CNA Conference - Dr. Roman Piotrowski - Randomized trials for CNA: what’s been done and what remains to be done

OK. Let's, let's go ahead. I, uh, now I have the great pleasure to introducing, uh, Doctor Roman Piotrowski for the next presentation. Uh, Doctor Roman Piotrowski is professor of the Center of Postgraduate Medical Education, Department of Cardiology in Groszowski Hospital in Warsaw, Poland. It's very important because the, uh, the, the group, uh, uh. group was developed the first trial, the first randomized trial about cardio neuroablation, and he is going to present randomized trials for cardio neuroablation. What's being done and what remains to be done. Good afternoon, gentlemen, ladies and gentlemen. Firstly, I would like to thank Doctor Patan and Doctor Clark for the invitation to the Second World Symposium on cardio neuroablation. Uh, today, I'm going to talk about randomized trials for cardio neuroablation and try to answer two important questions. First question is, what's been done, and the second question is what remains to do. So let's get to the point. But first, I would like to provide a definition because appropriate data will be presented based on it. So what is a controlled clinical trial? According to the definition, It's a clinical study that compares the experimental interventions with the current standard of treatment placebo or no treatment. And regarding cardio ablation, before there was a controlled study, there had to be the first report that showed that cardio ablation was feasible and effective, and this first step was initiated by Professor Paon, who with his two publications in 2005 and 2011, uh, not only created cardio ablation, but also showed that this new method is feasible, safe and effective. And since then, there have been many other reports on cardio ablation, but among them there are only a few randomized trials. For the purposes of this lecture, I use the PubMed database and the research gate portal to search for the data. The search phrases were cardio neuroablation or cardio neural ablation, so I found 141 articles for cardio neuroablation and 4 articles for cardio neural ablation. And what exactly did I find? I found numerous case reports and case series, a few studies with control group, but non-randomized and just retrospective, one small randomized prospective study, one small randomized prospective animal study, a few technical randomized technical reports, one big meta-analysis, one big report on controversies in carionary ablation, and a few review articles. So as you can see here, so of all publications, only 5 are randomized. And now I would like to present individual publications. So the first study is a study from my center, and this is the first randomized trial comparing cardio neuroablation versus optimal non-pharmaceutical treatment recommended by current guidelines for syncope. In our study, 48 patients were included and randomized into two groups, in cardio neuroablation group and non-pharmacological treatment group. Follow-up lasted 2 years, and the primary endpoint was time to sync up your recurrence, and the secondary end point in our study was the changes in quality of life. On the next slide, you can see clinical characteristics both study group and based on it, probably this is the most suitable group of patients undergo kind of neuroablation due to very symptomatic. Uh, and very long asystolic pause. And here are the results. After 2 years of follow up, syncope recurrence occurred in 2 patients in cardio ablation group, while in the conservative treatment group, syncope recurrence occurred in 13 patients. So the efficacy of cardio ablation was 82, and efficacy of conservative treatment was 46%. Moreover, as you can see here below, uh, cardio neuroablation significantly improves, improves quality of life. So to sum up, cardio neuroablation is not only more effective than conservative treatment recommended by the current guidelines, but also significantly improves the quality of life. The next randomized studies I would like to show are two technical reports conducted by Dr. Victor Reflom Ike from the Czech Republic and published as an abstract only. These two reports concern the issue of which aum, right or left, will provide full parasympathetic denervation of both the sinus node of the atroventricular node. In both reports, the cardio neuroablation was controlled by extra cardiac vagal stimulation. And as you can see here, here, and here. In both studies, the best approach was bilateralardioal ablation, which resulted in the highest rate of complete parasympathetic denervation. And here there is a study from my center. So this was the randomized study comparing a right versus left aual approach. In our study, 46 patients were enrolled, and the patients were randomized into two groups. In right atrial approach group and left atrial approach group, vagal elevation in both cases was conferred by extra cardiac vagal stimulation, and as you can see here in the right atrium group, efficacy was 37%. Why in the LA group, the efficacy was 82. In the right atrial group, 12 patients were cross overed, while in the left atrial group only 3 patients were crossoved. So finally, in all patients, parasympathetic devation was achieved. However, important conclusion from our study is left arterial approach is better than right aerial approach, but bilateral approach is probably the best. And the last study I would like to show you is the study conducted by the Shiv Kumar Group, and, and this study, uh, Included 16 peaks were divided into two groups, cardio neuroablation group and sham ablation group, and cardio neuroablation was controlled by extra cardiac vagal stimulation. And after cardio ablation and after sham ablation group, after 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation. And direct vagus nerve stimulation and moreover a proarrhythmic potential after left anterior anterior descending coronary artery irrigation was also assessed. So this study, this annual study showed that left sympathetic chain stimulation induced significant corrective QT interval prolongation in the cardio ablation group and ventricular arrhythmias. Such as ventricular tachycardia and ventricular fibrillation after LLA ligation was more prevalent and occurred earlier in the cardio ablation group. So this study is a warning sign. Yes, of course, but we don't know whether the study can be translated to humans because we know that pigs are about 3 times sensitive to the electrical induction on ventricular fibrillation than humans, and On the other hand, according to a study conducted by Doctor Wichterle during standard pulmonary vein isolation, total parasympathetic denervation was achieved in 100 for the sinus node and 90% for the atrioventricular node, so. Based on this and taking into consideration other data, we know that long-term mortality of patients underwent atrial fibrillation ablation is similar to general population. So this animal study introduced some uncertainty, but as I mentioned earlier, Um, it is an animal study and it's not known whether this can be translated to humans, and the data of patients undergoing AF ablation do not suggest an increased risk of proarrhythmia. So we need further studies assessing safety. And here, uh, I wanted to show ongoing studies which are listed below for you, and this studies covers important topics including comparing cardio ablation versus pacemaker implantation, cardio ablation versus pharmacological treatment such as midodrine. And most importantly, cardio ablation versus some procedure. So as you can see, over time, the results will appear and uh these results will position cardinal ablation in the future guidelines. So back to the title question, what has been done? So, so far, only two issues were resolved. First, the cardio ablation versus optimal non-pharmacological therapy. Uh, after first randomized trial, we know that cardio ablation is more effective than optimal non-pharmacological therapy and also improves quality of life. And the second issue is, uh, right atrial versus left atrial approach and, uh, from, uh, Technical reports we know that left atrial approach is better than right ale approach, but bilateral approach is probably the best. And the second title question, what remains to do. So we need to find an answer to the following question. The first question, cardio ablation versus placebo or sham procedure. The study is ongoing. The next question is cardio ablation versus spacing. These studies also are ongoing. The next, cardio neuroablation versus drug, uh, there is, uh, one study, a cardio neuroablation versus midodrine, and this study is ongoing, but there is no study which comparing cardio neuroablation versus the feeling in functional atraventricularro on the fluidrocortisone. The next, uh, question, which needs clarification is, uh, comparing right utter approach versus left utter approach versus bilateral approach. The next question is complete versus incomplete vagal derivation, uh, measured by extra cardiac vagal stimulation. Next question, full versus simplified cardio ablation. And also one most important uh question, very long term follow-up to determine the safety profile of cardio neuroablation. And going to the conclusions, we can conclude that cardio neuroablation is more effective than conservative treatment. Cardio ablation improves the quality of life. Cario ablation in the left atrium is more often associated with complete vagal denervation compared to the right atrium approach only. Uh, the next bilateral conti ablation may be a preferable approach. However, many specific issues still need to be clarified. Thank you for your attention. Thank you, Roman. Nice to see you. Thank you very much for supporting the meeting. It is an honor to be here. Uh, and, uh, with you. OK. And, uh, I would like to, to, to do some comments about the, the question of the studies of cardio nervation. Obviously, you, uh did in your service one of the most important trials about this technique. And obviously, uh, uh, several investigators that have been Suggesting the possibility of having shunt procedures, and as you know. So the problem I see is that it's necessary to put the patient in the lobby and put the catheters inside of the heart and also it's necessary to do ablations outside of the neural system. In another group, obviously we have to do the same, but ablating only. Areas of innervation. So I think it is very difficult because it is under the point of view of ethical. So to do ablation in without assessing the neurons and obviously in another group by eliminating the innervated areas. What do you think about it? So, uh, I think, uh, that, uh, cardio neuroablation versus shunt procedure is also unethical because how to explain the patient, uh, we, OK, introduced the catheter but maybe ablate, uh, the ganglionated plexi or not. So how to, uh, how to explain them. Uh, and on the other hand, uh, we should, uh, take into consideration, uh, AF ablation because, uh, AF ablation has a strongly class of recommendation. But, uh, never there is uh no studies which comparing AF ablation versus sham procedure, so we don't, I think, and there is the same like Diamond Vichterle uh said after AVNRT ablation we see that, uh, ablation of AVNRT works, uh, so the same is, uh, in the situation with cardio neuroablation. So I think, uh, the data. Uh, it's enough to obtain, uh, the, uh, maybe, uh, 2A class of recommendation and not, not more, but maybe, uh, the studies with, uh, sham procedure or placebo, uh, allows to obtain a higher class of recommendation. That's, that's my opinion, but uh in my center, it's, it's unethical, I think and uh I think uh your point of view is, is, is correct for me. Yes, we, we have to take into account that the cardio ablation has a very important tool to uh uh to separate the placebo effect of the therapeutic effect because it's possible to follow the patient by using the heart rate variability by All the timing of the, of the lifetime of the patient. So it's possible even to see if there is reinnervation in, in each case. So I, I think we have, uh, tools that may be enough and to avoid the unethical procedures. Yeah, I agree with you. Yeah. OK, John, go ahead. Yeah, you know, just listening to that discussion about sham procedures and, and I'm probably jumping the gun to another upcoming lecture, in fact, the next one. It, it seems like, uh, pulse field ablation for AF might, might be the area where you can get the sham procedure, uh, because that's gonna do minimal damage to the autonomics, and you could randomize patients blindedly, so they don't know if they got an autonomic ablation or not. Um, and maybe that's the way that we get to that point. OK. Yeah, and I think another area where lots of research needs to be done, of course, is the pediatric population as well. Um, these are going to be around for a very long time and that's another big area, um, that we need to, uh, focus on, uh, coming up soon. Thank you, Doctor Pierachowski. Thank you.