Hi everyone, I'm Eduardo Saad from Brazil, and on behalf of the Global Relations Committee and the Heart Rhythm Society, I'm pleased to welcome everyone to this live webinar called Global Relations Hot Topics, Where Are We Heading? We have a very exciting program jointly with the World Society of Arrhythmias. We're going to have three speakers speaking on three very important topics today. We're going to have Dr. Andrea Natale talking about BFA, Dr. Tolga Axel talking about Cardio Neuroablation, and Dr. Fogal Vijayaraman talking about conduction system pacing for Resynchronization Therapies. We have also a wonderful panel for discussion. We have four well-renowned experts in the field, so looking forward to an exciting discussion with all of you. During our discussion, we actually want you to interact with us, and if you can use the question and answer taskbar on your Zoom to send your questions, we'll be more than happy to answer that and interact. Without any further delays, I will ask my co-chair, Professor Ali Otto, on behalf of the World Society of Arrhythmias, to introduce himself and also his comments. Thank you, Dr. Saad. Good morning, good afternoon, good evening, everyone. Welcome to this joint educational activity of Heart Atom Society and World Society of Arrhythmias. On behalf of World Society of Arrhythmias, as the president of World Society of Arrhythmias, I would like to extend first my sincere thanks to the Heart Atom Society for this joint educational activity. Indeed, this session has been really realized by the great efforts of Dr. Tolga Aksu and Dr. Eduardo Saad. Therefore, again, my sincere thanks go to those colleagues, as well as to the Global Relations Committee of HRS, and Sarah and her team. Well, as Dr. Saad mentioned, we have a really esteemed group of panelists here with us for this session, Dr. Weiyan Huang from China, from the First Affiliated Hospital of Wenzhou Medical University, China, and Cheryl Teres from Lausanne University, Switzerland, and Tom Dearing from Piedmont Medical Center, Atlanta, and he is also the board member of World Society of Arrhythmias. Well, now, Eduardo, please introduce the speaker. OK, so it's my pleasure to introduce Dr. Andrea Natale from the Texas Cardiac Arrhythmia Institute in Austin, Texas. Dr. Natale is a well-renowned world leader, pioneer in many of the new technologies that we use today. So Dr. Natale is going to talk about PFA and AF. If you're ready for prime time. Thank you very much, Andrea, for being with us. Really a pleasure hearing from you. Thank you, Eduardo and Ali, let me share. So I was asked to discuss PFA the way we are now and if it's ready for prime time. So I think it's important to remind people that for the last 20, 25 years, we dealt with this issue by using thermal energy. And PFA has brought to our field a change because for is a non-thermal energy that causes tissue death by apoptosis and also as a better tissue selectivity so that we had to worry less about collateral damage, what we have called collateral damage, which includes. So we sort of this was the premise that has been verified before the technology entered clinical use in animal model confirming that PFA is less likely to cause pulmonary vein stenosis, esophageal fistula, neuroparalysis. But to review the data now that are available in the clinical use, which are very important. So let's start with a very small study performed by the group in Bordeaux where they look with MRI enhancement comparing PFA, radiofrequency and cryoablation. And what they show is that with both thermal energy, cryo and radiofrequency, they frequently see esophageal enhancement, which is not present with PFA. So this is sort of some really hard data confirming that the field of PFA has evolved rapidly right now, both in US and Europe. There are four devices that are approved and you see how the volume has rapidly increased. This is a sort of a is a testament to how this procedure very quickly has become the main way because of many reasons we review. This is some data with the most use because it was one of the first that was approved both in Europe and in US is the Farapulse. Actually, those days are more than 7000 patient was back in August, September. We're now above 100000 cases performed worldwide. So huge number. And what we're going to see in the next couple of years is an array of different device that are going to allow us to choose what is best for the patient on the table and will further increase the success and efficacy of this technology. And we're going to see a variety of single shot and a variety of larger footprint or single point catheter. So we'll have an array of system. But let's review the data from the clinical trial from the registry, which are really important to sort of define the role of this approach. So this is one of the first study that came out with the Pulse-AF Pivotal with the Pulse-Lex system. And what you see here is a sort of the first evidence of a procedure that is certainly more efficient success rate, really in the order of what we've seen with RF. This is not necessarily the important benefit of this technology. And this is really the first evidence of what I mentioned before, the three complication typical of thermal energy do not happen with the Pulse-Field Ablation. And other things that is important to realize is that we start and I'll show some other study, we start looking at the outcome in a different way, not with the traditional 30 second, but with the AFib burden and clearly patient with the AFib burden less than 0.1 percent of the one that are less likely to require repeat ablation, cardioversion, and they are less likely to utilize a care resources, a follow up. So that's a kind of a new market. And I'll show you why it's important. Second study, this is the first randomized study with a PFAS versus thermal energy, clearly show a more efficient workflow with a shorter procedure, despite the fact that all the operator involved in the study, they just had a couple of cases of experience with PFA, whereas we all had the last 15 to 20 years experience with thermal energy. So despite that, the workflow was more efficient with PFA, success rate is the same. But, you know, again, same success rate with something we just start using versus what we've used in the last 15, 20 years. So pretty good results. Complication rate, again, when you look at the typical complication of thermal energy, you see 0, 0, 0. And when you look at pulmonary vein narrowing, although there was no case of severe stenosis, but the CT scan, a follow up show virtually no change post PFA, whereas they show a 12 percent reduction in diameter after thermal energy, sort of reinforcing the benefit of this technology in reducing the risk of pulmonary vein stenosis. Again, when we look at, although the study, when you look at success rate based on the 30 second definition was the same, when they look at the success rate based on the burden, actually PFA had a more significant percentage of patients with a burden less than 0.1 percent. And that's why I showed the slide before with the path select, because this is the group where we expect less utilisation of health care resources, less redo, less cardioversion. So actually PFA, looking at the data in terms of burden, was a significantly superior to thermal energy with the impact in quality of life and again, impact on what you see here, redo ablation, cardioversion, hospitalisation as compared to the thermal energy group. And here is the sort of the full core results. And it's kind of to again, to summarise this, so this is an important finding and I think in the future we'll see more data be analysed in this way. Also, this is a recent study, it was presented at a late breaking trial, the European R meeting, comparing cryo to pulse field ablation, showing a reduced time and a more predictable workflow with PFA. So again, more data in support of this approach. Result with another system, this is the body pulse, they show an overall success rate, primary efficacy about 76 percent at 12 months. And the clinical success means freedom from any symptomatic arrhythmia above 90 percent. So really good result also with this system. And again, in terms of adverse event, 2.9 percent, so low rate without any occurrence again to PV stenosis, esophageal fistula and friendly nerve paralysis. Let's look at some regions, the manifest is the one that is most popular. And recently in Nature Medicine, they published a 17,000 patient follow up from 108 centres. So really, this is a reflection of worldwide experience, worldwide clinical practice experience. And when you see, let's look quickly at the complication. When you look at the complication that are typical of what we're worried with thermal energy, you see esophageal event at zero, PV stenosis at zero, friendly nerve paralysis at zero. There is some transient friendly nerve paralysis that result quickly, but in the order of 0.006 percent. There are a couple of things that we'll talk a little bit about that are typical of PFA, which is coronary spasm and hemolysis. Overall, you know, this has become a very safe procedure. And this is again, when you look at all the sites, the same trend. So really, again, more data about this, the huge benefit in safety of this approach. Let's look at the last study. This is a large single shot, is a mesh called Afera. This is also first randomized study in persistent comparing Afera with a standard of care, which is RF with contact force, published in Nature Medicine and showing equivalent, although you see the curve are separate, and actually the study means superiority for two patients. So really, this is a incredible result in a persistent group. So good outcome, a better workflow, and again, no evidence of the bad complication that we worry about with thermal energy. So more evidence. Something that we have seen, I'll show you some preliminary data, is something that may be less common in Europe, but is the standard in US. Use of eyes to assess contact when we perform most of the PFA product right now do not have contact force or contact information. So contact is important even with PFA and we have used eyes to assess contact. So these are a few examples where you see the eyes picture and how we advance the category to achieve contact with the area of interest. And I'll show quickly some preliminary data that we collect together with the other three groups, showing that differently from what people have reported without eyes with a reconnection rate in the order of 30%, if you use eyes to assess contact, the reconnection rate in the redo is less than 5%. So clearly we can do better with this technology the way it is right now by using imaging tool. Posterior wall also is an area where we struggle with thermal energy, certainly with cryo, but also with RF, and some preliminary data showing really nearly 100% persistent isolation in this small study by Vivek Reddy group. And this is a study that we perform that was published recently in Jackie P, where we did endo-AP remap, a follow-up, in a small number of patients. Obviously, in most of these patients, the epicardia was done for a, because of ablational adrearythmia in the ventricle. And we show in these four cases, persistent, durable, endo-epicardial isolation of the posterior wall with PFA. So very important data. And in this series, we compare to an RF group that clearly did not show the same benefit. PFA can also be used for additional site near UCDSVC, where we position a catheter based on intracardiac echoimaging at the lower border of the pulmonary artery. And by doing so, in this study that is impressed in Jackie P of 600 patients, we show, if you use just a basket modality, we did not have any evidence of renal paralysis or sinus node dysfunction. So important data. Coronary sinus also can be affected. Although we need the follow-up data by doing endocardial ablation in the bottom part of the posterior wall, you see here that the recording before and after. But also in some patients, we can advance the system in the coronary surface big enough. And certainly with that approach, we've seen good results in thermochronic isolation. Also the left atrial appendage, which is a target in some patients, especially long-standing persistent, can be isolated acutely very easily, much easier than with the RF, but we need more data about the best workflow for persistent isolation. And this is some preliminary data on the mitral isthmus. Acute isthmus bloss can be achieved in most patients. I think we need some more data on the chronic success. So clearly this is an approach that even with a current device that are going to evolve in the future, show the flexibility in the area that we can address. Let's talk a little bit about complication and then we'll conclude. So I mentioned that a typical complication adverse event with PFA is coronary artery spasm. This is a study from Vivek Reddy. So what I want to mention is that in this series, they saw the spasm because they did coronary angiogram at the same time, because actually there was no clinical event of ST elevation and the spasm could be prevented by a large bolus of nitroglycerin. I have to say that in Austin, we now perform more than 2,500 cases and we haven't had a single case of ST elevation, despite probably our group does more ablation than most people. But again, there is a solution for coronary spasm for those that are worried about, which is a pre-administration of a large bolus of nitroglycerin whenever you think you're ablating close to a coronary artery. The other one is a potential benefit of PFA is prevention of left atrial stiff syndrome. If you do extensive ablation, this is a study we published in Jackie P comparing patients that came to us after two failed RF with already evidence of stiffening of the left atrium and pulmonary hypertension. And when ablation, the two procedures was performed with PFA, there was no change in pulmonary artery pressure, where there was a further increase in pulmonary artery pressure with the repeat RF energy. So I think this is another signal so that PFA can be safer in patients where we need to be more aggressive with the ablation approach. And this is a confirmation of this data from a group in Israel that show by looking at left atrial strain that with PFA, there is no chronic impact on the left atrial strain. So another evidence supporting the fact that we have to worry less about stiffening of the left atrium. Hemolysis is a problem with PFA. And I think we have now data that can be more pronounced with certain device. This is the initial report that was published in Jackie P showing that when we deliver between 70 and more than 70, 80 application, the risk is real and that can result in kidney injuries. Also, it's important to recognize that if you want to completely prevent kidney injuries, the best time to do so is to give fluid before the procedure, not once you reach your 70 or 80 application because that is too late. And also in this series that is coming up again in Jackie P, we show that the inpatient with pre-existing kidney problem, even a small number of application in 40, 50 can be enough to cause kidney injury. So this is something we need to consider, but can be completely prevented with the pre-procedure hydration. So this is a good piece of information. The last thing I want to affect, we all talk about the cost, this is important because PFA is more expensive. In this single centre study, the operator showed that PFA is more expensive than RF and Cryo. However, this is a study from England, however, from the same country, when they look at the NHS data, the conclusion is that PFA is actually cheaper because it results in less redo and less complications that obviously create costs to manage them. This is from the NHS database. Although the single centre experience in the UK shows higher costs for PFA, but when you look at the global picture and the impact on redo and the complication, actually the data show that actually this is a cost effective procedure. So I saw here saying that PFA is safe and effective in creating durable transmural lesion in the post-pulmonary vein, post-seral wall. Beside this area, can be used in other regions like mitralismus, CS, left atrial pangea and SVC. Unlike RF, PFA does not work in pre-existing pulmonary hypertension, does not cause PV stenosis, frontal nerve paralysis and esophageal fistula. AKI is real but can be prevented with pre-procedure plan fluid infusion. The higher catheter cost is real, but the need for repeat ablation and management of complications result in lower overall costs than thermal ablation. So my conclusion is that yes, PFA is very ready for prime time. Thank you very much. Thank you very much, Andrea. That was a wonderful presentation. So I think we have a lot to talk about. So I'm going to open to our panelists. If anyone wants to make comments or ask Andrea questions so we can interact, please feel free to do so. I guess Eduardo, I'll get it started. First of all, Andrea, I want to thank you for that very detailed and superb presentation, putting this into perspective. And I too agree that PFA is ready for prime time. But remember, prime time began from an old television concept when there were a small number of stations. And it meant that it was after dinner when the majority of people watching an important show. But there would also be competition. So is there still a need for other approaches? And I'd like to look at your overall efficacy, safety, efficiency, and fiscal considerations in just about a minute. I think in efficacy, as Andrea nicely said, in small series and registries, in a meta-analysis, it was equal or better looking at the standard approaches. I do think in ADVIT, we know that it was neutral. But we also know from the updated late breaker that Vivek presented, with the burden, even at a very low burden, it looked more efficacious. So I agree with you that it's probably neutral to slightly positive with efficacy. I advance the positivity, but I think we do need a few more studies to confirm that. In terms of safety, I think overall, especially for those PFA–I mean those ablation-related situations like pulmonary vein stenosis, esophageal spasm, phrenic nerve paralysis, there's clearly, I think, strong evidence that it is a safer technique. For the others, the same vascular and other complications exist at the same level. So we've got to look at it that way. And I think the one caveat that's out there, though, is that if you look at ADVIT and you look at others, for those who are very experienced with traditional thermal ablation techniques, their complication rates for even those things that are problematic like pulmonary vein stenosis are very low and equal. So I think a lot of it depends on your experience, your expertise. Someone like Andrea can do it. Maybe the average person can't. But I think in terms of safety, we have more strong evidence than we do of efficacy. I think in terms of efficiency, you're right. It's clearly shorter procedure times. You know, an hour or less per case is clearly where we need to go. In ADVIT, it was about 105 minutes. I think in the manifest registry, it was down to just a couple minutes over an hour. And we're going to continue to improve that. But if you look at the differential, for example, in ADVIT, it was a little under 20 minutes, 17.3. And, you know, is that going to allow you to do more cases or just get staff home earlier and save costs? I think efficacy—I mean, efficiency is there. We need to look at real-world data and make sure that that manifests. So I think on those three points, it's there. I loved your last points, too, on cost-effectiveness, Andrea, looking at the big picture, not just the small picture, because the catheters are more expensive. Hopefully that will change with, you know, better codes allowing for more reimbursement and competition allowing for lowering prices. But I still think at this point, we've got to be careful with patient selection. You know, if you do an additional RF ablation for a CTI or something else in another area, you're going to have more costs. So I think at this point for primetime, it's for, in my opinion, more selected patients who are, you know, in that scenario where they have good LV function, more paroxysmal, for the majority of sites that don't have huge experience. And, you know, when you do add those additional ablation catheters, the cost does come up. But I think you're right. We've got to look at the overall recurrence rate and use of resources totally, not just in the case. So I would say on an efficacy basis, I think it's slightly positive. I think we need more data. Safety, I think it's very strong. Efficiency, it is more efficient, but I think we need real-world data. And fiscal components, I think we need to be a little bit cautious and look at it that way. So, Eduardo, thank you for allowing me to make a few comments. I'd like to hear what the rest of my panel contributors think. I have to say, Tom, that in terms of efficiency, I mean, we went through this issue with the cost with our, you know, administrator at the beginning, but very quickly they realized that our volume within, you know, a month or two has increased by 35, 40%. So the extra volume sort of immediately offset the extra cost. And I think now that we have more device approved, the cost probably will start dropping down because they're going to compete with each other. I agree with you, we have to be careful not to use additional technology, but I think most what we're going to see probably soon is an array of tools that allow us to use with a single catheter, even to do the majorismus and the righteous realism. So it's not going to be less of a problem, the risk of having to use another catheter as the technology evolve. And also company to compete are going to offer package, you know, where you have a set of tools to do the entire thing. So I think we're moving in the right direction, but already the data, I think even we've seen it in our own practice, they really show that overall this is the way the future. I think you're absolutely right, Andre. And I think the way you look at it, looking at the broad picture, not just the cost of the catheter, but the total utilization and engaging administrators is important. I think it would be great if you and your team could put together that fiscal data so that it can be out there in the literature, because that will help the rest of us be able to go to our administrators and make a strong case that would be hopefully effective in moving this forward. And I agree with you, new catheters that allow us to, you know, utilize one catheter for everything you need to do is key. Thanks, Andrea. Thank you. So, Cheryl, they wanted to give us an European perspective, what are your thoughts? And I was particularly impressed when Andrea mentioned that the reconnection rate when using ice versus non-ice. I am very much biased because I, you know, I use ice on the left atrium, you know, every single case. And I realized the importance of the contact with that. Can you give us an European perspective on what's your thoughts on that? Well, we can't really generalize Europe because there are some places in Europe where ice is already implemented. Like I know in Italy, public hospitals can really afford it. But like here in the Swiss system and in other systems, it's really difficult in terms of cost. So as you said, we don't have widespread use of ice. Of course, we can use it for some papillary muscle or specific settings. But yeah, from the administrative point of view, we don't really have this access. And for us, it's really important to have that feedback on contact. And I think maybe some of the Farople's competitors are going to be more implanted here because of that, because we can use just one tool to map and ablate and we can have this feedback on contact without needing another technology that makes it more costly. And also, I wanted to comment on the fact that it's true that you're faster and that you can do more cases, but not all hospitals can accommodate more patients. Like here, I work in the public system on a very big university hospital with a transplant program where patients stay in hospital for one month. So we are constantly working under a very tight bed occupation. And we already told our administrators that we can do three more AFib ablations per day. And they said, that's very good, but they can't stay in hospital. And for the problem of reimbursement, we can't do same day discharge. So yeah, I guess we are facing different challenges, right? Absolutely. Thank you. Henry, do you want to make any comments on your side? Yeah, I thought it was a great presentation. Seeing all the data that we have now in the real world makes us more confident in terms of the safety. With AFib ablation, patient access is an issue. And I do think in the big picture, being able to do more AFib ablations and having there be durability that's at least equivalent to other modalities is important. I'm looking forward to the new technologies that are coming, although most of this data is done with one catheter and showing that it can be very successful, very different anatomic sites, kind of like with cryoglobin. And so we see that we can already do a lot with this tool. Hemolysis may be an issue or may be a limitation, but if you plan your case, I think knowing what lesion set where your plan is, you know, you can do it and it's possible with different catheters, focal catheters that don't have as many electrodes. Hemolysis may not be as much of an issue and perhaps might even been useful for lines and perhaps even in the ventricle. So it's a very interesting space. There will also be single shots. And I guess the question is with single shot catheters, you may not have the same versatility. So hopefully the pricing will sort of equilibrate. And so we'll see if it can replace RF. Okay. One last question, if I can, for Andrea. Do we have evidence? I think you showed just a couple of cases, but do we have evidence of transmorality and durability for PFA, which I think this will be very important. And how important do you think that this contact issue may be in terms of achieving those goals? So I think in the posterior, the pulmonary vein posterior wall, certainly much easier. I mean, if you look at the, even in the latest couple of three years, 75% recombination rate in the posterior wall, we will not see that with PFA. With PFA, there will be some in certain patient. I think that's going to change with the next generational tool that are going to make a little better visual. I think already with the affair system, it could, but certainly even with the existing system is very unusual to see reconnection in the posterior wall and the pulmonary vein. For the other area, I think we need better because I show the CS, the appendage, those are the area where we struggle with the existing technology. And I think those are area where I think we need to wait for the next generation to have a first time high success rate. We get very easy acute success, but high rate of reconnection in the appendage in the CS, but PV posterior wall, I think, and SVC also, I think are going to be much easier for everybody differently than what we've seen so far with the ref. Could I have one question? Yes. Andrea, excellent presentation. Well, it's always a question, the ventricles for PFA, what is your visionary on this? I think it's going to replace it. So beyond what we have today, that certainly is not a fair, it's some preliminary experimental model data showing that can reach about nine millimeter depth with multiple application. Some of the technology that is coming out that really designed for ventricular arrhythmia that you are now, Vivek and I are doing some cases in Europe. We're also done some compassionate use in US. I think we're going to see PFA for VT very soon. So I think it's going to happen. And I think as for AFib, one of the benefits is going to be deeper lesion. So maybe less need to go epicardial. Actually, what we're trying to see in the European study with these new devices, that the ability of this lesion to reach the epicardium when we need to, and to avoid that we have to achieve epicardial access. And again, the workflow that is much safer and faster, especially for the patient with structural disease, they are sick people, you can do a substrate ablation very, very quickly, which really benefit those sick patient. Well, thank you so much, Andrea. I think we have to move on for the next presentation. So I'll move to Professor Otto for presenting. Thank you, Dr. Saad. Now, it's my pleasure to introduce Professor Tolga Aksu from Istanbul, from Aydin University, who has been a real pioneer in cardioneural ablation. And now we'll hear from him the odyssey of cardioneural ablation, and whether it is really for primetime now. Tolga, please. Dear Chairman, dear colleagues, it's my distinct pleasure to present the current status of cardioneural ablation in patients with vasovagal syncope. Actually, enhanced parasympathetic tone or autonomic imbalance between sympathetic and parasympathetic system may cause some different clinical conditions. And we know a strong relationship between autonomic imbalance and reflex syncope and carotid syndrome. But in some patients with sinus bradycardia or sinus asystole, paroxysmal or even persistent AV block, in some patients with atrial fibrillation, there might be some relationship between parasympathetic overactivity and the diseases. So also, there are some, although there are some arguments about pathophysiology of vasovagal syncope, we basically know that after occurrence of any trigger activity, we see an increase on sympathetic tone. It causes a forceful ventricular contraction and then stimulates C-fibers. Stimulation of C-fibers may cause three different responses. In the first arm, we see severe bradycardia or asystole due to parasympathetic overactivity, and which is called as cardio-injury type. In the other arm, we see a hypertension due to sympathetic withdrawal and which is called as vasodepressor type. But in almost 70% of patients, both parasympathetic overactivity and sympathetic withdrawal contribute to occurrence of global cerebral epiparfusion. So basically, if we can eliminate parasympathetic arm, we can eliminate cardio-injury type vasovagal syncope. This is just a theoretical explanation. But in some patients with mixed-tip syncope, this is the great majority of group, if there is still vasovagal syncope episodes, despite increase on blood pressure level, we can still try cardio-enablation according to this theoretical background. But the issue is, can we really detect the localization of this parasympathetic system during our 3D mapping or electrophysiological study? If you look at the real anatomical spaceman, we know that intrinsic cardiac autonomic nerve system mainly contains parasympathetic motor neuron. So if we can detect the localization of this intrinsic cardiac autonomic nerve system, but please don't forget that in human, there are at least 1,500 autonomic ganglia around left and right atrium. But fortunately, in some well-defined area, we are seeing clustering of this autonomic ganglia and this area called as ganglionated plexus, like a right superior GP, right inferior GP, posterior medial left GP. I will not explain the details. So anatomically, we know the possible localization of this GP area. And if we can achieve this area, we can eliminate parasympathetic system. If you look at the latest ESC guideline about the treatment of reflex syncope, as you know that if there is low blood pressure phenotype, we can try midodrine or fluid to cortisone. I usually prescribe midodrine as a first option because after the POTS-IV study, we are seeing too many positive data about the midodrine treatment. But if the patient has recurrent and severe vasovagal syncope due to dominant cardiomyopathy response, we have only one option and this is cardiac pacing. But according to guideline, you should select cardiac pacing in older patient. Why? Because we tried to combine all published data about pacemaker, randomized controlled trials for pacemaker and CNA, observational studies for CNA and one randomized controlled trial. But if you look at here, in only two study, the patients younger than 40 years old were included in the study. And at the end of the study, pacing has no effect to prevent reflex syncope episodes in this younger population. And then only patients older than 40 years old were included for cardiac pacemaker studies. But if you look at the mean age, mean age was older than 60 years old. So we have no data about the efficacy of cardiac pacing in a younger population. We have no data. But if you look at the CNA paper, the mean age was lower than 40 years old and we have one randomized controlled trial, not a sham controlled, but we have one randomized controlled trial demonstrating the positive effect of cardiac pacing in this patient population. And in this EHRA document table, we tried to summarize all published data about CNA in patient with vasovagal syncope and we checked the tilt testing result because in all CNA studies, authors use tilt table testing to select their patient. In great majority of publication, pure cardiogenic type or mixed vasovagal syncope patients were included in the study. But just two study, Chinese group tried to demonstrate the efficacy of CNA in patient with vasodepressorative reflex syncope as well. But according to theoretical background and our anatomical knowledge, I think CNA should have no effect on pure vasodepressorative reflex syncope cases because I cannot explain the positive effect, the reason of positive effect. But there are two studies, small studies demonstrating the efficacy of CNA in vasodepressorative cases as well. In one study, we compared CNA and conservative therapy. This was not a randomized controlled trial, but we compared these two treatment method and at the end of study, CNA demonstrated 77% relative and 36% absolute risk reduction of four-year syncope recurrence rather than conservative therapy. And then we compared CNA and cardiac pacing and then as you see in here, at the end of one year, CNA and cardiac pacing demonstrated a similar success rate, but in almost 60% of patients, closed-loop stimulation systems were used in cardiac pacing arms. So if you compare CNA and Littlest Pacemaker, for example, or if you compare CNA and Rate-Drop-Response Pacemaker, I believe that CNA will be more effective because I don't believe any role of Rate-Drop-Response or Littlest Pacemaker in patient with vasovagal syncope due to mechanism. And then we published the first meta-analysis and we compared the efficacy of CNA with different approach and different mapping methods. And at the end of study, we found that GP mapping method has no role in success rate. This was very surprising finding because too many groups use very, very different techniques. But we certainly found that if you just perform right atrial ablation, you will see more syncope recurrences. I believe that the reason will be re-innervation after two or three years because if you just ablate right atrium site, superior vena cava area, you will mainly ablate post-ganglionated fibers rather than a real epicardial ganglia site. So you will see more syncope recurrence during follow-up. And then Poland group published the first and only randomized control trial. This was very, very small study and again, this was not a sham control study, but demonstrated if you see, you are seeing the inclusion criteria in that study. They mainly included the patient with pure carbine imbibitive reflex syncope patient and primary endpoint was time to first syncope recurrence. And they demonstrated very high success rate in the CNA arm. The primary endpoint occurred in only two patients in CNA arm versus 13 control patients group. And you are seeing the increase on quality of life in patient with CNA arm. And then a couple of months ago, we published the scientific statement of EHRA, HRS, Latin American Arthritic Society and Asia Pacific Arthritic Society. And again, we checked the data in all published CNA work. And then we suggested such a flow chart for patient selection. We strongly suggest to use tilt table testing or carotid sinus massage to demonstrate the dominant contribution of cardio-inhibitor component and to demonstrate real reflex bradycardia episodes. But of course, to exclude hypotension, we can use 24-hour ambulatory blood pressure monitoring or standing test. And if you see more than three second asystolic reflex syncope during tilt testing, data are in favor of CNA efficacy. No doubt about that. But if there is associated hypotensive susceptibility, in the first step, we should try mid-odorin or fluid recortisone. If there is still recurrent syncope episode despite this medication, we can try CNA with moderate success rate. But if there is just vasodepressurative reflex syncope, you shouldn't try CNA according to our scientific statement. We write this figure with Mina Chung. This is just my personal approach, not the approach of scientific statement. There are some differences, but I strongly believe that CNA shouldn't be tried in any dominant vasodepressurative reflex syncope patient. We should try mid-odorin as a first option and we can also try fluid recortisone. If the patient has dominant cardiomyotry reflex syncope and if the patient is younger than six years old, we have too many positive data and CNA should be the first option in patient with vasovagal syncope. But if the patient is older than six years old, we have very, very limited data with CNA because it's not easy to differentiate structural disease of sinus node or AV block in this older population. So pacing can be tried as a first option, but in mixed patient, we should try medication first, but there is still recurrent and severe syncope episodes. And if the patient is younger than six years old, CNA should be the first option. But in older patient, again, pacing should be selected. Thanks for your attention. Thank you, Tolga, for this excellent presentation. And now I will turn to our esteemed panelists. Henry looks ready to comment. Thanks. Thanks a lot. You know, congratulations, Tolga, you and your colleagues and everyone in the field for moving this particular field forward. So you know, congratulations also on the guidelines and giving us clarity. So, you know, I think it's important if we look at these studies is that, you know, we're not treating an ECG and patient selection is very important. You know, these are patients with hard outcomes of syncope, you know, presyncope, you know, with that are cardio-inhibitory. You know, again, vasodepressor syncope is not the type of patient we're trying to treat. Now it can be difficult, though, because, you know, with monitoring without a loop recorder, you know, you may not necessarily document the pause, but it can be very suspicious. And again, this is the difficult part of managing syncope. You know, it seems like healthier, younger patients with less structural disease seem to benefit more from this. And it makes sense in that population to pursue this first rather than, you know, doing a pacemaker up front. We still have a lot to learn, I guess, in terms of, you know, what ablation targets are, you know, should it be right, left-sided, you know, biatrial, you know, are we hitting the GPs? Are we hitting the postganglionic fibers? You know, if we don't hit the GPs, for example, you know, we know that there'll be nerve regrowth. You know, if we do a PBI and we try to ablate fractionated areas later, you know, we may not affect the GPs. And we also have PFA now, you know, which, you know, probably doesn't permanently affect the GPs, but gets a response. You know, there's a lot more data, a lot more studies that have reproduced, you know, your group's data, the data from Brazil. So it seems like there is a real effect. There is a treatment effect with it. We still need long-term data, you know, looking at possible complications, you know, possible efficacy. But then again, you know, some of these patients, you know, do get better on their own over time. So still much to learn. You know, we hope one day that we'll have a randomized sham-controlled study to look at it, to make sure there's not a placebo effect. But it seems like the field is moving forward. And congrats to all the work you have done. Thank you, Henry. We haven't heard from China during the first talk. Dr. Wang, Dr. Wei-Chin Wang, are you online? Yeah. Would you think that the CNA is ready for the prime time? Yeah, I think in a special condition, yes, it's true, because we find that some patients with bradycardia may be caused by a vagal condition. So for some patients, yeah, for sinus bradycardia, and even in some patients with the AV blocker, I think it is a choice. All right. Any other comments, Dr. Wang? So if I can make a quick question. So you all mentioned that this procedure lacks some sort of standardization. Everybody's doing it a little bit differently, or with different endpoints. So I'd like to hear from panelists such as Cheryl and Henry, and maybe even Tolga, what's your approach to CNA? What do you do in the case of vasovagal syncope? We select the patient appropriately, as you mentioned. And then what do you do in the lab? And when do you stop ablating? What's your endpoint? You can start, Cheryl, you can start. So we are actually currently using a sort of off-label, but already published means of trying to prove the response to jugular stimulation. This has been published by other colleagues with a small series of patients. And to guide, to target the ablation, we are actually, in my center, we are using a CT scan-based approach. So 100% image integration. We are not really looking at signals, trying to do point-by-point ablation, and going to both sides for the moment, waiting to have more evidence on what kind of patient you can just stick to the right side. Actually, we just, we had a recurrence with a patient who came with sinus arrest, and we only treated the right side, and like the higher part, we didn't go for the avenote ganglia. And then he recurred with avenote blocks. So actually, for the moment, we're trying to treat all the ganglia. But I want to thank Tolga for his presentation, because it was very comprehensive. And I also would like to ask you something, because many people have a lot of reserve concerning long-term safety. From your point of view, because of course you have a much more longer experience, have you seen any kind of, because people fear like recurrences, like arrhythmias or atrial tachycardias, because we sort of somehow create some substrate. What is your say on this? Thanks so much. This is, I think, the most important question. Fortunately, we cannot completely eliminate parasympathetic system. This is not possible. This is the first one. And the second one, always we will see reinnervation. The reason, for example, why all technique demonstrate a very, very similar success rate, is because we just follow our patient one year, two years. So to see the reinnervation, the effect of reinnervation in the long term, we need at least to follow this patient five years. Because according to my personal experience, after five years, I'm seeing some reinnervation and I'm trying to do RADOC procedures for this patient. And after five years, completely change everything. This is my first point. Why we are seeing increase on any ventricular arrhythmia, because we are seeing too many reinnervation in follow up. So it's not like animal experiments, because in animal experiments, you are completely eliminated by surgical removing of the GP area and you completely change parasympathetic and sympathetic system ratio. And then you are seeing such a result. Of course, in all published data, we just included younger population. But after five years, we will see a little bit reinnervation. It will prevent any ventricular arrhythmia. But after RADOC procedure in older population, I'm not sure. Because for example, if the patient has a cardiac disease and if we do a CNA in older population, I have no data about possible risk. But we should all be aware of that. Tom, would you like to comment? Sure. Thank you, Ali. Yeah. Tolga, first of all, I want to thank you and your team for all the great work that you've done in advancing knowledge about this field, combining the anatomy with the pathophysiologic understanding of the mechanisms, and then translating that into procedural considerations. But I have a question for you here. And it's largely related on, you know, how and what we should be looking for, you know, over the mid and the long term on these patients. You know, I think in some cases, phrenic nerve, you know, paralysis or, you know, problems can be very much under-recognized and can manifest subtly as dyspnea. I also think with the higher resting heart rate that can, again, occur, some people may have some exercise, you know, functionality diminution. And then there's the certain issue about the long-term, you know, sinus node or AV nodal premature degeneration, because most of the patients we're doing are obviously, you know, very, very young. So I wonder, you know, what you think about those folks. And then a quick follow-up question is on the folks over the age of 60. I agree with you that the pathophysiologic situations operative there are different, but do you think there's a need for a trial to compare pacing and CNA in those patients who are over 60? So I have those two questions for you. And again, I thank you for all your help and work in this field. Thank you so much. I think that, yes, we can do a comparison study with older population, because especially if we are talking about carotid syncope, for example, in very older patient, for example, in 90 years old man, we can easily perform CNA, because in such a situation, there is no mixed-tip or pure vasodepressor-tip carotid syncope option. So CNA works very well in this population. So the main point, we should differentiate structural involvement of sinus node by using a Holter recording or ILR or maybe exercise stress test, we should demonstrate increase on sinus rate during exercise or something like that to exclude any structural disease. The other issue for long-term, I think that ventricular arrhythmia or other arrhythmia will not be a problem for CNA, because it is not possible to eliminate again, it's not possible to eliminate whole parasympathetic system. Because again, I try to mention during my anatomical slide, there are 1,500 epicardial ganglia. Of course, in some area we are seeing clustering, but they are everywhere. So there is still parasympathetic innervation, there is still parasympathetic effect and very surprising finding, for example, in some radio cases, after five years, I found completely different fragmented area. Maybe because, you know, after cardiac transplantation, in transplanted heart, we are seeing new nerves. So maybe we will see new nerve roots after first RF ablation in this population. Tolga, I'm going to ask a difficult question, if it's okay. So some patients, you know, get inappropriate sinus tachycardia and then, you know, most of the time it recovers, but occasionally we have high school or collegiate athletes who sometimes when they bear heavy load, you know, they can have presyncope, you know, or pauses. You know, as an athlete, you know, particularly if it is, you know, cardiovascular running or exercise, you know, an elevated heart rate could be a problem. Is it possible to do it? And if you did it, would you do more limited ablation or would you avoid any particular sites when you do ablation in these patients or would you just not do it in these patients? It's not easy to say any, but Sherry said, for example, we didn't perform a high level ablation in supravenicular area, you can prevent increase on sinus rate by keeping your ablation point in left atrial roof area in supravenicular site. But of course, we have no data, for example, if I perform a little bit more ablation in the upper part, I will increase 10 BPM level. We don't know that. The last issue about the extracardiac vagus stimulation, for example, just to demonstrate the effect of extracardiac vagus stimulation, for example, in some patients I am doing just two RF point in supravenicular, I completely eliminate extracardiac vagus stimulation response. Why? Because all post-cognitive neuronal fibers travel in myocardial and endocardial level and you can easily eliminate these fibers, but you have no effect on epicardial ganglia. So extracardiac vagus stimulation only demonstrate parasympathetic innervation to sinus node, not epicardial ganglia effect. So we still don't know our ablation endpoint. This is the most important limitation of CNA. Just a quick question. Do you have concerns about the circumflex artery when you do ablation around the AV nodal ganglia? Coronary spas may be... As a personal experience, I didn't see, but in sinus node artery, I have one cases during ablation in supravenicular site, we caused a damage on sinus node artery. So to aware of this, for example, you are doing ablation and you should see an increase on sinus rate during ablation on right superior GP site, in supravenicular site or right superior pulmonary artery. But if then, for example, heart rate increase, increase and then if you see deep decrease on sinus rate, you should aware a vasospasm on sinusoid and stop the ablation in that point to prevent permanent damage. But I didn't see for coronary sinus, sorry, supravenicular site. Tom, would you like to say something or just... Just very briefly, I think, you know, in my opinion, this is ready for prime time, but it is, and I'm sure you would agree, Tolga, and I'd just like your thoughts, you know, in a very subselected population, you know, these young people often have variation over time. So they've got to be, in my opinion, very symptomatic, significant impact on their quality of life and fail behavioral pharmacologic and non-pharmacologic chances. And I think a tincture of time before jumping in is appropriate. Obviously, you and your colleagues do it appropriately, but so I think in a subselected group, that's really where it's ready for prime time. The other populations, it might have benefit, but I think we need more data. What are your thoughts in a summary perspective here, Tolga? I would like to mention that CNA is not less invasive than cardiac pacing. So the indication should be similar to decide any intervention in patient with vasovagal syncope. Because for example, if there is just one syncope episode during blood sampling, and then you saw a 40-second asystole until testing, there is no draw. So for example, if we can prevent this trigger activity or trigger issue, we can eliminate it. But you are talking about patients less than 60 years old, right? Yeah. Okay. All right. So thank you very much again, Tolga. That's exactly. And we have to move on to the final speaker, Eduardo, please. Yeah. Before I move on, just like 30 seconds, do you foresee in the future for people 60 and older, an indication for CNA trying to postpone a pacemaker implantation? Let's say patients with sinus nodal dysfunction or patients with second degree AV block that you do have structural disease, but let's say if you remove or reduce significantly parasympathetic tone, will you be able to try to postpone pacemaker implantation or in some of these patients even avoid it completely? Perfect question. I am doing that. But it's not easy to do such a research, you know, because I am checking everything and then I'm talking with the patient and family, but I'm using that to postpone cardiac pacing because in future, cardiac pacing will be better. So are you personally using that or on a personal basis? Do you think there is room for that? Yes, exactly. Okay. I'm doing that also on a very off label, but you know, that's something that for future research, I think this will be, you know, an important subject. So thank you very much. It was masterful. Thank you so much. So let's move on to our next speaker. It's going to be Dr. Pugal Vijayaraman from the US, from Pennsylvania. He's going to be talking to us about conduction system pacing or CRT. Looking forward to that. Thank you, Pugal. Thank you very much for being with us. Sorry about that. Try to stay quiet on the background. Thank you. Thank you for your kind invitation. And the topic for my presentation is CSP and heart failure. Is it ready for prime time? These are my disclosures. So biventricular pacing has been the main therapy for cardiac resynchronization therapy. Unfortunately, we've been using it as a one glove fits all approach. If you look at patients who have left bundle branch block, we have significant shortening of QRS and activation times, but there's still not a complete resynchronization. So there is missed potential and opportunity for improvement. On the other hand, in patients with non left bundle branch block patients or with narrow QRS, we have unnecessary ventricular activation time prolongation. Or in this respect, very early studies using endocardial biventricular pacing resulted in greater improvement in activation time. So that has been proposed as an alternative approach and studied early on. Where conduction system pacing comes in place is that the idea of conduction system pacing in patients who require pacing is to be able to maintain synchrony, prevent dyssynchrony. On the other hand, in patients with dyssynchrony from various conduction disorders, we are able to restore synchrony. And we have multiple options currently in terms of his bundle pacing, left bundle branch pacing, or a combination of those approaches using his bundle or left bundle plus coronary sinus pacing. And the type of pacing will depend on the site of block, conduction disease, and the pacing parameters we achieve with this. So in looking at what is the mechanism, if you look at left bundle branch block patients, if you, here's a patient with fairly wide QRS, 190 millisecond, and you can see when you do his bundle pacing, you can achieve complete electrical resynchronization in this patient. And so it gives us an instantaneous answer in terms of whether you can achieve full resynchronization of the electrical dyssynchrony. However, his bundle pacing is limited because if you look at the conduction disease in patients with advanced cardiomyopathies, most patients do have conduction block in the proximal his bundle or in the proximal left bundle branch itself. And there are significant number of patients, especially those with advanced heart disease, is intact Purkinje activation where there's diffuse conduction disease or distal disease, where conduction pacing may not give us the answer or the type of results you were looking for. So for example, here's intracardiac recordings done in the left septal mapping studies. Pacing on his bundle is complete restoration of conduction, activation of Purkinje system. And in patient with left bundle branch pacing can also see similar restoration of activation of the left Purkinje system. And this results in more synchronous activation of the left ventricle. And when you compare patients who have left bundle branch block and who undergo his bundle pacing or biventricular pacing acutely using cardiac imaging, ECG imaging technology, we're able to show that there is greater degree of QRS shortening, left ventricular dyssynchrony index, and improvement in LV activation time and improvement in hemodynamic status in same group of patients compared to biventricular pacing using his bundle pacing. Similarly, if you're able to do body surface mapping using ECG belt, a simplified technology and acute hemodynamic studies using TVDT, DPDT measurements and his bundle pacing and LV septal pacing resulted in similar hemodynamic effects but greater electrical resynchronization. So the same technique can be applied in patients with right bundle branch block. Here's the patient with a fairly wide right bundle branch block and his bundle pacing similar to left bundle branch block patients can result in complete electrical resynchronization, normalization of the right bundle branch block as you can see here, selective capture and resynchronization and even selective capture of the right bundle fibers itself by pacing in the his bundle. And this approach has result being able to be done even in patients undergoing left bundle branch pacing, although the degree of resynchronization electrically may be somewhat less pronounced. Here's a patient with right bundle branch block when you do non-selective left bundle branch pacing, the transeptal activation is fairly rapid and results in reduced right ventricular conduction delay and simultaneous anodal capture on the RV septum can further reduce the ventricular activation times. And in patients with mixed conduction disease, there are many patients who have left bundle branch block in addition to having peripheral conduction delay as you can see in this patient, his bundle pacing results in decrease in QRS duration from 210 to 146 milliseconds, but still a significant degree of dyssynchrony left even though the QLV is decreased by about almost 65 milliseconds. And so in these patients combining his bundle pacing plus sequential CS activation can result in further electrical resynchronization. This approach can be also done in terms of using left bundle branch pacing. Here in this patient, left bundle branch pacing still results in a fairly wide QRS morphology due to delayed right ventricular activation, but combining with left bundle plus LV pacing can result in further narrowing from 210 milliseconds to 144 milliseconds. In a series of advanced conduction disease patient, both the HOT-CRT and LOT-CRT approach, you can see that it provides incremental benefits in terms of electrical resynchronization in both approaches. Has this translated into improved clinical outcomes? And this was our early approach to look at patients undergoing his bundle pacing or left bundle branch pacing compared to those undergoing right ventricular pacing. In a case control study, not in a randomized fashion, we were able to demonstrate significant improvement in heart failure, hospitalization, death, or need for update to biventricular pacing. So there is evidence that we can prevent the dyssynchrony induced heart failure and the adverse cardiac outcomes. While we were able to show that in a small two center studies, now we are able to demonstrate in this Medicare clinical evidence development study looking at almost 24,000 patients, about 7,000 patients undergoing conduction system pacing compared to 16,000 patients undergoing traditional right ventricular pacing. There was significant reduction in the incident heart failure, hospitalization, and overall mortality, even at six months of followup, suggesting that this approach can be translated into the general real world evidence. Since the early description of use of his bundle pacing for left bundle branch block in 2013 from the Spanish group, there's been numerous studies of using conduction system pacing, including the recently published data in 2024. So our evidence for use of conduction system pacing for cardiac resynchronization therapy is steadily accumulating and increasing. Early observational experience from Dr. Weijian Wang's group in China, looking at about 74 patient, our success rate for his bundle pacing was about 76%, but what it demonstrated the feasibility of significant improvement in LV function in this observational experience. And when tried in left bundle branch pacing, we're able to demonstrate similar degree of success, higher degree of success, about 92% in patient left bundle branch block and similar degree of improvement in LV function. When tested in randomized studies very early on, small studies with his bundle pacing, there was a significant crossover, even though there was a greater improvement in LV ejection fraction. Another study called HIS-ALTERNATE, which was a 50 patient study, similar observational evidence of 70%, 72% success in permanent his bundle pacing, resulting in greater improvement in LV ejection fraction when observed in a per protocol analysis. Recently, a smaller randomized study pilot study showed in 40 patients that left bundle branch pacing can be more successful than biventricular pacing acutely, resulting in greater improvement in LV ejection fraction, greater degree of hyper response. We performed a hundred patient randomized study, similar concept, but primarily using conduction system pacing to guide the type of therapy, whether to use HIS-bundle left bundle pacing or combination of pacing compared to traditional biventricular pacing. We had a very high success rate by acute implant, 96% compared to 82% with biventricular pacing. The intention to treat analysis, the primary endpoint was change in LV ejection fraction, greater improvement in LV ejection fraction, and a greater degree of echocardiogram response was observed in this study. How about in patients with right bundle branch pacing, you can see greater electrical resynchronization resulting in greater LV ejection fraction. This was a small observational study. Similarly, another study for more than a hundred patients with left bundle branch pacing, improvement in LV ejection fraction and functional class was observed. No randomized studies exist in the right bundle branch block space, although we are almost nearing completion in the HIS-CRT trial, combining HIS-bundle or left bundle branch pacing compared to biventricular pacing in 120 patient randomized study and NIH sponsored study. Hopefully enrollment will be complete this year and we'll have results within the next 12 to 18 months. The combination approach has also resulted in greater improvement in the LV function. And this approach is being tested in clinical studies, but primarily used for patients with advanced conduction disease. When looking at a large series of patients in a case control study, about 1,800 patients, 15 centers across the world, we were able to demonstrate greater improvement in the depth of heart failure hospitalization compared to biventricular pacing. Biventricular pacing already achieves great response, clinical outcomes in the sick patients. And we're able to achieve further incremental improvement by using conduction system pacing. And when tested specifically in the left bundle branch block patient, this effect was even greater in terms of reducing depth of heart failure hospitalization. We're also able to see that the improvement in LV function, echocardiographic response and hyper response rates were greater when you use left bundle branch pacing compared to biventricular pacing. What about the other physiologic effects of this physiologic pacing? In a more propensity match analysis in the same population, we're able to show that the time to nuance and sustain ventricular tachycardia ventricular fibrillation was significantly reduced, suggesting that there may be a reduced pro-arrhythmic effect of using physiologic pacing in this population. And even in patients with no prior history of VT or VF or any anterior therapy use, this effect was seen. More importantly, in patients with no history of atrial fibrillation, we're able to demonstrate reduced incidence of atrial fibrillation also in this population, suggesting physiologic pacing approach using conduction system pacing may reduce atrial and ventricular arrhythmias in follow. What about mid-range, mildly reduced LV ejection fraction, 35 to 50%? This was a recently presented study. We looked at about a thousand patients undergoing pacing in this population, predominantly conduction system pacing. It looks like this approach has taken on more than biventricular pacing in this population. And we're able to show similar degree of decrease in depth of heart failure hospitalization when you look at all patients or those with left bundle branch block. Finally, another randomized clinical trial with more long-term clinical outcome was recently presented in the APHRS at Sydney from a Chinese group. GM Chen presented this data of 200 patients with very high success rates of 98% for left bundle branch pacing, predominantly non-ischemic cardiomyopathy and STRESS criteria left bundle branch block patients, about 94% successful biventricular pacing, resulted in greater QRS duration reduction compared to biventricular pacing, resulting in greater improvement in LV ejection fraction compared to biventricular pacing. And the incidence of death of heart failure hospitalization was also reduced in this first long-term data or median fall of about 36 months. In terms of bradycardia, you can see that the approach of conduction system pacing is rapidly expanding, and we anticipate that this will continue to improve and RV pacing may be a history. However, in resynchronization therapy patient, there's a lot needs to be desired. Current guidelines would suggest that in patients with bradycardia indications with LVEF 35 to 50%, either conduction system pacing or biventricular pacing may be used as a class IIa approach. However, in patients with heart failure, conduction system pacing is recommended only as a class IIa indication if effective CRT cannot be achieved based on the current data. And in that sense, we continue to improve, and there are more clinical trials on the horizon. The large trial of protect heart failure in terms of bradycardia population, and the left versus left trial, US-based trial, about 2,200 patient trying to assess hard outcomes in this population. Hopefully in the next few years, we'll have an answer. In terms of the question, is it ready for prime time? There are still many unresolved questions in terms of assessing conduction system capture. How do we enhance conduction system capture in all of these patients? How do we improve this technique so everyone can achieve similar clinical results? So in conclusion, I wanna say that the Hispokinji conduction system pacing is paceable and safe, and it should be considered in all patients requiring ventricular pacing. It is an excellent alternative to biventricular pacing for CRT. Lot more needs to be improved in terms of tools and techniques and understanding of our methodologies. And hopefully the randomized clinical trials will give us the answer whether it's ready for prime time use for all patients needing CRT. Thank you very much. Thank you very much, Foucault. That was a beautiful presentation. Thanks a lot for us to ask. So I'll open for our panelists. Dr. Hwang, do you wanna make any comments? And what's your approach today for resynchronization therapy? Do we use conduction system pacing as a first line, or do you still use biventricular pacing and only use conduction system pacing if you can't have an adequate result of conventional biopacing? And what's your end point? Do you wanna prove that you have conduction system capture in those cases? A lot of questions. Yes. Thank you for Dr. Foucault give us excellent presentation. We know now implantation is no longer is a significant barrier to the implantation of this technique before at the early stage his bundle pacing is a challenge. But now I think it's no problem because we have a multi choice for pacing site for choice from proximal to distal to indicate the different conduction system disease. And now we know on comparative studies show that their conduction system is not inferior sometimes in superior to bivariate pacing although they are not large sample randomized study but it is true to compare bivariate pacing conduction is superior, including economical and feasible and less complication and better pacing parameter and a high percentage of super response to conduction system pacing. So now it may be we, yes, we need a large randomized clinical trial, but it's very hard in a center. We always choose conduction system before how to feed it a full with bradycardia or a typical CRT indication, because we know, conduction systems have a potential to maintain electrical synchrony in patients with a network complex, but by we cannot. So for avoidance or prevention of heart failure a conduction system is, can be used for avoidance of heart failure. We can start early conduction to to have a better clinical outcome. And in typical left bundle branch block if can be credited by conduction system pacing we tried his bundle pacing first to see whether there were complete left bundle branch correction. So if it can be corrected, then we will try conduction-sensitive pacing. For most patients, 80% of patients with left bundle branch pacing and 20% with his bundle pacing. According to pacing plan, whether we can have an acceptable pacing parameter. That means whether we have pacing beyond the side block. In a sense that we will try distal his bundle pacing, then we have a very low threshold for left bundle correction. And yes, in patients with IVCD, we will try by way pacing. Sometimes with a lot of CRT. In a sense, we think if no effective conduction correction, we think it is just automized by way pacing, not a lot of CRT. If there is a partial correction by left bundle pacing or his bundle pacing, then we call it low CRT or high CRT. So whether the pacing side is important or conduction-sensitive capture is important, then we choose a different pacing mode. And also, what we wanted is a complication, long-term complication. For example, tricuspid regurgitation and lead fracture. There is one case with lead fracture in our center. And also we have many information about lead fracture. So what we wanted is complication. So we should improve the lead design and maybe implantation technique to reduce indication for tricuspid regurgitation. So in our center, we tried to reduce damage right above the branch block and tricuspid damage. So we should avoid screwing into tricuspid valve. It's very important. I think conduction-sensitive will become one of the main pacing modes for physiological pacing. Yes, we need a lot of randomized clinical trials to confirm it. And I have a question for Pogo. We know his bundle pacing has many advantages but disadvantages. What do you recommend in clinical practice? Yeah, so we all started with his bundle pacing. We are very strong advocates for his bundle pacing. The current environment, the challenge is that in our lab, even with experienced hands, about 10 to 15% of patients develop unexpected rise in threshold, even if you have good thresholds at implant. So that is a deterrent. But most of the time, these are slowly progressive increase. The tools have to improve. As you pointed out, the ability to successfully do distal his bundle pacing and membranous septum, that's probably the most important technique to achieve good his bundle pacing threshold. Perfect. Henry, do you want to make any comments on that? What's your approach? It seems like nowadays you go to the lab and it's important to have all those tools available. And then you end up starting by one technique or the other, trying at the end, even if you have to combine them. But at the end of the day, what you need is the best resynchronization possible for that particular patient. Is that something that you are actually doing on your practice? Actually, right after this webinar, I have this exact situation. But we used to say that, well, there's randomized trial data for traditional CS by V pacing. But the amount of data has become more robust as we reboot these views. And obviously, some randomized studies are coming. Physiologically, it makes sense. When you're doing CS lead pacing, it can be technically difficult. There could be scar or the patient may have proclivity for VT and get dispersion. We see that. It's very clear when you should try conduction system pacing. And also renal failure. I guess the question I have for the experts is, if I were to try physiologic pacing first and I could only get LV septal pacing or RV septal pacing, it does narrow the QRS, though. But it's not getting into the conduction system. Should I take that or should I attempt then to do a CS lead? Yeah. Henry, that's probably the most important question that we haven't really answered for several reasons. One is when we first tried to write our how to do left frontal branch pacing paper, Dr. Wong and I tried and worked hard. And if you go back and look at the paper, that has all of the criteria for confirming left frontal branch capture. There is no other criteria that has been established that's better than that in terms of getting you high specificity and sensitivity. There are lots of indirect criteria that's gone into the mainstream. And I'm part of some of those articles because in an effort to democratize this process, we've tended to water down some of these criteria. But when we do a conduction system pacing for bradycardia indication in the hope of preventing disincarnation induced heart failure, I think your approach of accepting LV septal pacing when you cannot demonstrate left frontal capture is reasonable because these approaches are definitely better than RV septal or RV apical pacing. But when it comes to CRT, when you have such robust data for CRT with IV pacing, and the reason we went to left frontal branch or his frontal pacing is to achieve greater electrical resynchrony with the physiologic pacing. And that capture criteria has to be confirmed. And as I've done more and more, our approach is to do conduction system pacing first, but to evaluate, is that the best approach for the patient? These criteria become very, very hard for an average implanter to grasp and use it successfully and often tend to use peak R-wave time as a guide. Peak R-wave time is a very crude guide, unfortunately. And people get fooled into thinking, not intentionally, but unintentionally, thinking that they've achieved conduction system capture. So we do not have highly sensitive criteria and specific criteria that confirms conductions to capture. So I wanted to make that point, that's why I gave a long-winded answer. But in CRT patient, our goal should be to prove proximal conduction system capture. If we cannot achieve conduction system capture, I think we shouldn't hesitate to move to IV pacing. And I would accept an LV septal pacing if I cannot get a reasonably good biventricular pacing, whether in terms of threshold, frenic know, or QLV, any of the parameters that you would think that would give you the best outcome. Thank you. We'll have a couple of quick questions for you. And I first of all want to thank you and Dr. Huang and others who have so much lit this field and created a new innovative opportunity for us. And I do think it's ready for prime time. And I think the tools, as they continue to advance, will make it easier for all. And the studies will answer some unanswered questions. But I have a couple of very quick questions. You can get a quick response to them. Assuming that the individual is capable of doing conduction system pacing and IV pacing, what do you think should be done for those particular patients today? How do you think the approach should be? And number two, is there ever a need for a backup pacer in another location? For example, in someone's status post AV notablation with underlying a systole or a very intrinsically low heart rate. And thirdly, you know, some patients with IV pacing are non-responders, about a third. And then there's under-responders. Is there ever a mechanism either by wearable devices or implantable devices to create a template to make sure that you're capturing effectively and establishing biventricular pacing or conduction system pacing? Because I think that is one of the reasons why we fail to respond. There are multiple reasons, but that is one. So if you could tackle those questions. As usual, Tom, you ask the tough questions. The first one, I think you're right. Conduction system pacing is physiologically superior. So when you have both options available, I'm always going for conduction system pacing first. So that's been established in our lab. And we have 10 implanters. All 10 of them choose conduction system pacing first. Although we try to be very rigorous in telling each other that we should not accept anything less, especially when you're doing for biventricular pacing. The second question, I think, was AV notablation. The reason many moved on from hispinal pacing to left frontal branch pacing is you don't need to have a backup lead. Left frontal branch pacing is very good enough in terms of providing both conduction capture as well as LV septal pacing. We do have some acute or subacute lead dislodgement, no different from right ventricular or maybe less than biventricular pacing approach. If you do hispinal pacing alone, then maybe there is a reason to use some backup lead. And sometimes I use left frontal branch pacing as my backup pacing to hispinal pacing. I missed your third question. The third question was, is there a mechanism or need potentially for monitoring to determine capture on a conduction system pacing manner? Yeah, that's the most important thing. So we've learned the hard way. Hispinal pacing, when you lose conduction capture, it's very easy to demonstrate. Anybody can do it or device staff can do it with just a couple of surface leads itself. Conduction system pacing using left frontal branch pacing is a lot harder. Forget left frontal branch capture. To confirm that you have LV septal pacing itself, you need to use 12 lead, which is not the routine in many labs. And incidence of leads coming back causing RV septal or mid-septal pacing, it's no small number. We are realizing that that's anywhere from 5 to 10%. So that's the number of almost similar number of patients as we used to have with hispinal pacing in terms of the lead moving back. It can happen within first few months. I've had patients happen after two years and six years. Those are rare occurrences, but you need to be vigilant to watch and use 12 lead ECGs in all of these patients. And lastly, you asked another question about non-responders. We have some data in non-responders. If the non-response is due to inappropriate or incomplete resynchronization with IV pacing, then there's absolutely room for conduction system pacing to improve, and we've shown that it is feasible. It may not be as good as first-time responders. Non-responders, up to 50% of those patients may respond with conduction system pacing. Thank you. I have two comments. One for how to perform distal hispinal pacing. We know distal hispinal pacing will have better electrical synchrony, and also we will have a better threshold for hispinal capture and high IV amplitude. But it's challenging. Implantation is challenging, but it can be realized. I think maybe it's a future pacing mode, because I think it's better than left-of-hand pacing. And another is criteria for true airway capture. I think now many, many criteria may be useful, but in a sense, I think threshold for both local myocardium and conduction is not always similar, identical. It's not possible. So you test early and test more, you will find that you always will have selective or abrupt change from left ventricular septum to true airway capture. So if no signs of selective airway pacing or abrupt change for still airway P, that means 90%, more than 90% is only local myocardial capture. So, but for most patients, for example, not CRT indication, maybe left ventricular septum is okay, but I agree with Pogo. If patient with indication of CRT, I think true airway capture is a key point. Thank you so much. The discussion is fantastic, but we're running out of time. So Sharon, do you want to make any final comments so we can have you participate on that part as well? Is there anything that you want to say or answer or ask? I think it was pretty much covered. And I also had this comment on saying that CSP is a big bucket where people are putting many things inside. And maybe standardization is the main thing here to make sure that we are really using a better therapy than biventricular pacing. And I think in the end, we all hope to get rid of longer procedures and more complicated that depend a lot on anatomy. And maybe conduction system pacing would be this way for heart failure patients. But I think it's been enough stress by everyone. And I think the talk was really amazing, showing all the latest evidence. But just standardization of what conduction system pacing we need for helping patients is the most important thing. Yes, perfect. Thank you so much for your comment. I think it's very, very appropriate. Thank you. So, Professor Atle, do you want to come to a closing? Thank you, Dr. Saad. Well, we have had three excellent, excellent presentations and fantastic discussion. Thanks to our esteemed panel. Well, if I summarize in a very, very short and brief way, we first had Dr. Natale's talk on PFA, really stating that the PFA is very effective, at least as effective as the other energy sources and safe. But of course, there are several issues left. I mean, in terms of technicality, in terms of new catheters and also new data on the expansion of the indications, if available, for example, for the ventricular arrhythmias. And also, we have learned that ice was very important in the success of the procedure. In the second talk, Tolga has really taught us that CNA has reached the prime time, but only in carefully selected patients. That is, patients less than 60 years of age and with dominant cardio-inhibitory type of syncope and type of disorders. But again, there are issues left, like need for a sham control study. And the issue of re-innervation is not really clear yet. And of course, there are some concerns about the long term safety. Finally, Uga has taught us about the conduction system pacing is now possible, safe, and is an alternative to biventricular CRT. But still, there are some issues left. Well, actually, I should say that it's for the prime time at the moment. But there are issues left, like the access to the conduction system and again, some technical issues, technical catheter developments and long term issues about the current, the available conduction system catheters, etc. And also, we need some randomized control trials for the decision making for the prime selection of the conduction system pacing. Well, with this, I would like to really conclude this session. But at the same time, on behalf of my co-chair, Dr. Saad and myself, thanking to all the speakers and our panelists. And of course, to the HRS Global Relations Committee members. Thank you again.

cardiac care

Pulmonary Vein Isolation

Pulsed Field Ablation

Cardioneural Ablation

Conduction System Pacing

Cardiac Resynchronization Therapy

Dr. Andrea Natale

Dr. Tolga Aksu

Dr. Pugal Vijayaraman

pulmonary vein stenosis

vasovagal syncope

His bundle pacing

left bundle branch pacing

cardiac synchrony