just before we get going with the debate today, which hopefully should be a lively and educational one. If you do wanna ask questions, there's that QR code there. We'll be monitoring the questions and we'll try to get them in at the very end. So we'll let our two debaters go at it. They'll get 15 minutes each to talk about their pro and con side, and then a quick rebuttal, and then we'll do Q&A at the end. So really interesting session today. I'm super excited about it. And the topic is asymptomatic PVCs with normal left ventricular function to ablate or not to ablate. And so our first speaker will be Jean-François Sarrazin from the Quebec Heart and Lung Institute. And he'll be debating that we should wait, do not ablate those asymptomatic PVCs. Thank you so much. So thank you for the kind introduction. So let's get started. So in fact, as you'll see, I have no disclosure for the talk this afternoon. So as he mentioned, so we're going to discuss about asymptomatic PVC in normal heart. And I was asked to demonstrate that we should wait and not do ablation as a first-line intervention. So to reach that goal, this is my plan of the presentation. So I want to go over, what is the natural history of frequent PVC? Then should we consider also the significant burden of PVC? What happened if you treat and there's a recovery of LV function, what happened? Still go over what are the outcomes of PVC ablation that might change your decision sometimes on should we go or not do ablation? What are the risks of the procedure? And then ends up, what are the consensus and the guidelines? What people are telling us at this moment? So I'm just going to start with a short clinical case that go with what I'm going to talk about. So this is a 57-year-old woman that had very frequent PVC, quite mildly symptomatic, but she had an alter that show 11% PVC. This is about five years ago. So she had an echo, normal ejection fraction, and she was following our arrhythmia clinic. So on serial monitor, so the following year, she still had a lot of PVC. So there was 9%. But more striking is that without treatment, last year, she was at 1% PVC burden, still asymptomatic. And then when I just saw her in clinic a few weeks ago, the last alter showed that there's not almost none PVC, 200 PVC in a day only. So this is as a start. Let's start with something very basic. So PVC are very common. So if we look, there's PVC on the EKG in 1% of patient, very frequent on alter monitor. And when you ask most of these patients, it's very tolerated, and a lot of them are asymptomatic. So what is frequent PVC? So this is a definition from a textbook that I used to teach my resident. So they usually, above 1%, it would be numerous. And as you get to more than 10%, we talk about very numerous. And if you look at the definition, it can be up to one at 4% of population who has a very high or numerous PVC burden. This is an old study, but I think it's still relevant. So it goes back almost 40 years ago, but they look at people with very frequent PVC. They had a PVC burden of 13%. And they compare to people who had coronary artery disease. They notice that their prognosis over time was really good, but people with heart disease had a worse prognosis. So let's get further. What is the natural history of frequent PVC? So I have a few studies to show you. So this is a still old study, but one of the first one in kids. So it was a Japanese study of 163 children, around nine-year-old. And these patients were at three groups. There was a group of very frequent PVC, some children at couplets, and some of them at VT. And in the subgroup with frequent PVC, mean burden of 10%, they were mostly diagnosed because of school screening. So they were followed over time for six years. And what's been quite interesting is, without treatment, 28% of these children had no more PVC on follow-up. Even if you look at patient with our children with much more complex arrhythmia, ventricular couplets or VT, even in that group, there's spontaneous resolution of the PVC. This is a more recent. So it's another group of 239 patients with very frequent PVC, normal heart, mean of 12% PVC. And they've been followed clinically with echo and alter over a 5.6 year, so quite significant follow-up. And what was interesting from that study is that no patient developed heart incomes. So no one had sudden death, no one had nuanced VT, no syncope, no overt heart failure, showing that the prognosis was pretty good. For sure, if you go down further in that study, you can see a subgroup of patient with much higher PVC burden, greater than 20%. Yes, there was a significant decrease in injection fraction, but when you look at that diagram, it's a bit small, but you go from 65 to 61% ejection fraction. And in that group that had these changes, the PVC burden was 33%, so quite significant PVC burden. However, in that group, there's only 13 patient over five years that had PVC-induced cardiomyopathy, so roughly a 5%. So this is showing us that over time, with following this patient, we can detect LV dysfunction that occur, and overall, the prognosis is good. A more recent study, this is a Canadian study perspective, where they look at asymptomatic and minimally symptomatic patient with high frequent PVC, and they decided to select greater than 5% PVC, because this is the cutoff where some of these patients can develop PVC-induced cardiomyopathy. So they had normal ejection fraction, no suppressive therapy, and they had these alter and echo on a yearly basis. So there was 100 patient, very high PVC burden, 18% PVC burden. And what is interesting, without treatment, 44% of these patient had reduction of their PVC burden to less than 1%. So if you look at this graph, so the first one showed that over time, there's gradual disappearance of these PVC, and even if you subdivide by PVC burden, so even patient with high PVC burden also have spontaneous resolution. If we use the cutoff for PVC success rate of PVC ablation, that is often used as 80% PVC reduction, you go up to 52% of patient with a significant reduction. Another interesting thing is once it goes down, the vast majority remains with a low PVC burden. There's only four patient that develop LV dysfunction, and they all had very high PVC burden. So I think that approach that I'm trying to convince you is that active surveillance is probably appropriate for most of these patient. So if we go back to that natural history, so 28 to 44% have resolution of their PVC burden, and what we talk about PVC-induced cardiomyopathy is not that frequent. So it might be about 5% at five years. So let's get further down. So if we look at PVC burden, so this is a study that was quoted several times from the Michigan group where they took consecutive patient with idiopathic PVC, and I would say about a third of the group, so 57 patient, had LV dysfunction. Again, when you look at the cutoff of PVC burden, 33% PVC burden was in patient with LV dysfunction, and quite high PVC burden in patient with normal ejection fraction. Then they further cut down to try to figure out a cutoff, and they noticed that below 10%, in that study, there was no patient with LV dysfunction, and you need a cutoff that is quite high, at least 20%, and even for their better sensitivity and specificity, above 24%. So you need significant PVC burden before you even get PVC-induced cardiomyopathy. So what happen if you get PVC-induced cardiomyopathy? So that's the next study. This is a still old study, but 45 patient divided in three groups. So in white, this is the pre-intervention because they all got PVC ablation. You could definitely see when they have a very high PVC burden, your ejection fraction was lower, but also small difference. LV dilatation, but what is more interesting, after six to 12 month post-ablation, they all normalize. So you could expect improvement after PVC ablation, even if they had these problem. This is another study showing in the same direction. Also a group from Michigan where they had 87, sorry, patient with LV dysfunction, and in patient with successful ablation, there was a significant reduction in burden, and the ejection fraction improve, and either improve or normalize in all of the patient at the mean of about five months. So the vast majority have a very quick improvement in their LV function. So we can mention that even if there's LV dysfunction and we've been waiting, we can expect some improvement. So let's go to risk of the procedure and outcomes. And this is a risk-respective study that I was part of it, that we had more risk-respective data, but IPVC burden, and we look at the acute success of the procedure. So it was pretty good acute success of 84%, but then if you look what happen if you have no antiarrhythmic at follow-up, it goes down to 71%. And what is even more striking is the type of arrhythmia. If it's RVOT, you can expect a good prognosis, but if you go to multifocal, apicardial, and papillary muscle, your success rate is much lower. So I think that should be something that is considered. Also, these procedure are long, as you will see later, you might be able to do a lot of things in other patients when they have very long procedure. Clearly, as I mentioned, site of origin is important, the number of morphologies are things that you need to consider. Clearly, it's been shown that being asymptomatic, yes, can bring you a chance of having PVC-induced cardiomyopathy, very IPVC burden, but on the other side, you should expect some complications. So there's a roughly 5% risk of complication, 2.4% would be major. Although most of them are growing complication that could be managed medically, some of them are not as, are more significant like AV block, tamponade, or even stroke that could occur. So this goes back to the stroke VT trial to try to figure out what happened to these asymptomatic patient. Although this is a completely different population, I agree, a lot of VT ablation, but there was some patient with PVC ablation, and they were randomized to aspirin or anticoagulation post-ablation. And what is striking, in these patients, although they were symptomatic, there was a lot of events, either symptomatic or asymptomatic events. Although it was lower in patients that were anticoagulated, it was quite still significant. So you need to discuss that with a patient that is completely asymptomatic. So if we look at the long-term outcome, it could vary, but clearly, if you look at follow-up, just not acute success, it goes down, really depends on the site of origin, and you need to consider this complication. So what are the experts telling us right now? So one of the consensus, HRS consensus from a few years ago, first, they mentioned to monitor this patient to make sure they don't develop LV dysfunction or LV dilatation. And one of their recommendation is that routine catheter ablation for frequent asymptomatic PVC is not recommended. If we look what happened on the other side of the ocean, so in Europe, the ESC guidelines had a bit the same approach. So if you take structural normal heart, idiopathic PVC, symptoms, no, no symptoms, and then you can stratify based on the volume of PVC, or the burden, and even when it's higher than 20% PVC burden, they recommend to follow the ejection fraction and limit ablation to a class 2B intervention. So clearly, there's indication for symptomatic frequent PVC, but when you become asymptomatic, clearly, the data are not really there. So in their conclusion, they said that there's no data at the moment to support PVC ablation in this asymptomatic patient. So I think it's always a question of balance. So clearly, we want to prevent PVC-induced cardiomyopathy, but I guess the percentage of PVC is quite important. But what we're awaiting could be useful. First, there's a low rate of PVC-induced cardiomyopathy. Clearly, they need follow-up, unfortunately. You can expect improvement in the ejection fraction. You need to consider complication that could be present. The potential to be very invasive if you want to go epicardial. There's still a risk of recurrence, requiring medication, second procedure. And we didn't even talk with some of the medication that might be working before even attempting an ablation. There's clearly other consideration, patient preference, age, site of origin. So to conclude, very frequent to have asymptomatic PVC. I think we can be having a reassurance in most of these patients without structural heart disease. For sure, we don't need to forget, if they have a PVC burden greater than 10%, they need these annual echo to monitor. And if we diagnose PVC-induced cardiomyopathy, then it's time to do ablation. So as I mentioned, waiting, you can expect some benefit. So I think I try with that first part to convince that wait is probably the way to go. In most of these patients that are asymptomatic, there's maybe no early benefit to go right away to a PVC ablation. Thank you. But for our pro-oblate side, we have Dr. Greg Marcus from UCSF. And then we, again, will take some questions after both speakers have had a chance to do their rebuttal, and we'll do Q&A at the end, and remember to scan the code if you'd like to ask them. Thanks. Thank you. Pleasure to speak with you all. Give you my side of the story, different perspective. Those are my disclosures. So I'm going to try to convince you to not wait when you encounter a patient with frequent asymptomatic PVCs despite having normally F disclosures again. I do have a unique disclosure I'm going to wait until the very end to share, but I hope you will all stay, and that has to do with what I really think about this subject. This was assigned, and I very much believe in this sort of adversarial process to bring about the truth, and so hope to contribute in the good spirit with which it's intended. So there's an important context here, of course. It's not that these frequent PVCs have no effect. The concern is there's this high risk for heart failure, and it has been shown, and in fact, I think my opponent nicely demonstrated that ejection fractions can amazingly rise if we simply get rid of PVCs in those who already have a cardiomyopathy, and I would say that these success rates, which tend to be in the 80 percents, that's pretty good. If you consider AFib ablation in rigorous studies, generally exhibits about a 70 percent success rate, and that's at one year, and we know AFib tends to come back. With these PVCs, as those of you who ablate PVCs know, generally when you get rid of a PVC and you wait for that, you know, half hour, that PVC is pretty much gone, and the success rates, again, tend to be in the upper 80s percentage, and the rise in ejection fraction has been observed in many centers, many patients. Now you may say, well, come on, hold on a second. This is not a debate about people with a reduced EF. We're talking about people with a normal LV, and those people coming to those EP labs, they're highly selected. They're getting specialized care. Can we really extrapolate? What about the general population? In this particular debate, what we're trying to discuss is the person walking down the street who has frequent PVCs and doesn't even know it, and they have a normal EF. How can we study that? So we've tried to do this in a few ways. So we started many years ago just by looking at all the halters at UCSF. This was before the days of ZEO patches, so these were 24, 48-hour halters, and showed that among those who happened to have a high burden of PVCs, there was a threefold greater odds of heart failure, even after adjusting for multiple potential confounders. Now this was cross-sectional. These people were all undergoing halters for some reason, so perhaps they weren't truly asymptomatic. So then we looked at everyone receiving care in California, everyone who went to an emergency department or a hospital, this is more than 16 million people, and looked at a diagnosis of a PVC, 35,000 people with a diagnosis of a PVC without heart failure, no prior diagnosis of heart failure, no heart failure diagnosis when they had that PVC diagnosis. Then we followed them over time and found that they had a highly statistically significant heightened risk of developing heart failure in the future. Now again, a skeptic could very fairly say, well, these were people receiving care. They knew they had PVCs. Someone gave them that diagnosis. Is there any way that we could study the general population of the person walking down the street with frequent PVCs that doesn't know it? So enter NIH-funded research. So we were able to look at this. This is when Jonathan Dukes was a fellow with us. And this is using the cardiovascular health study, which is extraordinarily valuable, because it is a population-based cohort. These are not people coming in to receive care. These are not people with symptoms. They just were at least 65 years old. They had a very comprehensive baseline ascertainment, including study echocardiograms. So they did not have those echoes because of some medical problem. They were just members of the population willing to be part of a study. And then they were followed for decades for subsequent heart failure. And about 1,400 were randomly assigned to have a halter done. So again, not because of symptoms, not because they were seeking care. So as best as we can possibly do for a true population-based cohort. And indeed, we found that those with more PVCs had a heightened risk of heart failure. They also had a heightened risk for death. And this was after adjusting for everything we could, MI, diabetes, hypertension, BMI, et cetera, that were very carefully ascertained. One of the other really special things about this cohort is that there were repeat echocardiograms done at five years. Again, because they were part of the study, not because of care they were seeking. And we found that those with more PVCs were more likely to exhibit systolic, new systolic dysfunction at five-year follow-up. The specificity for predicting CHF exceeded 90% when PVCs included at least 0.7% of total ventricular beats. And the positive predictive value at 15 years was greater than 50% for PVC percentages between 1.24 and 3.55%. Now that probably seems like pretty low percentages. But again, these are people in the general population, not people coming to EP labs. More than 50% of these people developed heart failure over follow-up. Okay, so then the argument of course is, but hold on, ablation is an invasive procedure. And don't we have to be concerned about the adverse consequences? So what are the complications? And again, we wanna keep this in context. So here's one paper from a very large cohort. You don't even need to read the paper. Just look at the title. It's the safety of catheter ablation. It doesn't say anything about complications. So of 1,200 people, 2.7% had a complication. About half of those were relatively easy to address. Now to be fair, the rest were quite severe. ACS or MI, VF, PE, stroke, infective endocarditis, and death. So I will certainly concede that. This is another fairly large series where I will note that if the PVC was coming from the RV, the risk of a complication was .3%, .3%, not 3%. And even if you look at the LV PVC ablation complications, which were clearly higher, many of these can be addressed. So there was an ischemic stroke, which is clearly a real problem. But thankfully, tamponade, which occurred in almost 2%, can almost always be addressed. Pseudoaneurysm, AV fistula, of course, patients suffer, they can cause pain, they can lead to increased healthcare utilization. But in the long run, they don't lead to long-term disability. So again, we have to take this in context. It's not like we're doing this in a vacuum. What's the alternative? What's the counterfactual? So what if someone develops heart failure? What happens then? So this is mortality data. At one month, there's a drop in mortality. At one year, two years, we're talking about 10, 20% reductions in mortality. So magnitudes of risks are much higher than the ablation. This is another series. Patients who come in with heart failure, they develop heart failure, there's a substantially heightened risk of stroke, of renal failure, of cardiogenic shock, of course, of death. So again, this context matters. Now, some may say, but now we have GDMT, and GDMT works really well. So is developing heart failure really such a bad thing? But the reality is, and this is from the 2025 AHA statistics report, in a large database, only 6.2% of people diagnosed with heart failure and eligible for GDMT actually received it. So unfortunately, we can't count on that. Now, I finally wanna make a point about causality, because again, a very harsh skeptic could still argue, well, these are all correlations. You haven't really proven causality. And even the person who comes to the EP lab and gets their PVC ablated, and then their EF normalizes, maybe that's just the natural history of things. Maybe it's because they're in a referral center, so they're getting their GDMT. So can we prove that PVCs actually cause heart failure? Well, yes, one can use an animal model where you simulate the introduction of PVCs. And this has been shown now in several different experiments from different centers, that doing so does in animal models lead to, therefore cause a reduction in LV systolic function. Now, to be skeptical even further, you could then say, well, this doesn't prove that it's reversible. This doesn't suggest that ablation would help, but Ed Gerstenfeld, Thomas Walters at our place demonstrated that actually, turn off the pacing, which is in this case, akin to ablating, the EF will rise. So these things are not inexorable. So in conclusion, PVCs cause heart failure. Ablation is highly effective and low risk, relatively speaking, relative to the risk of heart failure to eradicate PVCs. Heart failure is really bad. An ounce of prevention is worth a pound of cure. So don't wait, ablate the PVCs. Thank you. Let me just get my slides. Okay, so I knew some of the slides were coming, so for sure, if we look at the prognosis of PVC, clearly it's been shown in several studies that frequent PVC or PVC can lead to cardiovascular event, stroke, total mortality, and this is the same study that they showed. But when they separated it by quartile, clearly it shows that the more PVC you get, the worse it is. But I want you to focus on what is the small footprint at the bottom. So in that orange line, the PVC burden can be at 0.12%. So what would you do in real life with these patients that are asymptomatic? So clearly, we didn't show that we could reduce mortality, and clearly, if a patient has a 0.1 or 0.5% PVC, I would not bring this patient to the EP lab. So clearly, definitely it can worsen the prognosis, but again, I think the PVC burden is important. Something that we didn't discuss yet, but I think it's important, this is a study where they look at what people thought were idiopathic PVC, and what they notice is by doing cardiac MRI to these patients, mostly when they have multifocal PVC, if you have scar, that's bad. So clearly, your prognosis is worse. So in some of these patients, when they have frequent PVC, I think it might be worthwhile to do more investigation to make sure that it's really a normal heart. And if you do that, and they have a normal cardiac MRI, then in the long run, these patients do well. So despite maybe having a lower ejection fraction at one point, the prognosis is good. We didn't discuss yet that, but if we change the strategy, and we say maybe it's because it's a retrograde approach that caused that, what I want to show, this is a paper from my colleague, Dr. Marcus. These are all nasty, asymptomatic event, and that are quite frequent. I know it's a severe population, a lot of VT, but some of these PVC are coming from the cusp, they're coming from the LV summit, so you might have to map also retrograde aortic. I want to continue that, if we look at the literature, Dr. Marcus published a very beautiful, and I encourage you to read his paper, it's really very well written, but I want you to focus on the right side of his suggestion workflow. So if we look, if you have a PVC burden greater than 10%, and you have no symptoms, we recommend to follow them with echo, and not to do ablation. The other part, this is our Canadian standpoint of view. This is our local information on wait lists. So this is data that has been collected for a while. So in blue is the wait list that we have in the EP lab. The red bar are ablation. So as you could see, over time, we're now over 1,000 patients on the wait list, mostly ablation. This is despite having a new EP lab, increasing the efficiency, and having a 5-10% increase in procedure volume every year. So if I have to choose between an asymptomatic PVC ablation, I would clearly favor a PSVT or AF ablation, before going to a PVC asymptomatic ablation. So I think there's, to probably make the bridge between our two, there's several important considerations that we need to take from this talk. One is the PVC burden. Clearly I would not consider the same thing in someone who has a 5% PVC burden, as opposed to someone who has a 50% PVC burden, couplets, non-sustained VT. I would be more concerned in these patients. Imaging, as I mentioned, very important for prognosis. We didn't discuss also for patients with short-couple PVC. When you see very short-couple and you're concerned about maybe VF in these patients, then that might still change my opinion. For sure, we talk about ejection fraction, but I think we also need to look at other features like LV dilatation might be a trigger to get a bit earlier. The good thing is most of these patients would improve, but also I think we need to consider the site of origin. Clearly RVOT is not the same thing than having a papillary muscle, apicardial VT, where sometimes you need a second procedure to get done. Also we need to consider, is it an experienced center or a center that started doing ablation? Also in my practice, if the patient is 40, 50-year-old, as opposed to 85-year-old, I think that would change my opinion. I'm still thinking that we should wait and not do ablation in the first line. Thank you. All right, so just a few more thoughts here. So Dr. Sarazen mentioned this evidence that brain emboli are common after these PVC ablation procedures. The first author of this paper is sitting right over there, Dr. Ziggy Whitman, when he was a fellow with us. First I would note that we found no such brain emboli with RV ablation. All these patients had brain emboli, but yes, the rate of new brain emboli was remarkably and surprisingly high, 60%, alarmingly high, which is what motivated our recent Traverse trial where, and I want to thank Dr. Sarazen for highlighting it, we did find a potential solution. So where with a transeptal approach you can get the rate down, in this case in 28% in the as-treated, because there was some crossover, it's even lower. And I will point out that this is very similar to the rates that one sees whenever they look at brains after AFib ablation, which is unfortunate, and we need to do yet more work to try to figure out how to mitigate these things and understand if they have clinical implications. But again, AFib ablation is first line in many guidelines, so this rate may not be a compelling enough argument to argue against ablation. Now I'm sure we can all agree when we think about, well, who are the optimal candidates, who are asymptomatic, who are going to develop heart failure? I think we're all really interested in that. And there have been several studies to try to look at these predictors, and interestingly, one of the important predictors that comes out fairly consistently is being asymptomatic. Now I promised at the beginning I would share what I really think, which is, and Dr. Sarazen showed, I don't offer ablation to these patients. I do recommend serial echocardiograms. But I think this is a research question worthy of investigation, and we need good science, we need strong evidence to help inform this. I can't say it's not the better thing for them. This is the sort of thing that, again, government-funded and investigator-initiated research is for. And then as someone that does a lot of work related to lifestyle, and this notion of trying to get at something before it occurs, trying to prevent the heart failure before it occurs, I would be remiss if I did not share the idea or try to disseminate the idea that maybe we can do something about these PVCs that's less invasive that is even more preventative. So we've tried to look at this in a couple of ways and have shown that those who exercise more do tend to have less PVCs on average. Those who smoke have more PVCs. So yet another reason to hopefully motivate our patients to engage in healthy physical activity. And then our recent CRAVE trial, which stood for Coffee in Real-Time Atrial and Ventricular Ectopy, where we randomly assigned people to caffeinated coffee versus essentially avoidance of caffeine day-to-day, the New England Journal insisted that we pick one outcome. I told them our primary outcome was PACs and PVCs. And they said, well, you've got to pick one. And because of evidence that coffee may not increase the risk for AFib, we decided, okay, we'll focus on PACs, which is the only one where they allowed us to include the P value. And we submitted the paper. It had P values next to everything else. Interestingly, and something that doesn't get a lot of attention because of that, there actually were more PVCs in both intention to treat and as treated on days assigned to caffeinated coffee. So suggesting that it may really be influenced by caffeine. Now an important caveat to that is these were quite healthy research volunteers. So it may be that people with a high burden of PVCs are different and those PVCs are going to fire whether they're exposed to caffeine or not. So I would say don't wait to conduct the rigorous science needed. Follow the evidence as best you can. Appreciate the good debate and look forward to your questions. Thank you. That was a fantastic job by both of our debaters. So thank you so much. We have 20 solid minutes here for questions and answers. And I want to make one comment, ask each of you one question. I see Jose is ready. This is a very knowledgeable man when it comes to asymptomatic PVCs. And then anyone else who has questions, come up to the mic here. And we also have a lot of good questions that have come in virtually. So the comment is it seems that both of you are basically in agreement not to ablate asymptomatic PVCs. And some data that I do think is interesting to think about is what do we mean that PVC-induced cardiomyopathy is fully reversible? We mean that the ejection fraction recovers. But your colleague Ed Gerstenfeld, who's done all these fabulous animal experiments, has shown that the fibrosis that occurred with the PVC-induced cardiomyopathy persists, and the electrical dyssynchrony that occurred with the PVC-induced cardiomyopathy also persists. So this is pigs. It's not humans. But I think it is some food for thought. Does everything really reverse? Or is it better to prevent the cardiomyopathy from happening the first time? So that's the common questions. So for Jean-Francois, the mechanism, you showed such a high rate of spontaneous resolution of PVCs without any intervention. Do you have any thoughts as to mechanism? Maybe sometimes it's the special period in the life of a person, their stressor, maybe more coffee, things like that, that could be a cause. For sure, most of these studies don't necessarily have a seven-day monitor where you can see if there's fluctuation in these PVC burden, although some of the studies have shown that a repeated alter showed that there was a decrease. So I think maybe it's life situation. I don't think we have a real answer to that. Okay, fair. And then, Greg, I was struck by the data from the prospective study where, do I understand this correct, with the PVC burden of one to three percent, the incidence of heart failure was 50 percent. It seems entirely different than the clinical numbers we kind of carry around and use commonly. Yeah, I mean, one thing to recognize with that cohort, and again, I was being a little strategic, is the follow-up was very long. So as I mentioned, decades. They are fairly elderly. I did not share the rate of heart failure in the people without PVCs, although clearly there is a heightened risk in that population. I don't think it's as extreme as I may have portrayed, but there clearly is a heightened risk. And a very fair and reasonable question that I don't know the answer to is, you know, how much of that is a marker of an underlying propensity versus in how many cases is it truly causal and sufficient to eliminate, to get rid of their heart failure. My suspicion is it's some combination. And just to comment on the variability of the PVCs, again, this just highlights, it's amazing to me that we all have PVCs. I mean, we know this from our research where we enroll healthy people. We all have a lot more PACs on average, but, and we still don't understand their origins. I mean, we really don't understand why these things happen, what affects the frequency. We have a little bit of randomized data now regarding coffee. There is some evidence that hormonal changes may be important, and I think we all recognize anecdotally, clinically, that sometimes perimenopausal women, suddenly that's when their PVCs arise, but it doesn't seem to be predictable. Sometimes a woman becomes pregnant and then she develops PVCs, or she becomes pregnant and then the PVCs go away. But clearly, there are many dynamic processes that we're all exposed to regularly that are affecting these things that we still need to understand. So I just have one question before we get to Jose. So it seems like a general consensus we will watch very carefully. We know, following up on Dave's comments, we know from left bundle literature, we know that the earlier you get to people who have, say, pacing-induced cardiomyopathies or left bundle-induced cardiomyopathies, the more likely you are to reverse. So what is your practical advice for how often and to screen and what type of screening? Are we supposed to be getting MRIs on everybody? Are we doing annual, six months? Is there a role for BNP monitoring? So forth, I'd just love to hear what both of you do, and Dave as well, too. For sure, in Canada, sometimes I talk about the wait list. It's long to see the patient, even in the clinic. Clearly, I think, as I mentioned, it happens over years, so you need to do your regular follow-up. So I think that's clearly at least once a year. For sure, if symptoms change, then the patient needs to be seen earlier. We need to look at different markers. As I mentioned, not just the ejection fraction, but the alveolation, that is important. So at least once a year is probably sufficient. Is there ways, and I guess it also depends on all the other factors I mentioned about the burden. Someone who has a low burden probably won't be as aggressive as someone who has 35, 40%. So I think we need to personalize the decision on each patient. Yeah, I would agree. I generally recommend an annual echo. I have some patients who have had normal echoes for many, many years. It's a major hassle for them to come to San Francisco or even their local cardiologist, where maybe I'll go to every two years. I'll be very clear about symptoms. Any decrease in your exercise tolerance, let me know, low threshold to double-check. I think the MRI, I don't have a clear-cut plan. For who exactly gets an MRI, I think it's some sort of combination of how frequent is it and where the PVC's coming from. Pretty much anywhere other than the RVOT, perhaps CUSP. I'll have a lower threshold, especially if it's fairly frequent. I think that threshold is decreasing rapidly. I'll just add a comment, quick comment. So I agree with the, sorry, with the MRI. A bit the same thing. If it's not RVOT, if it's very frequent, if you have couplets, and if they're multifocal, clearly these are patients that I suspect there may be something else going on. Or a patient who has syncope, oh yeah. Jose. Hi, thank you for a great presentation. I have a few comments. So, for instance, in Kansas City, I know that when they have high PVC burden, they frequently think of inflammation or some sort of myocarditis. So they usually get a PET scan to rule out some degree of subclinical myocarditis. And if it's positive, they treat them very aggressively with immunosuppressants. So that's one important point to make from some of these. I really believe that some of those transient PVC's may be inflammatory-related, that there's no, it's sort of asymptomatic of subclinical myocarditis, besides potentially some other factors, including stressors, right? So that's one point. And the other thing that I think is important to make a distinction here is, what do we refer with a normal heart function? And there's a study that was published about maybe six years ago from Europe. I remember the first author was Delgado. I think it's one of the groups in Netherlands, that they actually showed that patients that had PVC ablation with a normal EF, the LV strain improved. Meaning to say that there was a subclinical myocardial myopathy. They had a normal EF, but the EF barely changed. But when you look at LV strain, the LV strain had a significant improvement. So again, meaning to say that there is likely some subclinical myocarditis that is not really perceivable only by ejection fraction. And you could actually assess it better with LV strain. The other point I wanted to make is, as David mentioned, was the fact that you are gonna have, as demonstrated in animal models, you have histological remodeling. That you're likely not to reverse. And actually that's what Gerstenfeld showed on some of his models. Now what makes it even more complicated is that this institutional fibrosis, while it's not severe, it at least triples. And the fascinating thing is that, in my perspective, something we're missing here is that MRI is showing that fibrosis is a marker for sudden death. But even more so recently, extracellular bullying that is assessed by MRI is showing that it's also linked to increased mortality. And while you could say scarring or replacement scarring, such as myocardial infarction, is different. This is interstitial fibrosis that we see in PVCs. This is something that is likely causing increase in extracellular bullying. So I think we need more data to understand this extracellular bullying. This showing is a reflection of interstitial fibrosis in the patients that have potential normal heart. So again, we gotta be very cautious because I think there's gotta be some interstitial fibrosis that is persistent. And if we wait too long, we may improve the ejection fraction, but are we really making a favor to the patient? We may decrease some comorbidities, but at the end of the day, if there's a persistent remodeling histologically that we cannot reverse, then that's a problem. That's great comments, Jose. I'm gonna ask a couple questions from our virtual audience. So we talked about fluctuation from day to day. So what duration of monitoring? 24-hour halter, three-day ZO patch, how do you think about that? I guess for us, it could be quite expensive for patch monitoring. So our hospital offer it as the same price than a halter. So I guess for some of these patients, I would use a patch. For some of the patients that are outside of my hospital, I would recommend more halter monitor. I guess some are annoyed to have it that for a long period of time, so I would address myself based on each patient. Yeah, my sense is that the longer duration patch is now really more the standard, even though a lot of these data we both discussed stem from 24- to 48-hour halters. And it is important to think about how that might influence things. I think Ed Gerstenfeld did have a paper, and I apologize, I don't remember the first author, or even if it was published, essentially showing that, just analyzing a two-week monitor and demonstrating, look, if your 48-hour halter happened to be here, your PVC count's gonna be 1%. And if it was here, it would be 30%. So I think that's helped a lot. And I don't know if you can comment on the studies that show the decline. Were those 24 or 48? Could that be part of the explanation? Some of these, most of these studies were old studies, so patch monitoring were not present. So it might be interesting for further studies to include more patch monitoring. Thank you. Isabella from Canada. Thank you for two great presentations. I have a question concerning your management. So if a patient comes in and you, asymptomatic PVC, you decide not to ablate him, are you, how comfortable are you not treating him at all? Like not starting him on beta blockers or any other medical therapy? Because a lot of those patients come and they're already on some sort of therapy because the doctors are not comfortable not treating them at all. Although when we look at the data, we might not have to treat them at all. And on the contrary, the second part of my question would be if you decide that the patient needs a treatment, how comfortable are you starting with medical therapy instead of going directly to ablation? So thank you, Isabella. She's a colleague at work. So clearly, often when they're referred, they might already be on medication. Personally, if it's in the below 10%, probably I would not treat. If it's above 10%, there's no reason, there's no reason, but I would tend at least to try a beta blocker and see. Some of them respond to beta blocker. The safety profile is pretty good. Unless it's complex PVC, then I might consider flaconide if they have a normal ejection fraction. But most of these patients, I would not treat. Then your second question was? If you're the treatment agent, are you considering a priority? Okay. I guess, again, it's discussion with the patient. When sometimes you tell the risk to the patient, they might say, oh, I'm not that symptomatic or I'm not that interested. Let's wait and see. And as I mentioned, the wait list is quite long. So we tend to put them on treatment and see them back and follow up. If they're better, we might just cancel a procedure or do it. But I would still tend, when very high elevated PVC, to start some basic treatment. Some of them, if they're young, complex, frequent RVOT, then my cutoff might be to go on for PV separation earlier. So I might be a little bit more extreme in that if someone's truly asymptomatic, EF is normal, I don't treat. And in fact, I mean, in collaboration with, if some other provider had started a beta blocker in that person, I would often recommend just stopping it. I worry about, so quality of life, we haven't really talked about, but is important here in a couple of ways. One is beta blockers can really tire people out and it can be subtle enough that they're tired, but they don't attribute it to the beta blocker and that always, that haunts me a little bit, that among my many patients on beta blockers. Two is the anxiety about the PVCs and oh, I have heart disease now so I do share a true story, family story, which is my grandfather was denied life insurance as a young man because he had frequent PVCs and he died at age 97 of things unrelated to his heart and was super active up until the end, essentially. And patients love to hear that. I mean, these patients we're talking about. Now, the one exception in my practice might be sometimes it's not 100% clear whether they're symptomatic or not. Someone has frequent PVCs, they're not bothered by palpitations, but they're tired or they get winded and you can't find another reason. So in that case, then I might try, do a trial of beta blocker, but I always make it very clear. Look, if you feel worse, stop the beta blocker and let me know. The whole point is to try to help you feel better. In terms of your question, so given someone where we do decide we wanna treat them, someone who has symptoms, especially someone who, let's say, who has symptoms with a normal EF. I think in that case, I present, generally speaking, medications or ablation as fairly equivalent, reasonable first tries, and try to gauge and have a long discussion, usually with the patient, what do they prefer, what, you know, some people will say, I don't wanna take a medicine. Other people will say, you're not putting a catheter in me, you know. Of course, the other patient characteristics are important. So if this is a 90-year-old with, you know, horrible cardiovascular or peripheral disease, I'm probably gonna, you know, I'm gonna favor the medication. But otherwise, I think it's reasonable to consider them fairly equivalent. I think if they have a low EF, then pushing, you know, usually those people, because they have a low EF, they're already on a beta blocker and other GDMT. So usually their ablation is more the first line. You know, what we need is a cardio version for PVC, so you can test the symptomatic nature without putting people on drug, because I think the fastest way to get somebody symptomatic is just refer them to an EP, and then they start looking at their EKGs, they start measuring the pulse, and they start, all of a sudden, becoming very symptomatic from their PVC. So probably I agree with you, Greg, in that less is probably more if you're really, truly dealing with a normal ejection fraction. With the exception, what I just wanna make sure is that understanding that we're talking about asymptomatic PVCs, that they're really the same thing, and it's not the same thing. Some PVC that may look like it's associated with mitral valve prolapse coming from the papillary muscle, you may be more diligent about treating and understanding more frequent monitorings over the potential dangers of different sites of origin. I would just add, before your question, regarding the class Ic drugs, they're very effective for PVCs, and I think that you can use a class Ic drug and just as the same indications for ablation, and we've also published our experience using class Ic drugs for PVC-induced cardiomyopathy, and not surprisingly, they suppress the PVCs and the EF recovers, and no one dropped dead, as long as you rule out coronary ischemia ahead of time. Okay. So, my name's Ben Hale, I'm a pediatric EP, and I think of following our patients with frequent PVCs and no symptoms, normal LV function. The idea of following them for, I don't know how long, decades with echoes, maybe MRIs, clinic visits, like that's pretty daunting too. So I think from one perspective, sometimes the ones that we know aren't gonna go away, maybe that's the time where we say, hey, these things aren't going away. Maybe you're getting close to going to an adult EP, I think they're gonna burn it anyways, like maybe that's the time to go get rid of it. But maybe the other, maybe the right thing is actually, maybe we don't need to follow you. Is there any group of patient who you just wouldn't follow with these PVCs, or are you gonna kinda commit these people to years of annual follow-up and echoes that come into UCSF and all that sort of thing for pretty much all cases? I guess clearly if the PVC burden is on the lower side, let's say less than five or 10%, clearly I would send them back to their regular cardiologist and they can do the follow-up and said, if it comes back higher up, if they develop symptoms, then send them to us. So I guess the cutoff of PVC would be one of my, one of my way to do. For kids, good question, we don't follow kids. I could ask my colleague to see what he's doing. He's coming to our center to do all his ablation, and over the past 15 years, I've never seen a PVC ablation in an 18-year-old and younger. So probably they do well, that's what I imagine. Yeah, same, same, I don't think I have much to add. I mean, those are the patients where, again, if they've done really well for a long period of time, I might spread it out a little bit more so it's not every year, every couple years. And then, I mean, another question is, well, how often do you recheck their PVC burden, which is also a variable thing, but that is a reason to do it, is to see if it does decline, especially some, presumably the pathophysiology in kids is maybe different than those in adults, I don't think we really know. Or the natural history, again, I don't think we really know, but to see if it's gone down, and then you can hold off and maybe discharge them from your clinic. Dr. Whitman, last question of the session. Oh, great, thank you. I hate to bring up, or potentially open Pandora's box and talk about anticoagulation and atrial fibrillation, but one of the appealing things about risk scores is that it's pragmatic, and that a lot of us make decisions as imperfect as it is about whether an anticoagulated patient with atrial fibrillation is by the CHADS-VAS or CHADS-VAS-GAR score, and we may include other factors as well, but it's helpful. And I may have missed it, but I was surprised that neither of you brought up the ABCVT score, which is a way to, in a pragmatic way, look at a halter and say, this is their score, and maybe we should get rid of it. And just as a small point, which surprised me from that paper, that one of the elements that got you more points was a longer coupling interval, whereas I usually think of shorter coupling intervals. I wonder if you could comment on both those points. So, well, and we've also published that a variable coupling interval, and that's actually now been a couple of studies, one from cardiovascular health study I shared, another from, I think, just patients coming to UCSF. Variable coupling interval may be important. I think there are a couple of reasons that score has not been widely adapted. To my knowledge, it's a score of a predictor, which is a step before using this score leads to better outcomes, right? Whereas in AFib, we have the latter. Well, we kind of started with using the anticoagulant, you know, clearly in a placebo-controlled randomized trial. We don't even have that, you know, first step in these patients, right? We don't know in a randomized trial if ablating the PVCs, especially in people with asymptomatic AFib, whereas we know in the large population with AFib, on average, you treat them with anticoagulants, you can prevent stroke. So I think that's the next step, and it's trickier in this population because it's just not as common, and especially this very specific population. So, you know, I think I would be hesitant to use that score to make a definitive decision. Maybe that's the kind of thing that you would make to say, okay, I can see this person back in two years rather than every year, but I wouldn't say like, okay, you're low-risk, I don't need to see you again, or you're high-risk, I'm definitely gonna ablate you. I don't think there's sufficient evidence for that. I'd like to thank everyone for coming. I'd like to thank the speakers and Dave Frankel from UPenn. That's the end of the session. Thank you so much. Thank you.

PVC ablation

asymptomatic PVCs

normal ventricular function

cardiomyopathy

echocardiograms

heart failure risk

ablation complications

PVC burden

early intervention

individual patient factors