CNA Conference - Dr. Vivek Reddy - My experience with CNA controlled with extracardiac vagal stimulation and use of implantable loop monitor.

Steven. Wonderful. That was, that was great to hear, um, those young men, um, great work for sure. We'll now move on to Doctor Vivek Reddy. Um, Doctor Vivek Reddy is the director of, uh, cardiac arrhythmia service at the Mount Sinai Hospital, the direct, director of the EP service, um, over there. Many of you already know that he is a world premier cardio electrophysiologist. And he leads a team of physician assistants, uh, scientists who are developing advanced therapies for cardiac arrhythmias and heart failure. And I will look forward to his presentation on my experience with CNA controlled with extracardiac vagal stimulation and the use of implantable loop monitor. Really delighted to be part of the 2nd World Congress on cardio neuroablation, and I want to thank Dr. Picone and Dr. Clark for the very kind invitation. Please note that I do have a number of disclosures, but none specifically regarding cardio neuroablation. The extra cardiac vagal nerve stimulator is a concept that was obviously forwarded by Dr. Paho and his colleagues, and this is the actual stimulator itself that you see. In fact, Dr. Paho was kind enough to provide us one such generator. You see the actual stimulation protocol here frequency 50 Hz output at 1 volt per kilogram of the patient's weight up to a max of 70 volts and a pulse with a 0.5 milliseconds. Usually the train duration lasts about 5 seconds. Um, the goal, of course, is to put these, put two Decapolar catheters next to the vagus nerve by going up the jugular veins and stimulating. And when you stimulate, there's a characteristic response. You can see sinus arrest as noted here, as well as AV block, and here you see AV block while atrial pacing. Now I should note this is not an abnormal response in patients with vagal syncope. You can Get this response in virtually everyone. So, the purpose of this is to identify the response of the heart to vagal to aggressive vagal stimulation, so that when you actually then ablate the ganglia, you can use this as an endpoint for that particular procedure. And obviously this again was just explained by Dr. Paon. case that was actually done recently by my colleague Mohit Toragam just last week actually, and I asked him to record this case. So at the beginning of the case, we do put the catheter, the two Decapolar catheters up the jugular, jugular veins on both sides, both the right and the left. Now I should note sometimes this can be tricky as you traverse the catheter up, particularly on the left side. So oftentimes we use a long sheath to help support to get the catheter up. You, you position it at the level of the jaw on fluoroscopy, point it medially, and you'll get stimulation. So at baseline you can see here with right vagal stimulation there's a sinus arrest and the same with left vagal stimulation at baseline and again this is fully expected. Here we'll move forward and you can see my colleague and the patient I should note is under general anesthesia as we do these procedures. So here's the catheter and at points we're going to speed it up here at 10x speed and you can see the position, note, note the position. This is on the posterior local. Well, and then if you look at the right atrium, I should say, and if you look on the superior view, notice that it's mainly posterior, not too much lateral, and if you look at the level based on this posterior view, we're not really going too far above the level of the left atrium. Part of the reason, of course, is that there is a sinoatrial artery. So one of the rare but important complications that can occur is during ablation if you affect the sinoatrial artery, as recently published by Mauricio Scanavaca, then you can actually cause intense sinus bradycardia requiring pacemaker implantation. So after that ablation, then we do stimulation, but, and I didn't show you this, but you still had a vagal effect. So here, Mole went to the left side, the left atrium, and is ablating from the left atrium to, to, uh, consolidate the, um, uh, this lesion. By ablating from one side and then the other side, you're able to ablate this superior paraseptal ganglia. Then you repeat the stimulation, which I didn't show you, and then we'll come for this inferior paraseptal ganglia, and you can see our inferior posterior. Notice that the catheter is looped around. You can see on the, on the ice, we try not to use too much fluoroscopy, but anyway, we can see on the ice and at times you'll see the catheter loop down at this position to ablate this location. Um, when we ablate this location, again, this is at 10x speed, sometimes it's this is not effective enough, and you have to also ablate from the right side or from inside the coronary sinus. Here, by the way, you can again see on ice, and you can't see this very well, but periodically the other hand is reaching for the ice catheter to just assess the positioning. We definitely like to use ice quite a bit. And I think the key here is good quality lesions for both the superior and the inferior lesions. We don't want to do high power lesions. We want to do low power 30, 35 watts irrigated with long duration lesions. And at the end, we repeat the stimulation here with both right-sided stimulation and left-sided stimulators. Notice there's no significant change in the sinus rate, nor is there a significant change in AV intervals. So at this point, we feel like we've ablated sufficiently to remove the influence of the vagal system on both of these ganglia. This is just another case. In fact, this is the very first case that I did, 1st or 2nd, I can't remember. But anyway, this is also a young patient, and notice, um, this is a baseline, we have sinus arrest again, just as we expect. With ablation of the right superior ganglia, when we repeat the stimulation, we see the sinus beat, but no AV conduction. So that shows evidence that we've removed the influence to the, to the sinus node, but not necessarily the AV node. Then we'll go to inferior, and here you see on the ICE image, the location of the catheter again, and uh repeat, and just as we saw in Mohit's case, the influence is now removed. So this is our data. You can see the total number of patients is 46 patients. This is data between our group at uh in uh in Mount Sinai, as well as uh Peter Nuzzo's group and with with Honza Petru at Homolka Hospital in Prague. So the mean age as expected, is relatively young. You can see that the number of syncopal or pre-syncopal episodes in the prior year was 3.3, with the longest RR duration of 77 seconds. The comorbidity is relatively minimal in this young population, and importantly, just over half the patient population had implantable continuous recording, mainly an ILR at 48%. The mean ejection fraction, as expected, is preserved with normal left atrial size. If we look at the reasons, you can see it was bradycardia, sinus arrest in just over half the population, and secondary or higher block in the remaining. The atropine test was performed in most patients and was positive in the tilt table test as shown. If we look at the procedural details, we did use this extracardiac cervical vagal stimulation in all patients, but note that, um, and note that it was positive in in X number. Now, we weren't always able to get the catheters in position. This is something that's improved over the course of our experience. We do all of our cases with electron topical mapping to minimize the fluoro exposure. And you can see the procedure times again. These are procedures under general anesthesia. The fluoscopy time has shown about 11 minutes and you can see the RF ablation time and post ablation atropy testing we did in a subset of the patients and when we did it was always negative. Uh, and again we did post ablation, uh, extracardiac vagal stimulation in all these patients, uh, obviously during the procedure and it was negative, and acute procedural success in all patients. If we look at complication rate, there was one complication, and it was a vascular complication. If we look at the follow-up duration, uh, just, uh, just around 2 years mean follow-up. Again, this is the number of patients who received Holter or continuous monitoring, mean of 2 Holters, and you can see that um in follow-up 3 patients had syncope and 3 patients had pre-syncope or dizziness, and we did redo cardio ablation in 2 patients. And here's the efficacy data on KM curves. If we look at the primary endpoint of freedom from syncope on follow-up, you can see that the freedom from recurrence was 93%, and the secondary endpoint of freedom from syncope or pre-syncope was 87%. Quite good data, I would believe. This is our heart heart rate trends using the ILR or Holter data, and here's what we see. If you look at the minimum heart rate, which you see in all of these, you have baseline, post-procedure and last follow-up, and this is repeated, by the way, for the remaining data. What you note is that compared to baseline, the minimum heart rate is elevated in both post-procedure and at last follow-up. This is also true for the mean heart rate. But not for the maximum heart rate. That was relatively similar between baseline and follow up. Here we see the SDNN, sound deviation of the NN intervals, as well as root mean scare, and again you see a significant decrease. All of these asterisks represent significant differences. Now I should note there has been an evolution of our technique. In reality, in the beginning we did much more ablation, as shown here on the top left, and we evolved to the bottom right, as you just saw in this, in the cases that I presented. And this is an important, I think this is something that's been going on in the field to try to minimize the amount of ablation in these oftentimes very young patients. I'm just going to show you some data comparing these two, and on the left you have our extensive ablation, our initial approach, and on the right, a little more focused strategy. You'll see that the number of prior pacemaker or implantment loop recorder is very similar between groups, and the reason for cardio neuroablation is also similar between groups. So both groups are well matched. Here you see that the overall radiofrequency ablation time was less in the focused ablation group, as you'd expect, since less sites were targeted for ablation. Overall procedure success was again similar between groups, and complication rates were, there was only one complication, so really no significant difference. If we look at the outcomes, the overall follow up duration, while there was no statistically significant difference, not surprisingly, the follow up in the focused ablation was less, since that was later in our experience. But importantly, the syncope or pre-syncope dizziness rates were statistically no different between the two strategies. So this focused ablation strategy was just as effective as a more extensive ablation strategy and of course spares the patient from additional left atrial or right atrial ablation. I'm here, I'm going to show you some uh meta-analysis data, including our own data plus others in the literature, and overall, this includes a total of 729 patients. You see the mean age of 39, the number of syncopal events, um, pre-ablation was 4.8, this is a mean follow-up of just over 2 years. standpoint of freedom from syncope, these are the different studies. This is the composite on the bottom, total of 729 patients, and you see the freedom of syncope, freedom from syncope is quite good at 93.9%. And in fact, the lower 95% confidence interval still exceeds 90% at 91.7% or 0.6%. If we look at freedom from prodrome, pre-syncope or dizziness, a subset of these centers of these studies reported the data, and here you see the outcome, 82%. These are outcomes based on the site of ablation, what you notice is that with bi atrial ablation, the success rate is 94%, similar with left atrial alone ablation at 95%, right atrial loan ablation was a little bit lower at 82%. If we look at adverse events, first, these are data again from all 19 studies, 729 patients. You see that the major event rate is 0.4%, so that's quite good. What are these events? One patient in this study had a pseudoaneurysm requiring an intervention, a thrombin injection. One patient in this study had a sinus arrest, though I should note that was at 14 months post ablation, so the relationship is less clear, but that patient did require a pacemaker. And one patient in this study, this was our study, who had a pseudoaneurysm required surgical repair. Minor adverse events occurred in 4.4% of the patients, but as shown here, the most common was inappropriate sinus tachycardia, which constituted 3.2% of these minor adverse events. They were minor because this was self-limiting in all of these reports. So if we exclude this sort of Excuse me, self-limiting, um, uh, short-lived inappropriate sinus tachycardia, then a minor adverse event rate would be 1.2%. Of the, of these. The majority were vascular complications at 0.4 0.8%, and three were arrhythmias, 0.4%. In the arrhythmias, one patient had atrial flutter, one patient had paroxysmal atrial fibrillation in follow up, and one patient had frequent PVCs in follow up. Hard to believe or unclear whether they were related at all to the cardio neuroablation. Importantly, there was no evidence of ventricular arrhythmias in this cohort in follow up. So final thoughts, cardio neuroablation is effective. Our own data with continuous monitoring, I think, furthers our conviction and certainly corroborates all of the other clinical trials that have been presented and published over the past decade or so. And I think certainly this is, this is further corroborated by the recent randomized trial by Dr. Petrowski and colleagues. Overall, cardio neuroablation is a safe technique and certainly it's been our experience. I think we'd still like to minimize inappropriate sinus tachycardia, even transient, so one wonders whether there may be a better way to titrate our ablation to the superior parasepptal ganglia. There's also this question of potential long term sensitivity to ventricular arrhythmias, particularly in the context of ischemia. This is a this is an issue that was raised by a recent publication of Heart Rhythm by Shiv Kumar and Olu from the University of California Los Angeles. So we'll have to see, and again that was a pre-clinical study, we'll have to see whether the data bears out. Certainly at this point we have no clinical evidence of this. I think the technique of cardio neuroablation is likely to evolve further. One interesting question is, is only right-sided ablation potentially efficacious? Philip Dubrin and others have been studying this. I think in reality we'll probably need improved technology to get better ablation lesions to get there, but I think this is certainly something that's possible. And also, is extra cardiac vagal stimulation necessary? We personally like this, and we use this in every single patient. It provides a very clear endpoint to the procedure and confidence that we're actually doing something properly. But of course, not everyone has access to neurostimulators in the United States. And while it's, I think, more prevalent outside the US, this has certainly been a problem in the United States. And one final plug, which is for our virtually EP Connect um series, and we hope you please do join us where we talk about new concepts like cardio nebulation, as well as others. Thank you very much for the kind invitation. Thank you, Doctor Reddy for that wonderful presentation. Thank you for, uh, for sharing with us your experience. Obviously, the results speak for themselves, so thank you very much for sharing that. There's a question in the chat I'll read out to you. It says from, uh, Kamal Kotak, and he says, RF time is still long compared to AF ablation. Is this due to relatively lower power and long duration lesions, but less spots? Yeah, that's exactly right. I mean, you know, we think that the goal is to get transmurality, but not just transmural atrial lesions, right? Then you have to get uh past the, uh, into the ganglia, which means you also have to invade through the periganglia um adipose tissue. So, I think for all those reasons, our preference is to go short duration, I'm sorry, long duration, but short, short amount of power. So, that's, usually, we start around 30 to 35 watts with an irrigated catheter. Um, my guess is in the future with larger tip catheters, that, you know, the large surface area catheters, that we'll be able to get deep RF lesions with, with probably less amount of, uh, uh, less amount of time. And probably, um, like, particularly, for example, the right, uh, superior paraseptal, um, ganglion, I feel like that one will probably be able to do just from the right side. Um, the, The inferior paraseptal, I don't know because, you know, it's very, let's say, safe and simple to position at that uh left side in that position. From the right side, I do worry that we may lose something in terms of safety if we try to be very aggressive on the right side. Worry a little bit about what if we, it sneaks anterior and um affects the AV node or something. But anyway, it's certainly, the idea of not having to go to the left side and not doing a transeptal is certainly attractive in these young patients. Yeah. Absolutely. Oh, Vivek, thank you for your, uh, assistance to our meeting. It's a, a great honor to have here. And this, uh, to have your, uh, enthusiastic about the cardio ablation is a great achievement for the procedure. I would like, uh, ask you because I know that you are, uh, uh, studying all kinds of energies in the ablation, for, for example, for atrial fibrillation. And do you think some experience with PFA in terms of denervation, have you seen some results? Have you been comparing the derivvation that is achieved with, for example, PFA and RF energy and also Cryoablation? Yeah, it's a good question. So, let me do the easy one first, which is cryo. I mean, we certainly have, have studied it. And during AF ablation, of course, um, you tend to get uh deep enough lesions, and you tend to get uh ablative lesions of the ganglia. But for a cardio neuroablation, I don't see anybody using cryo. It just takes too long. I, I, I think it's impractical. Now, with PFA, um, we've certainly done work, and I know that Dan presented earlier some of their work, um, and What seems to, and there's now several publications in the literature of using PFA again, not for cardio neuroablation, but for AF ablation. And what's very clear now is that the effect with pulse field is different than thermal ablation. That's not meaning that there's less effect on the ganglia and certainly less permanent effect on the ganglia. That's very clear. What's not clear is, um, or I should, I should say you shouldn't take that to mean that you can't ablate the ganglia with pulse field. You absolutely can. There's experimental work using pulse field catheters in the pericardial space. It's relatively easy to ablate. And even during AF ablation, um, it's not that there's zero effect on the ganglia, it's just less effect. So, I say it like this because eventually, when PFC when focal pulse field catheters become uh widely available, will we start doing cardio neuroablation with pulse field? I think very possibly, there are some uh advantages certainly to doing that, particularly in terms of thrombus formation and etc. There may also be some advantages in, in terms of depth of lesion, that still needs to be worked out. Now, as with most things, there will be some things we need to be careful about. Um, you know, I, I mentioned that case that Mauricio, um, Scaravaca present, um, published on on inadvertent damage to the sinoatrial artery. And it's very I think it's less likely that will cause, you know, uh, stenosis like with RF, but we may cause transient spasm that actually, not may, we almost certainly will cause some spasm. Whether or not that matters, I don't know. I, I think that maybe there'll be some transient bradycardia. I would be surprised if it caused chronic problems, but I, that really would need to be assessed. So I guess that's how I think about uh PF for cardio neuroablation. Thank you. There's a comment from, go ahead, go ahead, sorry, go ahead. No, no, I was just gonna say because, um, um, um, Jose started off by thanking me and I wanted to thank him. I think his work has had a huge impact on, as we just heard from two very young patients, um, you know, I, I, I, I'm sure I speak for all of us, and when I say some of the cardio neuroablation patients are some of the most grateful patients because you take them from, um, sometimes really debilitated situation to a, to a, well, normal situation, so. Uh, thanks for your leadership on this. Wonderful. I just wanted to read out the comment from Doctor Guru here that says he agreed to Doctor Reddy and about the, about PFA, uh, that, uh, he says we were getting myocardial injury at the thresholds needed for GP ablation in pigs and currently titrating power settings. Uh, there's so much more to learn. Wonderful. Yeah, makes sense. No. I noticed uh just a quick technical question. I noticed that on your, uh, initially you, you, you do uh stimulate both vagus nerves as well. I'm curious how you, how you decided on that and how that has evolved since then. I know most centers do just do 11 vagus. I'm, I'm curious how you've been doing yours. Yeah, um, well, look, we started off because that's how, um, Doctor Pashon was doing this. So we started off with that strategy, and the concern, and sometimes, you know, as you know, there's some degree of preferentiality, um, to the inputs from either side. Uh, of course, there's a lot of crossover and, and I get that. So our initial thought was we need to really try to sever all vagal input to the essay note. In the AV node. That was the strategy. So we really wanted to um go from both sides and really um do our best. So that was the initial thought. Now, having said that, I do think that particularly for the essay node, it, it probably is, I don't know the complete. Destruction of the input is the best idea, right? Probably something less than that. With the AV node, and I'd be curious to hear any other thoughts on this, with the AV node, I'm not sure it matters that much. Having too fast AV conduction is, you know, not typically a clinical issue. So I, I don't, I don't know that that matters. But in the essay node, I, I, I do wonder whether we want something slightly different. Yeah. Thank you. Thank you very much, Vivek. Thank you. Thanks for having me so much.