CNA Conference - Dr. José Carlos Pachón - The Great Impact of CNA in AF Ablation

Uh, our next presenter, I get the, I get the last presenter. I get the, uh, The pleasure of introducing last but not least, uh, Doctor Jose Paon. Uh, he's professor of electrophysiology at Sao Paulo University, Sao Paulo, Brazil. Um, his presentation will be on the great impact of cardio neuroablation in conjunction with AFib. Things to. It is a great pleasure for me to be participating in this amazing event. I'm Doctor Pashon, professor of electrophysiology at the Sao Paulo University and the director of the arrhythmia Servi of the Sao Paulo Heart Hospital. I'm going to talk about cardio neuroablation and it is great impact in atrial fibrillation ablation. Thank you very much for your attention. There is a closer relation between cardio neuroablation and atrial fibrillation. The origin of cardio neuroablation is based on the concept of the atrial fibrillation nest. Why does atrial fibrillation sometimes occur in normal people without significant fibrosis or tissue pathology? To address this question, we conducted a prospectivity control study in the 90s using a spectral analysis of endocardial potentials during sinus rhythm. Our investigation revealed that the atrial myocardium consists of two different types of tissues, the compact myocardium, composed of electrically well connected cells, and the fibrillar myocardium, composed of electrically poor connected cells. Clusters of the fibrlar myocardium give rise to the so-called atrial fibrillation. Which can be found in several areas within both the right and the left atria comprising a significant substra for atrial fibrillation. Above, we observe the spectral analysis of an atrial fibrillation is, while below we see the spectrum of a compact myocardial area. This spectra exhibit clear distinctions even though there is a minimal difference in endocardial potentials. In contrast, following the atrial fibrillation induction, the behaviors are very different. The fibular myocardial displays. Organize the high frequency electrical activity while the compact one displays lower frequency and highly organized activity. Through spectral analysis, we can realize that the fibrillar myocardium enters in electrical resonance well before the compact myocardium, thus playing a critical role in atrial fibrillation maintenance. Based on these findings, we base our atrial fibrillation treatment on the ablation of the atrial fibrillation nests. We have found at least 3 types of atrial fibrillation nests. The first one is the venous atrial fibrillation nest that occurs in normal heart and originates from the disconnection of cells in the transition between atrial myocardium and the venous wall. The second one is neural atrial fibrillation, also found in a normal heart. This type is formed by the blending of neural fibers with myocardial cells at the neuromyocardial interface. And the last one, they acquired the atrial fibrillation. This type occurs in pathological conditions like process such as fibrosis, ischemia, degeneration, myocarditis, mechanical stress, and others. All of these results in a poor electrical cells connections, allowing for easy electrical resonance and the maintenance of the atrial fibrillation. Ablation of atrial fibrillation as stabilizes the atrial walls and promotes important vagar denervation. It is currently used by us as a treatment for atrial fibrillation associated with pulmonary vein isolation. As I showed previously, we use the estra cardiac vari stimulation for checking the cardio neuroablation denervation. A catheter is a diversity through the internal jugular vein to the jugular foramen. At this point, non-contact vagal stimulation is easily achieved, causing a systolic or high grade AV block. The best cardio neuroablation any point is a time when this vagal response is completely eliminated. Assessment of the nervation in cardio ablation should be performed independently in three levels sinus node, AV node, and ather walls, given that different denervation may occur in each of them. Sinus node denervation is confirmed by repeating the extraracardiac vagal stimulation and observing the disappearance of sinus arrest or bradycardia induced before cardio ablation by the tracardiac vagal stimulation. AV node denervation is confirmed by the disappearance of AV blockage during atrial pacing and extraracardiac vagal stimulation induced before cardio ablation. And the atrial wall, the innervation is evaluated by 3 criteria. Before cardio ablation, the intracardiac vagal stimulation causes a huge reduction in the atrial refractory period, a large dispersion of the atrial refractoriness, and finally, induction of atrial fibrillation with a very short stimulus after cardjunal ablation. Atrial wall innervation is proven by normalization of the atrial refractory period, by disappearance of the dispersion of the refractory period, and finally by the impossibility of re-inducing atrial fibrillation with an extra stimulus. Induction of the atrial fibrillation by the vagal effect is clear in many cases, like in these patients, for example, that presented a spontaneous atrial fibrillation just induced by vagal stimulation. Therefore, the vagal denervation by cardio ablation added to the pulmonary vein isolation is highly desired. We may see that after the elimination of the acetylcholine, the sinus rhythm is recovered. In the same patient, a newest cardiac vagal stimulation identical to the previous one showed no more vagal effect and no more atrial fibrillation induction. Paterson and now showed that both cholinergic and adrenergic stimulation can abnormally increase the intracellular calcium load, giving rise to the calcium transient phenomenon which induces trigger activity that in turn may start the atrial fibrillation. In this interesting study, Sharifaveto demonstrated that both acetylcholine and adrenaline, when injected into the sinus node artery of dogs, each of them induces atrial fibrillation. This response is consistent with the calcium transient phenomenon described by Patterson. However, when adrenaline is injected after a tropinization, which blocks the vagal action. Atrial fibrillation is no longer induced even with high doses of adrenaline, showing that the vagal effect is the most powerful inducer of atrial fibrillation. Atrial fibrillation has predisposed to atrial fibrillation for several reasons, such as Their cells have a shorter refractory period. The separation of cells allows for multiple microreentries under the heterogeneity of the vagal innervation, promotes intensive dispersion of the local refractoriness. In the effect study, Dressing all observed that no atrial fibrillation ablation success increased when epicardial ganglion. A plexi ablation was added to the pulmonary vein isolation. That may be explained because the epicardial ablation do not remove the disconnected cells of the atrial fibrillation that remains in the atrial wall. On the left we can see that under baseline conditions, the atrial refractory period determined with programmed atrial stimulation is 260. Seconds. However, on the right we observe that during vagal stimulation there is a significant reduction in atrial refractorines reaching 50 milliseconds. Consequently, atrial stimulation with such a short interval as 60 milliseconds is able to cause a response and immediately induce this atrial fibrillation. This confirms that vagal. promotes intense electrical instability of the aromyocardium and reinforces the idea that vagal denervation is very important for the treatment of atrial fibrillation. After the cardio nerve ablation, a new refractory periodic determination under vagal stimulation was performed. However, instead of reduction, the atrial refractory period show is. Light increased to 280 milliseconds, and the two significant changes occurred during vagal stimulation. Firstly, the atrial refractory period no longer decreased with vagal stimulation. And secondly, it was no longer possible to reinduce the atrial fibrillation with programmed atrial stimulation. This fact demonstrates the great value. Of a vagal denervation in making the atrial walls electrically more stable, in this illustration, we observe an atrial fibrillation as with cells A and B, both having the same refractory period of 280 milliseconds. However, due to heterogeneity of your vagal innervation, only cell A experiences a significant effect from acetylcholine. Causing its refractory period to decrease sharply to 80 milliseconds, resulting in a substantial refractory dispersion of 200 milliseconds between cells A and B. This phenomenon is short-lived due to the fast inactivation of the acetylcholine by acetylcholinesterase. However, it is more than enough to trigger atrial fibrillation. To assess the impact of cardio ablation on atrial fibrillation ablation, we compared the outcomes of two groups of patients with paroxysmal and persistent atrial fibrillation who underwent radiofrequency ablation with a follow-up period up to 54 months. The group represented in blue was treated with pulmonary vein isolation, PVI only, while the group represented in Red in addition to PVI was performed the cardio neuroablation with confirmation of the denervation through tardiac vagal stimulation. Acutely complete vagal denervation was achieved in 89% of cases. Comparing the recurrence-free survival curves, it was observed that in the PVI cardio neuroablation treated group there were 6 recurrences, whereas In the PVI only group there were 17 recurrences. It shows that the risk of atrial fibrillation recurrence in PVI plus cardioc neuroablation is 4.81 times lower compared to PVI only group with a highly significant log rank of 0.001. This study demonstrates that the addition of cardio ablation to PVI. Confirming the innervation by extraracardiac vag stimulation significantly reduces the atrial fibrillation recurrency in atrial fibrillation ablation. Currently, several studies are replicating the finding that the greater the vagal denervation, the greater the success of atrial fibrillation ablation. In this meta-analysis, Zhang Tao studied 2,352 patients undergoing RI ablation and confirmed that vagal denervation was inversely related to atrial fibrillation recurrence. Several studies have shown that atrial fibrillation ablation causes some degree of vagal denervation. In the ATRI study, there was an association between reduced the vagal effect and mortality. However, association is not causation. Therefore, it is essential to investigate whether vagal denervation increases mortality. In this regard, Ackerson et al. studied 5,628 patients undergoing atrial fibrillation ablation, comparing them with a group of. Of equal size under clinical treatment at the end of 4.5 years of follow up, the ablation treated group which naturally experienced the nervation had a significantly lower mortality, nearly half of the mortality observed in the clinically treated group. Therefore, the association of cardio neuroablation to atrial fibrillation ablation. Appears to be highly desirable in all aspects. In conclusion, we may say that vagal action is one of the most powerful inducers of atrial fibrillation. The recurrence of atrial fibrillation after atrial fibrillation ablation is higher when heart rate variability is greater, indicating that a low vagal denervation is associated with high recurrence rate. Adding cardio neuroablation to atrial fibrillation ablation, confirming the innervation through extraracardiac vagal stimulation, significantly increases the success rate of atrial fibrillation ablation without increasing complications. Considering that atrial fibrillation are found in both the venous and the neuroinar phase, we concluded that under ideal conditions, atrial fibrillation ablation should include both the isolation of the veno atrial junction as well as the neuroatrial junction. Thank you so much for listening to my presentation. Thank you, Doctor Pashan. Thank you. Thank you so much. Thank you, Brian. I'm really looking forward to what unfolds with all of that, with everything we saw today. Um, with PFA and what it's gonna do to, to CNA and a fib ablation, um, and your work with a fib, um. It's, it's really going to be interesting. I expect that as PFA becomes more and more available, we're going to see the greater and greater need of, you need to do CNA at the same time. Yes. Yes, it's a, it's a good thing to, to, to see because we have to, to take into account that PFA is used to ablate Afib. And if you, if you want to denervate to get better results of atrial fibrillation, we have to think about it. Yep. Fortunately, being in pediatrics, I don't have to think about it at all. Yes, yes, it's one question, uh, sorry, from, uh, Jesus Daniel, a question for the table. Could CNA abolish not only bradycardia but the basal gerri reflex itself, eliminating the interplay of parasympathetic fibers from the atria to the ventricle? It could explain its supposed efficacy in vasodepressor syncope. Yes, I, uh, uh, uh, the, the question of, uh, uh, vagal fibers in the ventricle, it's very interesting, very important because we have, uh, it is difficult to, to prove this. But we have been doing with my, my team, they are very skillful in this. Uh, uh, we are doing a, uh, uh, an, a study, uh, comparing the, uh, behavior of the HOO and the vent. during vagal stimulation and it is easy to see if there is a vagal effect or not in one chamber studying the refractory period and we are comparing the refracted period during a vagal stimulation in the atrium goes down to 260 milliseconds to 60 milliseconds. It's incredible. Reduction of the atrial refractory period, but in ventricle, there is no change in the refractory period. We have been studying even in brugada syndrome in the region of the brugada in order to see if there is some vagal innervation in these patients, but there is no change, thanks God. Thanks God, because we know that vagal innervation causes fibrillation. So in the ventricle, there is no response of the waggle in relation to the refractory period. So I think it probably, it will be we have no change in this case. So a couple more questions. Uh, Jamie Roddey had a question about uh your typical uh CNA candidate patients about approximately how many you would see in a year and then uh to understand the future of CNA. If you would see all EPs offering CNA uh uh for their patients, and will there be limited offerings from selected institutions, so how do you see the future of CNA within uh EP in general? And in, in how many cases? For CNA, uh, nowadays, we are doing cardio ablation, uh, obviously in all patients presenting a good, uh, cardiac condition and, uh, symptomatic functional bra arrhythmias. In all cases, it is, uh, uh, I, I can see that is, um, a small population. However, we are doing cardio ablation in all cases of atrial fibrillation ablation. So the number is too high, and we are observing that doing cardio ablation in atrial fibrillation patients is possible to reduce 5 times the recurrence rate in the outcome. Looking at the, the pediatric world, you know, 1 out of 300 children has SVT and I've, I've made a career out of blading SVT and, but 1 out of, Three children pass out. Um, so syncope in the pediatric age age group is 100 times more common than SVT, and a third of them pass out recurrently. So I think once the FDA approves CNA as a procedure. I anticipate the floodgates are going to open. I, I, I do believe that, yeah. I don't see uh any other questions. I actually, I did have one question, uh, for you, Doctor Sean, uh, and that comes to imagery, uh, pre-procedural imagery. Uh, you know, with your talk on, uh, fibrosis and, uh, AF and as it relates to AF, it seems that there's starting to be more and more pre-procedural imaging happening. Do you see that as help with not only identifying your ganglion plexi locations but your fibrotic fibrillatory zones. It is a very important question, Brian, and during the mapping, it's possible to, there is a very important finding. If you see the high frequency uh superimposed, overimposed to the low frequency, it's innervation. But if you see the high frequency aside of the low frequency, it is fibrosis. It is obviously there are some uh uh mixing about these uh figures, about these pictures, but the innervation causes a high frequency over the, the low frequency at the same time and the fibrosis causes uh the, the, the, the high frequency is late in the fibrosis. And, and, and, and about the imaging, uh uh uh pre-procedure imaging, for example, and I, uh, probably the, uh, obviously, the magnetic resonance of the H2O, it probably would be uh very, very important. Obviously, it's possible to see that there is a high amount of fibrosis in the ATOO. But I think for um the, In our population, probably only you see a low amount of fibrosis in our patients with cardio neuroablation, but for atrial fibrillation, I think it's very important because if you see a high amount of fibrosis, obviously it will be a case with not so good outcome. Obviously the size of the atrium as well. Once they do you have a cutoff as far as size of the atrium goes, when you start to think success? Yes, obviously in my population of patients submitted to cardio ablation, the size of the atrium is normally under 245 millimeters. And, uh, obviously, if the atrial is enlarged, uh, surely there will be a fibrosis and obviously, you, you, you have in this case, the third type of atrial fibrillation is. That is not related much related to the innervation and it's more related to fibrosis. This kind of atrial fibrillation is more difficult to eliminate and depends more from the mapper. It's more your issue. The mapper's fault. Yes, yes, yes. Uh, lastly, from Amir Nawar, can you mention alternative intracardiac sites for vagal stimulation? Um, that is, uh, uh, the, uh, it is a, a, a very interesting question because it's many authors are using high frequency simulation in, in, in stimulation inside of the EO. So, it is very interesting. However, there is a problem. If you want to treat the tree. You don't have to stimulate uh the levels, OK. Uh you have to, if you use it to uh stimulate the, uh, the vagus, we, we will see how the whole innervation. But if you uh stimulate the last portion inside of the aer wall, you will see only a short. more warrior more warrior. So you know that the cardio inhibitory reflex is a massive reflex. It's a reflex from the trunk of the vagus. So to study, to deal with this condition, it's necessary to stimulate the trunk. Of the vagus in the, in the origin of the vagus to see the effect in all parts of the atom. So it's possible obviously to study a small portion of the atom, but probably it will be more difficult to solve a problem that is a massive response.