Hello, all. My name is Fred Kusumoto, and I am honored to host this session on what the 2023 AF guidelines tell us. And this is going to be a really exciting one. We're going to talk about catheter ablation as first-line therapy for atrial fibrillation and some other topics, particularly with heart failure, et cetera. So really thinking about this a little bit more. So I'm joined by our two speakers that are going to have them introduce themselves. So Rakesh, go ahead and introduce yourself, and then we'll move on. Thank you, Fred. My name is Rakesh Gopinathaner. I'm a cardiac electrophysiologist at the Kansas City Heart Institute in Kansas City, and honored to be here and to talk to you. Super. And Prash? And I'm Prash Sanders. I'm a cardiac electrophysiologist at the University of Adelaide in Australia, and I'm very, very glad to be here at this session. Thank you. And Cara? Hi, I'm Cara Pellegrini. I'm a cardiac electrophysiologist affiliated with UCSF and the San Francisco VA, and it's an honor to be with you. And Ed? Hi, everyone. Ed Gerstenfeld. I'm an EP also over at UCSF in sunny California. Great to be here. So before we get started, you saw the disclosures that went by with all of the speakers and the panelists. Know that everything that has been spoken about, et cetera, really, we have been really sort of thoughtful about this and all of the sort of lectures, et cetera, free from any commercial input, et cetera. The one disclosure that I have to make is that three out of the five of us are from UCSF, either currently or in the past. I used to train there many, many years ago. And so thus, not only am I from UCSF, but I'm super old. So I'm going to turn it over to younger people here. So Prash, you're on first for thinking about rhythm control and AF ablation. So Prash, the floor is yours. OK, so let me quickly share my slides. OK, so look, thank you for having me and for HRS for hosting this session. And what I'm going to try and do is set the scene for what we talked about and how we came up with the recommendations for the rhythm control and also AF ablation. And I've done this really to put the scene of where first line AF ablation kind of fits in. One of the key things that came out in this document is that we introduced a paradigm shift in terms of treating AF early and considering this as a treatment for reducing AF burden in terms of rhythm control. And this kind of went through most of the document as such. And this is highlighted by the need to minimise AF burden. And I want to kind of show you some of that data. We want AF to be thought of as a long term strategy where we look at rhythm control early. There was an emphasis that this is a progressive disease and that we need to focus on early rhythm control in order to minimise AF burden. And it also built on what we already introduced in the previous session about the importance of lifestyle and risk factor management in terms of that kind of longitudinal disease management of AF ablation. So the guideline emphasises the importance of early and continued management in the patient with AF, focusing on trying to maintain sinus rhythm to minimise AF burden. Now this has come out in a number of the recommendations that we have included. And this is not just for catheter ablation, but also for rhythm control. I'm not going to talk about the first one because Dr. Gopinathan is going to be talking about that in detail. But what we have introduced as 2A recommendations is that in symptomatic patients, it's useful to maintain sinus rhythm for symptom control. We've also introduced the concept that there's randomised data to suggest that it can reduce hard endpoints such as hospitalisation, stroke and mortality. And then we've introduced the progression of disease, that it can be used to reduce progression of disease. So these are three new things that are kind of dimensional paradigm changes that we have introduced into the guideline document itself. Now, why should we be considering rhythm control strategies? And there's a number of reasons, but there's some good data in terms of improvement in quality of life. This has been shown now in multiple studies, it's been shown in randomised studies. So that's hard data. We have randomised data to suggest that your combined endpoint of mortality rate, stroke, hospitalisation due to heart failure or acute coronary syndromes is significantly helped by maintaining sinus rhythm. Less clear, but there is data, is that we may be able to slow the progression of AF. This has been shown in now a several series of observational studies. And while there are a number of factors that determine progression of disease, this has been one of the factors that rhythm control is associated with less progression of disease. And then finally, that we have non-randomised data, which really suggests that this may reduce the incidence of cognitive impairment long term, and also the development of heart failure. And so we have a lot of reasons why we need to be considering rhythm control and a shift in paradigm from simply rate management to a rhythm management strategy in our patients with atrial fibrillation. I want to highlight some of the randomised data, because East AF net 4 was one of those important studies that pushed this agenda forward. So this looked at early within 12 months of the onset of atrial fibrillation in a mixed cohort of patients to randomise patients to early rhythm control or early rate control in terms of outcomes. And if you look at the figure here under the early rhythm control, one of the notable things is in the blue is AF ablation. It's only 8% of patients at the initial start on a rhythm control strategy increases to 20% in this group of patients. So this is a combination of both early ablation and early drug therapy. And the important thing was a primary outcome, which is a composite of death from cardiovascular causes, stroke or hospitalisation with worsening heart failure or acute coronary syndrome was significantly lower. And this is on the figure on the left hand side, significantly lower in those who had early rhythm control. Now, importantly, what they also saw was that group, as expected, if you had rhythm control, they were more likely to be in sinus rhythm and hence the correlate with what we do with AF ablation as well. Now, one of the important sub studies that has come out from this is also the fact that if you looked at the symptomatic and asymptomatic patients, the benefit existed in both groups of patients. And that's shown on the figure on the right hand side. So this was sustained in both groups. And so, again, with the early use of rhythm control becomes an important factor in the consideration of guideline recommendations. So new in the guidelines is that we focused heavily on AF burden. We've up front given in this flow diagram that heart failure needs to be considered and Rakesh is going to discuss that further. And then you have this important concept of this being a shared decision making. This is not a one way street. This is something that involves a patient and needs to consider a number of factors. But there are three strategies to try and maintain sinus rhythm. And if you look at the central pillar there where we're talking about catheter ablation, you can see we've upgraded the recommendations for catheter ablation in terms of antiarrhythmic drugs are ineffective. This is now a class one indication. And then we've introduced that in selected patients. First line therapy is very reasonable. And I'll go through some of that data. And in fact, we've also put in as a two way recommendation that even in non selected groups of patients that in the context of shared decision making where there's disclosure with the patient and it's discussed that it may still be appropriate in some of our patients in terms of offering catheter ablation to manage rhythm control. Important to look at how the guidelines changed from what we have on the left, which is what was published in 2014 to what we put out in the 2023 guidelines. And one of the important factors is in the earlier iteration of the guidelines, we focused on class one being for after ineffective drug therapy in paroxysmal AF. And we made this distinction between paroxysmal persistent and long standing persistent AF where we had a 2A and then 2B for the latter two groups. And really, with the emerging data in this field, we've now moved this along to really say that if you fail drug therapy, this is now a class one indication and a 1A because they are randomized studies that show that it's beneficial to try and rhythm control using a catheter ablation. Now I'll try and show you three of these studies. And these have been around now for some time. This is the STOP-AF study. It looked at randomizing patients two to one into cryoablation versus drug therapy, a blanking period, and then looking at AF control. And you can see the dimensional difference in terms of the Kaplan-Meier curves in long term follow up, where ablation was significantly better at maintaining sinus rhythm than drug therapy. And this is a repeated story. So here's a thermocol ablation study, again, a randomized design. This is again in paroxysmal AF and whether it was protocol defined treatment success, asymptomatic or any arrhythmia, there was a dimensional difference between maintaining sinus rhythm with catheter ablation compared to drug therapy. And so there's some good evidence to suggest that we ought to consider offering this early. Equally well, I think Cabana moved this story along further, particularly when they look at the inclusion criteria in Cabana, which expanded this to a much more diverse population, including persistent atrial fibrillation patients. And in the middle figure here, you have the AF recurrence in terms of arrhythmia recurrence. And again, we see that catheter ablation performs much better. Now we know Cabana didn't meet an intention to treat analysis in terms of hard outcomes, but in fact, on a protocol analysis, this was improved as well. But in terms of maintaining sinus rhythm, the middle figure is there, and it's consistent with what we have in the prior studies. And hence the reason to bring this in earlier in the persistent AF population as well. And so moving that to all patients who failed drug therapy, this is something that we ought to be offering as a class 1A recommendation. I want to now turn to the fact that, you know, first-line therapy in patients with atrial fibrillation, and this has been a little bit controversial, you know, in the previous guidelines shown on the left-hand side, we talked about a 2A for paroxysmal, there was some evidence, and in persistent, it was less and it was 2B. Now we've changed that around a little bit to really say that in selected patients, and we did go to a lot of effort to discuss this on the guideline, what that selected might look like, and I'd like to kind of take you through that. And definitely for symptomatic paroxysmal AF, catheter ablation could be considered as first-line, and it's not only for symptom control, but it's also to reduce the progression of disease, given the evidence that's coming out there. Now, in terms of a 2A recommendation, we did have that perhaps people outside that ideal selected group of people could also benefit from this, and in the context of shared decision-making, certainly for improvement of symptoms, we gave this a 2A recommendation. And then finally, we kind of started to touch on the fact that we're evolving data in asymptomatic patients, and whether this may be suitable or not. Now, this is a 2B recommendation, so it's really downgraded, and it's non-randomized, so observational data that it's based on, but it's something that people can start to discuss if it's appropriate in the context of the discussion that the patient has. Now, we again have a fair amount of studies that have been shown in this regard. So, in mantra PAF study, although the time to first event was no different, when we followed the patients out to 24 months, the group that underwent ablation had a lesser burden of atrial fibrillation during the follow-up period, and so there was a change in the progression of disease. Similarly, in RAFT and STOP-AF, we have a reduction in the arrhythmia recurrence during follow-up. These are all randomized studies. And then early AF, the initial study showed a reduction in arrhythmia recurrence. The long-term follow-up showed that less people went on to persistent atrial fibrillation. So, there's that insight into that progression of disease. Now, we've highlighted this in yellow to really show you the population that this data is based on. And while it's similar to the populations we're dealing with, the number of comorbidities that this population has was fewer. So, most of these patients had hypertension. They had normal left ventricular function to a large degree. There were paroxysmal and persistent patients. And so, it needs to be kind of put into that context. And we had a lot of discussion on the guideline committee to see how we would word this. And I think that's where the selection of the patient is going to be very important. So, this figure was introduced into the guideline. I think it's a very useful figure for us to be having in that there are a number of variables that can be used to kind of for the clinician to decide, look, should I favor sending someone off to catheter ablation for rhythm control, or should we favor rate control? And patient choice is right up there in terms of a patient factor. But again, age, you know, a younger person may do better with the rhythm control if they have a shorter history of AF and if they have more symptoms. And these are things that tend to drive people to have a rhythm control strategy. And then, in terms of other factors about the patient itself, if rate control is difficult, that's more likely to steer you. If there's a smaller atria, we're going to talk a lot more about the LV dysfunction group. And also, if there is AV dyssynchrony to agree with the AV regurgitation. And so, suddenly you start to form a bit of a picture. This is a little bit flawed, but it kind of gives you an idea where the selected patient may benefit from this being as a first-line approach to maintaining sinus rhythm. So, the take-home point here was catheter ablation is now a class one indication of first-line therapy in selected patients. And this is based on randomized studies showing a superiority of catheter ablation over drug therapy in this population. And I've gone through what the ideal person that this may look like. One of the other reasons for these recommendations to change, and I think this is an area that's going to change dramatically over the next few years, is we did consider the potential complications that occur from AF ablation. And while there have been significant complications described, what we are seeing this trend towards a reducing amount of complications. And this summary table really was put in there to try and highlight that there are complications, but actually they have come down significantly and hence the weighing towards doing a first-line therapy. Also, we were cognizant of the fact that pulse field ablation is now a reality. And that again, will change this equation, although we're waiting for data and we certainly didn't have adequate data at the time we were writing this document. Now, before I finish, I just want to highlight a couple of other things that we did put in to set the scene for catheter ablation itself. We're all doing ablation with either uninterrupted anticoagulation or minimally interrupted anticoagulation. We did specify the use of vitamin K antagonists, but also importantly, the direct anticoagulants where we have much more evidence now, and that's given a class 1A recommendation. We also suggested that this should continue for at least three months based on post ablation, based on data that we had. And then finally, the long-term anticoagulation, we recommended that being used based on the individual patient's stroke risk. And I think this is a useful addition to those guidelines. Now, it'd be wrong for me not to talk about the fact that although we're talking about AF ablation, we have clearly put in that there is an importance of upstream modification and treating risk factors that contribute to the outcomes of AF ablation was put through the whole spectrum of the AF disease. And we did introduce this important figure. I think it's a beautiful summary figure where that modifiable risk factor sits in the middle. And we introduced the concept of the head-to-toes approach to looking for risk factors to manage. And this was in fact introduced also into the AF ablation consensus so that there could be continuity of what we suggest for the PERI-AF management group. Now, we did recognize that there are areas in the AF ablation component that we didn't have a full handle on. And while we still have things to evolve, we know the pulmonary veins are an important structure for us to target. We recognize that we're still evolving in our knowledge as to what else that we need to do in the standardization of the procedures. And we also recognized an important thing for future studies was that really we needed to try and define our populations perhaps a little bit better, and that this is an area that we felt was going to change over the next few years. So let me summarize my component of it before handing over to Rakesh. We've introduced a paradigm shift of trying to manage a rhythm earlier on and continued through the journey in the patient. And we've introduced a class one recommendation for the use of catheter ablation as first-line therapy in selected patients, but perhaps in others also, in the context of shared decision-making. So thank you for having me here and I'll hand over to Rakesh at this point. So before Rakesh starts, Prash, congratulations on just a tour de force. Phenomenal. And I want this audience to remember that in the 2014 guidelines, you know, there's a two-way recommendation for rate control, but there was essentially nothing for rhythm control. In the text, it was basically, well, in selected people, you could do some rhythm control if you wanted, but really that was it other than a 2B recommendation for heart failure. So this really, as Prash just emphasized, has been a huge paradigm shift, thinking about rhythm control and elevating that, whether by catheter ablation, as Prash has beautifully spoken about, that has evolved super quickly. Our old tried and true antiarrhythmic drugs, et cetera, so important for us to think about. And, you know, Prash and his group has really pioneered the importance of thinking about risk factor modification. And, you know, for us not only to think about it upfront, but throughout the entire process. And I think that that is really critical of Prash. You and your group are to be congratulated for really making sure that, you know, we just don't do the ablation and kind of wash our hands and we're kind of done, right? It's like doing anticoagulation. We were taking care of the stroke risk and we're done. It's so much more of a holistic approach. And that's even that much more critical in patients who have lots of comorbidities, et cetera. So I get to have Rakesh now take over talking to us about catheter ablation as first-line therapy for atrial fibrillation, but in the setting of heart failure. So Rakesh, we look forward to hearing from you. Thank you, Fred, Prash, that was fantastic. So hard to follow that, but I'll try my best. So I'm going to talk a little bit about catheter ablation as first-line therapy for atrial fibrillation and heart failure. And we'll go over some of the recommendations and discuss some of the studies, the trials that sort of made the guideline committee reach these recommendations. So let's say, I want to start with a couple of cases so that we all understand, you know, it's a common scenario that AF and heart failure are intricately linked, either through shared risk factors and also comorbid conditions. And it's called them the evil cousins so that the one worsens the other. I just want to make sure you can hear me okay, right? Okay, great. Okay, perfect. So let's look at a case. This is a 64-year-old female, hypertension, diabetes, presents to emergency room with worsening shortness of breath and inability to walk for more than a block. Blood pressure is 108. A systolic heart rate is irregular and tachycardic. EKG shows AFib, XM is consistent with heart failure. Psychocardiogram shows a dilated LV. Ejection fraction is 30, 35% and moderately enlarged left atrium. Underwent a cardiac cath, no coronary disease. So diuresis is initiated. Cardiology team has started the patient on heart failure medication and anticoagulation. So how do you deal with this patient further? What's the relationship between AF and the heart failure cardiomyopathy in this patient? So that's one of the points that I want to talk about. And the second case is, this is a 70-year-old male seen in clinic for an ICD evaluation, referred for ICD. Patient has ischemic cardiomyopathy, coronary artery disease with multiple stents in the past. He has been persistently in atrial fibrillation for at least two years. On rate control with Carvedilol and Digoxin. Also on lisinopril and Warfarin for anticoagulation. Ejection fraction is about 35%. Mild mitral regurgitation, moderately dilated left atrium. Last echocardiogram, two and a half years ago, LVEF was 53%. So the ECG shows AF with a ventricular rate of 68 beats per minute, narrow QRS. He espouses that he gets easily tired when walking around. So how do you deal with this particular patient? Is it what the next step is? Do we need to do something about the atrial fibrillation or should we just proceed with ICD implants since the patient has significant coronary diseases? So in this context, so let's talk, so the question for the, especially the first case is, and both the cases in this case is, what is the chicken or what's the egg? Is AFib related to the heart failure or is it a bystander or how are they related? So there are typically in this, especially in heart failure with reduced ejection fraction, which is where most of our data for atrial fibrillation, ablation, and therefore the class one recommendations that I'm gonna talk about are based on the studies that are done in HEF-REF patients. So atrial fibrillation can induce heart failure with a reduced ejection fraction where atrial fibrillation is the sole reason for ventricular dysfunction. And interestingly, this can happen with rate-controlled AF or AF with fast rate, so it's not just the tachycardia alone. And the second is arrhythmia-mediated, meaning that patient has underlying structural heart disease but then atrial fibrillation can exacerbate ventricular dysfunction or worsens heart failure in that particular, or it could be an innocent bystander. How do we know which type of AFib we are dealing with? The answer is we got to treat the atrial fibrillation and specifically rhythm control to see how the response, the clinical response to that. And that pretty much kind of establishes the relationship or the diagnosis that atrial fibrillation is a culprit in the patient's myopathy as well as clinical worsening, regardless of underlying structural heart disease. So what does the new guidelines tell us in terms of first-line recommendations? So there are three in terms of rhythm control and ablation in this case. So the first one is that in patients who present with a new diagnosis of heart failure with reduced ejection fraction and atrial fibrillation, arrhythmia-induced cardiomyopathy should be suspected and an early and aggressive approach to AF rhythm control is recommended in this case. So the specifically single-celled condition where atrial fibrillation is responsible for cardiomyopathy and heart failure. The second class one recommendation is that in appropriate patients, and we'll talk about who are the appropriate patients in a little bit, with an appropriate patient with AF and HF-REF who are on guideline-directed medical therapy and with a reasonable expectation of procedural benefit against patient selection. Catheter ablation is beneficial to improve symptoms, quality of life, ventricular function, and cardiovascular outcomes, meaning death and heart failure, hospitalization, or a composite of both. And there is also a recommendation for AF and HF-REF for preserved ejection fraction. This is a two-way recommendation. It says that in appropriate patients with symptomatic atrial fibrillation and HF-REF, again, with reasonable expectation of benefit, catheter ablation can be useful to improve symptoms and improve quality of life. So again, I would say upfront that we know much more about AF ablation and rhythm control in HF-REF than HF-REF, although more studies in that are coming along. So let's talk a little bit about what are the HF-REF data, what are the studies that sort of underpin these recommendations? So the first one I'm gonna talk about is called the ATAC trial. It's a randomized control trial of 203 patients who had persistent atrial fibrillation, dual-chamber ICD or CRTD, NYHA class two or class three with an LV ejection fraction less than 40%. They were randomized one-to-one to a catheter ablation group or amiodarone and those who needed and received cardioversion. And they followed for about 24 months. Over a two-year follow-up, the AF-REF survival was 71% in the ablation group versus 34% in the amiodarone group. They also looked at mortality as well as heart failure or unplanned hospitalizations. Basically, they noted that the hospitalizations were much lesser in those underwent catheter ablation, 32% versus 58% in the antiarrhythmic arm. And also catheter ablation resulted in improved survival compared to amiodarone and almost a 56% relative reduction in mortality. This was followed by the... So this is the Kaplan-Meier curve that looks at the catheter ablation group and the amiodarone group in terms of time to recurrence of atrial fibrillation. And this was followed by CASEL-AF trial, which is still today, this is one of the largest studies done in... For ablation studies done in AF and REF. So there were 363 patients. Again, 30% were proximal, 70% were persistent. They were anywhere from NYHA 2 to 4 and LVEF less than 35%. All patients had a device so that AFib can be monitored and burden assessed. They were randomized to catheter ablation and medical therapy. Of the medical therapy, about 30% received rhythm control with antiarrhythmic drugs and cardioversion, whereas the rest underwent rate control. They followed a very strict rate control target where 60 to 80 beats per minute at rest and 90 to 115 beats per minute during moderate exercise. And this is also an important point that guidelines speak about in terms of your planned rate control in this particular group, HF-REF. The guidelines recommend a stricter rate control strategy compared to a lenient rate control strategy. Median follow-up of about 38 months and the composite primary endpoint of death and heart failure hospitalization. At about 60 months follow-up, the LV ejection fraction increased by 8% in the ablation group versus no increase in the medical therapy group. And 63% in the catheter ablation group were in sinus rhythm compared to 22% in the medical therapy group. So let's look at the data. And so if we look at the composite endpoint, death or hospitalization for worsening heart failure, you can see that the curve separated around six month mark and they stay separated from still then. So there was almost a 38% reduction in composite endpoint in the catheter ablation compared to the medical therapy arm. And when you look at mortality alone, also there was a 47% reduction in relative risk reduction mortality over the follow-up period. So substantial improvement in both these categories in the catheter ablation arm. These are the two, when you look at the like a meta-analysis of patients who underwent catheter ablation in HFREF and compared to medical therapy, you can see that overall among the studies, I mean, there are a couple more studies since these were done. And you can see that there's about roughly 45% reduction in survival as well as heart failure hospitalization with ablation for atrial fibrillation. So then the question becomes, why should this happen? Why should anti-arrhythmic drugs don't work that well? So one of the interesting studies, which I want to, even though it's didn't look at the heart clinical endpoints, this illustrates a very important point. So CAMERA MRI trial, about 68 patients study from Australia. And they looked at patients who were well rate controlled to begin with. And they were pretty well rate controlled. Like I mean, heart rate was in the low 70s and then they all had reduced ejection fraction and persistent or longstanding persistent atrial fibrillation. These patients were randomized to catheter ablation for atrial fibrillation versus continued rate control. A subgroup of this particular cohort had cardiac MRIs done to look for late gadolinium enhancement and scar. And so they looked at this particular group separately to see if those who has late gadolinium enhancement or scar, do they get better? So if you look at the first graph here, this compares catheter ablation to medical rate control in this cohort. The primary endpoint in the study was ejection fraction improvement. They didn't look at heart clinical endpoints because it's a smaller study and not powered for that. So as you can see here, catheter ablation in well rate control patients resulted in an 18.3% increase in ejection fraction compared to whereas the medical rate control only resulted in a slight improvement in ejection fraction. So when you look at the people, patients who had positive late gadolinium enhancement, that particular group improved the rejection fraction by 11.6%, but they didn't improve as much as those who did not have late gadolinium enhancement. However, if you look at the improvement in the medical rate control arm, these patients, even with underlying structural heart disease improved the rejection fraction more than continuing to be in medical, continuing to be in atrial fibrillation. So the point that me, what it tells you is that, again, the point I made was that this is not a tachycardia mediated cardiomyopathy issue. It's more like an arrhythmia. So the well rate control AFib can also substantially decrease the ejection fraction. And so this kind of speaks to the second case that I discussed where patient who has non-coronary artery disease and persistent AFib coming, well rate control coming in with the decline in ejection fraction, that that particular patient, before you implant an ICD, attempt should be made to see if you can restore and maintain sinus rhythm. And again, the best method of sinus rhythm maintenance is catheter ablation, as multiple studies against antiarrhythmic therapy have shown superiority and improvement in heart clinical endpoints. So arrhythmia-induced cardiomyopathy is a blanket term given for any arrhythmia-causing cardiomyopathy. Dr. Gersenfeld, who is with us today, has done a fantastic work on understanding PVC-induced cardiomyopathy. And so similar, AFib is the most common cause for AIC or arrhythmia-induced cardiomyopathy. Unfortunately, we see these patients often and they are under-recognized. The multiple mechanisms are including patient factors and arrhythmia-related mechanisms contribute. There are cellular and extracellular remodeling that happens. The important thing about arrhythmia-induced cardiomyopathy, it's a reversible form of cardiomyopathy and with arrhythmia control, especially rhythm control of the arrhythmias. So why should ablation positively impact clinical outcomes in HF-REF when antiarrhythmics did not? So it's likely that AF patients with HF-REF have an occult AF-induced or mediated cardiomyopathy that could not be reversed with rate control and require rhythm control. And this is even true in the presence of underlying scar or longer duration of AF. Ablation has better success than antiarrhythmic therapy that has been well-proven and it also avoids potential adverse effect associated with long-term antiarrhythmic therapy. And as Dr. Sanders mentioned, I think the burden reduction is likely the secret sauce and that may halt any occult arrhythmia-induced cardiomyopathy in these particular patients. So if you look at CASEL, the mean AF burden per patient was reduced to 25% versus 60% in the antiarrhythmic drug therapy. And if you look at the median, for example, median AF burden is like night and day in that case. So they also did a postdoc analysis of CASEL that showed that a 50% reduction in AF burden at six months of follow-up after catheter ablation was associated with almost a 67% reduction in composite primary endpoint and also about 77% reduction in mortality. So that means that we don't have to cure anything here. It just means longer duration in sinus rhythm is what matters basically in this case. So how would you view this as a paradigm? So right now, this is a modified version of what is in the guidelines. And one other thing I wanted to say that the current guidelines are a much bigger update than the last 2019 ACCA-HHRS-AF guidelines for which AF catheter ablation in HEF-REF was given a 2B recommendation at that time. Since then, multiple studies have come that have broadened our knowledge and so this has been updated. And even actually the ESC-2020-AF guidelines had a 2A recommendation for first-line therapy for catheter ablation in HEF-REF. So how do you, the paradigm is like you need to start a patient in AF and HEF-REF to guideline-directed heart failure therapy. As Prash mentioned, lifestyle and risk factor modification is huge, orlandic coagulation, rate control and cardio what if needed to. And then one should assess these patients for catheter ablation candidacy. So patient selection-wise, some of the sub-analyses of these trials in HEF-REF show that those who have advanced heart failure, significant ventricular scar or severe atrial myopathy or fibrosis or even longstanding persistent atrial fibrillation and other advanced agent comorbidities are less favorable. Doesn't mean that you couldn't do ablation on them but expect the success rates may not be as good as, especially in people who have suspected AF-induced cardiomyopathy or early NYHA, low NYHA class, no significant scarring and early persistent or proximal. And you go ahead and they choose to ablate, then they're successful. An important aspect of follow-up would be to monitor for any AF burden or recurrences, especially true in patients with arrhythmia and this AF-induced cardiomyopathy who improve the rejection fraction. And we know that these patients over time can, if their AF recurs and becomes persistent, they can have a recurrence of cardiomyopathy and heart failure. So one has to be vigilant and need constant surveillance going forward. And the less favorable patients, there are multiple options. You could consider anti-arrhythmic AV node ablation and CRT would be a good option in some of them. And some people may just, we may have to resort to more than one, multiple ablations didn't help in this case. So in terms of timing, Prash mentioned East AF Net. So there was a sub-analysis of East AF Net that looked at patients with NYHA 2 or 3 heart failures, patients with LVF less than 50%. There were about eight, close to eight or seven 98 patients. Majority were HEF-PEF and there were a few people who were HEF-REF. And they looked at the primary endpoint of early rhythm control versus usual care. And what they found that the early rhythm control in this patient when compared to usual care had almost a 26% reduction in composite endpoint in this particular group. So again, this is not a dedicated study on the heart failure population, but it again points the fact that the earlier you get these patients in, earlier you do it when before their heart failure becomes too advanced that then that's beneficial. So clinical benefit is there when initiated within one year of diagnosing AF patients with heart failure. And this is Kaplan-Mayer curve in this case. What about HEF-PEF? So we, as I said, our knowledge base is a bit limited in HEF-PEF. This is a sub-analysis of the CABANA trial that looked at about 778 patients with AF and NYHA class II heart failure, about roughly 35% of the study population. And about 75% had EF less than 50%, so they had HEF-PEF. The primary endpoint was a composite of death, stroke, and bleeding or cardiac arrest. And what you can see here is that patients who underwent ablation had a significant reduction in the primary composite endpoint and with a hazard ratio of 0.64, 36% reduction in composite endpoint, and also about a 43% reduction in mortality. So there are also a couple of meta-analysis and a very small randomized trial that shows benefit, but this is a particular arena that we need to focus on going forward. And more studies need to be done with dedicated randomized trial to understand this better. But compared to HEF-PEF, this is a much more sort of a variable population, heterogeneous population. So patient selection would even be more critical in this case. So in conclusion for my section, in eligible patients with AF and HEF-REF, catheter ablation should be first-line therapy. And it is, by the latest guidelines. And significant reduction in AF burden is associated with reduced death and heart failure hospitalization. A significant proportion of patients with AF and HF potentially have an underlying arrhythmia-induced or arrhythmia-mediated cardiomyopathy that is corrected with the restoration and maintenance of sinus rhythm. Even with the recovery of LV function, long-term monitoring to detect recurrent atrial fibrillation is important. And it's also a recommendation in the guidelines. Interrelationships between patient factors underlying structural heart disease and ablation outcomes need further study. And no large randomized trial data evaluating ablation outcomes in HF-PEF currently exist. And that's a knowledge gap that we need to work on going forward. And thank you again for the opportunity. Appreciate it. Outstanding, Rakesh. Really super good, giving us a full sort of discussion about both the evidence that's there and some of the limitations of the evidence. Really absolutely important. A couple of things I want to emphasize to this audience before I turn it over to our panelists. First, Rakesh points out importantly that it's not tachycardia-induced cardiomyopathy. That not only in camera MRI, but in other trials, in fact, patients with atrial fibrillation with great rate control, in fact, when you return them to sinus rhythm would in fact have improvement in their ejection fraction. So it really is incumbent on us, as Rakesh pointed out, this is a potentially reversible cause for cardiomyopathy. And we really ought to think about it. As Rakesh implied, there are a host of randomized control trials that are underway looking at the use of rhythm control, particularly with AF ablation in the setting of heart failure with preserved ejection fraction. And I do want to comment about the use of amiodarone in this setting. I use amiodarone as I know many people here on this call, but in specific patients. When Sanjeev Saxena looked at the affirmed data, post hoc analysis, so I get it, but fascinating when you looked at those rhythm control patients, those patients who were on the amiodarone actually had the worst outcomes compared to some of the other medications. So again, amiodarone is used a lot or has been used a lot. And while again, a valuable medication in the appropriate population, particularly for a shorter sort of period, nonetheless, not something that is really a long-term option in many of our patients. Now, one last thing before I turn it off to the panelists. One of the exciting things about this is the interaction. So put your questions into the chat so that I can then ask the panelists, they'll be seeing it. Make sure that this opportunity to have your voices heard and really provide this a two-way interaction, really just a valuable component of these webinars. So with that, Cara, I'm gonna turn it over to you first. So comments and reactions. And when you were looking at sort of the AF guidelines, your thoughts with regards to rhythm control and ablation, we have the most recent ESC AF guidelines which have just come out last month and there are some differences. And just what are your thoughts about the sort of the US guidelines, et cetera, and comments and reactions to both of these wonderful presentations? Gosh, well, my first thought is I have excellent job security. I think there's a lot of great data here about how useful AF ablation is and gosh, it feels really good to be doing something for people that we can feel really confident in how beneficial it is. So I say that in jest, but in all seriousness, I think I really have drunk the Kool-Aid and we'll come back to that in some of these questions. But since you brought up the ESC guidelines which just came out, maybe we'll start there. I think one of the differences in comparing the ESC guidelines with the guidelines we've been presenting on is the level of confidence and recommendation for first-line therapy AF ablation and those with persistent atrial fibrillation. So Prash, I noticed in your presentation, a lot of your data on first-line ablation was really in the paroxysmal atrial fibrillation population and yet the American guidelines AHA, HRS, AACC guidelines open the door that it can be a 2A indication recommendation for persistent atrial fibrillation patients as well to consider first-line atrial fibrillation ablation whereas the ESC guidelines give it a 2B and cite lack of evidence. So I was just wanting to open that up for discussion how we might think about those patients. Prash, why don't you go first, take that. I think that's a very fair point. I mean, so as you know, a lot of the guidelines involve a whole committee of discussion and so it can get swayed slightly one way or the other. I mean, the fact in this guideline is that we've kind of relied heavily on the data from Cabana which did include people with persistent AF. Now it's true, we don't have data on persistent AF alone as first line, but we have it in combined populations and we often use that in a number of other situations. For example, the SGLT2 inhibitors for heart failure, well, we don't have a separate study in AF but we know AF patients were included in those studies and so it's been listed as a class one indication there. So very similarly, I think it's very reasonable for us to upgrade the level of evidence that we have but depending on the group that you have, this can go slightly one way or slightly the other way and I think that's all that the difference that we're seeing between these two guidelines. Ed, we'll turn to you, comments from your perspective. You're on mute. You'd think I'd know this by now. No, you're good. I was covered by the questions. So yeah, I guess I would just put us a bit of a real world maybe insights. So as you know, has been posh mentioned, you know, for the longest time, a firm, all the older studies, there's no real benefit that we could prove even though we sensed it would be there for heart endpoints with maintenance of sinus rhythm. You know, the first study to show it as he showed was East AFNet4, but keep in mind, you know, this was predominantly a drug trial, right? It was, you know, 20% of people got ablation but 80% were treated with antiarrhythmics and we've talked about Cabana, but you know, again, the intention to treat ARM was negative in terms of heart outcomes but if you got ablated in the on-treatment analysis, those people did better. So I could interpret that as saying, you know, if you were randomized to ablation upfront, you did well or if you randomized to drugs and then you crossed over to ablation, you also did well. So I guess I just wanted to say, you know, I think the important thing as has been mentioned is sinus rhythm, right? That we don't leave these patients in AF. I think we like, and I do a lot of ablations because ablation just works better to keep people in sinus rhythm with fewer long-term side effects. But if I see a patient like I did in clinic today who said, hey doc, you know, hearing everything, I'd rather start with a drug. I think that's fine. You know, as long as you're following the patient, they're staying in sinus, it's great. But if they have more AF, then they get ablated. You know, I think we don't wanna go too far and say, hey, everybody needs an ablation. I think it's a totally agree, should be an option as first-line therapy, but some patients may wanna try a drug first and that's fine. And then the second comment I was gonna make, which I think is a line I steal from Peter Kistler, which is just to remind everyone, you know, first-line ablation does not mean first-episode ablation. So I've seen a couple of second opinions where someone like has their first episode ever of AF and they're told you need an ablation. And it's like, well, maybe not, you know, maybe, you know, lifestyle modification as Prash has taught us, you have to realize this is a chronic disease. So, you know, so some of those patients, you know, you can have time. I always tell the fellows in clinic, you're all gonna come back eventually for ablation, but there's not necessarily a rush if they're in sinus rhythm. So don't leave your patients in AF. I agree sinus rhythm is better, but drug therapy is an okay first option. But for people who don't like that idea or prefer going straight to ablation, I think absolutely I would do that first and then, you know, incorporate all these other aspects as well. Ed, you bring up a really important point because, you know, in East AFNet 4, which Prash showed, you know, at the end of two years, there's a third of patients who actually had not undergone ablation nor had had, you know, were on an anti-rhythmic drugs. You know, from my perspective, and we talk about that in the guidelines, it's really a pay attention, you know, type of thing. So if someone has AF, you know, make sure you pay attention if you're gonna watch them for a little bit. And, you know, do you call that rhythm or rate control? Right, you're keeping, you want them to stay in sinus rhythm, but you'd be quote a rate control because you're not using one of those traditional anti-rhythmic drugs nor ablation, but I think your points are well taken. Now we've got to get to Nora's question here. So Nora is online here and is just, for those who don't know, just a giant in the electrophysiology space. I was honored to be taught by her when I was an internal medicine resident. She thought I was an anesthesiologist. I don't know if that was because I wasn't very good as an internal medicine resident or not, but she wants some hard outcomes. We talk about reasonable expectation of benefit, right? So I'm gonna turn this over to you, Rakesh, and then to Prash. What's the benefit, right? I mean, what are the numbers that we can expect when we refer our patient for a catheter ablation? So again, we know this from a lot of studies in paroxysmal versus persistent. I think in the, you know, in an otherwise healthy person, like with normal ejection fraction proximal, I think approximately, you know, 75 to 80% for proximal atrial fibrillation is a reasonable target. And I think they need a second ablation with their recurrence. And I think we know that any kind of benefit is incremental. In terms of persistent, we are kind of, I would say it really depends on multiple factors. I would say somewhere between 60 to 70% is what we see. And I think we have seen similar kind of success rates with paroxysmals in PFA as well as RF if you look at different modalities. In the heart failure patients, it really depends on how much underlying substrate they have and how advanced their heart failure process. And in a lot of these, some of the criteria that are like, they're not really set in stone. It's just something that the guideline committee came out and they thought, okay, earlier in the disease process, less comorbidity, so low NYHA class. And they seem to have a better, they can maintain sinus rhythm better and compared to someone who is, you know, class three, class four, or, you know, severely dilated LA and LV and everything. So I think that it's somewhat arbitrary. And, but these data, these characteristics come from post-hook analysis of the studies that looked at a catheter ablation versus medical therapy in HF-RF. And so again, we have to take it with a grain of salt in that case. Yeah, and I think it is hard to put numbers. I mean, you see a lot of published numbers. What is realistic? And I think a lot of it too, and I'll be interested, Prash, to hear your thoughts on this. You know, we, AF is kind of a garbage basket, EKG diagnosis, having been doing this for a long period of time. I mean, I am struck, you know, that particularly for the persistence, there can be a lot of different mechanisms for their atrial fibrillation. So your thoughts on sort of outcomes and et cetera, before I move on to Ed? Yeah, look, a really important question, but I think one of the difficulties interpreting the data is what we're dealing with a spectrum of disease and spectrum of patients. And really the outcome depends on the patient. And it's also a bit of a team sport here. So, you know, we have our role in terms of looking at treating the important areas with catheter ablation, but then there's this whole role of modifying the patient and how that influences the outcome. So our results are critically dependent on what else is going on in that individual patient. So I don't think I can give you a one-off answer. The person with persistent AF obviously has a lot more comorbidities going on, which is gonna cause AF to come back again earlier. And so if you can modify those, then your success is gonna be higher. So it really depends when you interpret the literature, how much of that is controlled in the particular study. I think we're also looking, and I think where Nora's question's going, is we want hard endpoints. And I think we are starting to get hard endpoints, whether it's based on AF burden reduction or something like Castle AF, which showed like a 40% reduction in kind of the composite of mortality and cardiovascular hospitalization. I mean, that's a hard endpoint, but it is in one study. And so we kind of need to know other studies as well, but I think they're all heading in the same direction. So it's a complex answer to a complex question, huh? Great, Ed? Yeah, thanks. Yeah, Nora always has great questions at all our meetings, so I'll try to address it. But I guess if you wanna hang your hat on a number, we can take data from this recent ADVENT trial, which randomized people to PFA for paroxysmal AF to current irrigated thermal ablation, either RF or cryo, right? Success rates at a year were sort of 73% freedom from AF in both. You can kind of say, well, roughly 75% freedom from AF at a year. But again, the challenge with all these studies is you need some dichotomous cutoff, right? Which we know is still this 30 seconds of AF. So I know I had one patient in ADVENT who had two minutes of AF on a monitor, and they're a failure of ablation. So if we look at people even with recurrences after ablation, in general, their burden is less than 1%. So I think these numbers underestimate potentially the benefit in that even people having some AF do better. We came up with one cutoff from ADVENT that if you had less than 0.1%, you really didn't need any sort of interactions with the healthcare system. But I think that's something else we need to figure out is what is the burden where we're helping people in terms of these hard endpoints, which is probably better than the sort of arbitrary kind of 30 second cutoff, especially for persistent AF. Ed, you bring up such an important point. We love Kaplan-Meier survival curves. They help with the statistics, et cetera. But to your point, that one person who had two minutes of AF and never has another episode, although, quote, a failure, I know that patient considers it a clinical success. So let's move on. Carol, I'm gonna ask you the next question asked by this anonymous attendee, thinking about, you know, we always talk about antiarrhythmic drugs versus ablation, and part of this happened, but they often sort of work together. I mean, it's really kind of what you do first, et cetera. And so the question that the audience asks is basically, so tell us a little bit, and you can be more general, you know, kind of your sort of strategy with antiarrhythmic drugs after a patient has undergone an ablation. Yeah, I think that's a great question. And I think it depends on where the patient is on the continuum of atrial fibrillation and what kind of symptoms they have. I would say my common practice is for patients with persistent atrial fibrillation, I'll generally continue them on an antiarrhythmic drug after an AF ablation until first follow-up, and then based on how they're doing symptomatically at that time, we'll think about a trial off the drug at that time if they're doing well. Conversely, with those with paroxysmal atrial fibrillation, depending on burden and what things look like at the time of ablation, I may or may not stop the antiarrhythmic right at the time of ablation, or certainly would be more aggressive about doing that sooner rather than later. There is some data that's looked at whether or not we have patients on an antiarrhythmic drug after ablation, whether that impacts their long-term freedom from atrial fibrillation. And we found that while having patients in that first three-month period on antiarrhythmic drugs does decrease their AF episodes during that time period, it doesn't impact their long-term freedom from atrial fibrillation or other endpoints. So I don't think we're compelled to think that we're doing disease modification by having patients on antiarrhythmic drugs during that time period. And I do just want to expand from there and say that I wanted to underscore a point Rakesh made earlier about the heart failure population and why AF ablation might outperform antiarrhythmics. And I think that we should not underestimate the downside of some of these antiarrhythmic drugs, especially in certain patient populations. And I hope at some point during our conversation, we'll talk about the real gap we have in serving underserved patients and the interesting dichotomy that we see looking at some sub-studies from Cabana in particular that those of African-American heritage and some other ethnic groups might actually derive a particularly large benefit between ablation versus antiarrhythmic drugs. And that's thought perhaps to be due to the harm that comes from antiarrhythmic drugs in this patient population. Great point, Carrie. For the slide that was shown earlier that Rakesh showed, you know, you have overlying everything is really trying to get health equity for all. And it's really critical. And I'm gonna ask you and Ed about that in just a second. But before I go to that, I'm gonna go to the question piece. So when do we pull the trigger, Prash? It's a patient with paroxysmal AFib has three episodes. Is now the time? So when do you start thinking about pulling the trigger for the ablation? Give us some sense. I mean, obviously it's gonna be different for everybody, but what is that sort of arrhythmia burden, duration, et cetera, that would make you think more aggressively about recommending catheter ablation? So I think this really brings out that shared decision-making as a crucial element because everyone's AF affects them in a different way. And their threshold for when they're willing to consider ablation is very, very dependent on the symptoms that they're experiencing. So I think there's a bit to do with us in terms of, okay, the atrial size is getting bigger. The episodes are getting longer. Maybe if we do the ablation earlier, it's going to have a better success. And that's our bit of trying to tell the patient, but a lot of it's based on the patient's symptoms. If that one episode is debilitating them and they're having to go each time to hospital as a rush and use healthcare services, and then they're going to say, well, look, actually, I don't care what you're saying. I wanna get this fixed. So I think that's a really important, I don't think it's a one size fits all. Now, what it does do is it gives us an opportunity to work on other factors that we may be able to influence in the outcome. So we should be looking at treating all patients, but when we offer ablation is a shared process with the patient. Great points, Ed. Yeah, I agree totally. And all patients ask this, like, how much do I have to have before I have ablation? And it's totally patient-driven. The only thing I'll add, I think this came from Jason Andrade's data in SarcoDose that he talked about recently, is when your episode duration is getting to 24 hours or more, that kind of puts your outcome more into the persistent group with ablation. So it's kind of something I tell patients, as long as you're having an hour episode here and there, not so bothersome, you have time to wait. But when you start getting out towards episodes lasting 24 hours, that might be a cutoff point where you might think about doing something about it. So we've talked about the early piece. Let's talk about sort of the late. Rakesh, I'm going to turn this to you. When do you say, because you brought up the notion of thinking about AV node ablation and either biventricular pacing, as shown with Sinead Pafford now, with, let's say, some sort of conduction system pacing. When is enough enough? When do you decide sort of that you are going to not try for rhythm control, but you're just going to do the AV node and do physiologic sort of pacing of some ilk? Give us some insight into that. I know it's a big question and everything's different, but just some guidance. You know, I mean, like anecdotally, I would say that some of my most satisfied and happy patients are those who underwent AV node ablation. They really do well. But I think to your point, I think it depends on, you know, our underlying condition. Like, for example, somebody with emphysema, severe COPD, you try at least maybe two ablations and try ticusin and still no. And those patients are, you know, probably the next best option should be, or someone with really advanced heart failure, you know, late class three. And again, we can't maintain sinus rhythm after giving it a reasonable try. I mean, even though we know that ablation improves outcomes, it's not for everybody. I think, you know, in such a situation, there is absolutely no, I mean, I think that this is a great option that we have in that. And with CRT or now with conduction system pacing and the, we can, it really, and the right patient, it can make a significant improvement in quality of life. And they really, I mean, like most patients. And so I think, you know, comorbidities, how much we have tried and, you know, it's a decision in my mind. Great. Thank you very much. So, Care, I'm going to turn it back to you because I don't want it to be the last thing, right, that we talk about. It's got to be something that's critical. It is thinking about access to care, you know, just to set you up for, I'll be really interested to hear what you're going to say for the audience. Know that when we looked at advanced therapies, whether it be left atrial appendage occlusion, whether it be catheter ablation, you look at the get with the guidelines, registries, all of them that are U.S. based, clearly underrepresented minorities, underrepresented. When you look at anticoagulation, whether it be with warfarin or doax, same type of thing. And so I'd like to hear your thoughts on that, but also expand it worldwide too, because again, we're thinking about an expensive technology potentially or drugs to maintain sinus rhythm, stroke prevention, things like that. So I'd like to hear both your take on sort of maybe what we could do as sort of the United States for just as a policy piece here in the United States to improve health equity, but also maybe what could heart rhythm society or others to do sort of on a more worldwide basis. So I'd love to hear your thoughts. Wow. Well, that's a small question. Yeah, indeed. I wish I had answers for all of that, Fred. But let me, let me give a couple thoughts. So, so one piece within the U.S. that I think is helpful is getting patients to cardiac electrophysiologists quicker. I think that there's some good data to show that going from ER to, to cardiac electrophysiologists, you know, speeding up that process is one way to improve access. And I think if you see an electrophysiologist, then it's your, as a patient, you're going to be presented with more options. So, so I think just increasing access to providers, I think having more providers that come from disparate backgrounds and, and will perhaps open the door to people thinking more broadly about the patient in front of them. And again, thinking more about, you know, what options are being offered. I want to just add on to some of the things you were talking about that, that women is another category that we know that, that women have, you know, are more at risk for stroke from AF and yet are less likely to be anticoagulated as well. And so I think there's, there's a lot that we can do there. I also would suggest going back to a point that Prash made earlier about lifestyle. And I think that that's another piece that, that can be perhaps accessible to, to many, you know, to many people. As far as, you know, how to do this on a more global scale, I'll be interested in some of the other panelists' thoughts, but I think that, you know, HRS, we're, we're certainly trying to create more global network of care. So I think I was just learning on the education committee meeting last night that HRSTV is, is something that's really being taken up on, you know, by, by listeners all over the world. And I think it's an opportunity to propagate our, you know, the knowledge of, of some of these trials that we've been talking about today. Prash has been doing an amazing work with some digital education through HRS as well. That again, just democratizing knowledge I think is, is a really important piece. And I think making HRS represent not just an American opinion and American voices, but having people from lots of different places have a space and have a voice on HRS, I think is another way to improve care of patients and improve our understanding of what are some of the barriers to care and lots of different places. Outstanding. Yeah. I couldn't agree with you more. And really thinking also too, with HRS being, I like it as a method for making more links, right? So that we become more tightly linked as an electrophysiologic social network. I think that that's so important thinking about it, not just within the US, but also sort of globally. Prash? Look, I was going to add to that. I mean, that was a really super, super answer because it really does is it takes a community to kind of get this right. And, and one of the things I wanted to highlight is we, we need to be starting to do our studies to include, be inclusive of these populations. And you know, I think we're starting to see the early phases of this and to Sam Awosny's credit in Avant Garde, they have a actually strict criteria that they're going to enroll 50% women. And so it's actually starting to occur. And we're looking at minority groups as well. And I think it's a top down kind of phenomena as we get more evidence that's hard, we're going to start seeing it being implemented a lot better. So I'd like to add that in as one of the strategies that we need to be focusing on. Absolutely. And we can talk about, Nora brings up in the chat along with the other, with, with Martha, actually. So all these people who are involved in EP, so exciting, you know, thinking about getting that education out, how does that sort of work? You know, not having it be just with believers, right. And within our small little community. So Martha, Nora, thank you very much for those great suggestions. And we absolutely need to sort of work on that. They, that's exactly right. We need to not only the way, the way to increase access is to way to increase access to information and democratizing. It was just brought up, you know, thinking about all of this data, not to say that this is absolutely the right way, but really to share the evidence as it comes out. Rakesh? I had a quick question for the panel. You know, one of the, this is regarding implementing or executing lifestyle and risk factor modifications and Prash you have shown that, you know, the, an integrated approach to these problem is the best, but however, what we face in the US here is sort of retail medicine for the most part. And so it's very, you know, not very well interconnected. It's sort of point of care for the most part. And there are so many, you know, rural freestanding hospitals and patients who seek care there. So what are your thoughts and other, other panelists thoughts about how you can effectively deliver, you know, the, and monitor and to assess success for risk factor and lifestyle modification? Yeah. I mean, Rakesh, you bring out an important point. And one of the issues that we're facing kind of translating this widely is that each geography deals with healthcare very, very differently. And so it kind of needs to be tailored to that geography. The approach that we've been taking is we're trying to put it into an app-based function, which trains a trainer and trains the patient at the same time. So there's a little bit of self-training for the patient, but also the advice that the person has to give, usually a nurse practitioner who's working with an EP is able to get some clues as to what the advice should be. So that's the approach we're taking. We just started to build something in the US to see if this is something that we can deploy in the US environment. We're also creating a separate one in India, for example, because the advice is going to be totally different. We have a program here now in Australia that is deployed in five sites and is achieving the results with minimum training of staff on the site. So I think there are going to be different approaches, but we need to work with each healthcare system. And I think one of the things that Apple showed us is, you know, that self-care section may actually just take off. And that may be the way that in some geographies that we need to be addressing this. Self-care linked to a clinic where the person thinks they're getting advice from their physician, but actually most of this can be automated. So that's where we're kind of trying to go. Yeah. Outstanding. When we think about, you know, AI in this space, et cetera, I mean, because I think about my clinic, I have about five problems that I see over and over and over and over again, different permutations, of course, which is the nuance of it. What do you guys do at UCSF? So Kerry, you're in the VA. I mean, that's a kind of a unique population. How do you manage this? Or how do you sort of try to implement that in that system? You're on mute. Sorry. I wasn't sure if Ed was just about to jump in. Oh, sorry. Go ahead, Kara. I can go after. Okay. Yeah. Well, I was going to say that it's been interesting. I feel like COVID, this has been one of these interesting COVID gifts is that they're at the VA as a post-COVID consult clinic that brings together all these different pieces of healthcare. And so I've been trying to piggyback on this model to expand beyond the COVID piece. I think another space that has been interesting is the weight loss drug space and the partnership that's come together with Endocrine and us. And that has been another kind of backdoor way to get people into a more cohesive, more collaborative team-based weight loss program that Endocrine seems to have more of a structure for than we do in cardiology. So kind of looking for those little kind of doors to find that kind of collaborative program, I think has been useful. Outstanding. I don't have a perfect answer though. We could do better. We could always do better, but it is trying to strive. And I love the taking what's already been there because we have learned a lot from COVID. We have had increased acceptance of these sort of video kinds of calls and having multiple people sort of interact. It's exciting to think about using that and deploying that to our patient care. Ed? No, I agree. It's a real challenge. You know, when I, for a return patient visit, I think I have 15 minutes. Usually five minutes is getting them onto the Zoom or getting them checked in the clinic. So to do some of these, you know, weight loss, lifestyle modifications, and then, you know, we try and refer them back to their cardiologist or their internist, but in the U.S. at least to get these GLP-1 inhibitors approved, it's like such an incredible amount of time and paperwork and show they're doing something over so much time that everyone passes it on to somebody else. So, you know, we're working with one of our nurse practitioners who kind of as a champion for sort of a lifestyle modification clinic. And I think that, you know, we can use our EPPs to really help us. There are ways to bill for those visits where someone can really see the patients more regularly than we have time for and walk them through this. And as I think, you know, Prash has piloted maybe some combination of AI, but I think it really takes just constant reminders. And we have seen some patients turn around. So having a nurse run, you know, separate clinic just for these issues, I think we can, if we pass it back to their internist, their next visit is eight months and they don't have the time. So I think it's something we have to, you know, really take on ourselves because we know five years later, these patients are going to be back, right, with more AFib if we don't handle these issues as has been outlined as a chronic disease. And that's a big part of it. So we're all right. And that's just, yeah. And that's just it. I mean, my patients will come to me, you know, with the AF ablation, they think it's going to be some Star Wars-ian, you know, epic battle between Darth and Luke when I have to tell them, no, it's not quite that. It's trench warfare. You have AFib. We're going to be partners with you. For a long time, you know, for many, many years. And then I think you just emphasize that in our last 10 minutes or so, I wanted to give each of you an opportunity to kind of summarize sort of what you think are sort of the most important points to the guidelines, sort of these paradigm shifts that we have gone through. So Rakesh, I'll go to you first. So maybe just a couple one-liners, not too much of really what is super important from the guidelines and sort of our new way of thinking about atrial fibrillation. Oh, you're on mute. Still on mute. Okay. One of the things that the guidelines, I think, put forward was the sort of risk-based stroke risk, basically. I mean, the stroke risk, rather than, you know, kind of hanging your hat on one particular scoring system, which I thought was good because I think that's what we, you know, there are pitfalls for every system out there. And then the sort of progression of disease that Presh outlined and how the, you know, the work actually really starts pre-AFib and continues through that. And I think that's a great development as well. And I'm also really pleased to see that the early rhythm control, first line ablation that we talked about for both, you know, standard, regular AF patients with symptoms as well as in the heart, to see the heart failure section also given the adequate, you know, the data behind that has been represented very well in the recommendations provided. So those, you know, three things that I think they are really welcome and progressive steps. Before I move to Prash, just know that there are four of these webinars that are going to be out. So Prash and others have led, the first one was thinking about risk factors, really focusing on that and risk, modifiable risk factors and taking care of that. The second one was looking at specific and special populations and sort of what does that mean? That's kind of like the AF that occurs after surgery, things like that. What do you do for those patients? The third is been thinking about stroke risk with anticoagulation and left atrial appendage occlusion. And this last one, thinking about rhythm versus rate control and also catheter ablation. So there are going to be four. So I want the audience to know that Prash, maybe one or two points to the guidelines, and it could be similar to what Rakesh said, if you think that those are, bear more emphasis. I mean, there's so much in these guidelines, right? So much new stuff. I think one of the keys for me is obviously the co-morbidity management and putting that up front was kind of a really important step for our field is my feeling. And I think the second one in relation to this webinar is the importance of maintaining sinus rhythm. I think that's, we've tried hard to bring that out in this, whether that's drug therapy, whether that's ablation to emphasize the benefit to patients. And I think that there'll be my top two that I would say from these guidelines. Super. Kara. Yeah. I feel like if I could give it one word, it would be early. I think that this whole process of just thinking earlier about everything, and I'm going to extend that to the thought about whether population-based screening in some subset of patients might be kind of interesting. The new ESC guidelines specifically gave a recommendation for population-based screening in patients over 75, or perhaps spot screening of patients over 65. And I think we have ongoing studies looking at the potential for screening. And I think that's important because of the benefit of AF ablation early, as we've been talking about, as well as I just want to underscore one more time, the risk factor modification, not only for people once they've had AFib, but that we understand that things like controlling blood pressure is important for primary prevention of AF as well. Outstanding. Super. As Prash said, if you would have only been in the room with all of these discussions and sort of which way things would go, because there was a big discussion with regards to screening, that's for sure in the U.S. guidelines, which was adopted by the European group. Ed, I'll give you the final words. Wow. Final words. I'll just add, you know, again, I agree with everything that's been said, so these aren't the highlights, but two other comments. One is just the effect of, you know, wearables. It's amazing how many people come into clinic because their watch, smartwatch, picks up AFib. And everyone has one of these. So, both before they're seen and then monitoring afterwards, it's really just a huge change in terms of how we manage these patients. And then the second thing I'll just add, because it hasn't been mentioned, you know, young patients with recurrent episodes, obviously early, you know, ablation, especially with PFA is a good option. But I think it's in the guidelines, you know, if you're under 45, to think about genetics as well, it can be an initial presentation of another arrhythmogenic cardiomyopathy. And we've picked up several of these who present with AF, but they really have a laminae mutation or filament C or something that requires other treatment. So, think about that also, not just ablating people, but, you know, is there any sort of other underlying cause that might be contributing? Super. And there was a question then on pulse field ablation. Thank you, Prash, for answering that. I really appreciate that. Again, thank you to all of you who have gone through this. Hopefully you found it really fascinating. I always learn something every time I do one of these things. It is really great to get together with my colleagues about this, because, you know, management of patients is, I think you heard throughout, is nuanced. And it really is very, very individualized, even though I laughed about my five patients, you know, with those problems, the individual management's absolutely critical, nuanced, and evolves and changes over time as their goals change and really taking their thoughts into our discussion and our decision sort of management and how best to do that. So, with that, I want to call an end to this wonderful webinar. Thank you very much. Just know that this will be, this has been recorded. It's going to go through the different HRS educational environments to then make sure that it's good. And then it'll go then for enduring content. I want to take the opportunity to thank Rakesh and Prash, two wonderful talks, really outstanding. And Karen, great insight as panelists thinking about sort of all of the issues that we brought up here. And since it's the last webinar, I have to make sure that Sarah and Stephanie, who have put all of this together, get their thanks. So, thank you to both for just putting on a great series of webinars. Thank you very much all. Have a great night. Good night. Thank you. Thank you.

2023 AF guidelines

atrial fibrillation

early treatment

rhythm control

catheter ablation

heart failure

reduced ejection fraction

EAST-AFNET 4

CASEL-AF

integrated approach

equity in healthcare

individualized treatment