CNA Conference - Dr. José Carlos Pachón - History and technique for CNA

I now have the pleasure and honor to introduce Doctor Jose Patton. Um, of course, he needs no introduction amongst us here. Um, he's a director of the Sao Paulo Heart Institute, uh, arrhythmia Services, and, uh, certainly the, as we know, the pioneer of cardio neuroablation, um, and therefore, his knowledge and experience in this field is, is unmatched. Um, but even more than that, I, I find him to be a great man, and he's become a great friend as well. And so, um, I think we will, uh, enjoy his presentation on the, um, history and technique of cardio neuroablation. Greetings to all. 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 servicing of the Sao Paulo Heart Hospital. I'm going to talk about cardio neuroablation, history, and techniques. Thank you very much for your attention. In the 90s, through online spectral analysis of the atrial electrical potentials during sinus rhythm, we found that the atrial myocardium consists of electrically well connected cells, the compact myocardium, and disconnected cells, the fibrillar myocardium. They later comprises the atrial fibrillation nest. In a normal heart, most atrial fibrillation are related to the entry of atrial innervation and also to interface of the pulmonary veins, being the most important atrial fibrillation substratum. We observed that the ablation of the atrial fibrillation had two remarkable consequences. It causes a notable atrial stability, allowing the atrial fibrillation ablation, and in addition led to a significant vagal denervation, giving rise to cardio neuroablation. We developed the cardio neur ablation in the 90s and patented it in the USA in 2005. The aim was to get long term vagal innervation attenuation for treating functional brady arrhythmias without pacemaker and also for treating atrial fibrillation. We proposed the short CNA to remember the origin of the procedure. Cardio neuroablation is an endocardial atrial ablation to get vagal effect attenuation. Only the parasympathetic neural body is located in the atrial wall, and only this can be eliminated by endocardial RF energy. In normal conditions, it releases acetylcholine that acts on muscarinic receptors in the atrium, causing extreme cardio inhibition, transient cardiac arrest, and a huge atrial refractory dispersion. The muscarinic effects are completely eliminated by atropy. Sympathetic and the sensory neurons are away from the heart and protected from RF. Therefore, their neural bodies are preserved and their fibers recovered in a few weeks. After cardio neuroablation, there is an important and persistent chronic reduction in both the parasympathetic and the sympathetic tone. During cardio ablation, longer radiofrequency applications are required in the presumed areas of the four main gangrenated duplexites. They place one between the superior vena cava and the aorta, they place you near the insertion of the right pulmonary veins, the place 3 in the region of the coronary sinusoum, and the place 4 near the insertion of the left pulmonary veins. Cardio neuroablation mapping tools. In 2005, we developed a software in cooperation with Saint Jude Medical to mark innervation on the electroanatomical model. In this figure, the gray areas show regions with a high probability of innervation, while the purple areas show myocardium with a low likelihood of innervation. A significant part of the innervation map overlaps with the main ganglionated plexi. In these areas, ablations should be longer to achieve a transmodal effect. Here there is a map reaching complete acute elimination of the vagal response. The most important elevation area is called point because it gives us. to most innervation of B cells and sinus node. It is in the left interatrial septum between the insertion of the right pulmonary veins, roof of the left atrium, and fossa valleys. The GP2 area is usually near located in the insertion of the right superior pulmonary vein. The GP3 area is typically assessed at the insertion of the coronary sinus and in the region of the marshalls vein in the roof of the coronary sinus. The GP4 area is closer to the insertion of the left pulmonary vein, and the GP1 area is assessed immediately in the superior vena cava. In some cases may be necessary ablation of the Waterstone groove and other areas indicated by the fractionation mapping and two vagal effect elimination controlled by the intracardiac vagal stimulation, cardio neuroablation control and end point in addition to the mapping system. It was necessary to create a way to directly measure the vagal denervation. We developed the intracardiac vagal stimulation to confirm the denervation during the cardio ablation. A catheter is a diversity through the internal jugular vein into the jugular foramen where we can easily obtain non-contact vagal stimulation. The typical response is a systolic or high grade AV block, and at the end of the procedure, these vagar responses must be eliminated as the best end point. Here there is a real example of the tach cardiac vag stimulation in a patient with neurocardiogenic syncope. In the upper tracing, we see that 5 seconds of vagal stimulation causes an immediate pause due to the action of the acetylcholine on the M2 muscarinic receptors of the sinus node. With the rapid metabolization of the acetylcholine by acetylcholinesterase, that is a fast recovery of the sinus rhythm. In the lower tracing, the extra cardiac vagal stimulation was repeatedly after cardio neuroablation was ended. There is a complete absence of the vagal effect with no bradycardia, no pulses, and neither AV block, demonstrating that the cardio ablation was successful. The tracardiac vag stimulation offers the best ending point for cardio neuroablation. In this study we compared the anatomical cardio nerve ablation with the electrophysiological cardio neuroablation controlled with vagal stimulation to get the best the nervation end point. The cardial nerve ablation controlled with vagal stimulation by eliminating. The Wegl effect has a 5-fold lower recurrency of syncope in 5 years. In addition, vagal stimulation is very important to mitigate the undesirable effect of the operator's learning curve. Cardio neuroablation results. We performed the first cardio neuroablation in 1998. In this trial, we found a remarkable effect in five cases of neurocardiogenic syncope, 7 functional atrioventricular blocks, 13 sinus node dysfunction, and 90 cases of paroxysmal atrial fibrillation. Covering the main indications for cardio neuroablation, Cardio neuroablation should be indicated only in patients presenting functional disturbances without significant cardopathy. Based on this, the patient may have symptoms clinically refractory, absence of significant cardopathy, and good response to atropine. The first randomized controlled trial was published in 2022 by the Poland Group of Roman et al. showing the effectiveness of cardio neuroablation in cardio inhibitory neurocardiogenic syncope. There was 8% of recurrence of syncope with cardio neuroablation versus 54% recurrence with clinical treatment in two years follow up. In addition, there was a very significant increase in quality of life. The cardio neuroablation results have been improving significantly with the progress of the technique and with evolution of the learning curve. In the red plot, we can see the syncope-free survival of empirical cardio ablation without vagal stimulation control. The survival plot in blue shows the clinical follow-up after cardio neuroablation controlled with extra cardiac vagal stimulation, ending the procedure with confirmation of denervation. In green, we see the results of the clinical treatment published in the trial by Roman et al. In purple, we see the results of the Roman trial. They first randomized trial of cardio neuroablation. Finally, in blue, there is the result of the Spain trial using. A pacemaker. However, the comparison is hampered by the short follow-up. In our experience, cardio neuroablation controlled with vagal stimulation allows syncope-free survival in near 90% of cases in a long follow-up, up to 60 months. We observed a low incidence of complications with only 8% of cases comprising sinus tachycardia, sinus bradycardia, accelerated junction of rhythm, and inguinal hematoma. All of these were successfully managed with clinical treatment. Surgical intervention was not necessary. Symptomatic sinus tachycardia is. Exceedingly rare, occurring in less than 3% of cases and typically resolves with beta blocker treatment within a few weeks. Is there any risk resulting from the cardio neuroablation vagal tone reduction? In this picture, we see the Kappler Meyer survival curves from the ATremi study illustrating a rise in cardiac mortality. Falling myocardial infarction in the group exhibiting non-sustained ventricular tachycardia and low heart rate variability, specifically with uh SDNN less than 70 milliseconds. Given that the cardio ablation also induces a heart rate variability reduction, it becomes imperative to assess the potential risks associated. Associated with cardio nerve ablation. In the myocardial infarction, the autonomic nervous system initially increases the myocardial function through a primary surgery in sympathetic to, which consequently raises the risk of life-threatening arrhythmias and soothing death. There is also a secondary and reflexive reduction in parasympathetic tone. Mortality is due to the association of the myocardial injury and the high sympathetic activity with the high risk of ventricular arrhythmias. The reduction in vagaltonin is only an associated consequence. Conversely, in cardio neuroablation, myocardial function remains normal, totally different from the post-myocardial infarction scenario. In cardio neuroablation, there is a primary reduction in vagal tone and also a secondary reduction in sympathetic toning, resulting in a decreased risk of arrhythmias, an outcome highly desirable in clinical practice. After cardio neuroablation, there is a physiological partial brain nervation. In this study of 83 patients without myocardial infarction. We found a clear and significant reduction in both the sympathetic and parasympathetic tone in 2 years post cardio ablation. Fagal denervation also occurs from the atrial fibrillation ablation. In that study, Ken et al. reported significant vagal denervation following atrial fibrillation RF ablation. Consequently, atrial fibrillation RF ablation serves as an excellent model for cardio neuroablation study, and its extensive worldwide utilization involving over a million cases provides robust evidence supporting the safety of vagal denervation. In the Cabana and in the case of AF trial, there were a significant mortality reduction of 28 and 38% respectively in the combined end point, even in high risk population with heart failure. This powerful data illustrated the high safety profile of the endocardiovagal denervation. In this study involving 83 patients who underwent cardio neuroablation followed it for 2 years. We observed a significant reduction in our atrial and ventricular tachy arrhythmias as well as brady arrhythmias. No proarrhythmia effects were detected, reinforcing the high safety profile of cardiac neuroablation. This graph plots sympathetic effect on the vertical axis against the parasympathetic effect on the horizontal axis. The high risk group post myocardial infarction is placed in the upper left quadrant due to an increase in sympathetic activity and the reduction on parasympathetic tone. In contrast, the cardio neural ablation. And the atrial fibrillation ablation group fits into the safe lower left quadrant due to reduction in the both sympathetic and parasympathetic tones. Thank you so much for listening to my presentation. Doctor Peon, thank you very much for that wonderful presentation. Uh, thank you very much for sharing with us, you know, how this technique was developed and how you've been able to share it with the rest of the world. So thank you very much for that. There's a question in the chat I'm going to read out from, um, Kamal Kotak, um, who asked the question, uh, when did you do your first CNA and what did you tell the patient, um, especially when it was a time where there was basically zero experience at that time. OK. Yes, it is a, a, a very important question because the first procedure was performed in 19 in 1988, and 1988. So, um, it was in the last millennium. And, uh, we are doing, uh, having now uh more than, uh, in about 2025 years of follow-up. So in that time, it was easy to, uh, propose the procedure for the patient because it, uh, he was a very young patient with very long pauses, very symptomatic, and he was referred to pacemaker implantation. So, the question was to Choose between the pacemaker implantation or a possibility of having an ablation to solve the problem. And the patient was completely accepted the, the uh indication of ablation. And obviously, he was uh clarified about the uh possibility of the ablation, about the pros and cons of the ablation, and fortunately, the results were, uh, were, were very, very good. Yeah, wonderful to hear that story. I mean, it's, it's incredible what these things, what, what this procedure is doing for, for patients. So, it's very, very wonderful. Another question from the chat, um, it says, Doctor, Doctor, uh, Professor Pishon, beautiful presentation, I would like to ask you and the panel, how do you set up your ablation catheter during CNA? That is, how many watts, um, during the duration of the lesions and, uh, how you're using some same, some lesion parameters, um, or similar. Many thanks. Uh, OK, thank you very much for your question. I am using now the same uh Uh, set up for atrial fibrillation, uh, because obviously, it's a new procedure. So, um based on a procedure that was very well known in that time, and we, uh, uh, uh, we as a, uh, enthusiastic about to increase the energy, but uh I preferred in that time to use the same setup of atrial fibrillation in order because this setup is very well known. And it's very safe. So you use the same setup for uh atrial fibrillation ablation, 30 wards. And obviously, uh, during the procedure in areas of uh uh presumably areas of the AGP we use it to apply, until 1 minute, 60 seconds of energy in order to get the probably a more deep effect of the air. So, uh, use the same setup of atrial fibrillation because I think it is the most safe. Uh, the, the possibility of using high energy in order to get more, uh, epicardial surface is, uh, uh, enthusiastic, but I have to, we have to take care about complications, right, right, right, good point. Another question from the chat, uh, this is from Wei Shanqi, who asked, um, let's say we do a sham control, uh, if we perform ECVS for normal subjects without syncope, do we, uh, do we able to see the pause as well? Yes, thank you for the, the question. Yes, uh, the palsy of the vagus is, uh, occurs in all people. If there is no palsy during the extracardiac vagus stimulation, it's because there is a pathological condition. There is a previous denervation. It is rare, but some patients present a very low response to vagus. But probably if you stimulate the left vagus, there is a higher response. There is only unbalancing of the response. But in all people there is a vagal response, but it is. Easy to get information about it. It's only to see if the patient in Holter presents some SDMN value, because if there is vagal representation during the heart rate variability, it's because this patient will have a very good response to the cardiac vagal stimulation. Thank you. Thank you, Jose, so much for your experience and your willingness to share your information. Yeah, thank you. You know, let me ask you a personal question, Doctor Fan. Um, you know, since you've been doing this for so many years and, and having developed this procedure, um, what kind of challenges did you face when it came to disseminating this procedure and How did you deal with that kind of a thing? That it is very important because my, I was worried about uh uh the popularization of the procedure without criteria. The most important for me is scientific criteria because of it, after developing the procedure. I developed the the stach cardiac vagal stimulation because it's easy during any ablation to see an increase of the heart rate, but it doesn't uh uh mean uh the nervation. So, my, my challenge was to disseminate it, uh, uh, uh, disseminate the pro the process uh without popularization and with scientific criteria. Hence the extra cardiac stimulation. So thank you. That's, that's very helpful. Thank you.