CNA Conference - Dr. Juan Zerpa - Atropine test to estimate response in potential CNA candidates.

OK. Our next speaker is Doctor Juan Zerpa. From The heart hospital in Sao Paulo, Brazil. Uh, a colleague of Doctor Bashan and a, a good friend of ours, and Juan will be speaking today about atropine test to estimate response in potential CNA candidates. My name is Juan Carlos Herva. I'm a cardiac electrophysiologist from Sao Paulo, Brazil. I'd like to thank Doctor Patro and Doctor Clark for extending this pleasing invitation to me. It's an honor to be part of the history of the cardio neuroablation. Now, at the 2nd War Cardio Ablation Congress. We are increasingly convinced that the critical step in cardio neuroablation procedure is the patient selection process. In the following minutes, we will explore how we can unlock the potential of the atrophy challenge in predicting the outcomes of the carbon neur ablation. We will also discuss its application as a valuable tool, estimating responses in potential candidates and when venturing into new scenarios. I have no disclosures for this presentation. Atropin is an active anticholinergic agent derived from various belladonna plants such as the deadly nightshade. Its roots trace back thousands of years ago to India, where distract from belladonna plants were used to relieve respiratory symptoms. In 1831, ropy was isolated as its pure form by Dr. Mayne. And a few years later, in 1867, Doctors Besso and Bluman demonstrated that atropine could block the cardiac effects of vagal stimulation. Atropy primarily acts on the type 2 muscarinic receptors in the heart, located in the sinoatrial node, atraventricular node, and cardiac muscular fibers. Activation of these receptors by vagus nerve, leads to a parasympathetic response, resulting in a decrease in the heart rate and cardiac force of contraction. As you well know, the postganglionic parasympathetic neurons are short and are located near the heart within the outer wall. During vagal stimulation, acetylcholine released at this point caused asystole and AV block. By blocking these receptors, atropin prevents the action of the vagus nerve and increases heart rate and force of cardiac contraction. Cardio neuroablation was created in the 1990s by Professor Pashon with the aim of achieving vagal denervation through ablation. This involved ablating the atrial wall via endocardial axis. At this time, Doctor Bashon recognized that this approach could be employed to treat various conditions, including vasovagal syncope, functional bradyarrhythmias, sinus node dysfunction, and atrial fibrillation. All related to elevated vagal tone without the need of the pacemaker implantation. Numerous studies have demonstrated that cardio ablation also results blocking the vagal reaction by partially eliminating postganglionic parasympathetic neurons and nerve fibers. Vogal innervation typically maintains autonomic tone predominance for the most of the time. When we study isolated innervated hearts, we observed higher sinus rates and bankable cycle lengths compared to non-dennervated hearts. The effects of the atropine help us replicate this situation, highlighting the significance of the atropy test in the pre-procedure evaluation. During cardiac ablation, there is a typical increase in the heart rate and be back point like this obtained after administering atropine. There is an ample evidence available regarding the indications of atropy in symptomatic bradycardia. Atropy is used as first-line therapy of symptomatic bradycardia in the absence of reverse reversible causes. And when the heart rate is less than 50 beats per minute, with unstable vital signs. It is crucial to rule out structural conduction system disease as the cause. Almost 20% of the body arrhythmias are caused by the structural damage. The standard dose recommended in the guidelines for emergency use is 1 mg every 3 to 5 minutes with a maximum dose of 3 mg, and it is most effective in sinus and biodal disease. This may be a subdose in the atropine test challenge, but what is the exactly dose recommended for the atropine challenge? And for that, let's go back a little to see studies involving intrinsic heart rate. These studies use beta blockers and atropine to achieve autonomic blockade. Aiming to record a stable heart rate and the differences between populations. This is related in some ways to the functional state of the myocardium. A combination of 0.2 mg of propranolol and 0.04 mg per kilo of atropine injected intravenously over 2 to 3 minutes is used to measure the intrinsic heart rate, and we measured this frequency five minutes after completing this injection. Atropin can mimic vagal denervation, leading to an acceleration of the sinolateral node, pacemaker cells, and atroventricular conduction, resulting in an increase in the heart rate and Winky buck cycle. In patients with bradyarrhythmias and sinus cell dysfunction, possible caused by vagal overactivity, the use of atropine can partially or completely restore heart function. In this table, adapted from the work of Doctor Simon Kai in Frontiers of Physiology, we may see that there is no unified standard. For this protocol and interpretation of the atropin test results. The doses used for the parameters for, and, and the parameters for the positive test are very similar. Distracted from these experiences, we may consider that the recommended atropine dose for the atropine challenge is 0.04 mg per kilo with a maximum dose of 2 mg, considering positive when there is an insignificant increase in the heart rate over 50% of the basal heart rate or higher than 19 beats per minute. Half action and time of action of the atropin. The action time of the atropin on the heart depends on the dose administered and the route of administration. When injected into a vein, atropin has a rapid onset of action, typically around 1 minute, with a duration approximately from 4 to 16 hours. The timing and elimination of the bagal effects of the bagal effects. Blockade can be different from patient to patient. Therefore, we recommend a window allowing at least 24 to 48 hours between the atropine test and the cardio neuroablation procedures. This ensures that the effects of atropine have sufficiently dissipated and will not interfere with the CNA analysis. Let's consider an example of a patient with a significant bradycardia, and during the atropin test, this heart rate increased to 103 beats per minute, which each, which is a remarkable 123% increase from the baseline. Additionally, the Wenkeb was 100 beats per minute before and increased to 182 beats per minute afterward, marking an important 82% of improvement. These results demonstrate an excellent response to atropy, making this a patient an ideal patient for cardio neural ablation. Helping us in the decision-maker of the process whether to indicate or not the cardio neural ablation. While atropin does not carry FDA boxed warnings and contraindications, we have to consider some specific situations. For example, an acute angle glaucoma or myasthenia gravis. In situations with elderly patients and patients with chronic lung diseases, patients suffering from obstructive diseases or prostatic hypertrophy. Tachycardia is the most common side effect of the atropine. Patients may also experience transient side effects, dry mouth, difficult to near vision, transient difficult to urinate. Lightheadedness and vague sense of discoordination and nausea. Atropine also inhibits secretions of the respiratory tract. This effect is particularly useful in pre-anesthetic medication. Therefore, it should be avoided in cardio nerve ablation procedures as it compromises the analysis of the nervation effects. But how can this information be useful? Let's see an example of an EP evaluation of a possible candidate for cardio ablation. Caheters are places in the heart, and this one for ECBS. Up to the internal jugullary vein close to the vagus nerve emerging site. We carried out a complete electrophysiological assessment, and when stimulating the right atrium just over 100 beats per minute, we observed a compromised AV nodal conduction. Breyback cycle of 104 beats per minute. Followed by a baseline tracardiac vagal stimulation, confirming the massive effect of the vagal stimulation with immediate release of acetylcholine, resulting in this tracing asystole due to the inhibitory effect over the sinus node. On the sequence, another extra cardiac vagal stimulation demonstrating the vagal effect now over the AV node with induction of a transient high grade AV block. And recovering conduction 1 to 1. And now let's see what happens after atropine infusion. When we do the atropine infusion and repeat this traccardia vagal stimulation, there is no systole. And considering that atropine blocks the vagal stimulation effect, we perform now another tracyric vagal stimulation. Now during a pace. And we may see that there is no atroventricular block. Knowing in advance that the heart rate sinus will increase and the winkyb point will improve is a crucial information in the indication of cardio neuroablation. In this work presented at the HRS 2022, we highlighted the value of the atropy test in predicting cardio ablation outcomes. The objective of this study was to assess whether there is a correlation between the heart rate and bunkeba point results from the atropin test and those obtained from the cardio ablation. We included 76 patients with situations caused by higher vagal tone such as neurocardiogenic syncope, sinus node dysfunction, and vagal atrial fibrillation and AV block, functional AV block. The mean age was 37 years old, and the atropin test was conducted at least 2 days before to ensure that any residual pharmacological vagal block was active. Bilateral cardioal ablation was performed by ablating the P point and the presumed areas of the four main glonic plexuses. The procedure was closely monitored by tracardiacc vagal stimulation to achieve complete elimination of the vagal response. We compare the maximum heart rate and the Winkyba point obtained under atropine administration with values measured at the end of the cardio ablation procedure. This comprehensive approach aimed to provide a clear understanding of the relationship between the atropin test and the cardio ablation outcomes. We observed initial baseline values of heart rate and winnkeback cycle, both of which showed significant increase after atropine administration. There was a consistent significant increase in the heart rate and Winkyback cycle both after with atropine and with cardio neuroablation. The reins, this reinforces the correlation between the effects of the atropine and cardio neuroablation on heart rate and Winky bicycle with minor differences in levels reached with cardio neuroablation. And one last example where we analyze a case treated with cardio nerve ablation where partial denervation was achieved with elimination of the specific cardio inhibition of the sinus node. This patient had a recurrence of the syncope crisis. Now in a different scenario. This cri this crisis now were related to periods of AV block triggered by stimulation of the carotid sinus. During electrophysiological reevaluation, a new carotid sinus massage was performed, achieving the reproduction of the symptoms caused by high-degree AV block. And after administration of atropine, this cardiac inhibition was eliminated. This helped us guide the treatment towards a new cardio ablation, now aiming the result obtained with atropin on the AV node guided through intracardiac vagal stimulation. As we conclude this presentation, we can affirm. That there is a strong correlation between the atropine effects of atropin and cardio ablation on sinus rate and Winkyback cycle changes. The atropy test serves as a reliable predictor of the carrier ablation results. Atropin is a valuable marker for identifying functional bra arrhythmias and to exclude organic causes. Cardenal ablation should not be considered if the atropin test yields negative results. Finally, it is important to note that the use of atropine during the ablation procedures blocks the vagal effect and can compromise the understanding of the results of the cardinal ablation. Hello Juan. Hi, how are you doing? Doing wonderful. Really happy to see you all guys working on a You look like you're suffering miserably in Mexico. Yeah, this is, this is a hard life in here. It's so cloudy day. I cannot see the sun. How are you guys? Great, thank you for that presentation. We are enjoying the, the Congress already. These are amazing presentations. I'll be following all of them. Yes, and the diversity of the information that we have here today has been great. And yours included, and thank you. Thank you. I have a couple of questions. Um, First, does, does everybody need an atropine test before the procedure, i.e., if I have a 19 year old healthy female with vasovagal syncope and documented cardio inhibition, um, is there any reason for me to expect that her atropine test is not going to be positive beforehand? Maybe it's, it's gonna be a great response with atropy, uh, as we are starting work, this work with cardio ablation, the most information that you have before the procedure helps you to prepare to what you're gonna expect during the ablation. It's not, uh, a, a significant indication that you only have to do the atrophy for everybody if you have. The record and register of the asystole of the car inhibition. Maybe you cannot, you, you don't have to use the atropy because you expect to have a good response. But in some patients that you want to prevent, predict predict the the response, it's gonna be useful. Um John, this, this aspect is very important because we, uh, many times, uh, several, um uh uh uh uh uh physicians of the team are doing a procedure. And say that there is no increase of the heart rate during the ablation of the ROPE of the, uh, the ganglia. There is no increasing. So, uh, Doctor Paon, what is the problem? Uh, I ask them, how was the atropine response. Uh, the atropin was not performed. The atropin test was not performed. So, uh, uh, uh, obviously, the atropin test give us that information about the possible response. One showed that there is a, uh, a, a close correlation. Uh, between the response of atropine and the response to cardio neuroablation. So, obviously, it, it, it will be very interesting to have the atropine testing in all patients. Uh, and the atropine testing is possible to do, uh, 2 days before or 111 week before the procedure in uh in uh ambulatory environment. It's not necessarily the A lab to do the atropine test. However, obviously there are a lot of patients with high heart rate variability, very high heart rate variability, and clinical conditions without signs of cardopathy, and I think in this case it's not necessary to do the atropine test. I think it would be great for the database in terms of looking at patient age. Because my prediction would be in, in an otherwise healthy person 20 years or under, their atropine response would always be to accelerate the heart rate. And so I, I think, uh, let me see something. If you want to eliminate a vagal reflex response, there is no issue about age. You may do the procedure in any age, but if you want to eliminate the basal vagal tone, obviously the age is very important because as uh age is higher, there is less response, right. We have a, a couple of other questions. Um, From Jesus Daniel, if you cannot pace the vagus, is there any other alternatives? I'm thinking aortic caval ganglia or left superior pulmonary vein. Pulmonary artery. Pulmonary artery. Sorry. Well, you have for sure other, uh, options that you can use. The atropine is one of those, but it's gonna be reserved to the end of the procedure. You cannot use it during the procedure at the beginning, so you have to work with your anesthetist and make this be clear that atropine is forbidden on the end, on the beginning of the procedure. High frequency stimulation helps us to evaluate these kind of, of responses but have some limitations. So we have to try some alternative. I think Doctor Paon is working on that and he has some comments on the alternatives that we have for vagal stimulation. Uh Uh, let me have only, uh, a comment about the Javier, um, question, OK, and, because it is reasonable highlighted question. Yes, yeah, I'll, I'll ask the question so everyone knows what you're, what you're answering. Uh, Javier Banks, is it reasonable to use atropine screening and heart rate response as a surrogate of success and skip the ECVS? Yes, uh, uh, uh, this question is very important, OK, because obviously if you use the atropine, you are seeing only, you, you are looking for only the end point, but if you use the. vague stimulation, we are having a control during the procedure. It is completely different. If you needed to have a control to, the cardiova stimulation is very important and necessary. Because after the atropin, there is, we, we destroy completely all vago parameters. So the atropin may be used as a last, last end point, but for control, the progress of the procedure is necessary to extracava stimulation. And if I may comment too, that, that is an issue that, that we can discuss because you perform the whole ablation procedure and at the end of the procedure, you go for atropine infusion and you have increase of the heart rate. So you don't, you didn't achieve the, the highest level of vagal denervation, and this is something that we solve using this tachardiovagal stimulation. You do a logical and sequential denervation to get you. To the highest level. At this point you can finish and do the atropy if you want or not, but the atropine test is an endpoint that has so many limitations if you have no, no high denervation level achieved at the end of the procedure. There is a, a, a very important point, Juan, that uh after the procedure at the, at the end of the cardio ablation, when we decided to, to do the atropin test again, uh, the patient is different. From the patient that was tested before we testedropine because now we have a lot of uh uh sympathetic endings that were destroyed by the procedure. So it's, the patient is completely different. Before of all, there is an increase of the heart rate. So the sensitivity of the atropine test after the increase of heart rate is not, is, is not complete. So there is a different condition. And also, There is an elimination of part of the sympathetic system. So it's another situation. Obviously, the entropy testing, if you have, if you see a, a, a high response to atropy at the end of the procedure, we may conclude that your procedure was not so good, right? I think you have to ablate more and you don't have that control at the end. Yes. So, Juan, there's several questions still, but we're gonna have time for just one more from Moises Rodriguez Monaro. In case you had a treadmill test, observing appropriate AV recovery, in the case of functional AV block, do you still perform atropine test? For the AV block the nervation, the cardio nervation directive for AV block, I always perform the atropy test because I want to know under the conditions of the procedure, how, how am I gonna, how am I gonna improve this AV conduction. So you can, you can decide that this is an ideal patient with the atropy is gonna be a stronger, uh. Signal that you're gonna consider. Uh there is a very important question, John, about this situation comparing the treadmill test with atropin tests. They are very, very different because during the, the treadmill, there is a reduction of the waggle tone but increase of. Symphoecton. During the atropin test, there is reduction of the phalton and reduction of the sympathecton. So it is completely different. It's not possible to transport the results of the treadmill testing to the atropin test are completely different. Good point. You can use it as a marker. This patient goes good and they induce the atropine. Thank you, Doctor Zerpa. You're gonna be getting a few other questions in your email box. So, OK, I got it. Appreciate your Nice seeing you. Good luck. Safe travels. Big hug.