meeting of the Heart Rhythm Society. If you've not already done so, please download the HRS 2025 mobile app from your preferred app store. This is how you can participate in the live Q&A during the sessions. And please scan the QR code on the screen. It's gonna come up and you can have access to the current Q&A for this session. My name is Hakeem Ayinde and I will be one of the hosts for this session. And my co-host is. Good morning, I'm Ken Mayuga. I'm one of the electrophysiologists at Cleveland Clinic and the director of the Sinkipi Center in Cleveland Clinic. So this session is entitled Controversies in Cardio-Neuroablation. This is a special joint session with the Heart and Health Foundation of Turkey. The first speaker, Dr. Tolga Aksu, unfortunately could not make it in person due to earthquakes in Turkey. Fortunately, he and his family are safe and he was kind enough to upload his talks. So we'll start off with Dr. Aksu's uploaded presentations. Uploaded presentations. Dear colleagues, please accept my apology because I couldn't be attend in person at this time in HRS due to recent earthquakes in Turkey. Today in this debate session, I will try to explain why cardio-neuroablation should be the first line therapy for vasovagal syncope in young patients. And this is my disclosures. Enhanced parasympathetic tonus or an imbalance between sympathetic and parasympathetic system has a strong relationship with reflex syncope and carotid sinus syndrome. And if you look at the pathophysiology of vasovagal syncope, we know that after occurrence of any trigger activity, we see an increase on sympathetic tone, it cause a forceful ventricular contraction in unmet chamber, it stimulates C fibers and stimulation of C fibers may cause three different responses. In the first time, we see a bradycardia or asystole due to parasympathetic overactivity, which is called as cardio-initiatory type. In the second time, we see a hypertension due to sympathetic withdrawal, which is called as vasodepressory type. But in great majority of patients, both sympathetic withdrawal and parasympathetic overactivity contribute to occurrence of global cerebral hyperperfusion and then syncope. So theoretically, cardio-neuroablation can try to eliminate parasympathetic afferent arm. So if we can eliminate parasympathetic system, we can eliminate occurrence of syncope in great majority of cardio-initiatory type or in patient with mixed it with dominant cardio-initiatory response. According to ESC and ACC guideline, in case of severe and recurrent vasovagal syncope episodes, after education and lifestyle measures, we should demonstrate the type of or phenotype of the reflex syncope. If the reason is low blood pressure phenotype, we can use two medication, uterine cortisone or midodrine, but if the reason is dominant cardio-initiatory type, we have only one option. This is cardiac pacing, but please look at the publication about cardiac pacing. Actually in two studies, VPS2 and SynPACE, the patient younger than 40 years old were included in the study. And if you look at the results, during follow-up, cardiac pacing has no effect to prevent reflex syncope episodes in this younger population. After that, only patients older than 40 years old were included in the study. But if you look at the mean age in that studies, like issue three, Spain on biosign, actually mean age was older than 60 years old. And another important point, if you use rate-drop response pacemaker, you are seeing just a modest effect after cardiac pacing, but by using closed-loop stimulation system, you can be more effect in patient with vasovagal syncope episode. So we have no data about the patient younger than 40 years old, but for patient older than 40 years old, we have only one pacing option and this is closed-loop stimulation system. But if you look at the CNA studies, the mean age was younger than 40 years old. In all study, in all that studies, authors use tilt-table testing to select their patients. So I believe that tilt-testing is a good option to select vasovagal syncope patient because by using tilt-testing, you can discriminate the contribution of vasodepressory components. So in that slide, you are seeing the cardiac ablation study and the results of tilt-table testing for patient selection. Actually, in great majority of publication, authors select pure cardionegative reflex syncope patient, but just a couple of studies, Chinese group used CNA in patient with pure vasodepressory reflex syncope patient as well, and they demonstrated a similar success rate. But according to our physiological knowledge, we still don't believe the potential efficacy of CNA in pure vasodepressory reflex syncope patients. Let's see some observational studies. In the first one, Patron followed their patient longer than three years, and by using biatrial approach, they demonstrated more than 90% syncope-free survival, according to their results. And then Chinese group published the largest series, 115 patient, and followed their patient 18 months, and they demonstrated a similar syncope-free survival, but surprisingly, in 75% of patient, they used this technique in patient with mixed-tip syncope patient as well. And then we published our cohort, there was 51 patient, and we demonstrated almost 95% syncope-free survival during two years follow-up period. And then we compared CNA and conservative therapy. This was not a randomized control trial, a case control study, but after that, CNA caused 77% relative and 36% absolute risk reduction of four-year syncopal recurrence rate. This was very promising result. And then we compared CNA and cardiac pacing in almost 50% of the cardiac pacing arm, they used closed-loop stimulation system for pacing, and at one year, CNA and cardiac pacing demonstrated similar success rate to prevent new syncope episodes. And then finally, first prospective randomized control trial of CNA was published by a dear friend, Roman Piotrowski from Poland, rest in peace, Roman. They compared CNA and non-pharmacologic treatment, including fluid, salt, compression socks, tilt training, and avoiding triggers. And at the end of two years of follow-up period, the primary endpoint occurred in 8% in CNA arm, but 54% in control arm. So CNAs has a good effect to prevent new syncope episode. They also checked the quality of life during follow-up period, and they demonstrated a very good success in quality of life parameters in CNA arm. And then we published the first meta-analysis, compared different technique, and we found that biatrial and left atrial ablation is related to more than 90% syncope-free survival. But if you just perform right atrial ablation, the syncope recurrence may be higher, like 20% during a long-term follow-up period. And then a second meta-analysis was published. There was more than 500 patients in this meta-analysis. And again, we found a similar finding, biatrial and left atrial ablation was related to very, very good syncope-free survival during follow-up. According to all this data, you are seeing my personal suggestion for reflex syncope patient. If there is severe, unpredictable, and recurrent vasovagal syncope episode, after education, avoiding triggering situation, physical counter-pressure maneuvers, and fluid and salt intake, we should demonstrate the dominant mechanism by using ILR alt-tilt testing. If the reason is dominant cardiomyopathy response, and if the patient is younger than six years old, according to our data, CNA should be the first option. But if the patient is older than six years old, it is not easy to differentiate structural involvement of sinoatrial node or AV conduction system, and we have too many data about the potential success of cardiac pacing, pacing should be the first option. In patient with mixed-tip syncope, at the first attempt, we should try mid-uterine or fluid recortisone, but if there is recurrent syncope episode despite this medication, and if the patient is younger than six years old, again, CNA should be the first option. In patient with dominant vasodepressory syncope, you shouldn't try CNA, because there is too less publication about the efficacy of CNA in this arm. Thanks for your attention. In the first part of the discussion, I mentioned some of observational studies, random mass control trials, meta-analysis, and my personal suggestion about cardioneureablation strategy in younger population. Now, let's see what scientific document says. In the last year, we published the first scientific document of cardioneureablation with endorsement of EHRA, HRS, Latin American Heart Rhythm Society, and Asia-Pacific Heart Rhythm Society. In this document, we propose an algorithm for selection of reflex syncope patients for cardioneureablation based on available evidence. In patients younger than six years old, if there is typical syncope triggers or syncope scenario, no clue of intrinsic sinoatrial node disease or atrioventricular conduction abnormality in ECG, no structural heart disease, failure of non-interventional conventional therapies in preventing syncope, and if there is severe, unpredicted, recurrent, or traumatic episodes, this patient should be accepted as potential candidate for cardioneureablation. In the next step, we should demonstrate the phenotype of reflex syncope, low blood pressure or cardiometric type. To do that, we can use cardiovascular autonomic function tests like HIDAP tilt table test, carotid stenosis massage, standing test, or 24-hour ambulatory blood pressure monitoring. If there is more than three-second asystolic reflex syncope during tilt testing, data are in favor of CNA efficacy. In case of associated hypotensive susceptibility, data on CNA results are still accepted as debatable. Of course, you can also use implantable rib recorder to select potential candidate for cardioneureablation. If there is paroxysmal asystole more than three seconds during syncope or asymptomatic pulse more than six seconds, this patient should be accepted as potential candidate for CNA. In mixed-tip patient like bradycardia with lower than 40 bpm heart rate level more than 10 seconds during syncope, of course, there are a couple of publications demonstrating efficacy of CNA, but the data are still accepted as limited in this patient population. And in pure vasodilator reflex syncope patient, CNA shouldn't be selected. Recently, Chinese group compared left atrial and biatrial ablation in a randomized controlled trial, and they follow up their patient one year. And after that, both technique demonstrated almost 90% success rate to prevent reflex syncope episodes during a 12-month follow-up period. This is a very, very important point. So, well-designed, randomized, and sham-controlled trials are needed to evaluate the clinical efficacy of CNA in highly symptomatic patient with vasovagal syncope duty, the variable symptomatology, intermittent nature of symptoms, the complex pathophysiology with inter-individual variability, and diverse medical and international treatment options. Considering the long-term follow-up data, it is important to follow this patient as of whether they are enrolled in a clinical trial or treated after shared decision-making due to pronounced symptoms in the months after CNA with 12-week ECGs, whole-time monitoring, autonomic test, and symptom evaluation as appropriate. Thanks for your attention. Appreciation to Dr. Toga Aksu for being committed to help us with this session, even though he could not attend. The next speaker is gonna be Dr. Brian Olshansky, who will deliver a counterpunch. The line will be what's, you know, cardio-neuroablation should not be first-line therapy for vasovagal syncope in young patients. Chairs, discussants, colleagues, it's a pleasure to be here today. I have no conflicts. But I would like to remind you, and I want to first say that Tolga, I consider a friend. I also consider him to be one of the pioneers in the area, and I have deep respect for him. But I will say that the debate today is cardio-neuroablation should not be first-line therapy for vasovagal syncope in young patients. And I would like to start with a case, and I'd like your opinion. This is an 18-year-old healthy female who is giving a talk in front of her high school class, becomes diaphoretic, pale, and passes out for a few seconds. She has had an episode of syncope in the past, and her evaluation is normal, including an EKG. What would you recommend? And here are some of the choices. Very interesting. You just heard a passionate discussion from Dr. Aksu, and nobody is going to perform a cardioneuroablation on this patient. Isn't the discussion about young patients with vasovagal syncope that cardioneuroablation is the first line therapy? But no one thinks so, even after his discussion. And I agree, because indeed, cardioneuroablation can work for cardio-inhibitory vasovagal syncope. It can alter the responses to the vagus, and it still is not first line therapy. Again, it depends what you consider first line therapy. But in my mind, it is the initial and preferred treatment, considered effective and lowest risk. Now, you've seen this already, and this was guidelines that we put together a couple of years ago. I think we would all agree that the first thing you're going to do when a patient has vasovagal syncope is to educate the patient, to consider the triggers, to consider ways in a very non-pharmacologic way to treat the patient, and then consider further therapies. But notice over here, there's no mention of cardioneuroablation. That doesn't mean it shouldn't be done, but it's not the first line therapy. Now, as we think about the vasovagal reflex, it's actually very complex. And I don't think we understand it completely. There are many moving parts of this reflex, including afferents, including the brain, including efferents, including the vagus and the sympathetics. And the presentation can be either a transient single episode due to a trigger. It can be persistent and recurrent. It can be very severe. And there are different ways to diagnose it. But as we think about this, many of the triggers are fairly obvious. And with treatment or prevention, no more episodes are going to occur. Keep in mind that 35% of people at some point in their life will have a vasovagal syncope. I mean, we should be ablating all these people. Consider that of the 35%, the median lifetime episodes are two. And the episodes cluster. So you may see a patient that has several episodes and then never has another episode again. Also keep in mind that the tilt table test may not identify the clinical event. You may see a cardio-inhibitory response on the tilt and a vasodepressor response in real life and vice versa. Consider this. Here is a retrospective analysis of over 2,000 consecutive tilt table tests. Out of that number, 52 had a cardio-inhibitory response. 149 had asystole. And some had prolonged asystole. But most people either had a vasodepressor response, a mixed response, or had a normal or inconclusive response. How do you say, based on these data, that first-line therapy should be a cardio-neuroablation? It just doesn't make any sense. In fact, conservative management, even with long asystole, is certainly possible. And I want to give you an example of a patient that I'd seen many years ago, a 20-year-old female with recurrent syncope, multiple, multiple episodes. The tilt table test showed relative greater cardio, but the event monitor showed asystole. Now, this is way back. And maybe in the present time, I would consider cardio-neuroablation, maybe. But I put a pacemaker in. And we can argue about the value of the pacemaker. Because in young people, we know that many people that have asystole also have a vasodepressor response. So we don't know if CNA is better than a pacemaker or not. It does something different. When you do CNA, you're changing the autonomic nervous system chronically. And in my opinion, vasovagal syncope is present in somebody with an intact and normal autonomic nervous system for the most part. You're taking that person who has an intact nervous system and now altering it and changing the autonomic input. And I'm not sure that's a good idea any better than a pacemaker. And I think that should be compared. Now, I also want to point this out. This is a patient, a young patient, who passed out on the tilt table test. Notice where the nurse here wrote out. Notice when the patient was laying flat, she became asystolic. Now, you would say, if you had a loop recorder in, that this patient has asystolic vasovagal syncope and deserves having CNA. But if you knew that two seconds before she passed out from a vasodepressor response, you may change your mind. Now, when you think about the autonomic balance, in my opinion, the vagus nerve is a very important nerve. It does a lot of things. And when you alter the autonomic nervous system, you're tilting things to the sympathetics, which could have all kinds of long-term consequences. In fact, the vagus has not only protective cardiovascular effects, but anti-inflammatory, anti-arrhythmic, and it provides efficient cardiovascular function. Also, when you do CNA, you change heart rate. The average heart rate goes up a little bit. And some people even get inappropriate sinus tachycardia. Now, as you can see on the bottom, it may be hard to read, Dr. Aksu has said that it is not yet known whether post-CNA state shares increased morbidity and mortality. And I agree with him completely. In fact, I agree with most everything he says. But that's not what we're discussing here today. That's not the debate. The debate is first-line therapy for vasovagal syncope. Keep in mind that there is a relationship between heart rate and mortality, and that when you alter the autonomic input and you change vagal activation, you're going to increase heart rate. We don't know if that's the reason that there's an increased mortality in people with faster heart rate, but it certainly could be a possibility. Now, you've seen this information from Dr. Aksu. This was just recently published. But I want to point out something. And he said this, actually, that when you look at patients with vasovagal syncope, that you need to consider specific patients who may be candidates for cardioneuroblastion. Yes, I agree. But there are many candidates who are not candidates. I mean, there are many people with vasovagal syncope who are certainly not candidates. And we're talking today about first-line therapy for vasovagal syncope. And I can never see the possibility in the future anytime that cardioneuroblastion will be the thing that we're going to be doing for all patients with vasovagal syncope. Now, you've seen these data from Dr. Aksu. And it is a small, randomized study. It's somewhat surprising that it's such a small study since vasovagal syncope is so common. How many people were excluded? Who was included? When we look at these data, it's really tremendous. But notice, there's no sham control. And we know that people with vasovagal syncope can certainly have a placebo effect. And when you compare using fluid and salt to a cardioneuroblastion, they're just two completely different things. Also, consider who was included in this trial. When you look at the patients, cardiodepression, tilt only with asystole, asystolic episodes of 17 seconds to 19 seconds on the tilt table test. How often do you see that? Well, certainly we see it. But we don't see it in every patient. And so every patient is not a candidate, necessarily, for this study. This is a very highly selective group of people that were in this study. Now, I also want to point out one other thing. We need reproducibility in our data. We can't look at one study, a small study, and say, this study is definitive and tells us what we need to do with our patients with vasovagal syncope. So consider this. Here's another study that was just published. This is 77 people that were under a CNA over five years at 22 hospitals in Spain. 37 of these people had CNA. And half of them were under the age of 50. Notice the heart rate increase was greater than 16 beats per minute after CNA in 43% of the patients. Also, I don't know. Also, consider the fact that where the lesions were delivered differed depending on the condition. So the green is for vasovagal syncope. Whether this is the right place to ablate or not is open for discussion. But notice this. These are the data. It's stunning, isn't it? Under the age of 50, look at the syncope-free survival after CNA. It's terrible. Look at the data for mixed syncope and cardio-inhibitory syncope free of syncope and recurrence. It's terrible. We need reproducibility in our data before we can then say CNA is the next step for patients with vasovagal syncope. So there are many questions that I have. How many people actually need this intervention? Is CNA actually superior to pacing? And for which patients? We're talking about select patients. How many people actually get a placebo effect from the procedure? And then what about the long-term risks of having a faster heart rate over a period of time for young people who are undergoing this procedure? The other issue is, based on the data I just showed you, does CNA really work? So there are plenty of controversies. And as I mentioned, Dr. Aksu is a friend of mine. And we have published together. And we've discussed controversies. And this was recently published. And basically, just to sum up, we have to identify the right patient. We have to know where to ablate. We have to verify with good controlled trials and prove those in trials that are not necessarily by people that are enthusiastic, but just for the overall population of patients and for us as clinicians to get the data on a large number of patients. So controlled trials are needed. We need to have a multi-centered design. We need long-term follow-up and adequate placebo control with good unbiased oversight. And so therefore, colleagues, cardioneuroablation should not be first-line therapy for young patients with vasovagal syncope. Thank you. So we are fortunate that Dr. Prashanth is here and agreed to also give a rebuttal for this topic. Is he ready? Are you ready? Yeah. OK. And for people who are not familiar with this, this is Dr. Prashanth. And he's going to give a rebuttal for this topic. And for people that don't know, Dr. Prashanth is the person that coined the term cardioneuroablation. Good morning. Thank you very much. I was invited yesterday in the afternoon by Professor Bryan to be present here. I would like to thank Professor Bryan for this opportunity. And cardioneuroablation is a word we created in the 90s to name a new procedure. That is the ablation of the vagus. Vagus is one of the most old nerves in our organism. Vagus was created before the skeleton, before muscles. So the vasovagal syncope was modified by nature during the last 600 millions of years. So we have very different types of neurocardiogenic syncope. Because these modifications, we have a primitive neurocardiogenic syncope, and we have a modern neurocardiogenic syncope. It's impossible to think that a test like TUT table test may solve, may diagnose all kinds of neurocardiogenic syncope. I have to pay attention about the possible origin for each patient. Here is the first publication about cardioneuroablation. We performed, we began this study in the 90s, and we published in 2005, because it was necessary to study the results. We found that the cardioneuroablation presented very good results in neurocardiogenic syncope, in functional AV blocking, in sinus node dysfunction, and atrial fibrillation. The first five patients we treated presented no recurrency after the cardioneuroablation. However, obviously, these patients were very well selected. And I agree with Professor Bryan. Cardioneuroablation is not the first therapy for young or for old patients. It's not the first therapy. We have to indicate the cardioneuroablation when we think indicate pacemaker. At the end of the trial, not at the beginning of the trial. Cardioneuroablation, we create the cardioneuroablation for exception, not for rule. For exception. It was absolutely clear in our first publication. It is not a rule. It's only for exceptions. So if the patient is treated clinically, and he is presenting or she is presenting problems, there is no possible solution for the clinical condition. Obviously, we will think about the pacemaker. In this case, cardioneuroablation may be inserted in the options for treatment. Cardioneuroablation is an excellent new option for patients and for physicians. But it is not the first line of therapy. The rationale of cardioneuroablation is very simple, because it is based on elimination of the visceral neuron. This visceral neuron is extremely old. It was created in viscera before the neural crest, before the brain, before the spine. It is extremely old. It presents very, very specific behavior. I have a lot of information. I have a lot of new information about it. But unfortunately, I was not invited to tell this information to all of you. This type of neuron is very specific. This neuron was created before the ganglia, before the ganglia, that now we are trying to ablate. There is, obviously, at the first trial, we found very good results about cardioneuroablation. But it is possible to improve the results. It is possible to improve the methods. How is it possible to get an improvement of the method? Doing the controlled cardioneuroablation, many trials that were presented for Professor Bryan, by Professor Bryan or Axel, were performed without control. Do you think it's possible to treat diabetes without measuring the glycemia? Is it possible? Is it better to treat diabetes measuring the glycemia? Nowadays, we are doing, not me, but we are doing cardioneuroablation without control. Why? The neurologist works with neurostimulators. We need to work with neurostimulator. It's easy. We have to do the controlled cardioneuroablation. The empirical cardioneuroablation may present many different results. The trial that was performed and published by Barriolops that was presented by Professor Bryan was performed without control. It is kind of treating diabetes without measuring the glycemia. It is similar to treating hypertension without measuring blood pressure. It is not the right way. It is easy to get a rational, a control of the procedure. And this possibility is very easy. We developed, we published in 2015, the extracardiac valve stimulation. That is very easy to get. And in this case, we will see two situations. The first tracing is vagal stimulation before cardioneuroablation. The second tracing is the vagal stimulation after cardioneuroablation. Obviously, the second situation represents a good result of the method. And here, we can see the comparison. In blue, patients that were submitted to cardioneuroablation with vagal control. And in red, cardioneuroablation empirical without control. Obviously, cardioneuroablation controlled presented bad results. And here, I would like to show you a very interesting result. In the red dotted line, we have the cardioneuroablation for neurocardiogenic syncope. And we found that the results are very good and the same for patients, young and for old patients, the same. If the patient has less 40 years or more than 40 years, the result is the same. And the result is very good. We have, nowadays, several studies showing very good results. But many of these studies are performed without control. And with short time, we needed to take care about these results. And at the end, I would like to say to you, why perform cardioneuroablation? Because it is a curative approach. It targets to neutralize the vagal reflex, rather than merely pacing over the poses. The cardioneuroablation makes possible to treat the reflex, not the consequences of the reflex. Why perform cardioneuroablation? Because of high efficacy. More than 80% long-term freedom from syncope. It allows us to have a device-free treatment. It presents excellent safety profile with very low complications. The sinus tachycardia occurs in less than 10% of patients and is very well treated clinically and temporarily. It's not necessary to treat the whole life. Gains of quality of life in the trial that was performed by Kulakowski and Roman, they found a very important improvement of the quality of life. And the guideline momentum in 2024, Ida and Lars presented a consensus recommending the cardioneuroablation as a good option for treating neurocardiogenic syncope. Thank you very much. Thank you, Dr. Pochon. If you would like to stay on the table. You can go around, sir. Thank you, Dr. Pochon. I'm going to have Dr. Olshansky come to stage for his counterpunch. And after that, we're going to get interesting with some cases. Yeah, Dr. Olshansky. I was going to, without a counterpunch, exactly, I wanted to at least show an example of a case. Well, I will say this, that there's, there are obviously two sides. And there are publications now about trying to figure out who would be a good candidate for cardioneuroablation. And actually, Dr. Shelton and Satish Raj, Dr. Raj, have come up with these thoughts about identifying patient by a physician who is expert in vasovagal syncope, recurrent frequent episodes, episode recently that failed conservative management, and trials of medication, and that the outcomes are collected systematically. And to me, that makes a lot of sense. So we need to get good information. And I think we would all agree with that. I want to show you a case. This goes back a long ways. And maybe we can talk about this. This is a woman who had multiple episodes of passing out. She came to my clinic. And she did this in the clinic. This goes back 15 plus years. And I didn't know what to do. So I put a pacemaker in her. She never passed out again. 10 years later, when the pacemaker battery wore out, she came back in. She now was married, had three kids. And she was doing fine, never passed out again. I said, tongue in cheek, maybe we don't need to put a pacemaker in. And she looked at me like I was out of my mind. And I put an ex-pacemaker in. She's done fine. Now the question is, and maybe we can talk about discussion, would this be a better candidate for now, a cardioneuroablation or a pacemaker? And I think this is one of the key issues we may have to think about. But I'll just leave it at that. Thank you. All right. So I think this is the cliffhanger right here. When you see patients like this, do you, and I'm going to open this to Dr. Westerman first, what do you think about these young patients, especially that Dr. Olshansky mentioned, sometimes these episodes cluster. And they may not have future episodes. When you have your discussions, do you tell them early, like, do you want to wait? Do you think they're good candidates for CNA or permanent pacemaker, knowing that they will have these leads permanently, probably? Well, these were just such amazing talks by really leaders in this field. So I don't think putting pacemakers in young patients is ideal. We do have the option of leadless pacemakers. And so that does present another option that eliminates some of the risks of transvenous system. But I think when patients come in, one of the tough things is really talking to them about the nature of syncope. People want things to be fixed. And so having the conversation of this could cluster, this could get better over time, setting expectations that you might not be able to eliminate all episodes of syncope, that it's not necessarily dangerous, all those things are really important. And if you had Dr. Olshansky in front of you giving the talk on all the potential negatives of cardioneuroablation, then I think when somebody is informed in that way, they might be able to say, OK, well, let's see how I can do with these measures. But a lot of times, people come in, they want to fix, it seems wrong, and so you're ending up offering them options of intervention that we don't know the outcomes in the long term. I think, to Dr. Pichon, how he put it, if you're considering pacemaker, you should consider cardioneuroablation. So if somebody is having trauma from syncope, they can't work because of their syncope, I think those are patients that I would say, we have this other option. And I don't know what would be preferred, and I'd love to hear from other people, a leadless system versus cardioneuroablation, with us not knowing the long-term effects of cardioneuroablation on young people. Great points. I would like to respond to Dr. Pichon. This case is very interesting, but the first step for us is not cardioneuroablation, is not pacemaker, is the study, the patient. So this patient, we have to see, is presenting, she is presenting a sinus sick syndrome, or is she presenting a hypervagotomy? Or both of them, a sick sinus plus hypertonic of the vagus. So for us, the first step is atropine test. It is extremely important. We will take any option, any way, after to see the atropine test. After to evaluate if there is intrinsic sinus nodal disease, extrinsic sinus nodal disease, or dysfunction, or both of them. So my answer is, the study the patient, the first is the atropine test. So I do some cardioneuroablations, but I'm very careful about this because two major concerns. I think everybody should know that. The first is, I could only find two studies that actually showed a control arm. One is from Dr. Oksu's study. That's an observational study. The other one is from that randomized trial from Dr. Piotrowski's group. Both control arms means you don't do anything. The patient, 50% of the patients, would not have any syncope. When you ablate the neurons, 90% of patients do not have syncope. So if we have a SHAM controlled study, that takes away the placebo effect, where do you think the curve will be? It has to be between the 50% and 90%, right? Is that going to be close to the 90%? Or is that going to be halfway? We don't know. So since we don't know, I do this very carefully. I'll tell you why I do it carefully. The first time I did any animal study on the autonomics was year 2000. The first time I put a burn to the GP to treat AFib was year 2003. After 25 years, I still don't know what GP do. Let me give you two examples. There is a GP. It's always included in the lesion set of the cardio-neuroablation. It's called SVC Aorta GP. That's the one that Doug Zipes' group in 1992 found out that that's the gateway GP. That means if you ablate that GP, you stimulate the vagus nerve. You don't see any heart rate slowing anymore. So that means vagus nerve probably has to go through that aorta. So we stimulated that GP. We only get SVC firing. So that can explain why some patients have SVC firing. Others don't. So we ablated the GP in animals. Guess what? The animals get more AF. Some of the animals actually got persistent AFib. So that GP we think is causing AFib and actually is also protective. The second example is the GP in animals. And actually it's also protective. The second example is the four GPs around the pulmonary veins. That's the ones, no, we, we, we, we, our PVI lesion with RF or cryo will transect. So in open heart surgery patient, we ablated the four GP. That was randomized to trial. It reduced the post-op AFib by 60% in patients undergoing coronary artery bypass. It didn't do anything in patients with aortic valve replacement. It actually increased the post-op AFib in mitral valve regurgitation patient. So the GPs are doing different things in different patients. We don't even know what they do. The same ablation in open heart surgery produces three different results because it looks like in MR patient, GP is protective. So we ablated the GP, they got more AF, right? So if we put a cluster of burn at the atrium to target the GP, we produce two things. One is a patch of scar. And when we burn the neural tissue, the neural tissue will regenerate. We're not just ablating neurons. There are lots of autonomic nerves around. So they will regenerate. Regenerate is disorderly regeneration. It's called the sprouting. Sprouting will cause more dispersion of the refractory period. Now we got seven, eight patches of scars with dispersion of refractory period around it. Are we setting those patients up for future AFib? These are very young patients. So if you ask me, Sonny Poh, if you have a daughter who had a terrible vasovagal syncope, her life is turned upside down, do you have any problem to send her for cardioneural ablation? I said, I will send her to get a cardioneural ablation if everything else fails. But I will tell the doctor, please only do the two GPs, close the sinus node and AV node, and wait. Because all the signs we get from GP are coming from AFib. AFib and a vasovagal syncope are completely different animals. Even today, if I burn the GP, I get a vagal response. I would make a slide because it's so rare. But if you do the GP for vasovagal syncope, you get a long vagal response all the time, or suddenly the heart rate goes up. So they are completely different animals, vasovagal syncope and AF. Before we know how much placebo effect we're looking at, let's be conservative. Don't ablate too many GPs. We don't know what we do to the patients. Let's be conservative. I have no objection to do the GP ablation for those people. But don't do this excessive ablation. Can I mention something? So I have the exact same approach to my patients. I think that's an excellent take. And I ensure that I have a link monitor implanted in every single patient to ensure that I follow them before and even after the ablation. I always tell them also, once they've exhausted everything, and although it says flugocortisone and mitadrine, there's other newer type of, adamoxetine is a new one, stratera is a new drug that's being looked at by Dr. Sheldon. And these are other types of medications I think are going to be useful for this patient population. But if they've exhausted those, certainly even then the approach for me is not to go, and I know, sorry Dr. Pichon, maybe I'm a little bit more conservative than going full vagal denervation. I start a little bit, I always say I can go back in and do more ablation. My first case was done about three and a half years ago in a young boy, 23 years old, who had horrible syncope. They essentially referred him for a leadless pacemaker. And he did, I did his first ablation and I did it exactly the way that was mentioned and both sides by atrial. And then six months later, he had another syncope and it was clear on his ILR that it was cardio-inhibitory. So I went back in and I just touched up the SVC aortic GP here. And now it's been two and a half years, three years, I just took out his ILR. He's been completely syncope-free. So these certain patients, I think, just taking a conservative approach, you don't need to do a full ablation the first time around and then kind of deciding where to go if they have further symptoms. I think that's a really good approach to cardioneuroablation. Let's not forget vagal activity is anti-inflammatory. Almost every cardiovascular disease is centered around inflammation. So if we take out too much of the vagal input, what's going to happen to those patients when 10, 20 years from now? We're gonna get a myocardial infarction or some other disease, we don't know. So let's be more conservative. And I agree, we can always do it again like AF, but let's be a little bit more conservative until we have the data. We have Dr. Aksu on video chat here. So I don't know if it'll work, but we'll try. Dr. Aksu. Yes, I can hear you very well. Can you hear? Can you hear me? I can hear you very well. Did you have a comment, sir? So can you hear me now? Yes. So I totally agree with Brian about that. CNA is an interventional therapy and there is some complication with that. I would like to mention that we have some patients with recurrent or traumatic syncope despite lifestyle modification, education, and of course, physical counter-pressure maneuver. So we should do something for this patient because the patient and their families feel very uncomfortable about this recurrent syncope episode. So I think that if you decide to perform some interventional therapy, then CNA should be the first option and choice before cardiac pacemaker implantation because we still know that there is no serious complications after cardioneural ablation, but of course, there are too many, there are need too many interventional therapies if we decide cardiac pacemaker implantation. This is our point. Thank you, sir. So I wanted to bring this up too because I think it's something that I've not seen a lot about in literature. And I think to your point, what's important from what Dr. Josa, Dr. Olshansky, Dr. Westman have been saying is, I think it's shared decision-making where for pacing, things like leadless pacemakers can come in play, especially when a patient is right in front of you, had like a 28-second pause, traumatic syncope, and then there's the other hand that, okay, you do a good CNA, you have good follow-up. Now, I had this interesting patient. She was a 20-year-old who had syncope, and we did CNA, followed her. Her resting heart rate then was like 40, but she did have like two episodes of syncope, did CNA, and she was fine. Resting heart rate went up to 60s. Now, after like six to 12 months, the resting heart rate went down to 50s, and she felt a little fatigue, but no more syncope. And then one day, she went for a competition in Utah, and she said, I felt great for the first time in my life because my heart rate was a little higher, and then I started reading into hyperbaric hypoxia causing elevated heart rates. What do you have to say about elevations and people that have vis-a-vis gal syncope? Let to do some comments. And after PVI, there is denervation. We have found 40% denervation, and even many patients present 100% of denervation. This denervation is the clue for the sussex of atrial fibrillation ablation. So obviously, we have to think about denervation, but we have to include the AFI ablation because it causes denervation. So if we are worried about denervation in the cardiac nerve ablation, we have to be worried also the denervation during AFI ablation. We know that if the renervation goes up, we have recurrences. So in our experience, in our lab, the stimulation of the vagus causes atrial fibrillation. The ablation of the vagus makes the atrium extremely stable. The CASEL study have been showing that ablation of the atrial fibrillation with denervation presented a 30% better survivor curve, 30% less mortality. So obviously, denervation must be studied. About the possibility of a placebo effect, if we observe the patients and there is a reduction of high rate variability, obviously, the procedure was not only placebo. The reduction of high rate variability shows that the procedure was really causing the modification of the physiology. And many patients after the cardiac nerve ablation, most of them showed this kind of situation, better improvement of the exercise and better quality of life. Thank you, sir. We have time for one or two questions. If you wouldn't mind introducing yourself and asking your question through the mic. Yeah, Jim Hansen, Copenhagen. Great session. And I think we can agree that there can be indication for cardiac nerve ablation. So just a couple of questions to the procedure, maybe for the panel. What's your standpoint on right atrial versus biatrial ablation in the first procedure? And do you do anything for mapping the GPs or just go on an anatomical approach? Maybe Dr. Po? Oh, I'm sorry. The question was, yeah. There was a study just published, biatrial and the left atrium appears to be good. I go by the randomized trial. The one published three years ago was the randomized trial from the Polish group. They only did the two GPs, the one close to the sinus, so the AV node from both RA and LA. That's what I would do based on the randomized trial. And then this trial comes up saying, biatrial and the left atrium are the same. But if I do it, I will still do the two GPs from the right and left atrium. Thank you. So we only have a very short amount of time. I'll finish Dr. Olshansky and then Dr. Otto from Turkey. Dr. Olshansky, you asked the question for your patient. In your long experience seeing a lot of patients with syncope, if you're considering CNA versus pacemaker, how many pacemakers have you implanted in your patients with syncope? Extremely few. I mean, as far as I know. I mean, I think some of the patients we call having sinus node dysfunction, older patients likely have some autonomic issues. I don't know how to characterize that, but for younger patients, extremely few, maybe three, four handful. And I just wanna get back to the case that you presented just real quick. We were dealing with a brake and an accelerator when we talked about sympathetic and parasympathetic. It would be perfect if we could get just the right speed, but unfortunately we have not figured out the way to get perfect heart rate changes under all circumstances. Thank you, Dr. Olshansky. And we'll finish off, since this is a joint session with Turkey, Dr. Otto, would that be okay? I'm sorry, sir. A quick question. Go ahead. Yeah, quick question. On the issue of leadless pacemakers, are you talking about dual chamber, single chamber? Because according to my own understanding, VBI pacemaker can actually provoke vasovagal syncope. Would you like to take that? Yeah. Very good question. And think about it. Now we have the option of atrial pacing now with leadless devices, but I still think that before putting in a device, I would definitely proceed with cardioneural ablation. Okay, Dr. Otto. Yeah, very quick. First of all, I would like to thank HRS program committee for this joint session, giving this opportunity to the Heart and Health Foundation of Turkey. I would like to express my concerns about the leadless pacemaker. Well, my threshold is really high for implanting pacemakers in young vasovagal syncope patients. But at the same time, my threshold is also high for, or would also be high for the leadless pacemakers because it's true, yes, you have some advantages without having the leads and pockets, et cetera, but still you are implanting a foreign body to the body. And also we don't know the long-term problems of leadless pacemakers. So again, my threshold is high for any foreign bodies to the body. Thank you very much. Thank you, Dr. Otto. This concludes the session. Thank you very much for attending.

cardio-neuroablation

vasovagal syncope

young patients

Heart Rhythm Society

pacemakers

autonomic function

syncope-free survival

conservative management

shared decision-making

individualized treatment