Good morning, everyone. I'm Patricia Tung, and I'm delighted, along with my co-chair, Dr. Larry Jackson, to welcome you to this session, Rhythm Control Strategies for Atrial Arrhythmias in Special Populations. It's a pleasure to welcome you to San Diego and Heart Rhythm. If you've not already done so, please download the HRS 2025 mobile app. That's how you'll be able to submit questions during the Q&A. We're going to start off this session with Rhythm Control Strategies for Atrial Arrhythmias in Elderly Populations. Dr. Annabelle Volgman from Rush University will be presenting. Good morning. So I'm Annabelle Volgman. I'm from Rush University Medical Center, and these are my disclosures. So my talk will be, Should I Choose Antirhythmic Drugs or Catheter Ablation for Patients Who Are Elderly, which is defined as greater than or equal to 75 years of age? Again, these are my disclosures. These are my parents when they were young, and this was their honeymoon picture. As you can see, they were just full of life and so wonderful, but unfortunately, my mom had a stroke in her early 70s, and it really ruined her life, and the family was severely affected. So I really wanted, as a cardiologist, to be able to prevent strokes from the time that she had a stroke, and my father lived a little bit longer than she did, five years more, and this is my father when he was 90, and he turned 91, and he just passed away. But at the end, he had atrial fibrillation, and it was a really tough decision to what to do for a man who was 91 years old. He was on dialysis. He had hypertension since he was in his 40s, and so he had a long life with hypertension, but eventually his kidneys failed, and he went into a-fib, he had half-path, and it was a decision by the cardiologist, and I told them I could not make that decision for him, but they decided not to cardiovert him, and he died a few days later. So it is a tough decision when you're treating older people because they have so many comorbidities and so many complications from our procedures and our drugs, but the hope is that my grandson, who is about to turn two, his spirit will live on through him, and I absolutely adore my grandson, just an FYI. We have an aging population, as you all know, and people who are over 75 years old will have about a 30% risk of having atrial fibrillation, so we need to be prepared to take care of these older patients that will have atrial fibrillation, and what is the best thing to do for them? As you can see here, the people over 65 will outpace the children under 18, and by 2060, there will probably be as many people in their 60s and 70s and lots of people in their 80s, more than the children who are under 18, so we do need to know what to do with these patients. Because of that, because I'm an electrophysiologist in Chicago, I often get called by my friends who have aging parents asking, Annabelle, you know, my mom was told that she has AFib and they want to anticoagulate her, but she's 90 years old. Should we anticoagulate her? And the answer is yes. The answer is yes, they should be anticoagulated, but the question of whether we should treat them with catheter ablation or antiarrhythmic drugs is another question, and that's what this talk is going to be about. What we did highlight, my co-authors and I looked at all the papers that have been written. This is a narrative review that we published in 2022, and we found that older patients with atrial fibrillation have both a high risk of strokes, but also they have a high risk of bleeding, so the risk-benefit ratio is not perfectly clear, so we need to always look at that risk-benefit ratio, and there's a lot of older people with risk of GI bleeding, and we have to think about left atrial appendage occluder in those patients. We all know that patients with atrial fibrillation and renal impairment and warfarin use have a high association, a close association, with a risk of bleeding, but also with greater than 75 years of age is associated with bleeding, and then the risk of false is never a contraindication to anticoagulation. You have to fall over 200 to 400 times before you offset that risk of stroke, so for most patients, you have to think about oral anticoagulation or left atrial appendage occlusion, and always think about a shared decision-making. Of course, the doctor should always make the recommendation, but you have to talk to your patient about all the risks and benefits. The mortality is very high as people get older, and patients with atrial fibrillation, as you can see in the slide, after you get diagnosed with atrial fibrillation, after five years, patients in the age group of 75 to 79 have a 40 percent mortality, and it just keeps getting higher so that over the age of 90, that mortality in the next five years is 84 percent, so we do have to die of something, so, you know, patients who live to learn 90 are definitely at higher risk, but I think that they've had a good life, I hope, and it's acceptable, and so, but we have to give them the best quality of life for the time that they are alive. What else did we find from this review? What about rate versus rhythm control? We all know that rhythm control is what is the superior treatment now from the CABANA study and from the East AF NET study, but what we wanted to emphasize is secondary prevention is so crucial. We need to encourage our doctors to counsel our patients to lose weight, to decrease or eliminate alcohol altogether. Of course, cigarette cessation is always important as well, but optimal control of their diabetes and hypertension is also very important. There's not a clear difference in mortality in rate versus rhythm control in this in this older population, but syncope and fall-related injuries were higher with anti-arrhythmic drugs, especially amiodarone. Mortality is increased also with the use of digoxin, so if you're going to use digoxin, and I'm not sure there are too many people who should be ever treated with digoxin for atrial fibrillation, but if you are going to treat them with digoxin, make sure you always check their serum digoxin concentration, and if it is greater than 1.2, that's associated with increased mortality, so I would decrease that digoxin dose if you see that a higher level. Unfortunately, catheter ablation may not be more beneficial over anti-arrhythmic drug use for rhythm control in patients over the age of 75 in randomized controlled trials, so let's delve into that because this is the topic of my talk. Why is that? Why is catheter ablation not ideal for this age group? Well, they have more complications. The major complications of catheter ablation in this age group are pericardial tamponade. They have a 2% rate of pericardial tamponade, pneumothorax, hemothorax, stroke, TIAs, and splenic bleedings at 1%, but this study showed that if you ablate them second or third time, that complications actually decrease, and they do have a higher recurrence of AFib after ablation. This age group tends to have more occurrences than the younger age group. In terms of safety and efficacy of ablation, patients who this one meta-analysis actually showed that in patients who were less than 60 had the same risk and benefit, efficacy and safety in patients who are over 75, so it's a little bit conflicting, but so we don't really know what is a perfect treatment for these patients, but what they also found was that this elderly group had a lot of comorbidities, and I'm sure you can imagine diabetes, hypertension, heart failure, coronary artery and artery disease, and again, there were a lot of comorbidities that increases the risk of recurrence of AFib and atrial tachyarrhythmias. The CABANA study showed that patients, regardless of age, had more symptomatic atrial fibrillation, but if you need to treat them for the AFib because they can't tolerate the atrial fibrillation, they can be given antiarrhythmic drugs, and if they can't tolerate the antiarrhythmic drugs, catheter ablation is actually a reasonable treatment, so there is some benefit to catheter ablation if they cannot tolerate antiarrhythmic drug treatment. We can't talk about the elderly population without talking about frailty. Of course, it makes sense. This study showed that there is a 14% lower risk of primary cardiovascular events in the non-frail and even in the medium frail, but if they have high frailty, they actually have no benefit from catheter ablation, so we have to think about frailty as well. This meta-analysis showed also that in patients over the age of 75 years, they had a higher rate of arrhythmia recurrence, especially persistent atrial fibrillation, and they had safety endpoint occurrence that was higher than the patients who were less than 75. They concluded that in patients who were over 75 years of age, catheter ablation for atrial fibrillation has a higher risk of arrhythmia recurrence and more complications. What do the guidelines say? The guidelines say that because of the new findings that rhythm control is superior to rate control, we should always focus on maintaining sinus rhythm, and they increased the class, the recommendation for catheter ablation as a first-line treatment in certain patients, and I have a feeling that those certain patients are the older patients that they were thinking of, but catheter ablation for patients with reduced heart failure with reduced atrial fibrillation is a class one recommendation, so for patients who are over regardless of age, if they have half-raf or heart failure with reduced ejection fraction, catheter ablation is a very reasonable treatment for them. So in conclusion, should we choose antiarrhythmic drugs or catheter ablation for these patients? Well, for your patients who are over 75 years old, antiarrhythmic drugs may be better, but if you absolutely need to because they can't tolerate the antiarrhythmic drugs or they have half-raf, you may be able to do catheter ablation. Thank you so much. Thank you, Dr. Volkman, for a fantastic talk, and we certainly appreciate your personal touch and your delivery. Our next speaker will be Dr. Zama Ikuru, who will present, is catheter ablation preferred over antiarrhythmic drug therapy in underrepresented racial and ethnic groups with AF, a battle of different rhythm control strategies? Thank you so much for the introduction, and thank you to HRS for inviting me for this talk. So I'm going to be talking about catheter ablation versus antiarrhythmic therapy, specifically in underrepresented racial and ethnic groups with atrial fibrillation. And so I want to start off with a representative case of a 65-year-old woman who was diagnosed and so I want to start off with a representative case of a 65-year-old woman who, you know, like most of us might see, has a recent diagnosis of persistent atrial fibrillation, six months in duration, and is complaining of palpitations, fatigue, dyspnea on exertion. With the past medical history and her age, as well as her gender, she now has a CHAZ-VASc score of four, and so of course she's going to get anticoagulation. She's failed rate control therapy, and so the question now becomes, well, what else do we do? Do we do catheter ablation or antiarrhythmic drug therapy? And a lot of times these patients are going to, not an electrophysiologist because they don't know who we are, but basically they're going to their primary care physician, sometimes they're going to their cardiologist, and so before they get to an EP, you know, this is the question. So first thing is, you know, rate control versus rhythm control. You know, a lot of times they say it's complicated. Well, is it really? We have the ECF trial that's come out, and it basically shows us that in a group of patients where they looked at patients who had atrial fibrillation for less than a year's duration, if they actually randomized them to early rhythm control, they did much better, and those were patients who both were on antiarrhythmic therapy, and actually the minority of patients were actually had an AFib ablation, but rhythm control definitely surpassed rate control in that situation. So it seems like this is settled science now, except in specific populations if it's a contraindication. So the next question to ask is whether you're going to use your antiarrhythmic drugs or if you're going to use ablation. So there's some key trials that have been done asking this specific question. Mantra AF that was completed in 2015 showed that you had a lower AF burden at 24 months with ablation. You had early AF that in 2021 showed recurrent arrhythmias was lower when you did ablation versus when you used AADs. Stop AF showed the same thing, and then of course the Kavanaugh trial that was completed in 2022, there was no significant difference, but there was reduced atrial fibrillation recurrence and improved quality of life, as well as a mortality benefit with ablation for those who received the ablation treatment. So also there have been meta-analyses that have been done looking at exactly the same question, and looking at the results of that, they showed that you had similar benefits regardless of AF type. So whether you have paroxysmal or persistent atrial fibrillation, and it was also effective even in patients with comorbidities. So let's move forward. So looking at that and all the data that had been presented, it's no surprise that there has been a change in the recommendations where AFib ablation went from being a procedure of last resort, till now when you actually have atrial fibrillation ablation being class 1a in a lot of cases, and class 2a in some cases, and class 1a also in patients with atrial fibrillation and heart failure with reduced ejection fraction. Now with our minoritized patients with, or patients who have, are racially, racial minorities as well as ethnic minorities, we still, we know that gender disparities exist. For instance, in a paper that was, and I'm not just using this paper because he's on the stage, but in a paper that was published by Dr. Jackson, they looked at 77,000 patients with atrial fibrillation, and they found that black males were less likely to receive antiarrhythmic therapy. They also saw that they were less likely to receive an ablation, and all minority groups were less likely to receive cardioversion compared to white males, and Asian females had the lowest rate of cardioversion as a whole. So really we don't know the reason why, and this was in spite of higher risk profile, risk profiles. So this is a problem. When we look at the procedural outcomes, there really is no difference, and you know, basically you can find that you have similar procedural success rates when access is achieved. So the difference is, is it that these patients are just not getting referred to get ablative therapy? There are a lot of problems when we look at, we look at the gender disparities and the racial disparities. They're both on the side of the provider as well as the side of the patient. With regards to the provider, there's implicit bias. Sometimes there's vilification of implicit bias training efforts, and then also there's decreased adherence to guidelines where you have minoritized populations with lower socioeconomic status. If you look at the patient, there's also this, you know, distrust of the medical system. Sometimes because of cost, there's reduced healthcare access and utilization. If you have to decide between whether to eat or get your medicines or go to the hospital, you decide to take care of life and let your health take care of itself. Because of that, you might have increased comorbidities. Sometimes you have low socioeconomic status, and as a result, lower insurance coverage. That affects how you treat your disease and how aggressive you are with your disease. There could be reduced health literacy and disease rate and treatment options, and also there are language barriers, cultural factors that can affect care. So with regards to that, you know, what can we take from those problems and putting them and shining the light on specific EP procedures or EP procedures that could be provided to patients? Well, we have to look at the geographic distribution of EP specialists. This can definitely affect who is getting offered more aggressive therapy versus not, and also the other things that go into the bias that occurs when you have racialized, racial minorities and ethnic minorities. So what can we do? Well, if it is that we're able to refer these patients to EP specialists, there's actually been evidence that showed that this can improve access to specialized care. You can actually address EP procedures, EP problems more effectively. You shorten lengths of stay, and you decrease emergency department visits. And so this can have a huge impact on disparities of care that are seen. So if we go back to the case, if you have this 65-year-old woman with persistent atrial fibrillation, you should consider early rhythm control, looking at the data that has been presented. Based on 2023 guidelines, it should be a class one recommendation for catheter ablation. And then you should also consider the fact that this patient has a higher CHAZ-VASc score as well as an Alex Hauser score. And as a result, you should recommend catheter ablation. And definitely refer this patient to start the discussion about rhythm management. I'm going to end with the statement by Dr. King of all forms of discrimination and inequalities and justice and health is the most shocking and inhumane. And I know that we're all dedicated to that, and that is one of the reasons why we went into medicine. And we should always consider that when we take care of our patients. And thank you. Thank you very much for that wonderful talk. Our next speaker is Dr. Andrea Russo from Cooper University. Thank you so much to the chairs, to the program committee for inviting me to speak on this important topic. Thank you. Okay, my disclosures again. So sex differences in epidemiology of atrial fibrillation have been well described. The incidence of atrial fibrillation is lower in women than in men. The incidence increases, you know, rapidly after the age of 50 in men and after 60 in women. Compared with men, women are older. When they develop atrial fibrillation at that time, they also have more comorbidities. Atrial fibrillation is also associated with a higher risk of stroke in women than in men, and strokes are more severe and disabling in women. So what about symptoms? What do we know? So the frequency of AFib symptoms was examined in several studies, including the Orbit AFib Registry. You can see that, actually, you can't see my pointer, but you can see on the darker green that women are more likely to have palpitations, darker green is women, lighter is men, more likely to have dyspnea, more likely to have lightheadedness, and more likely to have fatigue as well as chest discomfort than men. This was also seen in several other studies, and women are also more likely to have a worse quality of life than men. So why is that? Well, it's not really clear, but what about heart rates during atrial fibrillation? This was from monitors, 30-day monitors performed in over 27,000 patients. Over half were actually women, but in this monitor, these are clinically performed monitors, you could see that the heart rate during atrial fibrillation was more rapid in women than men, so perhaps that might have contributed to symptoms. What about treatment? What are the types of treatment, either rate or rhythm control? Well, first of all, this is a multivariate analysis for factors that are associated with rhythm control strategies, and you could see here that female sex was, women were less often treated with rhythm control strategies than men. In addition, not shown here, but they're less likely to maintain sinus rhythm, as you might expect, within one year of follow-up. In addition, in elderly, more elderly population, the Medicare population, women are less likely to visit an EP physician, less likely to undergo catheter ablation, less likely to receive oral anticoagulation, and in several different studies, women are less likely to undergo cardioversion for atrial fibrillation. So what about catheter ablation? You're seeing a pattern here, I think. In the national inpatient sample of over 122,000 individuals, you could see that female sex was associated with a lower likelihood of undergoing ablation. Ablation, this is a number of years ago, but ablation was going on more frequently, still lower in women, and then an updated analysis of that same database shows that that still held true in 2018 in Quebec, also not just unique to the United States. You could see that the similar pattern also occurred, and even over time, the gap did not decrease. And even if you look at a lot of our clinical trials of catheter ablation, a lower percentage of women, about over half of the population, the prevalence overall is at least 50% of the population who have atrial fibrillation are women. Again, they tend to be older when they get atrial fibrillation, but you could see even in the randomized trials of ablation, we're still relatively well less than 50%. At Cabana, we did much better at 37%. What about outside the United States? Are things any different? Well, this is looking at a study from China. It's a medical insurance database, and this is 30 million subjects from the database. You could see that ablation was happening more often overall in the top left graph there, but women were less likely to undergo ablation than men in the bottom left graph. Cardioversion, again, less common in women. In China, antiarrhythmic drugs to maintain sinus rhythm, again, less often utilized in women than in men. So why do we care, right? Why is this important? Well, as we heard already from the previous talk, we know that early rhythm control is associated with a lower risk of adverse outcomes. If you look at the picture on the top left, you could see the natural progression of AFib when you're having paroxysmal episodes initially. You then, again, eventually progress in most patients to more persistent AFib. The more AFib you have, the more you have in this atrial remodeling that occurs, not just with age-related changes, but with having more AFib. So if you don't treat it, and you don't treat it early, chances are you're going to have more and more of it. You can get structural remodeling. You can see on the MRI scan on the bottom left there, as well as scarring in the atria, structural changes, as well as electrical remodeling and autonomic remodeling. So we want to treat it early and maintain sinus rhythm, and this is the results of East AFibNet, looked at treating early within a year or less is what the definition, although it's a year or less, it's actually the median time from diagnosis was only 36 days in this trial. And they randomized early rhythm control versus usual care, and you could see that those who received early rhythm control did better from, these are big outcomes, right? It's a composite of death from cardiovascular cause, stroke or hospitalization, or worsening heart failure or acute coronary syndrome. So it's actually, these are, it's rhythm control. Most of the patients actually had rhythm control with antiarrhythmic drugs, a minority had received catheter ablation. And what about, so does that hold true for men and for women? Well, this is a post hoc analysis here. You could see the women on the left, men on the right, same primary outcome shown here, but there was no difference in the reduction in the benefit of cardiovascular outcomes with early rhythm control in women and compared to men. So this holds true in both groups. So overall in groups, not pertaining to that particular study per se, but overall in studies compared to men undergoing ablation, women are older, referred after having AFib for a longer period of time, are more likely to have comorbidities, less likely to have coronary disease. And in addition, those who come for ablation, female sex was associated with a higher post-ablation arrhythmia recurrence, and that was seen in several studies. Women at the time, when they got to the lab, had a lower endocardial voltage in the left atrium and a greater left atrial volume index. Again, all these things suggesting AFib has been around for longer and has had caused more remodeling in the atrium. Women are also more likely to have non-pulmonary vein triggers than men, and then we would assume that if you don't target those triggers, that might be one reason why they could have a greater recurrence rate. Women are also more likely to have fibrosis by MRI, as I showed, and you can see more extensively here on the left. The green is the more scarring, and we already know that extensive left atrial scarring predicts a poor response to catheter ablation. Women are also less likely to undergo repeat ablation procedures. Not clear why. Are they not offered, or they just refuse? So this is a meta-analysis showing sex differences in outcomes after catheter ablation. Please note that these are all observational studies, again, so they're not the same baseline characteristics between men and women, but overall, you could see that women, and there are different periods of follow-up there shown, but women are more likely to have recurrence of atrial arrhythmias than men by the time they get to ablation. And what about complications? This is 19 studies. Again, most of these studies are observational studies. Women were more likely to have vascular or groin complications. I think a lot of them, maybe we weren't using routine ultrasound guidance, perhaps. Major bleeding complications more often in women, and more likely to have tamponade or fusions in this meta-analysis. Perhaps a thinner-walled right ventricle, perhaps smaller vessels for access. Not really clear, but higher complication rates. But again, remembering these are observational studies, you can't compare apples to oranges per se. You could try to adjust for differences in baseline characteristics, but what did we see in cabana? In the cabana trial, this was randomized, catheter ablation versus drug therapy. You could see here, this is just looking at arrhythmia recurrence in cabana, and the solid lines are the ablation arms, and then the dotted lines are the drug therapy arms. You could see that if you're male or female, you did better with ablation in terms of arrhythmia recurrence than if you had drug therapy. If you're sitting in the room, you're either male or female, and either way, ablation gave you a better outcome in terms of drugs versus ablation as opposed to drugs. Adverse events in cabana, we did not see any difference in adverse events in cabana. Women were also, in terms of complications, women were also less likely to have ancillary procedures. They're more likely to have non-pulmonary vein triggers, but less likely to have these other procedures performed. Basically, cabana supports ablation for both men and women. Why might there be differences in undergoing rhythm control therapy? Are they less symptomatic? No, we know that's not the case. They're more symptomatic. Are they referred less for a specialist? Yes, we know that's true, and maybe EP docs are more likely to recommend rhythm control therapy. They aren't offered therapy. We don't know if that's the case. Are they thought maybe physicians think they're less likely to benefit or more prone to adverse events? I'm just guessing. Are they referred at a later stage? Yes, that might be a reason why people give an explanation as not ablating a woman. Do they refuse? Well, I don't know. My patients don't seem to be more women, but we don't have any strong data suggesting that yet. I'm just going to mention, too, there's other things besides these outcomes. I talked about dementia and looking at catheter ablation here. This is compared to medical therapy women. Catheter ablation was associated with a lower risk of dementia compared to antiarrhythmic drugs in both men and women. In short, we know that there's sex differences in epidemiology of AFib. Compared to men, women with AFib have a faster heart rate during AFib, have more symptoms, are less likely to receive rhythm control therapies, are referred less often, and at a later stage for non-pharmacologic therapy, and catheter ablation trials do support catheter ablation as an effective treatment. So we don't really, we can't use symptoms to explain differences in referring patients for rhythm control, and we need certainly more investigation to figure out why we have these gaps in therapy or differences. Thanks. Thank you, Dr. Russo, for a fantastic talk that was expertly delivered. Our final speaker will be Dr. Kelly Arps from the University of Michigan, who will speak on rhythm control strategies for the management of atrial fibrillation in younger populations. Thank you very much, and as my disclosures come up, I have one additional disclosure, and that's that I started losing my voice on Thursday afternoon, and it's hanging on by a thread. So we'll try to get through this. I'm here to speak today about rhythm control considerations in young patients. This is a group of patients that are a relatively small population of those total patients with atrial fibrillation, but it's a population in whom you really need some specialized considerations, as well as a population in whom we have the potential to make a really big impact over the duration of the lifespan. There's multiple phenotypes that you might see in this when you consider young patients, which are traditionally defined in studies as those less than age 45 for most studies, and these could be patients who, at a younger age, have some very traditional risk factors like sleep apnea, hypertension, and obesity. This could be patients with repaired congenital heart disease or unrepaired congenital heart disease. This could be a patient who has a genetic dilated cardiomyopathy with atrial arrhythmias as part of that presentation, or it could be someone with no risk factors at all, at least none that are known of coming into the presentation. For the purposes of time, I'm going to focus mainly on these populations of patients who either have some subtle afib risk factors or who are really coming in with what we sometimes call lone atrial fibrillation, because those other two populations are really going to be a talk in and of themselves. So the main points of what I'm going to talk about is, first of all, what evaluation these patients should get, second of all, what should be the approach to the decision about rhythm control in these patients, and then thirdly, what are the best ablation strategies. This is a summary of some considerations in evaluation for a young patient, maybe someone who's 35 or 40 years old, walking into your clinic who is just recently diagnosed with atrial fibrillation without a lot of other known medical history. Of course, we know that there's a lot of lifestyle factors that can precipitate episodes of atrial fibrillation, and this is not true just of the young patients, but maybe more present in the young patients. Things like binge drinking alcohol, stimulant drug use, and then exercise, which we'll touch on in a few minutes. Those known risk factors like obesity and sleep apnea. Taking a family history is going to be really important in this population, because those who have a strong family history of cardiomyopathies or sudden death should be really strongly considered for genetic screening, and then similarly, you can use EKG, echo, and other testing to screen for signs of an underlying arrhythmic or cardiomyopathic genetic disorder. These are some of the genetic cardiomyopathies that have a known association with atrial fibrillation. As you can see here summarized on this slide, you know, there's been different percentages of atrial arrhythmias described, but some keys here are that in ARVC, hypertrophic cardiomyopathy, and Bergada syndrome specifically, atrial fibrillation has been associated with the worst prognosis in all of these conditions. This is the spectrum of gene mutations or genes with known mutations that you might find in this population. On the left is mutations that have specifically been implicated in early onset atrial fibrillation, including some small family clusters that have a really strong penetrance of rare variants for atrial fibrillation risk. On the right is known cardiomyopathy mutations, and I want to draw your attention to the pink section in the middle there, and these are genetic mutations which have a known strong association with both cardiomyopathy and atrial fibrillation. This is things like Titan, Lamin, SCN5A, and KCNQ1. This is, I think, a really important study in this area, and this was a prospective observational study at Vanderbilt where patients diagnosed with atrial fibrillation at a young age, and the whole study was patients younger than 66 underwent whole genome sequencing. And to summarize what's shown here, of that group that was under age 30, 17% of them who had previously undiagnosed were found to have a pathogenic genetic variance that could then be used to guide their treatments. As you see on the right there, those dilated cardiomyopathy mutations like Titan were the most common that they found in that cohort as well. As a result, the AHA or the combined society guidelines that recently came out about atrial fibrillation do give a recommendation that for patients who are young with atrial fibrillation, they should be offered genetic counseling and genetic screening. I want to touch for a moment on athletes. There's a lot of definitions for high endurance athletics in the literature that includes cumulative exercise time, their degree of exercise training, et cetera. But there is multiple studies, including this one shown here, have shown that for those patients specifically with high endurance states, not necessarily high muscle strength states, do have an increased risk of atrial fibrillation. The exact reason is still being sorted out. It may have somewhat to do with high vagal tone and increased atrial ectopy, but this is a special population here. Some treatment strategies for young patients with atrial fibrillation. You know, the first question, as every one of my, you know, all the other presenters in this session have highlighted, is for every patient with AFib, one of the first questions is, you know, should we rate control them or rhythm control them? Just like in many patients, you know, the tradeoff that you're considering is knowing that rhythm control therapies all have some associated risk of side effects, but that particularly in young patients, you have, you know, a lot of their lifespan in which treating earlier atrial fibrillation, like was shown in the EAST trial, is able to prevent that progression of atrial myopathy and potentially reduce adverse events in the long term of their lifespan. And then secondly, in my experience, a lot of the young patients with atrial fibrillation are those that are particularly symptomatic of the condition, and of course you want to treat them and control their symptoms. This was an older meta-analysis, looking at all the studies that it showed that it evaluated observationally rhythm control with standard non-rhythm control. And this was mostly studies using anti-arrhythmic drugs. This looked at a youngish population, those that were under age 65, and actually found that in the youngish population compared to the overall population of these studies, there was more prefer, or more favorability for the outcomes for rhythm control in that youngish group compared to older adults. So this just supports what I think a lot of us would think is that those younger patients have a lot more to gain from rhythm control. And then what kind of therapies would be best for rhythm control? You know, this isn't a study, it's my representation of how I would think about treating a younger patient versus an older patient when choosing between anti-arrhythmic drug and catheter ablation. And that is that, certainly as shown on the bottom panel, catheter ablation has a, at a single time point, has some risk of complications and adverse events that is likely at that single time point slightly higher than taking a drug that day. But if you're talking about starting a 35 or 40 year old on anti-arrhythmic drug, you just have this cumulative rising burden of low but present risk of adverse effects. But then you consider the other effects of being on an anti-arrhythmic drug, and that is the cost of that throughout the lifespan. The monitoring associated with keeping an eye on their blood work and their EKG, as well as the potential side effects that may appear immediately or in the long term over the course of being on that medication. And so that leads me to favor offering catheter ablation to that younger cohort. What do we know about anti-arrhythmic drug strategies in this population? The short answer is not a lot. This is one study that looked back at claims data for atrial fibrillation patients started in the short term on anti-arrhythmic drugs after their diagnosis with AFib. This was patients younger than age 65 again, and found what I think a lot of us experience in clinical practice is that the patients who were getting readmitted for AFib most frequently were those on dronetarone, followed by those on class three or class one C agents with amiodarone being the most effective for preventing recurrent AFib hospitalizations. What they also found is among these drugs, there was no difference in all cause hospitalization between those drug classes. This is, I think, the other side of it, that we know that there is some attributable risk when you look at a large scale to being on anti-arrhythmic drugs. And this is that Sotilol has shown a signal over the long term with increased risk for all cause mortality. And the other anti-arrhythmic drugs have a known pro-arrhythmic risk. One more piece I'll touch on when it comes to anti-arrhythmic drug therapy is that in this younger population with low atrial fibrillation or few risk factors, pill-in-the-pocket strategy can be a good alternative to those particularly who may not be interested in catheter ablation. This was a survey that was done across the U.S. and Europe showing that in patients who have this paroxysmal AFib with no structural heart disease that around, pooled across the respondents, they were saying around 42% of patients were being offered this strategy. Finally, let's talk about catheter ablation. So this is the CABANA trial, which has been mentioned several times already today. And this was a sub-study that was published a few years ago that really showed that that benefit in the primary outcome of clinical events was most pronounced for catheter ablation versus anti-arrhythmic drugs in that younger age group, less than 65 years old. They also, they found that there was a direct association between age and the favorability of ablation. And this is despite the fact that all age groups actually had similar response in terms of recurrence of atrial fibrillation. So it just goes to suggest, again, that those younger patients just had a lot more to gain and a lot fewer competing risks for those primary outcomes. One of the questions that I think still hasn't been answered is do younger patients actually respond better to ablation? This was a smaller series that was presented by some of my colleagues at the University of Michigan. And they found that in their cohort, after a single atrial fibrillation ablation procedure, there actually was a higher incidence of recurrence in an older matched group than in those younger groups. But then once you accounted for multiple procedures, everyone seemed to have similar recurrence rates. This is in contrast to a large series that was published out of Italy that suggested that, and this is all cryoablation, I'll point out, as opposed to the prior study, which was mostly RF. And in this study, there did not appear to be a difference in response to first ablation success. Another difference I'll point out is that this one really had no, was an observational study and had no information about the antiarrhythmic drug use, whereas the prior study was all antiarrhythmic drug-free recurrence. This is another study that supports the suggestion that younger patients are more likely to achieve freedom off of antiarrhythmic drugs. As you can see, the overall freedom from APIV is similar across the age groups, but the freedom off antiarrhythmic drugs was better in the younger patients. Another promising piece of information in this study was that those younger patients were less likely to have complications. Finally, for a moment, I want to highlight the fact that several groups have published information trying to figure out the relationship between parasympathetic and sympathetic tone and atrial fibrillation. And younger patients have been reported to be more likely to have vagal triggers for AFib. And one of the things that we know about pulse-field ablation is that it appears to have more of a transient rather than lasting effect on the autonomic ganglia. I think it remains to be seen whether pulse-field ablation will be just as efficacious for those younger groups as thermal ablation. I mentioned athletes earlier. We know that those patients also respond well to ablation. And then finally, I want to highlight the finding that many groups have published showing that younger atrial fibrillation patients are incredibly likely to have inducible SVT. As a result, there's a guideline recommendation that for those with AFib under age 30, they should get an AP study to diagnose and treat that SVT. And that we know that in multiple of these published studies that ablation of the SVT alone can leave patients without recurrence of atrial fibrillation, potentially obviating the need for an AFib ablation. This highlights that some patients appear to have that reversible response, whereas some patients who were still inducible for AFib at the end of the procedure had atrial fibrillation recurrence requiring ablation of AFib as well. So in conclusion, young patients should absolutely be tested for both modifiable risk factors and underlying genetic cardiomyopathies. Young adults have a lot to gain from catheter ablation. We have a lot more to learn about pulse field ablation and what to do to better understand and treat athletes with atrial fibrillation. Thank you. Thank you, Dr. Arbs, for a wonderful and comprehensive presentation. We have about 12 minutes for questions. I would encourage any audience members to step to the mic to present their questions or submit them via the QR code in the HRS mobile 2025 app. I have a question for Dr. Volgman. Wonderful talk. Thank you. In your practice, how do you evaluate frailty? Do you use a frailty index and how do you use those interpretations to guide decision management with respect to anti-arrhythmic drugs and catheter ablation? Thank you so much. There is a frailty index that you can use that measures how much they can walk, whether they're ambulatory, and I use my Gestalt, is my frailty index. I have a vast array of patients who are in wheelchairs and, of course, they're gonna have a lot more frailty. But then I have some really young 70 and 80-year-olds that are encumbered so much by their atrial fibrillation. And those patients do extremely well with a catheter ablation or anti-arrhythmic drugs. And you can also use the pill in the pocket. These are very savvy patients. You can teach them how to use a pill in the pocket approach to atrial fibrillation. As you know, we're doing the REACT-AF study, which is in low-burden atrial fibrillation patients with CHATS-VASc score of two to four. We're randomizing them to pill in the pocket anticoagulation and, of course, also pill in the pocket, anti-arrhythmic drug use is not part of the study, but we use that all the time. So I think there are lots of different approaches. But in terms of frailty, I really just use my gestalt. Wonderful session. Thank you, everybody, for your talks. A couple quick questions. One was, in light of some of the data in regards to post-AF ablation, such as the option trial and things of this nature, is there any discussion or consideration about whether or not CHATS-VASc is still a relevant stroke predictor and how that may affect how we risk stratify or make recommendations for either very young or very elderly patients in regards to anticoagulation? And then I guess the second question would be, although Dr. Russo brought it up, the issue of some of the single-center studies in regards to dementia risks and how that could interact with both young individuals and possibly middle-aged and older individuals as well. Thank you. I could start with the latter. So I think we're still learning a lot more about dementia, the causes, lots of different causes related to atrial fibrillation. And they're not all necessarily thromboembolic-related, thought to be blood pressure and perfusion changes being part of it, too. And so not a lot of clear, detailed information. I think overall, in terms of stroke risk, CHATS-VASc is still limited. Even in the guidelines, one of the more recent updated guidelines, we recognize that there's other validated risk scores that could be utilized. So that's why we got that 2% risk of stroke as opposed to, not that you can tell for sure what exactly the percentage is, but you can use things other than the CHATS-VASc or another validated risk score. But please also recognize that these scores don't include all of the risk factors for example, renal dysfunctions, not in CHATS-VASc. Other things like left atrial morphology, whether it's chicken wing or cauliflower, all those kind of things are things that we wouldn't know on patients necessarily. Smoke in the left atrium. A lot of these other factors are not included in CHATS-VASc. Age is a really potent one. So it's not like all of a sudden when you're 65, your risk increases. So it's a kind of, so I think there's risk factors that are not included in the standard scores and things to consider for anticoagulation. I don't know how it relates to option. I think that'll be, that's I think a question that I don't know that we have the answer to yet, specifically how that'll pan out with putting in appendage occlusion devices. I'm not sure if I, maybe I didn't completely understand that. And I also wanted to mention that, I think that the more we study atrial fibrillation, the more we know. And then also sometimes the more we actually realize that we don't know enough just because, yes, there's this correlation it seems between atrial fibrillation and stroke and that's why we recommend anticoagulation. But we don't really know if it's more of a motor issue where, oh, the stasis is what is causing a clot that's causing the stroke. Or is it more that atrial fibrillation really is a marker for patients who are more at risk for stroke and anticoagulation just happens to be the mechanism. And I think that REACT-AF is going to tell us a little bit more about that moving forward. I know that in the precursor trial that they had, which was I think called REACT.com, it was just more of a 50-50 person. But one of the more interesting parts of it was that there were some patients who had stroke that didn't show a temporal relationship with their episode of atrial fibrillation. So I think it's a little bit more complicated. I definitely think that CHAS-VASc is not the only score. We definitely need to look at more things. But that's why I guess we have research. Sorry, to clarify, what I was saying was that option was felt to be potentially an underpowered trial due to the low event rate of stroke, right? And so the question moving forward is in a modern strategy of rhythm control, how relevant are the older models in regards to stroke or cardiombolic events? And are we potentially overestimating those risks based on traditional risk scoring? I think that's an excellent question. I think Ocean will tell us a little bit about that, is if you have a very low AFib burden after ablation, we're not having any AFib for a year or so, what is that risk? We know that AFib burden, which is another one of those risk factors not included in CHAS-VASc, a big important one, is important in determining risk. So I think you bring up, raise a really important question that we don't quite have the answer yet. Yeah, I think the REACT-AF study will also help answer that question because we are enrolling a lot of patients right after a catheter ablation. As a matter of fact, we just changed the protocol to be able to talk to those patients after a catheter ablation, during the catheter ablation. It's like, do you wanna be part of the study where you may be randomized to no anticoagulation? So I think that will, your question will be answered in about four to five years. I think it's clear CHAS-VASc has limitations albeit it's our most validated score, but who is it validated in, right? And so I think Dr. Russo brings up a great point and there's a little chart, I know exactly what she's talking about in the guidelines where these additional risk factors, uncontrolled hypertension, Holcomb, left atrial size, varying degrees of kidney dysfunction. I think they matter specifically in patients with low CHAS-VASc scores, that's how I use them, right? So certainly more to come on that topic. Other questions? Larry, can I just say along the lines of anticoagulation that we should not be using the risk of bleeding scores like the HAS-BLAD scores as a reason not to anticoagulate a patient. It should be used to find out what we can alter if they have a risk of bleeding, find out what the risk of bleeding is caused by. If they have a GI bleed, we should address that. But our goal is to always anticoagulate appropriate patients and use the bleeding scores as a way to mitigate those risks. Next question for Dr. Arps, is there an age that's too young to consider for atrial fibrillation, ablation, any potential concerns and thinking through that clinical conundrum? Yeah, excuse me, great question. So one of the, some of the studies I didn't show that I found during this research was that there are series presenting outcomes of atrial fibrillation, ablation in pediatric patients. So young adults who are younger than age 21 years old. So this has been successfully shown in that population. Of course, there's considerations in terms of the size of the left atrium and the size of the catheters. But I would say really in all young patients, particularly pediatric patients, it should be an individualized decision based on their underlying cardiomyopathy, if any, and their clinical status. Just while we're talking about age for Dr. Arps, building on the Vanderbilt data, there are places that routinely send young patients for genetic testing. Do you, in your practice, adhere to the 45? Or there are places that say they routinely test anyone who presents younger than 60. So I think, you know, I'd love to hear what you do in your practice. Yeah, I'm not sure I've ever thought about what the age cutoff is in my practice, but I think somewhere around 40 to 45 is the appropriate cutoff without a known associated condition. You know, if someone has multiple traditional risk factors, you can probably attribute it to that. I think the problem in our practice, and I don't know about yours, is that the availability of genetic testing is often delayed. And so you often, you know, for us getting in with a genetic counselor can sometimes take six or eight months. And so we often have to start a treatment plan before we can actually get the genetic testing. And, you know, to jump back a minute, I did have one additional thought about the question about how young is too young. And that is that another thing I didn't have quite enough time to talk about is how much evidence we have that treating lifestyle risk factors and things like exposure to alcohol use, drug use, sleep apnea, obesity, can really reduce AFib burden. And so I'd say in those younger patients, if there were really addressable risk factors, I would go after those before subjecting the patient to a catheter ablation because we can sometimes reverse this. I like that final point. And it makes me think of Rob Califf and the plenary session where we as EPs love innovation, but maybe we need to think more about the chronic disease and the prevention aspect of AFib. Thank you guys for a wonderful session. We appreciate your attention, audience participation. Thank you.

atrial arrhythmias

rhythm control

elderly

underrepresented groups

women

younger populations

catheter ablation

anticoagulation

personalized treatment