CNA Conference - Dr. Roderick Tung - CNA: Early experience in the United States

OK, let's go ahead, uh, to present, and now we have the honor to have the participation of Professor Roderick Tang. Uh, Professor Roderick is very well known in the electoral physiology of worldwide. And uh, he's professor of the University of Arizona College of Medicine and in Phoenix and University Medical Center, Phoenix, Arizona. And uh Doctor Rodericky, we will talk about the cardio ablation early experience in the United States. Thank you, Professor Teng. Kind invitation to be a part of this World CNA conference. My charge is to discuss the early experience in the US with reference and deference to all of the experience that has happened prior to this kind of sweeping the country here. Um, currently, we are actually approaching 20 cases in Phoenix, Arizona in a short period of time. And I still believe that this is probably one of the most exciting new areas in the field of electrophysiology, given its new applications, ability to help patients that otherwise had to resort to pacemakers. These are my disclosures. So the global evolution of cardio neuroablation really starts back to 2005 with Doctor Patone's first description, calling it cardio neural in 2005, and that has stuck now for almost 20 years. Then it's Doctor Yao Yan in Beijing, China, that started looking at this, and I remember this being one of the most impressive series that showed no recurrence of vasovagal syncope. After cardio neural ablation, Doctor Paone and his group has followed and found different ways to try to establish endpoints with extra cardiac stimulation. And then Doctor Aku, who has been a real pioneer from Turkey, has really accelerated a lot of this on the social media aspect and as well as this collaboration with many groups in the US, namely being present virtually on some of the very important and seminal initial cases. In AV Block, this can be very challenging, and Doctor Aku has also looked at that, and I had the privilege of presenting a US experience that was multi-center. In 2022, and we're waiting for longer term follow up and adding numbers. To be able to finally um submit this important multi-center US study. And more recently, Piotrowski in Poland in 2022 showed that in a very meaningful randomized controlled trial that CNA outperformed control in patients with vasovagal syncope, not sham controlled, but this evolution of cardio neuroablation is extremely exciting and all has occurred this explosion in a period of under 20 years. I still think that when we approach cardio neural ablation in the United States, we're looking for young age, which has been very clear from prior studies that these are more likely to be functional bradycardias. We're also looking to see if these patients have predominantly cardio inhibitory versus vasodepressor effects. It does appear that it's easier for this to be cardio inhibitory, but I personally believe that this could probably be expanded to vasodepressor given that it's all in the same baso gyros reflex. And then resting sinus bradycardia and AV block. The must-haves for us in Phoenix is that you must have an SRC, a symptom rhythm correlation, and that either is outpatient telemetry, inpatient telemetry, a rhythm strip, or an implantable lip recorder. We like implantable loop recorders cause they give us some sense, some sense of heart rate variability, as well to give you an autonomic index. And when they don't have this clearly a tilt table test, which we know is not very specific, that 30% of normal patients may tilt positive, it does allow us to stratify the physiology of whether this is mixed, cardio inhibitory, if this drops less than 40 asystole, or if this is a vasodepressor response. Functional reserve is very important with atropine dust testing as really popularized by Doctor Tolva Aksu, and this has to be done in advance because atropine's half-life is definitely longer than a period of electrophysiological procedure. So these are the must-haves for us, that it's important to be able to see a young patient with long pauses or paroxysmal block, and this is really helpful for us to be able to select patients if they are actually a good candidate. Now, with regards to endpoints. I do believe that extracardiac stimulation is probably the most likely to be the one that is going to be durable because intracardiac stimulation often accelerates the atrial rate triggers atrial fibrillation and provides a less reliable response, whereas extracardiac stimulation up in the vagus nerve at the level of the carotid bodies can be very useful to have a reproducible extent to understand when we are done. And obviously there are responses that occur during ablation, which is when the sinus slows, eliminating that slowing, but it's still not clear as to why some slow and some increase. And we know traditionally, you get more slowing at the martial track or the roof of the LSGP, but obviously, you often will see sinus acceleration at the right anterior RAGP. And we like to see acceleration of over 20 beats per minute as the procedural endpoint. So, we'll often see a patient and say, your heart rate resting is 55. I fully expect you to come out of here maybe 75 or higher. So, our goal is a 20 point increase in heart rate. The first compassionate case we ever did at University of Chicago was really a true gem because this patient read all of the studies by Paon, Yao Yin, and Toga Aksu. And looked to say, I have failed beta blocker midodrine, SSRI hydroxydopa and even had a pacemaker six years prior and continued to faint. She actually requested if we were able to do, if we would be able to do a cardio neural ablation on her. We first looked for objective evidence and did a tilt table test because remember, she already has a pacemaker, so cardio inhibitory response is less likely to be the predominant response. So, when we did a tilt table test. We could see that there was a very significant vasodepressor response, and the heart rate actually dropped transiently but then increased overall, suggesting that this might not be the ideal or historical classical patient for cardio neural ablation. We still went on and attempted this because this is a compassionate case, and then we did high frequency stimulation where we can show slowing of the RR intervals during atrial fibrillation. Here, you can see at the left superior GP region, and that also occurred with some RR interval slowing at the region of the coronary sinus ostium floor. So, these are the areas that we got responses and we proceeded to do most of the ablation in these regions at the LSGP and the LIGP. It was negative in the regions of the right anterior GP, but we did a couple isolated lesions because it was our first and we didn't know how thorough we needed to be. In total, the RF time here is 1,125 seconds, and these are where the traditional lesion sets are based on both anatomic and functional. We then went on to report this because we re-tilted this patient afterwards, who would often get syncope with blood draws and did not see that she would get blood draw syncope on her own. She did get dizzy one month after, but did not have syncope. And then in order for us to be more certain, we then repeated a tilt table again at one year. And this was here with no isoprol, and then we did it with isoprel as well, and there were no differences. This clearly is not the first case that's ever been done in the US, but it was the first reported case to the best of our knowledge when looking at literature. This was very encouraging for many reasons. Number 1, that we could safely perform this. Number 2, it was great for desperate situations. And number 3, it actually may be useful for vasodepressor predominant syncope. Now, AV block is definitely more difficult, and we had this very interesting woman that was 58 that had AVNRT ablation times 3, and we had to go left sided to ablate her AV node re-entry. Now, she ended up not having recurrences. But her PR interval 4 years later became very long in excess of 300 milliseconds. Then she had her first episode of syncope, and she had a monitor that was already in, and what you see is there's very subtle PP slowing at the time of high grade block. So, this would prompt 99% of people to implant a pacemaker, particularly given all of the AV. Nodal ablation that was performed. But maybe this is progressive, maybe this is a result of the ablation itself. And then what we did was we discussed pacemaker with her, but also talked about the possibility of doing a cardio neural modification. And what we did was we attacked the postermedial left GP ablation. And here you can see the AH here is 155, and during ablation with ablation artifact on, the AH shortened at 101. This is above the coronary sinus roof. And when we did right atrial ablation at the IVCLAGP region, we then had further prolongation. Of the AH interval, which was scary again, which is right where we do the traditional slow pathway. So, is it possible that some of slow pathway modification is actually cardio neural ablation? Well, of course, it's possible. And then we went back and we redid the left atrial, and then we also had some more age prolongation, and the question is, is that good? Is that a big response or do you keep going? But we were we were cautious about it. And then slowly with waiting, the age slowly got better, and then ultimately the PR was 320 with an age of 224. With time, with post CNA, the PR interval normalized to 192. And this was really a very successful case, and to this date, she still has not had syncope, and we did not put a pacemaker in. So AV block is definitely more challenging, particularly with its acute end points is when you get a vagal response, you're not sure if you should do more or if you should actually do less with injury. The overall results of the multi-center US CNA registry were shown in 2022. Again, this is ongoing work right now, and we are now over 100 procedures in this US registry. This was done at 13 US center sites, and 63% were done as concomitant procedures with atrial fibrillation predominantly. The average age here you can see is less than 65 with a standard deviation of 1, and most of these diagnoses are being obtained by either implant. loops or tilt tables or ambulatory monitoring. High frequency stimulation is not performed in the majority of them in the United States. Predominantly, this is anatomically based, and a lot of this is based on fractionation mapping that has been used with modern automated annotation. In general, the total RF ablation is just around 10 minutes. There have been one tamponade and two junctional rhythms. One of them was at University of Chicago, where we had great responses and we kept on ablating at the SVC aortic, the right, uh, the right-sided, uh, superior GPs. And the superior parasepals, and then this was probably related to maybe sinoatrial node injury or an essay nodal artery branch. At 8.5 months, 82% of these patients were free from syncope after a single procedure, but 5 did require redo. So it's hard to know how to tell a patient how successful this is. We don't believe it's 100%, but it's certainly over 50%, and I think that this will be very important for us to understand. But this is very much in line with the most recent randomized trial by Perkowski. The median episodes were meaningfully reduced from 6 to 0. The main questions that still are unresolved is its durability. I think Doctor Patone's data is the best here with 45 month follow-up showing that when you do have recurrence, this appears to be quite early within the 1st 6 months or the first year. And we have seen a couple late recurrences, and it's really interesting to watch the ILR to see when heart rate variability may recover. But this is clearly necessary to have longer term follow-up than 2 years, and that's where we believe that ILR is probably gonna be the most meaningful way of understanding the prevalence of reconnection, the timing of reconnection as well. As well as the incidence of reconnection. And here would be an example by Clinton Thurber that showed recurrent syncope after cardio ablation. And here we can see the heart rate availability drops acutely. And then there's probably some reconnection here that occurs within about 2 to 3 months. And then the patient waits this long to be able to have a date of recurrent syncope. So, I think how much we do and what our endpoints are will be really important. Just a little food for thought. We're very excited about some new data looking at the role of autonomic responses to ventricular tachycardia. During human monomorphic VT we look at the sinus rate and we analyze it to be able to show an index of sympathetic tone. In patients that have sinus rate slowing, they may have a predominant parasympathetic or vagal response to human VT, but there are patients that have an unchanged response, which is probably still inappropriate, and the only appropriate response could be categorized by sinus rate increase, which we arbitrarily said greater than 5 beats per minute as a sympathetic response. When we looked at total number of VT episodes over 200. Episodes led by Margarita Puljo Lopez, we found that almost 50% of patients during VT have an inappropriate sinus rate response, which indicates there could be an underlying vagal response to VT. And when we gave atropine to a prospective cohort, we improved human dynamic tolerance by 70%. The reason that I'm showing this. Is because number one, this may be a very cute and physiologically appropriate way of being able to improve the mapability of VT, but more importantly, All arrhythmias and all human conditions may actually cause autonomic reflexes, and this may be reflex syncope that's induced from VT and this may help us answer the question as to why some VTK episodes are tolerated and some are not. What we found with multivariable analysis is that the rate of the VT and actually the substrate with the ejection fraction was less predictive. Then actually the vagal or the autonomic response to VT. And here we see vagolysis with atropine after cardioversion of a patient with a sinus rate of 47 during VT and a map of 38, the atropine itself increased the sinus rate to 117 and increased the map to 134 as if it's functioning as a pressor. And then with sustained VT with reinduction of the exact same VT, the map was tolerated and allowed us. To be able to map this. This here is currently accepted and will be in press online September 5th in Jack. Very exciting for us because maybe cardio neuroablation has a role in even preventing syncope hemic collapse and sudden death on a larger scale from ventricular tachycardia that might not be overreaching. So, 20 years of exciting progress, but we still need to understand who, how, when. And then how do we even do this with Medicare, with the current straits constraints in the US landscape, because currently we look at this as an advanced electrophysiologic study with compassionate cases. So, multi-center studies are needed, sham controls are likely needed as well, cause that can influence autonomics, but we're very excited to report this larger experience from the US and hopefully within the next 6 months, we'll be able to finish. A series of over 100 patients with longer term follow-up. Thank you very much for the invitation and congratulations on a great world CNA meeting. And well, Thank you. Thank you so much, Roderick. It's uh an honor to, to have your presentation. Uh, Roderick was unable to join us here today for the live part of this. There have been a couple of questions that have come in from the audience. Um, One question from Eric Bronstein, how are you dealing with billing and reimbursement for CNA in the US? Um, and I will say how we've handled it at this hospital. My hospital has been very generous in that regard, and they've given me permission because we're trying to build a program. It's fairly easy to get insurance to approve an EP study for a syncope patient. Um, an ablation is a, is a completely different thing. I think we've had good luck with Um, patients who have pacemakers that we offer the insurance company a potential of getting rid of the pacemaker or patients who have an indication for pacemaker implant and convincing the insurance company that it's worth it. But my hospital has promised that if the insurance company denies the ablation but approves the EP study, I can still go ahead and do the EP, do the ablation without billing for the ablation part of it. Um, another question. Could you please give insight from patient standpoint, what should patient hear from MD with this being a new procedure, and, and I think that's very important. Um, you know, all my patients hear that this is a new procedure. It is not FDA approved in the United States, so it's done as an off-label procedure. Um, and I give them all the literature. I give them the history of Doctor Prashan and what's published to date and what are the indications, um, and what are the potential benefits and the potential reasons not to do it. And I let them make the decision. So this isn't something I try to talk them into, but there are certainly plenty of people out there that if you give them enough information and they know that this is not FDA approved, but they're either wanting to avoid a pacemaker or they're sick of dealing with what they're dealing with, then we go ahead and do it. That there is a very important thing because in our country, for example, our society is too activity. Our arrhythmia societies too activity, and they included. The procedure in, in the local guidelines. I think it is a good step to get reimbursement from the insurances. So it is very important because they are convinced about the indications of the procedure and about the results. So they included it in the local guidelines. I think it's a good thing, yeah. So there's another question from uh Rafael Correa uh asking about how here in the US uh getting an ECBS uh stimulator uh without FDA approval of the Pone stimulator. Um, there is a stimulator available here in the United States for neurological stimulation. Uh, DigiTer is the brand name of that particular stimulator. Um, there are other stimulators out there, uh, that can deliver the, between the 50 Hz and 70 Hz, um, but they're not necessarily approved. Uh, I think it is very important to pay attention about the, uh, setup of the system. Because it's necessary to have the, uh, obviously, the frequency, but it's necessary to have a limitation of current in order to avoid the lesions. But obviously, the, uh, uh, the system, the devices. That are approved for neurological indication are um are able to be used during our procedures and it's necessary to change only the setup and we'll show a picture of that in one of the upcoming slides too yeah.