It's my pleasure and my honor to welcome all of you and share this table with Dr. Carlos De La Fuente. Dr. Carlos De La Fuente is a cardiologist and electrophysiologist in the Cardiovascular Institute of Puebla. I am Dr. Ana Cláudia Venâncio, an electrophysiologist also in Monsenay Hospital in Juiz de Fora, Minas Gerais, Brazil. This is our last section in this fantastic 6th Latin American Heart Britain Society Congress. Also, I would like to thank Dr. Ulysses Roel and his scientific committee for inviting me and to take part of this fantastic and amazing with so successful lectures that we have been seeing the last two days. This is the last one, but not least important, and we're going to have lectures updating about atrial fibrillation. And I will invite Dr. Jason Andrade to speak about atrial fibrillation and heart failure, what we know, what do we know. Dr. Jason Andrade is a cardiologist electrophysiologist in Vancouver General Hospital, Canada. Thank you very much. It's my pleasure to be here. This is my first time at the Latin American Heart Rhythm Congress, and it's been a fantastic meeting. As you can see, my topic is rather broad. Here are my disclosures. So I thought I'd more take a step back and summarize a little bit of what we understand around atrial fibrillation and heart failure. So we know that these are two diseases that are very interrelated. The pathophysiology of atrial fibrillation drives the incidence of heart failure. We see that happen in about 3% of patients per year. Similarly, patients with heart failure have a pathophysiology that leads to the likelihood of developing atrial fibrillation, and that happens at about 5% per year. If we look across the spectrum of heart failure trials, it's very common to find patients with atrial fibrillation in these trials. Similarly, if we look in atrial fibrillation trials, we'll see that a large proportion of the patients in the trials have heart failure. So in recognizing that it's commonly interrelated, it's important to understand that when patients have heart failure and atrial fibrillation, they have an even worse quality of life than if they have any one of those diseases individually. You see that the heart failure progresses much more rapidly. Patients are at higher risk of stroke, ICD shocks, and mortality. So on the whole, atrial fibrillation and heart failure, when combined, are problematic. Now if we think about the management of atrial fibrillation and heart failure, it's very broad. So I'm not going to talk about each of these things listed on the slide, but it's important to recognize that we have to manage the diseases individually, but then also focus on the ways that they're interrelated. So really today, what I thought I would do is just cover this one aspect of care, which is just the rate versus rhythm control options that we have for our patients who have both of these diseases. And so this can kind of be broken down into four categories. So we have pharmacological rate control, pharmacological rhythm control, and then we have invasive options in terms of AV node ablation for rate control, or catheter ablation for rhythm control. And so we'll start with the kind of easiest one to address. So what's the evidence supporting pharmacological rate control in this population? Really it comes back to the AFCHF study. So this is a study of about 1,400 patients, a reduced EF of less than 35 percent, NYHA class one to four heart failure. At the time the study was performed, the background LV enhancing therapy was reasonable in terms of ACE inhibitors and beta blockers. Importantly, what this study observed was absolutely no difference in terms of mortality or worsening heart failure. So patients treated with medications don't seem to derive any benefit, whether that medication is a rhythm controlling agent or a rate controlling agent. And one explanation may be that the predominant medication used for rate control is beta blockers, which makes sense because they had a cardiomyopathy, so calcium channel blockers would be infrequent. The interesting observation, which I'm sure you already know, is that when you look at the seminal beta blocker trials in heart failure patients, the mortality advantage with those agents that was seen in the general population was lost once patients had atrial fibrillation. And so atrial fibrillation confers such a negative prognostic impact that the benefits of the medications are lost. So then if we flip to the other side and say, okay, well, what about pharmacological rhythm control? And for that, you know, there are many anti-rhythmic drugs on the market or available to us as clinicians, but the problem is as soon as you have significant cardiomyopathy, those options pretty much go away and you're left with amiodarone as essentially the only agent that is approved with some evidence for use. The problem with amiodarone is we all know is it's a fairly dirty drug. There's many side effects associated with this medication that often lead to discontinuation. But more concerning is the association between amiodarone and an increased risk of death. And so again, this is a placebo-controlled trials. So if you were at my talk earlier this morning, I showed other data from this analysis. So in a randomized trial, amiodarone was associated with nearly a threefold increased mortality compared to placebo. And so we know in randomized trials where amiodarone has been compared to catheter ablation procedures that amiodarone is much less effective than an invasive ablation procedure. So this is the ATAC trial, which took patients with atrial fibrillation that was persistent, an EF under 40 percent, and randomized them to catheter ablation or amiodarone. And you see that amiodarone was associated with a two and a half fold increased risk of recurrence. So ablation is much more effective. But the important thing is that ablation was also much more effective at preventing heart failure hospitalization. So patients treated with ablation had half the rate of hospitalization compared to drugs. And there were also fewer deaths with patients treated with ablation compared to amiodarone. And so we already know that amiodarone is equivalent to rate control, and pharmacological options don't seem to confer any mortality benefit. And here we're starting to see that invasive procedures may actually improve those outcomes. And so there are other trials that have been performed in this population. We have Nasir here who did the CASL-AF trial. This took 363 patients with paroxysmal or persistent AF, predominantly class II-III heart failure, and an EF under 35 percent. Most of the patients in this trial were non-ischemic in etiology. And the study observed in a primary endpoint a reduction in heart failure hospitalization or death. And what I've shown you here in the Kaplan-Meier curves are just those endpoints as the secondary endpoints. So you see after about three years there was a separation in the curve where there was improved survival for patients treated with catheter ablation relative to drugs. But heart failure hospitalizations as an endpoint improved almost immediately. Somewhat discordant to these results come from the Canadian RAFT-AF trial, I guess predominantly Canadian or maybe Canadian-led. This was a bit of a different population. So it was 400 patients, also included paroxysmal or persistent AFib, but did not have an EF criteria. So clinical heart failure could have been HF-PEF or HF-RAF. In the paper they defined it as about 60 percent of the population having an EF under 45 percent. And what I'm showing you here are the Kaplan-Meier curves from the supplement where in contrast to what you saw for HF-RAF in CASEL, there's absolutely no effect on mortality that was observed in RAFT-AF and very little effect on heart failure hospitalization. The more recent study that was presented just this past summer at ESC was the CASEL heart transplant study. So this was 194 patients, it was a single center study in Germany. Patients with paroxysmal or persistent AFib, again, predominantly class II to III heart failure, patients with a low EF, and these patients were referred for transplant assessment. Again, predominantly a non-ischemic population. What they observed was, again, similar to the original CASEL, a significant mortality advantage with catheter ablation over drug therapy, a significant reduction in other markers of severe outcome, so left ventricular mechanical assistance or transplant in addition to death. But in contrast to CASEL, these results were observed almost immediately. So if you take all of these studies combined with some others, which I didn't speak in depth about, in aggregate we know that catheter ablation is associated with about a seven to 10 percent improvement in LVEF. So the difference between potentially qualifying for an ICD or not, patients improve their functional status, whether you measure it by six-minute walk or VO2 max, and importantly, heart failure hospitalization and death were also reduced. So I think it seems reasonably clear that invasive intervention for HEF-REF does confer significant benefits to the patient as well as the healthcare system. The area where it's maybe a little bit less clear is in HEF-PEF. So as I alluded to, RAFT, the Canadian study, did not observe much benefit. There has been an analysis done of Cabana, and Dr. Packers here speaking in this session as well, which looked at patients with symptomatic heart failure. In this case, about 80 percent had preserved ejection fraction. And what they showed in this analysis was that the composite primary endpoint, as well as all-cause mortality, was significantly benefited with an invasive ablation procedure relative to pharmacotherapy. The Cabana HEF-PEF trial is, the dedicated new randomized trial is underway, so hopefully that will explore this analysis further. And just a last area to touch on if we're talking about interventions for atrial fibrillation and heart failure patients is the role of AV node ablation or AV junction ablation. I think there's two distinct populations where we have this conversation. So one is the patients who already have a CRT device, who have longstanding or permanent atrial fibrillation. We know that atrial fibrillation is associated with reductions in biventricular pacing and therefore worse clinical outcomes as a result of that loss of resynchronization. There's been some observational studies done which have highlighted the benefit of AV node ablation. And so in these Kaplan-Meier graphs, what you see in blue is patients with sinus rhythm. In red, you have medically treated atrial fibrillation patients, and you see significant reductions in all-cause mortality and cardiac death. But importantly, in those patients with permanent or persistent atrial fibrillation who had an AV node ablation, that green line almost returns them back to sinus rhythm. And so if patients have persistent or permanent AFib and already have a CRT in place, AV node ablation is an effective way to restore biventricular pacing and improve outcomes. The question that comes up is whether or not we have any evidence otherwise. So the PABA-HF trial is an older trial that was published in New England, I think it was about 20 years ago now, comparing PVI to AV node ablation. There was no clinical outcomes in here. Basically what they showed is that over a small time horizon of about six months, better EF and better six-minute walk with PVI rather than AV node ablation. But we don't have any direct comparative trials otherwise. More recently, we've seen two studies come out of APAF-CRT. APAF-CRT, the original study was about 100 patients, randomized patients to pharmacotherapy or AV node ablation. And what they observed was a significant reduction of the composite. So the combined endpoint of death, heart failure, hospitalization, or worsening heart failure, and that was reduced by about 60%. In this study of 100 patients, they did not see a significant reduction in mortality. And so a second APAF-CRT trial that included about 50 more patients than the original was published a few years later. And by this point, they saw a 75% reduction in death, which wasn't seen in that first trial. And so there's a suggestion that AV node ablation may be better than drugs. You know, at the very beginning, I highlighted that drugs don't seem to offer much benefit either way. And so at least based on what we know today, if we have our patients with AF and heart failure, the invasive options maybe are preferred due to the mortality advantages, but we can't really say there's one that's necessarily preferred to the other. So thank you very much. Thank you, Dr. Andrade. Next speaker is Professor Nasir Marouche. His lecture is about efficacy of MRI-guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation, the CAF2 trial. Dr. Marouche is Director of Heart and Vascular Institute at Tulane University School in New Orleans. Welcome, Dr. Nasir. Good afternoon, everybody. And thanks for staying for the last session. I'm learning a lot already. Ladies and gentlemen, chairs, this is, the topic is CAF2. You heard a lot about CAF2 in the last couple of years. I want to show you what we've been publishing and presenting, what we learned the last couple of years since the data came available to us, my disclosures. Let me start with this slide. This is an important slide, a great paper from Takahashi and partners. But I want to show here, when we go to the EP lab and look at myopathy and voltage mapping or MRI or echo, whatever you're using, or even CT, I want you to be aware of the fact that we're looking at this kind of tissue. This is what we're trying to define. We take it for granted that all this part of physiology of the myopathy is the same. And this is something we're learning a lot, a lot in the last years specifically from the data we learned from the CAF2 that we need to start differentiating this myopathy when we treat it, especially in the AFib population. Substrate modifications seem to work in some studies and others show that not work, but in terms of voltage mapping, if you've seen what I've seen before, you take a voltage and you try to ablate it. This is a study from a team in Nanjing, the STABLE-SR Sinus rhythm trial, the third trial. They showed benefits and outcome if you do substrate modification. And the group from RASAF, the group from Germany and Austria, they showed benefit when you map the voltage as 0.5 millivolts or less and try to connect and ablate these lines. So what we did, as you know, some of you already, that we took the different kind of myopathy and now highlight the fact that we're looking at tissue when we do an MRI scan, not the voltage one-sided only. We take everything where the gadolinium stays behind, in this tissue or in this tissue where delayed enhancement that MRI shows us back, and we process that image. So green or white is fibrotic where the gadolinium is slow to wash out, and we define this as a scar or as a myopathy. So we learned a lot as well over the years. This is a paper actually from Dr. Lee, who just joined Dr. Jodi Hurwitz in Dallas. And she looked at voltage maps and volumes and correlated them to MRI scans. And the reason I'm showing you this at the beginning of my lecture before I talk to you because it's important for you to keep this in mind, voltage, MRI, myopathy is three different things we talk about. I warn to put them in one box. What she showed that it's, if you practically, if I encourage you to go and look at this paper, if you go and play with the voltage, patient A would have a myopathy at 0.2 millivolts, patient B at 0.7 millivolts, patient C would have a myopathy at 1.1 millivolts. It depends. The correlation to MRI, it differs across. So when you look at MRI, you are more looking at where the tissue is differentiated versus other tissue, where the voltage is really specific to 0.5 millivolts and less cutoff that has, the studies has been published so far. DCAF1, we learned a lot that the more myopathy, we've showed that the myopathy is an indicator for failure or recurrent atrial fibrillation after ablation. That's all that DCAF1 did. So we took the fact that this patient did not do well. And then we tried to find a way to treat this patient based on the Nazima Koum's work, that if you cover the myopathy with ablation, you modify it, you improve outcome and sub analysis of DCAF1, and we defined DCAF2. DCAF2 took us six years to finish almost. We randomized 840 patients worldwide, I've seen this, all the centers in the world involved in DCAF2. So what we did, we randomized patient to PVI only. We gave the investigators images that not show any myopathy, just volume. They were blinded. They did PVI only. They were supposed to do PVI only. And group two, or the treatment group was PVI plus fibrosis, guided ablation, modification of the fibrosis, as you've seen in this example. And we looked at lesion formation at three months. So you've seen, I'm not sure what the number is, this is the cost of the MRI, and this is not to be here, not the subject today. This is the randomization and the follow-up in DCAF2. As I said, everybody got an MRI scan, fibrosis guided ablation versus PVI, and we followed the patients with a smartphone device, which is in 2016 was the first multi-center randomized trial to adopt this. And in retrospect, we learned a lot, especially in compliance and patient management. But that was, we tried to avoid clinic visits, that's why we used this smartphone device in the trial, and the patient used the smartphone to fill their questionnaire quality of life. We followed patient up to 18 months. The intention to treat showed only 9% difference in favor of the fibrosis guided ablation, no significant difference, as most of you know today. If we look at, sorry, if we look at the lessons we learned over the time from this trial, and then especially from the lesion formation part, not every ablation creates durable lesions. That's one lesson that I learned personally. We don't know why. We're trying to learn over the time, the more we look at the data, where the lesions are delivered, how to deliver it, and not only not every ablation creates durable lesions, what we learned from DCAF2, not every operator was encouraged to do a lot of fibrosis ablation. As you know, we mandated that people do ablations everywhere on the scar, but a lot of operators were intrigued or intimidated by the scar, and avoided lesion formation, so they did a couple of lesions here and there, and they stopped, unfortunately. But nevertheless, taking this approach, so this patient have some lesion formation, this patient have extensive lesion formation, and you can tell that every ablation lesion did deliver its curve. And one of the reasons, and this is an example I brought for me based on histology pictures. So if you take, let's assume we're taking these slices here from these MRIs, you could be dealing from the MRI scan you're looking at here from different variety of myopathy. Is it replacement fibrosis? Is it interstitial fibrosis? Is it amyloid and so on and so on? So this is something we at Tulane, at least now, we try to dig deeper, understanding what kind of myopathy and hopefully we start differentiating our scan for this treatment as we go forward, as we deliver forward. So baseline fibrosis affects scar formation. We learned that, and this is Akum's work. He's in the process, hopefully, of publishing this paper. What we learned is, like if you take these two examples here, the more fibrosis you have, the more intensive fibrosis you have, and you try to deliver lesions on this fibrosis. By the way, we have all the CARTA maps in Decaf2 and the Abbott or the Navex maps. So we could look at the lesion formation correlates every single point to the parameters of power and so on and so on and temperature and contact force. So what we learned is that it's easier to form fibrosis and if the fibrosis is localized, rather generalized fibrosis in this case, it was hard to form fibrosis in this patient population. So scattered versus localized, and the question remains, why and what's the reason? Is that we're dealing with different fibrosis or different myopathy? So to answer all these questions, we start looking more and more into the AI part of our analysis, and then Dr. Han Feng, who joined us from University of Houston, an AI engineer slash biostats experts, he started taking the Decaf2 data and putting all the information and then started looking further into what differentiators, what we learned from these groups in terms of lesion formation, in terms of outcome, with the end point of maintaining sinus rhythm. So there's five things I wanna share with you today. The ages are important. We're in the smurden that the daily ECG plays an important role in predicting outcome. We're in the blanking period as we know it. It's too long, we should shorten this. The predictors of recurrence and also the PVI, it doesn't matter how you do it, at least from Decaf2, we've seen the same outcome. This is the AI analysis. Practically, we asked the algorithm to tell us which groups in this whole population have different outcomes. And the AI came back with this cluster where patient less than 58 years old did very well without a 56% reduction in outcome if you do fibrose-guided ablation in this group versus the elderly population didn't do as well, or not elderly, but older than 58 years old did not do as well, as you can tell, no difference. And this raises the question, not only with the early intervention AFib, but rather the young myopathy. Are we dealing, as I showed you at the beginning, we need to start looking, that was very intriguing for us, into the type of myopathy we're dealing in this population versus the elderly population or the older population in Decaf2. It was very important finding for us, and hopefully we can get this published. But also, today, this population seems to do well if you target the myopathy in persistent AFib population, the younger population. We learned about the ECG strip a day, or ECG-based burden, which we call the SMRDN. Paper just came out in Jackie P., where we take the number of ECGs in AFib and divide them by the daily ECGs the patient deliver to us. And you can tell it's unfair to take a patient with persistent AFib. For example, this patient have no recurrence. These red strips are the ECGs showing AFib in the daily AFib recordings or daily strips they send. And it's unfair to compare these last two patients, say both of them have recurrence, which was the endpoint of Decaf2. But we need to start looking more and more of the amount of AFib we're seeing, which can be detected, as we've shown here, and it seems to be useful, using the SMRDN daily ECG and predicting outcome. This has been shown, if you take it, like, for example, that we do different groups, patient have a recurrence at the end, after three months, and no recurrence after three months. But if you compare these two groups, the group have no recurrence after three months have a SMRDN of only 7.4% of the time they're in the three months area. In the three months, 7.4%, sorry, have some kind of recurrence in the first three months. But if you look specifically, and look how wide the scalp and minor are separate, 18% seems a cutoff to look at. So if you have in first four months, four weeks, sorry, after ablation, 18% of the ECG showing, or less, showing AFib. This seems to be a good indicator the patient would do well long-term in terms of recurrent atrial fibrillation. And this is the same thing here, blanking period, the first four weeks seems to be, if there is no AFib, the couple of minor seems very closer to patient have never had a recurrence in terms of predicting long-term outcome. But if you have recurrence, or more ECG showing after these 30 days, you seem to have a high recurrence rate. Again, shortening the blanking period to first 30 days, if we can have 34 days, as Sherb and Jane showed in this example, 34 days and more than 34 days, you see how wide the couple of minor are spread in predicting recurrent atrial fibrillation. So use your, as I call it, accessible, easy-to-use daily ECG to assess long-term accommodate patient population. Also, we learned from deCAF2 that that's a clustering concept from Dr. Han as well. If you take fibrosis, LA vol, and BMI, and the amount of AFib, that seems a very powerful predictor in terms of clustering for long-term outcome. Doesn't surprise you, but if you're combining together in one patient, it seems a very powerful indicator, especially adding the LA volume and the initial fibrosis. Female did not do well as male in deCAF2. That's something that Mann-Kopf and Dr. Younis are putting together from Germany, and they're trying to publish this data. Unfortunately, the females did not do as well as men in terms of long-term outcome and burden in deCAF2. LA volume continues, as you've seen from the MACE trial, seems a very powerful indicator as well. We confirmed this in deCAF2 for failure and for burden. So what we're looking at is more the smurders now, not only the one-time ACG recurrence. And that's interesting. This is a paper from KILU. We presented this, which is similar with others we've seen, but doesn't matter how wide in the PVI group. If you did wide encircled box PVI, or a interim isolation, or more inside the vein isolation, cryo versus AFib, all show the same outcome, the same cryo versus cryo versus the frequency, which is not surprised to anybody. But interesting here is, doesn't matter what lesion were put in the PVI group, we've seen the same amount of burden or smurder recurrences in this patient population. They published this recently. So putting this all together, less than 58 years old, or less than 60, or younger patient seems to profit from fibrosis-guided or MRI-guided atrial myopathy, ablation plus PVI, with a significant, around 50% or more, reduction in outcome, including burden. Smurden, I think this is, if you have a continuous, and most of your patient, we talk about this in the morning, have a continuous monitoring on ECGs, Apple Watch, Samsung, whatever, or the LifeCore device, all the light on ECG, use it to help mapping and monitoring your patient. Blanking period, it's too long of three months, in my opinion, and the data's showing. I think waiting three weeks or four weeks seems to be enough. LA volume, continue to be, there's another study, we've seen this in a maze, a big trial, and this is a trial that, a very strong predictor of procedure failure, and PVI is a PVI. You do it with a cryo, you do it with RF, you do it outside, you do it inside. We've seen decaf, too, have the same outcome. Thank you. Thank you so much, Dr. Maroosh. It's not a predictable section with time for answering questions, so unfortunately, I do stimulate the audience to go directly to our lectures at the end. They will be delighted to answer your doubts. Next speaker, I invited Dr. Alberto Alfie. He is an electrophysiologist in Adventist Cardiovascular Institute in Buenos Aires, Argentina. He is gonna talk about how to perform catheter ablation in atrial fibrillation to avoid recurrences. Thank you very much, Lars, for this invitation and to be in this session with these distinguished speakers. So, my talk will be about how to perform catheter ablation in AF to avoid recurrences. So, I have three questions for this talk. First one, is ablation the most important aspect of AF treatment? Second, what should we know about RF biophysics, lesion formation? And three, how to efficiently perform AF ablation? So, from the group from Brush Standard in Australia, he ran my patient to have a standard ablation and another group that was called risk factor modification group in red in this graph. And the risk modification group was patient were aggressively treated risk factors associated with AF before and after the ablation. And there was a terrific change in the outcome between both groups. So, the risk modification group has a much better outcome when we treat the patient in an integral approach. As we see here, we have to understand that atrial fibrillation is just a tip of the iceberg that never comes alone, comes with several gifts, presents, and these gifts are all risk factors. So, we have to treat the patient accordingly, treating all risk factors to have a better outcome. It does not burn some veins in the left atrium. So, what should we know about lesion formation? So, from this study, and we understand how this preparation, so we are going to deliver the same power, the same amount of time, 20 seconds, the same contact force, and we know by the Ohm's law. So, if we decrease the resistance of the tissue, we have much more current as what it matters. It's not the power, but the current we deliver into the tissue that will create the lesion. So, if we have a lower basal impedance, the lesion is bigger. As we increase the impedance, we decrease the current, and the lesion becomes smaller and smaller and smaller. And translated to clinical settings, we like to work close to 100 Ohms. So, we, almost in all patients, we place two patches, two dispersed patches on the back. And also, we monitor, we're talking about cartel, the first in each system, but we live monitor the current in the smaller blade, and we want to be between 700 and 700 milliamps. So, we don't want to be higher, because there we can have complication, and steampunk is a fragile damage. So, if we monitor all this, we can reduce complications. And talking about more, about biophysics in the lesion, if we compare working with high power and low power, we know with high power, the lesion is shallower, and wider if we work with low power. And that is very important, because the lesion with high power could be shallower than low power, but this could be enough for the very thin left atrium thickness. At average, it's like two millimeters in our left atrium. And moreover, it's not only about geometry with high power, it's also about what kind of heating we deliver into the left atrium. With high power, we deliver, like almost all the power is resistive heating, with a very small ring of conductive heating, that translated that the acute lesion is quite the same as the chronic lesion. And with medium power or low power, the heating is balanced with average, the same with conductive and resistive heating. So, the acute lesion, we can have this connection, we can have more edema, and the chronic lesion reduced in size. So, this is important to know. And when we see this gross anatomy, we can see with high power, look at this gross anatomy, there is no gap and there is a nice transmurality as compared with medium power. And if we see at the very right panel, the histologic preparation, we see that with high power, we have a transmural lesion. And with standard power, in the asterisk, in the star, we have like a small strand of viable muscle. So, we don't have isolation there. So, makes sense, more high power. And it's not the same old catheter that was published in JAIS last year from a Spanish group. So, if we work with smart touch, that is in red, it's important to know that the lesion is bigger, working with 10 grams, close to 10 grams. If we go up to 20 grams, there is a paradoxic effect, the lesion becomes smaller. And it's very important to know this. And with Tacticat, the opposite, but the lesion with 10 grams is quite small, with 10 grams, and we go up to 20 grams, the lesion becomes bigger. So, that is very important. And what are determinants of having achieved a late pulmonary brain reconnection in contact force era? So, this was studied, and this group found what were the weakest link to have achieved a late reconnection. So, we can state that in relation to this, and we all know that, that over than six millimeters in relation to this, you may have reconnection, as well as having contact force less than 10 grams, or a very low impedance drop. So, knowing this, it was created the CLOS protocol, and the CLOS protocol came to us to homogenize the procedures among operators around the world. And that is very strong work, because we can homogenize and do the same all groups around the world. We know this protocol, 400 on the posterior wall, 550 anterior, with an interlesion distance less than six millimeters. But it's important to state that the interlesion distance average was 4.1, and this was reproduced in several other studies using the CLOS protocol. So, the median interlesion distance is around 4.something. But we never had to go less than four, because we can have a lot of overheating, and overlapping lesions, and overheating can lead to severe complications, like damaging the esophagus and many others. And it's important to know, as well, that we have a very nice first pass isolation. That is, the first pass isolation is nothing to do to be a contest for first pass isolation, but it's a surrogate of having contiguity in lesions, doing point-by-point ablations. So, from this study from Dr. Osorio, we know that we have first pass isolation, we have nearly 90% free cell barrier at 12 months, compared to not having first pass isolation. So, it's very nice to have first pass isolation. And even more, the CLOS study was tested with a higher power, with 45 watts, decreasing the procedure time and the RF time. So, it makes sense to work with higher power. And it's safe. That was stated in several studies, as well. And this is very important. This study is from the Porter, and this is an historical, it's a picture of what took like 20 years to reach to this point. When we do a CLOS protocol, and we have recurrence, and we take the patient to the lab with AF recurrence, and we put that patient in the lab, 62% of the patient will have their pulmonary vein disconnected. So, the reason for their recurrence is non-PBI trigger. And that was seen for the very first time in history, in 20 years, or 25 history of OEF ablation. So, that is the strength of, as I said before, the CLOS protocol. I once hear Dr. Andrada say that cryovalulin ablation homogenize operator, but we can say now that point by point, CLOS protocol doing RF ablation can homogenize, as well. Um, procedures among operators around the world. It takes more learning curve to achieve this point, but we, it can be done. And so, this study, it's amazing. It's from the, from Elan Hunter Group. And this is the impact of high power, short duration RF ablation, or long term relation durability for AA ablation. Look at this. If you have a catheter motion greater than one millimeter with high power and media power during more than 50% of the RF frequency time are related with PV reconnection. And this was seen in 80% of reconnection sites. And this makes sense, because for posterior wall lesions, we need only eight seconds. And anterior, 15 seconds of ablation. And half of the time will be for sacral posterior, and seven seconds anterior. If you're stable, less, for this amount of time, less than one millimeter, we will have a durable lesion. And compare, and look at this. We can do it in the lab, processing the BC-TAC annotation. If we annotate, we typically annotate with three millimeters stability. But if you go down, we can see that one millimeter. And this is like a variable for reconnection in the future. Look at this. High power, short duration. The catheter motion, less than one millimeter for half of the time was seen in nearly 90% of the cases, as compared with 72. And this translates in chronic PV reconnection. Look at this. Only 3 out of 18 patients, we are taking again to the lab, that's 16% only, have PV reconnection. And if you compare with low power, it's like a 52%. So it makes sense to work with higher power. We have more stability and so talking about stability it's everything. And that was taught for a very nice friend and colleague that is Dr. Osorio. We have three variables here, C-level sheath, ventilation, and pacing. So it was seen that it worked from Dr. Osorio. Using C-level sheath, we can reduce the procedural time, the RF time, and we can reduce, and you can see the graph, how we reduce the ablation time. And the catheter is more stable, we know that in how we work. And ventilation, look at this, this is from myself, from our group. Look at this curve, the catheter is stable here, but look at the contact force curve with normal ventilation. This is huge, a huge range of contact force. And we do high power, high frequency, low tidal, the curve flattens, so the catheter is more stable and safer to perform the ablation. We don't have that oscillation in the contact force curve. And this translates in a better outcome at follow-up, at one year during this protocol. And secondary alcohol landscape, we reduce the procedural time, the total RF time, and we improve the RF isolation. And so, pacing. We always try to pace, and that was stated by Dr. Cheney's group. So HR pacing resulted in reduced contact force variability and was associated with 30% greater decrease in tissue impedance guided ablation. And we know, I was talking before, that the impedance, the drop impedance, is a subrogate of stability. So, now we know this, we can answer the questions as the conclusions. Aggressive risk factor modification should be part of the ablation strategy before and after the procedure. Deep knowledge of RF physics is mandatory to have a better outcome in AF ablation. Closed protocol approach homogenizes operators with a very good outcome. Catheter stability by different means is a key point to build recurrences. And to finish, it took us like 30 years to reach this point with ablation. There are incoming technologies like PFA, but it's just the beginning. So, we had to take rid of this, of what we learned in 25 years. So, that's it. Thank you very much. Thank you very much, Dr. Ralfi. It's an honor for me to present you Dr. Douglas Packer. His topic is about age and outcomes of catheter ablation versus drug therapy for atrial fibrillation. Welcome, Dr. Packer. He's a cardiologist, electrophysiologist in Intermontane Medical Center and Mayo Clinic, Rochester. Welcome to Mexico, Dr. Packer. Or you can talk about the age of the disclosures, and we're not going to talk about that. So, let's talk about contributing factors. And I'm going to start out with these. These are not talking about the age of the atrial fibrillation. These are talking about the age and some of the comorbidities of the patients. And you can look at these, and there's weight and hyperlipidemia and obstructive sleep apnea and hypertension and diabetes. Okay, so there's a bunch of things that contribute to the effective age of the patient. Let's talk about mechanisms. Well, you can see all of these. There's everything from hyper to hypo anything, atrial tachycardia remodeling, genetic variance, atrial structural abnormalities, atrial structure abnormalities that then deal with fibrosis and dilatation, inflammation, inflammatory oxidative changes, RAS activation and abdominal nerve systems. So again, in terms of age, we have a whole bunch of different things that we could talk about age. Now, in terms of talking about new cabana results in age, I wanted to talk about this first. One of the things that we've learned in this last year is that there's an incredible role for aging inflammasomes. So what I'm showing you here is the NLRP3 inflammasome activity. And if you look at it, then there's a receptor. And then the NLRP3 activator hits the receptor, it fires the receptor off, and then you get an inflammasome key that triggers. And what it does is it changes cytokines, it changes interleukins, and it also changes histamines. And it does that right down in here. It breaks the caspase, and then when you have the interleukins, when you have the cytokines, you have the fibrosis that comes from collagen. The older it is, the worse the problem that you have with atrial fibrillation. And the point that I'm making here is we haven't said anything about the age of the patient yet, but we're talking about things that have a tremendous impact on the occurrence of the atrial fibrillation. If you look at it, you can see what the tissue looks like early on, and you can see what the tissue looks like later on. And this is using galectin-3. So if you're using galectin-3 and you use a blocker, galectin-3 creates fibrosomes, galectin-3 blockers block it. What happens is that for persistent atrial fibrillation, there's a dramatic decline in the amount of the atrial fibrillation. For persistent, either way, if you're using the blocker, it's going to drop it. If you're not using the blocker, it's going to go in the other direction. Okay, so Jared Bunch looked at age now. I've just told you a whole bunch of things that the age of those compounds cause atrial fibrillation, and that's the fibrosis. That's some of the things that we're stuck about. Let's talk a little bit about the age-to-age. Okay, so here's patients just before we did cabana under 50, 50 to 65, over 65. And you come down and you can see AF duration. As you get over age 65, AF duration becomes increasingly problematic. So now we've got a portion of age that is going to give us trouble. Sleep apnea is going to do the same thing, but worse than that is history of stroke is going to be even worse. And if you're looking at persistent or long-standing persistent, it's going to give you an even greater problem. So now the age, coupled with the age of the comorbidities, gives you a lot of trouble that could be even worse. Now let's look at the impact of age on underlying disease. Well, as you go across, let's look at hypertension. The more hypertension you have, it varies. If you look at hyperlipidemia, it also varies. If you look at diabetes, it doesn't vary as much. And so as you get older, then that becomes more of a problem. Coronary artery disease, as you get older, that becomes more of a problem. Valvular heart disease, as you get older, it becomes more of a problem. If you look at the impact of age on outcome of AF ablation, if you're looking at AF controls, that means you've controlled it, but it's not gone, versus the other side is AF elimination, and you're under the age of 73, you may do pretty well in terms of freedom from atrial fibrillation, but you're not going to do as well if you're over the age of 73. Now, Marouche talked about 58. In the experience that we've seen, especially if you've got comorbidities and fibrosomes, and 58 may be a little bit too low, but certainly 73 is too much. If you look at the influence of age and AF type, now here's paroxysmal. Paroxysmals do well all the way across the board. Those that are persistent or chronic don't do as well, so the elimination of atrial fibrillation is about 97% under certain circumstances. It can be even higher, or it can be lower, and so these combinations of age, so it's not just the age of the patient, it's the age of the underlying disease, and it's the age of the atrial fibrillation episode. If you look at age and its complications of AF ablation, again, 50, 50, 65, and greater than 65, then death, not much difference. None of these really make that much of a difference, but if you look at some of the other factors and you put in the fibrosomes, then that risk becomes significantly higher, and we found that that was the case even in cabana. If you looked at cabana event rates over time, about the same. The reason why it was is there were four centers that crossed over 10 patients. That's why cabana is neutral and not positive. If you look at the composite endpoint of cardiovascular mortality and hospitalization, or if you look at per point estimates, then those patients who did best were those that were ablated, and ablated early, so now it's a matter of ablation, early ablation, and younger patients that get us where we need to go. Propensity squaring is a huge difference between those patients who had atrial fibrillation and were treated with drug versus those who were treated with ablative intervention. So let's talk some more about age-age. Well, if you're under the age of 65, the hazard ratio is going to be about 0.53. It's going to be a dramatic drop. If you look at over the age of 75, it's going to be about the same, but then as you get older, then the atrial fibrillation burden is going to be even greater. If you look at heart failure, and this is what we're doing with cabana HF, in those patients that had heart failure, those who had treatment with drugs didn't do as well as those patients who had treatment with ablative intervention. Minorities were the same thing. So now we're looking at age in a couple of different ways. Age of the atrial fibrillation, age of the comorbidities, age of the patient. If you look at paroxysmal persistent or long-standing persistent atrial fibrillation, there's a huge difference between ablation and drug, ablation and drug, ablation and drug, until you get right out to about highly long-standing persistent atrial fibrillation, especially in patients who were over the age of 75. So Tris Bonson looked at it in greater detail, and I'm just going to ask you to go ahead and memorize this because I think it's important. The bottom line here is those things that contributed to problematic atrial fibrillation included older age, underlying disease, comorbidities, fibrosis, and a variety of other things that you can see there. Diabetes was problematic in the real cabana. Left atrial diameter was greater. So as you can see, if you're under the age of 65, you do fairly well. If you're over the age of 65 to 70, you don't. And if you're over the age of 75, then you don't do well at all. Here's now looking at K.M. Curtis. Really it's a forest plot. The bottom line here is in cabana, if you're under the age of 65, you did well. If you were over 75, you didn't. Patients who are under the age of 65 had fewer mortality events, and those that had an age under 75 had less death or cardiovascular hospitalization, and certainly all of them had left in the way of recurrence. So less age, less age of comorbidities, and less age that's contributing to the duration of the problem before you get them ablated. So we looked, and to make a long story short, the sooner that you ablate them, and this is looking down at a very short period of time, but the younger the age and the sooner you ablate them, the more likely this is to go away. So age becomes a very important component, but the total comorbidities is even more important, and not just the age of treatment, but the age of when you got to them so you didn't leave them in it. There are other considerations. The same thing was true with quality of life. The quality of life all the way across, whether you have had atrial fibrillation for three months or 60 months, these patients did significantly better, and the adjusted mean differences were significantly better, and the cost was substantially less. The same thing was said in a test. Now they were really looking for what happens when you smash down the atrial fibrillation, but once you do, then the chance of having ongoing atrial fibrillation is less problematic. East, if they were treated early, then they had less likely recurrent atrial fibrillation, even though they kind of didn't do this one right. It is some ablation, but mostly anti-arrhythmic drugs, and then just standard therapy. But I say let's give them two thumbs up for this, because it does tell us that if you do things early, then you're going to be better off. Now new methods and approaches, and then I'm going to stop, is this is nice from the CUNY's paper looking at cryoablation, and this is Freedom from AF, AFlutter, and Atrial Tag. 82% versus 67%. What's the difference? A couple of things. Number one, these patients had less in terms of comorbidities. What else was different? They were younger. What else was different? Their atrial fibrillation was younger. They had less of it. If you look at the early AF trial, it's the same sort of thing. Big difference here, atrial fibrillation patients did better with more freedom from recurrence, anti-arrhythmic drug therapy patients did less well, and you can see it here in the overall target plot. If you look at the irreversible electroporation, we know what we've talked about with that. You can have a field effect, you can have pulse width, it can be reversible, it can be irreversible or thermal, and as you get further and further along, and there's more thermal and less reversible, then there are more holes. The more holes you have, the more leak there's going to be, and the more atrial fibrillation is going to be there. That has to do with how you do the pacing, and whether you're using bipolar, how close the poles are to each other. But there's a couple of papers I just want you to think about. We're not going to have the time to spend a lot of time. This is Vivek Reddy, this is when he put two or three papers together. Those patients did very, very well in terms of recurrent atrial fibrillation. They did well because they were younger, they did well because they came to acute isolation quickly, they did well because they were 96% effectively treated. If you look at the compound of the impulse PEPF-CAT and PEPF-CAT2, then the thing that you see, the same thing, is if you get the means of doing the study right, then you're going to have less atrial fibrillation per patient, and less atrial fibrillation per pulmonary vein. So again, it's age, how long you've had the atrial fibrillation, it's the underlying problems, the comorbidities, and it's how long the patient's been in atrial fibrillation. Here you see that there's actually quite a bit of difference in the Fairpulse PFA study versus thermal ablation in terms of the durability of it. This didn't look all that different, there's a little bit more difference there. You know, it's a problem of going with a non-inferiority approach. Last slide, this is from John Pacini, and this is from Cabana. These are the episodes of atrial fibrillation that somebody has over time. Early on, you get more. As you go through, you might have a little spike, and later on you might have a spike. But if you look at Forest plots, the bottom line is the chance of having recurrent atrial fibrillation is significantly less. It's less because of the duration of the atrial fibrillation, it's less because of the duration of the age of the patient, and it's less because of the age of the underlying comorbidities. And so I think that we're going to simply say that, as we consider things finally, there's a whole bunch of things that have a role in whether you have atrial fibrillation and it stays. The bottom line is, if you are keeping track of burden and keeping track of complications and symptoms and pattern progressions and overall age and underlying disease, the chance of having ongoing atrial fibrillation in a major way is less. So my final comment is, don't sit around and wait for the horror movie. Go ahead and take care of it. Take care of the atrial fibrillation, take care of the underlying disease, and take care of the duration of the atrial fibrillation. And you do that, and you might have some scared chickens, but you're not going to have a whole lot of scared atrial fibrillation. So I'm going to close there, and thank you very much. Thank you so much, Professor Packer. I'd like to thank all the presenters and all the audience to be here until the end of this amazing Congress. In the name of the laws, we hope to see you again next year in Katha Henna. See you.

cardiologists

electrophysiologists

age impact

catheter ablation

drug therapy

atrial fibrillation

comorbidities

fibrosis

ablation techniques

individualized treatment plans