Welcome to the 2021 Quality Summit. Thank you for sharing your time with us today. I have the distinct honor to introduce our speaker for Patient Selection and Period Procedural Management of Afib Ablation Procedures, Dr. Zeitler. Dr. Zeitler graduated from Emory University Medical School in Atlanta, Georgia. She then completed an internal medicine residency at Massachusetts General Hospital, during which time she became enamored with the treatment of heart rhythm disorders and the medical devices that assisted that treatment. To explore this interest, Dr. Zeitler completed a one-year medical device fellowship position at the Food and Drug Administration, where she served in the role as medical officer. Then she returned to Duke to complete fellowships in cardiovascular medicine, clinical research, and clinical electrophysiology. In 2018, Dr. Zeitler joined the electrophysiology faculty at Dartmouth-Hitchcock with a dual appointment at the Dartmouth Institute and the Geisel School of Medicine. At Dartmouth, she continued her work in regulatory policy and outcomes and has initiated work exploring the delivery of heart rhythm care to rural populations. Dr. Zeitler has been so generous in sharing her clinical expertise and guidance with the ACC and is serving as a member on the EP Registry Suite Steering Committee. This registry serves both the Afib Ablation Procedure and the EP Device Implant Registry. Welcome Dr. Zeitler, and thank you for sharing your time with us today. Thank you, Christina, for that welcome and introduction. I'm delighted to be here to talk about a topic that is near and dear to my heart and the heart of really any electrophysiologist, which is patient selection and periprocedural management for Afib Ablation Procedures. As Christina mentioned, I'm Emily Zeitler and I'm at the Dartmouth-Hitchcock Medical Center and the Geisel School of Medicine at Dartmouth, and I'm excited to run through these topics today. Here's an outline of what I plan to discuss. We'll discuss the role of ablation, more generally speaking, for the management of atrial fibrillation, and then more specifically, the indications for Afib ablation as part of that management strategy. We'll talk about a few special populations of Afib patients and within those populations, some special risk factors, which play an important role in patient selection for the procedure. Then I will discuss medication management in the periprocedural period with specific focus on antiarrhythmic drugs and anticoagulation. Of course, there are other drugs which require periprocedural management, but they won't be part of my discussion today. And then I'll talk a little bit about the future of patient selection for atrial fibrillation as we look towards new technologies coming down the pipe. There are a few things that I won't discuss that you might expect for me to discuss, but I'm not going to talk about ablation techniques. My understanding is that there will be other discussants reviewing some of the more specifics about ablation techniques, so I'll leave that to their expertise. This includes things like when to pursue surgical ablation, as opposed to the type of ablation that I perform, which is endocardial ablation of Afib. What kinds of equipment to use, including what energy source to use, radiofrequency, cryo-balloon, laser, pulsed field ablation. These are all specifics of ablation that I won't go into. And even where to put the lesions, where to apply the ablation as part of the Afib ablation procedure. Some of these questions remain open and I won't be going into them today. And then while I will be discussing anticoagulation drugs as part of the periprocedural management of atrial fibrillation, I will not be talking specifically about stroke prevention as it pertains to Afib. I won't be talking about alternative methods for stroke prevention, like left atrial appendage occlusion, which in some cases is part of an Afib ablation procedure, and in other cases is a totally separate procedure, but I will not be going into details about this topic. Here's my toolbox for atrial fibrillation management. Rhythm control as part of that toolbox refers to attempts to restore and maintain sinus rhythm. This might be obvious, but for a really long time, cardiologists and electrophysiologists were focused on reducing the rate of atrial fibrillation rather than actually suppressing or suppressing the rhythm itself to maintain sinus rhythm. But in many cases we do pursue rhythm control. And when we do that, we have a number of tools at our disposal. Things like cardioversion or anti-rhythmic drugs, or if we really want to be most aggressive ablation procedure. And this is what we'll be talking about mostly today. But these tools don't exist in isolation. In fact, they are really part of a broader set of tools that require that we think about upstream therapy, therapies that can suppress atrial fibrillation through behavioral changes like treatment of sleep apnea and weight management. And these sorts of interventions, which I'll go into a bit more detail about, both reduce the burden of AFib once the patient's been diagnosed with AFib, but if undertaken aggressively, they can delay the onset of atrial fibrillation. Well, why even bother with rhythm control and atrial fibrillation? The reason is primarily, or the number one reason I should say, is that AFib has a profound impact on quality of life. This impact on quality of life has been appreciated for a long time, well over 20 years at this point, and was measured as early as around the nineties and early 2000s, some validated and rigorous methods for measuring the quality of life impact of atrial fibrillation have been undertaken. At this point, there are multiple validated scales by which one could do this. And I've listed a few of those here. But before these validated tools were developed, there were tools available for measurement of quality of life that were not atrial fibrillation specific, but did capture major components of quality of life. One of those was used here by the cited manuscript by Dorian et al in Jack in 2000. And in this study, the SF36, which is a quality of life scale used for other cardiovascular diseases was used to assess the quality of life in AFib patients compared to patients with other forms of cardiovascular disease, some of which were well-known to have profound impacts on quality of life. For example, you can see in the top line, which is highlighted that the general health report of patients with atrial fibrillation, and the scale is really not that important, but the comparisons are AFib patients had an average of 54 compared with, for example, post heart failure, post heart attack patients with an average of 59, or patients with chronic congestive heart failure with an average of 47. AFib patients are in the same range, which was a little bit surprising at the time before this was well appreciated. And perhaps even most important is the second highlighted line of mental health quality of life. As you can see here compared with these other groups, and granted, these were small numbers, small in number, the AFib group compared with the other cardiovascular disease groups had the worst reported mental health quality of life. This was really significant and pretty groundbreaking at the time when it was first appreciated. Another thing to note is that women tend to have greater quality of life impact from atrial fibrillation, meaning they report worse quality of life and greater symptom burden compared to men with similar forms of atrial fibrillation. Now I spent a lot of time talking about these validated scales for assessment of quality of life. In reality, in clinical practice, most of the time quality of life is assessed through informal or more general assessments of quality of life. And these validated tools rarely make their way into the medical record at the point of care. Now, the reason I spend so much time talking about quality of life is because it does form the real underpinnings of patient selection for rhythm control and more specifically for atrial fibrillation. I really like this aid here that was part of the ESC guidelines for management of atrial fibrillation published last year. And I'll show a few of the diagrams from this published guideline, not because the American guidelines aren't excellent, but because these diagrams are quite nice from the European guidelines and because the European guidelines have been updated since the most recent update to the American guidelines in 2019. Here you can see a nice depiction of how to think through a patient selection for assessment of quality of life impact from atrial fibrillation. Here more simply it's called symptom burden. In the case when symptom burden from atrial fibrillation is uncertain, these guidelines as well as other guidelines recommend an assessment of that. In other words, if it's unclear whether the patient is truly symptomatic, there's a recommendation to explore that by attempting to restore sinus rhythm and then make an assessment of symptoms at that point. Oftentimes patients believe they're not symptomatic, but once sinus rhythm is restored, it's recognized that indeed they were symptomatic and they feel much better in sinus rhythm. In these cases, we know that we have a more compelling reason to pursue sinus rhythm maintenance. So that's the general approach to evaluating the symptoms that could lead a physician and AFib patient to pursue a rhythm control strategy, but there are some specific populations when other considerations are made. One of these is heart failure with reduced ejection fraction. We sometimes call this group HEF-REF. I'm going to talk more about that later. Another group is hypertrophic cardiomyopathy. This population is special because they have a tremendous burden of atrial fibrillation. It is incredibly common affecting around 20% of patients with hypertrophic cardiomyopathy, which is far greater than the average person in the population age matched. Now the reasons to pursue sinus rhythm in this population, at least based on professional society guidelines, are not different than they are for the general population. However, it is true that the AFib phenotype in this population might be quite different than it is for age matched patients without hypertrophic cardiomyopathy. In other words, AFib in this population is quite resistant and often requires more aggressive treatment to restore and maintain sinus rhythm as compared with patients without hypertrophic cardiomyopathy. On the right of the screen, you can see a graph showing survival in patients with hypertrophic cardiomyopathy with and without atrial fibrillation. You can see that those with atrial fibrillation have worse survival compared with those without atrial fibrillation. This certainly does not prove that AFib reduces life expectancy, but it might signal that patients with atrial fibrillation have worse expected quality of life and worse expected quantity of life. And whether AFib contributes to that is somewhat uncertain based on these data alone, but it is certainly compelling. Another group is the tachycardia bradycardia syndrome group. In this group, bradycardia can sometimes lead to the need for a pacemaker. If we can correct the AFib component of this common syndrome, we can sometimes delay the need for a pacemaker, which while this is a common procedure and relatively safe, I think most of us would agree that if a pacemaker can be avoided, that might be preferable for patients with regard to quality of life and healthcare utilization. On the other end of the spectrum are athletes. Endurance athletes have a greater than expected prevalence of atrial fibrillation. The graph on the far right of this slide demonstrates the prevalence of atrial fibrillation in endurance athletes, and it is significantly greater than age match controls in the population. Now this is important because while deconditioning sometimes reduces or eliminates the burden of atrial fibrillation, many, if not most endurance athletes are not interested in deconditioning because they have put so much effort in achieving their athletic status that they're not interested in losing that. In addition to the unpopularity of the deconditioning strategy for reduction of AFib in this population, antiarrhythmic drugs are also relatively contraindicated in many cases due to resting bradycardia in elite athletes who often have a very normal heart rate in the forties or thirties or fifties at rest, making a typical antiarrhythmic drugs unsafe or unacceptable due to side effects related to these drugs in high performance athletes who tend to be more sensitive to side effects from drugs. Finally asymptomatic patients, whether to pursue rhythm control in truly asymptomatic patients is an open question. I emphasize the word truly because as I mentioned before, often patients who report being asymptomatic, once sinus rhythm is restored, they become aware that they were indeed symptomatic and they become highly motivated to maintain sinus rhythm based on the absence of symptoms. But in truly asymptomatic patients, this remains an open question about whether rhythm control therapy should be pursued. In this one study that I've exerted this graph from, we can see that hemodynamics do appear to improve on some measures in asymptomatic patients who are treated with atrial fibrillation ablation. The role of placebo effect, however, has not been sorted out in this population. And it is one of the several reasons why there are some very smart and very loud proponents for a sham controlled atrial fibrillation ablation study. And truthfully, it's hard to argue with that line of thinking because it would be important to know what the role of the placebo effect is for patients undergoing afib ablation. I promised that I would come back to the population of heart failure with reduced ejection fraction. And so I'm making good on that promise here by discussing the CASEL-AF study. The CASEL-AF study was one which randomized patients with heart failure with reduced ejection fraction, EF less than 35, many of whom, about half of whom had previously been or were currently being treated with amiodarone. So what this means is this was a population with well-recognized atrial fibrillation in whom treatment to achieve rhythm control had in many cases already been attempted. There were over 350 patients randomized in this study to ablation versus medical therapy. And I will note that nearly 90% of the enrolled population was male. So whether the findings from this study would apply more broadly to a more representative heart failure population remain uncertain. In the ablation group, ejection fraction, left ventricular ejection fraction improved by about 8%. And CASEL-AF is not the only study which has explored this question of ablation in heart failure patients. And this improvement of ejection fraction of around 8% has been consistent across these studies. In the medical therapy group, there was a negligible change in the left ventricular ejection fraction as expected. There were very rare complications, and this is an important message. More and more ablation studies, which have been published with contemporary tools and contemporary populations, the rate of complications is very, very low and on par with other elective cardiovascular interventions, which makes this a really reasonable approach even for sick patients. At the bottom of this screen, I've pulled the three main endpoint evaluations from the CASEL-AF study. On the left was death or hospitalization for worsening heart failure, in the center was death of any cause, and on the right, hospitalization for heart failure only. As you can see, the ablation groups in the blue curve did significantly better on all three of these endpoints over a period of several years follow-up. It's important to note though, however, especially in the death from any cause endpoint, that these curves didn't really separate until about three years into the study. This is really important because it means that ablation in this population can be seen as an investment for an improvement in quantity of life, in addition to an investment in improvement in quality of life, which was demonstrated in other studies, and I'll review one of those now. The CABANA study, which was published several years ago now at this point, was an international NIH-funded randomized trial of more than 2,000 patients with atrial fibrillation who were randomized to a strategy of ablation versus usual care with the primary composite endpoint of stroke, death, serious bleeding, or cardiac arrest. Now, the primary analysis from CABANA, which was published a few years ago, was negative, meaning there was no significant difference on this primary composite endpoint between the two randomized groups. There were some very interesting findings from that study, which I will not review here, but suffice it to say that the heart failure sub-study from CABANA was a pre-specified subgroup analysis. And in this pre-specified subgroup analysis, the intention was to include any patient with symptomatic heart failure, and this is regardless of ejection fraction. In other words, this included patients with heart failure with reduced ejection fraction, or HFREF, as well as patients with heart failure with preserved ejection fraction, or HFPEF. And in fact, most of the patients in CABANA who were included in the heart failure subgroup had HFPEF. So this is a nice complement to the CASLAF study, which was exclusively HFREF. The CABANA heart failure sub-study was primarily HFPEF. Again, we saw very rare complications from the ablation procedure, and we saw that the patients randomized to ablation within the heart failure subgroup did significantly better than those patients randomized to the usual care strategy. Now, this should be taken, of course, with a grain of salt, since the primary endpoint of CABANA was negative. But since this was a pre-specified subgroup analysis, I think it is quite meaningful, and it certainly is consistent with what we see in clinical practice. The patients with HFPEF feel very poorly with atrial fibrillation and have frequent heart failure hospitalizations due to AFib. And so suppressing AFib in this population makes good sense as it relates to this endpoint. In addition, I'll mention from the CABANA study overall, and in every subgroup analysis in which it was explored, the ablation strategy conferred benefit on the quality of life endpoints for patients. So why go through all of that about ablation and then try and convince you that ablation beats drugs for sinus rhythm? Well, we know that ablation was better than drugs for the achieved, well, we know that ablation has led to improvement in outcomes with regard to heart failure patients. And we know that patients who achieve sinus rhythm appear to do better than patients who are left in atrial fibrillation. And so the question is, what's the best way to achieve sinus rhythm? And I would argue, I think with the data to support me, that ablation clearly beats drugs for the restoration and maintenance of sinus rhythm. So here I've pulled some data from a meta-analysis. There have been multiple studies asking this exact question of which is better, ablation or drugs to achieve sinus rhythm. And this meta-analysis among others have clearly demonstrated that ablation does a better job of achieving sinus rhythm. Now in the bottom right, this was a systematic review which looked at rhythm control versus rate control. Because there's so much crossover in studies of atrial fibrillation for rhythm management versus rate control management, it's important to note that even when rhythm control is compared to rate control, it really may not reflect what actually happens in the trial. So this is just an example of that in the bottom right. You can see in blue are those patients in the rhythm control arm of various studies who achieve sinus rhythm. And in the red bars, these are patients randomized to rate control which achieve sinus rhythm, which demonstrates there was a lot of crossover from rate control to rhythm control, even in high quality randomized controlled trials. The point being that in many cases, patients ultimately reach a point that rhythm control is pursued. And when that is the case, ablation is the superior strategy in order to achieve and maintain sinus rhythm. So with all of that behind us, let's review the indications for ablation. Now, once again, these are from the European guidelines for AFib from 2020. This is very similar, not identical, but very similar to the American guidelines for catheter ablation of atrial fibrillation. I've highlighted once again, the role of the symptoms in atrial fibrillation. For symptomatic patients with atrial fibrillation who have a paroxysmal form of AFib, meaning it comes and goes, catheter ablation can be a first-line treatment strategy with a two-way indication. In patients in whom an antiarrhythmic drug is selected for rhythm control, if that fails, then catheter ablation is a class one indication for the restoration of sinus rhythm. Now, this is slightly different when we think about patients who have structural heart disease, including those patients with heart failure with induced ejection fraction on the far right of this diagram. In this population, based partially on the CASL-AF study, which we've discussed, catheter ablation is a class one indication for the restoration and maintenance of sinus rhythm. Catheter ablation in heart failure is not a class one indication in the American guidelines. It's a 2A indication, but there are many people who, many operators who based on patient preference and informed decision-making, offer catheter ablation as a first-line treatment strategy for patients with AFib and heart failure with reduced ejection fraction. Now, in those patients with persistent atrial fibrillation and without heart failure with reduced ejection fraction, catheter ablation can be performed either as a first or second-line treatment strategy. Those are the decisions that an operator and a patient make at the point of care when the AFib has been diagnosed and symptoms have been assessed. But what about other treatments but what about other treatment strategies either upstream of that or in combination with those kinds of decisions? Primary prevention and secondary prevention of atrial fibrillation can be achieved through treatment of these very important risk factors. Each one of these risk factors might look really familiar if you have ever considered any form of cardiovascular disease. These are, many of these risk factors are the same risk factors which contribute both to each other and to other forms of cardiovascular disease like coronary disease. So in an attempt to both prevent the development of atrial fibrillation as well as reduce the burden and symptoms of atrial fibrillation, addressing these risk factors can be highly effective. I'm going to review a couple of these as examples. The first example is obesity. There's been a lot of attention to the role of obesity in the development and persistence of atrial fibrillation. There is a extensive literature on this topic. And so I'm just going to mention a few things. The first is the effect of BMI on a fib recurrence following ablation. You can see on the far left that those patients with higher BMI had less successful or higher rates of a fib recurrence out many years following their ablation. Now this was only from a clinical perspective, only slightly worse than patients with BMI less than 30, but it was significantly worse, significantly greater a fib recurrence in the higher BMI population. And it's for this reason among others that patients with very high BMI may not be offered catheter ablation regardless of the indication, knowing that the risk of recurrence is simply too high. On the flip side for primary prevention of atrial fibrillation, a study of bariatric surgery was performed with an observational assessment of a fib recurrence thereafter. In those patients who underwent bariatric surgery compared with matched controls, a fib was significantly more common in the patients who did not have bariatric surgery. Now, again, in both populations, a fib was very common affecting about one out of four to one out of five morbidly obese patients, but bariatric surgery did appear to reduce the risk of developing a fib. And then finally, what is the effect of aggressive intervention for weight loss? Well, it's quite impressive in fact. On the far right in patients even without rhythm control therapy with ablation or antiarrhythmic drugs, there appears to be a dose response relationship between the effect of weight loss and atrial fibrillation recurrence with those patients over time who gained weight having clearly worse outcomes than those patients who either maintained their weight or lost weight with far less occurrence of atrial fibrillation. A second example is sleep apnea. The relationship between sleep apnea and atrial fibrillation has been recognized for quite some time. The pathophysiology underlying this relationship is incompletely understood, but this clinical relationship is well appreciated. The prevalence of obstructive sleep apnea in patients with AFib is very high, depending on what you look at it somewhere between 21 and 74%, which is quite high. And if you look at it the flip way, the prevalence of atrial fibrillation in those patients with OSA is around 5%, which is higher than patients without obstructive sleep apnea. In this population, there's also increased risk of AFib recurrence following treatment with rhythm control. And then treatment of obstructive sleep apnea with the standard of care, which in most cases is CPAP, this does appear to reduce the risk of atrial fibrillation over time, as you can see on the graph on the right. I'm going to move on from risk management, risk factor management to periablation management. First, we'll talk briefly about antiarrhythmic drugs in the periablation period. This can be summed up by saying that there is no clear consistent benefit seen in treating with antiarrhythmic drugs in the periablation period. There's wide variability among operators in terms of preference to other drugs in terms of preference to either start, continue, or stop antiarrhythmics during this period. And therefore, there are no clear recommendations for how to manage these drugs around the time of AFib ablation. And this is at least partially based on the fact that there's no clear benefit seen in the small trials that have been performed trying to answer this question. On the left, you see a bar graph of AFib recurrence after atrial fibrillation ablation in those with and without periablation antiarrhythmic drugs, and there is no significant difference. And the same can be said for the graph on the right, patients followed after AFib ablation with no difference in AFib recurrence between those who did and did not receive antiarrhythmic drugs. Now, that being said, patients who remain on antiarrhythmic drugs who are free of atrial fibrillation following the blanking period, continuation of those drugs is perfectly reasonable and is supported by the relevant professional society guidelines. Moving on from antiarrhythmic drugs, we'll talk about anticoagulation in the periprocedural period. Like all cases of management of anticoagulation, this is a balance between risks of bleeding and risks of clotting. And there are some specific considerations around the time of ablation. On the left, bleeding risks related to the procedure include complications from vascular access in the groin, as well as bleeding into the pericardial space as well as bleeding into the pericardial space in the setting of cardiac perforation, which in a fully anticoagulated patient can be a life-threatening complication. And it can be life-threatening even in the absence of therapeutic anticoagulation. These risks are weighed against clotting risks. Now, that includes both the traditional stroke risk associated with atrial fibrillation, which is cumulative over time, as well as those that are specifically related to the procedure, like prothrombotic state of a procedure in general with general anesthesia in many cases, and the prothrombotic state of catheters dwelling in the left atrium, often for several hours during the procedure. Historically, there was tremendous variability in the management of anticoagulation around the time of ablation. And this was particularly true in the setting of anticoagulation with Coumadin, which many of us know is a far less predictable anticoagulant than those we use routinely these days, the direct oral anticoagulants. Historically, warfarin was often bridged with heparin, whether low molecular weight heparin or unfractionated heparin. And this presented problems with regard to bleeding in many cases. There were multiple studies performed to evaluate the risks, comparative risks between bridged anticoagulation and uninterrupted anticoagulation around the time of ablation. And it's quite clear that uninterrupted anticoagulation was the winner. As you can see from this meta-analysis, in which the risk of stroke and transient ischemic attack was far less in the group of uninterrupted anticoagulation. These days, we're far more likely to use direct oral anticoagulants in patients who are eligible. This includes the most common drugs, dabigatran, rivaroxaban, and apixaban, as well as doxaban, which is used less frequently in the United States. For dabigatran and rivaroxaban, there are clinical trial data which support uninterrupted anticoagulation around the time of ablation. For apixaban and doxaban, there are no clinical trial data supporting uninterrupted anticoagulation, but non-randomized data do support uninterrupted anticoagulation around the time of ablation. That being said, holding of one to two doses of any DOAC preablation or periablation, including dabigatran and rivaroxaban is considered reasonable and is supported by the relevant professional society guidelines. Now, in many patients who undergo ablation, they are already anticoagulated due to baseline stroke risk from atrial fibrillation, but this is not true in all patients. For example, many of the endurance athletes, which we discussed previously, may not have adequate stroke risk to justify chronic anticoagulation. In these patients, it's reasonable to initiate anticoagulation in the three to four weeks preablation. In many patients, this is based on a shared decision-making conversation about the appropriate approach for anticoagulation around the time of ablation. At the bottom here, I've provided a comparison of DOACs to warfarin, and it's quite clear that DOACs are at least as good as coumadin around the time of ablation. And so this has been recommended as the primary strategy for anticoagulation in eligible patients in the relevant guidelines. Post-ablation anticoagulation decision-making is driven by stroke risk, meaning it is not presumed that AFib will be fully suppressed, thus eliminating the stroke risk in the post-ablation period. On the contrary, the decision about whether to continue anticoagulation is based on the risk of stroke, whether or not AFib is considered to have been fully suppressed. Now, of course, this will involve a shared decision-making conversation between patients and providers, and many patients will decide to discontinue anticoagulation based on this conversation after about a two-month post-ablation anticoagulation period, during which time there is an increased risk of stroke or TIA due to changes of the ablation procedure itself. I've listed a few of those here, and these amount to changes that occur due to the procedure itself. These are consensus recommendations based on expert opinion that anticoagulation be continued after the procedure, leaving room for discussions between operators and patients about the most appropriate strategy. Finally, I'll briefly mention some thoughts about the future of patient selection for atrial fibrillation. These are two of the most burning questions in my mind about how to most appropriately select patients as the field moves forward. First of all, I'm really compelled by the population of patients with heart failure with preserved ejection fraction. This population is compelling because they have so much burden of atrial fibrillation and so few treatments, both for the heart failure and the AFib, which are highly effective. And so if we can improve the quality and or quantity of life by effectively suppressing atrial fibrillation through ablation, then this would be a really attractive population in whom to focus our efforts and suppress atrial fibrillation through ablation. The second thought that comes to mind about the future of patient selection is whether or not we may be including sicker and sicker patients as candidates for AFib ablation as our tools become safer. For example, pulse field ablation, which is currently undergoing clinical trials and will likely be available for clinical use sometime soon, promises to be safer in some ways than traditional radiofrequency or cryo-balloon ablation of atrial fibrillation. If this materializes, then perhaps the risk-benefit balance for AFib ablation will favor performing the procedure in patients whom we might otherwise believe are too sick to undergo the procedure. Thank you very much for your attention. I was delighted to be asked to talk on this topic, and I appreciate the time to do so. Thank you very much. Thank you very much, Dr. Zeitler, for that very informative presentation. I know I learned a great deal, and I'm sure our audience did as well. Thank you again for your time today. We do have a few questions that have come in, so we'll jump right into those. Our first question here is asking, with new evidence on the effectiveness of ablation for the symptomatic AFib patient with heart failure, how does the AFib type factor in paroxysmal, persistent, in this particular population? That's a good question. I think as an AFib doctor, I think I speak for us as a group when I say we're really excited about the opportunity to improve quality of life and quantity of life for heart failure patients who have AFib. It's pretty clear from CASEL-AF and CABANA subgroup analysis and other studies that we can do that with ablation of AFib in this population. The question that is being asked is, how much AFib is enough to proceed to ablation? This is really a difficult question to give an exact answer to, but I would say that for heart failure patients, because of the pretty clear benefits of ablation, we're more aggressive in this population. So even for a heart failure patient with brief or infrequent paroxysms of AFib, we might be more likely to pursue an AFib ablation strategy than in a patient without heart failure and the same burden of AFib. This is partially due to the findings we've seen from clinical trials, but also because our antiarrhythmic drug options in this population are quite limited. So in a patient without structural abnormalities, we might be able to use a class 1C antiarrhythmic drug like flecainide, for example, whereas in a heart failure population, we have much fewer options for the treatment of AFib with drugs. We're really left with class 3 drugs, and these drugs have significant safety side effects and are generally less pleasant drugs to take. So it's for these two reasons that I think we'd be more aggressive in treating even paroxysmal AFib in this population. Thank you. I think a secondary or follow-up question to that, again, is just for clarity. So in this population of AFib and heart failure, as I understand it, it was looked at for the symptomatic AFib. Does it hold true for an asymptomatic AFib patient and heart failure as well, the same approach taken in those patients? I think so. Certainly the absence of symptoms in a heart failure patient may not preclude the aggressive rhythm control strategy, whether that's ablation or antiarrhythmic drugs, because of what we know about improved clinical outcomes with suppression of AFib in this population. And I also would argue that in many cases, we use the word asymptomatic. And in fact, patients are not asymptomatic, especially in our heart failure population. If we get those patients into sinus rhythm, and oftentimes this requires what I call an experiment. I tell a patient, we need to do the experiment. Let's start an antiarrhythmic drug or let's do a cardioversion or let's do both and really assess how the patient feels. And many times, perhaps most times, patients really aren't asymptomatic. And the hemodynamics that underlie heart failure, whether it's with reduced or preserved ejection fraction would suggest that AFib would not be conducive to absence of symptoms. In fact, we would fully expect patients with heart failure to be quite symptomatic. So I think even the asymptomatic patient, we would consider a rhythm control strategy with or without ablation. But more importantly, we would want to be absolutely certain we're not missing symptoms. And that often requires aggressive treatment to try and make that assessment. Thank you. Yes, I found that point very interesting where patients don't even realize how bad they feel until they feel better. I think the analogy to that I have is remembering the first time that I got glasses as a teenager and you thought, oh, I can see the leaves on the tree, but you never knew that you couldn't see the leaves on the tree because you didn't realize how bad your vision was. So it's the same thing with symptoms. And until you actually feel better, you never realize how bad you did feel. Oh, it's so true. I've heard that many times from patients who once they sort of get a taste of what sinus rhythm feels like, they never want to go back. And while patients may have been reluctant to take on the burden of what it takes to maintain sinus rhythm, it's not a walk in the park. But oftentimes, once they know how good they can feel, they are willing and enthusiastic about taking that on in order to continue to feel well and engage in activities they thought they couldn't engage in anymore. Very nice. Another question here, in one of your slides, you talked about the endurance athlete. What is it about the endurance athlete that makes them more prone to AF? You know, what is the physiological piece that triggers that? Yeah, that's a good question. And there are a number of different answers to that question. On a basic level, the left atrium of an endurance athlete can be quite enlarged, severely enlarged in some cases. And we know that there is a relationship between left atrial size and risk of atrial fibrillation. In fact, there are some animals, I think it's the blue whale that spends like its entire life in atrial fibrillation because its left atrium is so large. And while I don't treat many whales, the endurance athletes with really enlarged left atriums, when we talk about management of their atrial fibrillation, we can talk about treating the problem, doing an ablation. But as I mentioned, we'd be remiss if we didn't also talk about deconditioning to try and shrink down the left atrial size for long-term suppression of atrial fibrillation. So that appears to be part of it. There are some other elements as well, like enhanced vagal tone. These patients or these athletes can have really robust vagal tone, and that can put patients at risk for developing atrial fibrillation, especially at night. I see. That makes sense. Thank you. Very nice explanation. It's sort of like a cruel joke. And I say this to my patients, it's like, you know, I always say no good deed goes unpunished. They spend their lives being healthy and active and are stuck with atrial fibrillation. And as I mentioned, many, I can count on one hand, really the patients who agree to undergo deconditioning to treat their atrial fibrillation. Most of them are just begging to sign up for an ablation in part because they can't tolerate the drugs because of resting bradycardia, and because they are so committed to their athletics that they're willing to be quite aggressive to support that. Thank you. Another question on one of the slides you presented, you talked about a variety of different specific risk factors, which may make a patient more like, is it more likely to have AFib or more likely to have a reoccurrence of AFib? Are there specific risk factors that make a patient more likely to initially develop AFib in the first place? And like, what are the top contributors? I know you talked about obesity and sleep apnea. Are those top, the top contributors? Yeah. You ask a really good question, you know, or the, this question is a very good one. The risk factors both contribute to developing AFib in the first place, they contribute to the persistence of atrial fibrillation, and they contribute to recurrence of atrial fibrillation after even aggressive treatment, like with ablation. And I think, you know, I showed some, quickly went through a couple of studies that looked at AFib recurrence after ablation in patients with these specific risk factors, the obesity and sleep apnea. And it's pretty clear that these risk factors contribute to recurrence, for example. I don't know that I would put my finger on like the one or two most important risk factors, but you know, I think obesity and sleep apnea are two of the most well understood risk factors for atrial fibrillation. There are high quality data to support intervention on these risk factors. They're tangible risk factors that can have dramatic results if treated effectively. And so, you know, I don't know that I'd put these risk factors in order of most important versus least. It has a lot more to do with the patient in front of you. So, you know, if I have a very fit patient with no cardiovascular disease, but he snores at night and his, you know, his wife says that he wakes up all night long and he feels tired in the morning. Well, for that patient, OSA, obstructive sleep apnea is the number one risk factor because it's probably his only risk factor other than things we can't control like age and, you know, genetics. So in terms of risk factors we can control, it's a real patient specific sort of evaluation because there's so many things we can't control. And that's, it's not helpful for me to tell a patient, you know, they should be younger and you know, less male, that we're not very effective at fixing those problems. I see. Thank you. That's very helpful. Thank you. I think we have time for one more question here. How is patient selection evaluated for repeat ablation procedures? Is that the same as an initial procedure? Oh, that's a good one. I think that there, there are kind of two populations of people who would have a redo ablation. So for patients who have early recurrence falling an eighth of ablation, you know, either, you know, just after what we call the blanking period, this like three month period after an ablation, if a patient has recurrence in that period, we might think that there's an area that requires some touch up, you know, that there has been some reconnection of one of the pulmonary veins, for example, the kind of thing where just a small amount of ablation might fix the problem and get, and then get that patient, the, you know, the long benefit that we had hoped in the first place. And so for patients like that, who are, who had a good experience with the eighth of ablation, didn't have any complications and have early recurrence. I think that's one group that we might might be frequently offered quote redo ablation in order to address sort of like a, a small, a small problem, a small breakthrough or a reconnection of a pulmonary vein. And then the second group is the group with more late recurrence. So patients who had nice results from an eighth of ablation for a year or two years or three years or five years, and, and then have recurrence in those patients, you know, we consider all of the options that we considered before the first ablation. Perhaps we consider antiarrhythmic drugs or rate control or or ablation, but that patient made the decision to pursue ablation for one reason or another, either drugs had failed or they just preferred an ablation strategy. And so we, this, the patient selection at that point is pretty similar to the first time around, except that the patient who's, who chose to take, get an ablation the first time is likely to choose it the second time or the third time too, because, you know, while risks and benefits and preferences change over time, they tend not to change that dramatically. Now that being said, following an AFib ablation, if there's a recurrence of AFib, sometimes drugs that were incompletely or inadequately effective preablation might be adequately or acceptably effective post ablation. And so sometimes we can kind of limp along and push that second ablation out by using drugs that we didn't, that didn't work the first time around. This is all sort of part of all our toolbox. I showed that really kind of elementary diagram of a toolbox of, you know, of things we can do to suppress AFib. And I think, and I really, I use that imagery in my mind. We have these tools and we have to use them thoughtfully and deliberately, and, you know, we don't use a screwdriver and then throw it away. We use the screwdriver and then we use something else and maybe we need the screwdriver again another day. So I'm giving you a really long answer to your question. But I think this, the second population, this late recurrence of AFib is kind of like the first time around. We look in our toolbox and figure out what's best for that patient. And oftentimes once patients have had an ablation, they, in many or most cases, it's a good experience. And so they're, they're interested in doing it again. Thank you. Yes. And each patient is unique. So each one may be treated in, you know, a different manner based on their unique presentation. So that makes complete sense. Well, I do want to thank you very much again for your time today, for sharing this presentation with us. We hope it will be very helpful for our audience as they're using the AFib ablation registry and understanding their patient populations better. So we sincerely appreciate you being with us here today. We also thank our audience very much for sharing your time with us today. We appreciate all you do to support optimizing patient care. Thank you for everything you do, and we hope you have a great rest of your day. Thank you. Thank you.

patient selection

peri-procedural management

atrial fibrillation

AFib ablation procedures

sinus rhythm

rhythm control

risk factor management

heart failure

left ventricular ejection fraction