the maps had also three or four ablations that the right bundle was after some ablation of the conduction system somebody attempted to be also tried. We actually didn't know the disease back then and we just just do you have to think out of the box and we then said well this looks strange in the end of the hit rock unity actually the Canadian worked pretty good for those patients and they just really normalize the ECG. So I believe this is quite a really nice niche kind of for anti-arrhythmic therapy for those patients because it makes sense that you just works in a global level not the focal localized level. So no we don't do genetic analysis for all of our patients but those that really look like a strange but they sometimes also come with this other strange things like this inductively. It's a funny story because we never look at the toes in the cardiology. To be honest when I asked the patient he said she said it was a lady. He said yeah well I was always like a shame when I want to do to the swimming pool or to do some and then because I might just look strange and never came up during the medical kind of interview or kind of taking the patient history so says it's funny but this is how the things are. One of the audience members asked thoughts about stellate ganglion block when when do you use it. Where do you think it's effective versus not left versus right bilateral. Can you comment on that. Yeah I was I was thinking it was going to come up in Constantine's talk but I haven't used it a lot honestly probably should have used it more but certainly those patients where there needs to be more work up for potential bridge afterwards so it takes time to work somebody up for transplant. I know a lot of the centers have these really expedited you know stat consults but there's a lot of things you have to uncover to see if someone's going to be a vet or transplant candidate. So we have used it in that context and certainly the polymorphic patients where you're still working at myocarditis and things like that where it's not appealing and generally we've done bilateral. Yeah yeah I can answer. I think it's a logistical issue oftentimes and depends on the institution that you're at. So even in my institution it was initially very difficult not much easier so we're much more likely to do it in patients who are likely to be transplant candidates anyway and there's really not many choices even in the absence of much evidence and for monomorphic VT it's usually in our institution is just one side. So in our CCU they're pretty aggressive at doing it often before we've seen them sometimes which can complicate things. If it doesn't work I don't know that it means that it's not going to be effective for example if you did a vats guided one. But I think it's a pretty niche thing and usually at least in our practice we reserve it for the difficult to treat patients who failed ablation drugs things like that. But yeah I think it's worth exploring further still our current practice is our current practice to use this for patients in electrical storm to stabilize them somehow to bridge them to the ablation as a therapy so it can be down in some local center and then transfer to us as a kind of bridge. Usually they show that there's a very active or very effective to decrease the number of episodes but just really to see the net benefit you have to randomize we run the randomized trial around nowadays to compare the cell line infusion and a little kind to to compare because even if because those patients usually get a lot of things like anti-arrhythmic drugs and the ganglion blockage to suppress the storm. So even if you just use the same line there is some effect because of the cooling down the down the patient and sedation obviously and then the other other stuff. So it's just that we have more than 100 patients randomized to both and hopefully some data out for further to see the kind of real benefit net benefit and it's it's not that like 90 percent decrease if the if you do for electrical storm it's it's probably less. Just I think just last last quick one. We've got one minute. So any insights on how to predict PBC mediated cardiomyopathy. What do you look for on the ECG I guess characteristics that make you worry about from I think it's I don't think there's an ECG characteristic that will predict reversibility or or cause I think it's the frequency and certainly you know it's really easy when there's 30 percent. But you know we've we've found that even 10 percent and some people there is enough of a burden and they again if you if you use a drug and if you can use it safely you've lost nothing by giving it a try and the one C's are so effective to suppress act to be that if there is no ischemia and I do do stress tests and these people before starting the drug there's no ischemia start it and if it works great and if it doesn't you know you've given it a shot. I think for me the concern is when the sinus rhythm isn't normal. So when the sinus cures isn't normal there's something different about that substrate and you wouldn't be offering a class 1 C usually if there's conduction system disease or fractionation or something that's a problem for me or the PVC is not a usual suspect so it's generally outflow track muscles that cause that if it's a random free well when those are just more unusual. So maybe it's just smaller numbers but I would say the usual suspects in a normal cure as those are positive signs. And certainly I mean if you see something that is clearly RV outflow tracked PVC and you've got a transition before say yeah I'm not going to have a 25 year old and put them on a drug for the rest of their life and go after that. Well we're out of time. I'd like to thank our expert speakers and everyone for their attention and questions. So thank you very much. Have a good rest of your conference.

Heart Rhythm Society

ventricular premature complexes

ventricular tachycardia

ablation

antiarrhythmic drugs

personalized treatment

deep learning

CMR imaging

heart failure

risk assessment