So, good morning, late morning, early afternoon. Good to see you all. We finally have made it to the last day of the scientific sessions. I hope you all have been motivated and invigorated in the same way I have with the sessions. It's just been tremendous science and inspirational prerogatives and initiatives for us to engage in as an organization. And so I am incredibly delighted to be here with you today for this really important session on the management of atrial fibrillation in the setting of congestive heart failure. And we have an outstanding group of speakers to share with you today and some really incredibly provocative content as well. It is my pleasure, I'm Kevin Thomas from Duke University, and to sit next to one of the legends of electrophysiology, Dr. Doug Packer from Mayo Clinic. And we're excited to get engaged with you all for this discussion today. So we're going to start with our first speaker. Again, just to remind you, AFib and heart failure, ablation and AFib management in heart failure patients. And our first topic will be led by Sandeep Prabhu. He'll be talking to us about atrial fibrillation and heart failure, reduced ejection fraction, rate versus rhythm control. Thank you. Thank you very much for the kind invitation to talk today. And thanks to the HRS committee for the opportunity. And it's a great privilege to talk about this area, which I feel very passionate about. And these are my disclosures. So the question really asked by this topic is, should patients with atrial fibrillation and coexisting heart failure with reduced ejection fraction, should they receive rhythm or rate control? And the answer to that question is actually rhythm control. I thought that left for a very short talk. So I thought perhaps I'd go and explain it a bit more. And I think we talk about why that is, looking at the physiological benefits, the clinical benefits of sinus rhythm, when is the best time to achieve rhythm control in this unique group of patients, what's the best way of doing that, and then spend a little bit of time on some specific patient considerations, and even a little bit of time on who maybe shouldn't get rhythm control, which are those groups of patients. When it comes to the drivers of heart failure in the setting of atrial fibrillation, I like to think of three key drivers. That's tachycardia, that's the rate itself, that's a loss of atrial contractile function, and also the irregularity itself. And these are the three things we need to treat to try and get the best result from treating the heart failure that's driven by the AF. Now medical rate control, at best, is a partial treatment of tachycardia. And I'll explain that a bit later on. It does nothing for atrial contractile function, it does nothing for irregularity. A patient in a BLADE strategy, on the other hand, does treat tachycardia, does treat irregularity, doesn't restore atrial contractile function. When you compare that directly with sinus rhythm, as they did in 2008 by the Parber HF study, we still see that sinus rhythm is superior with respect to fairly well-established endpoints. Sinus rhythm is really the only treatment that treats all three aspects of the drivers of heart failure in the setting of atrial fibrillation. So when it comes to why rhythm control, well, now we have really good data about hard clinical endpoints. And the CASEL team have published some really pivotal studies in this. We have Anissia Marucci's study, which was a long-term study of about five years follow-up on all comers with heart failure showing significant improvements in both mortality and hospitalisation. Over that five-year period. And more recently, data from the CASEL HDX series, looking at those sicker patients who were eligible to be considered for transplant workup, and showing that hard endpoints, such as progression to transplant, mechanical support, or death, showed a significant improvement in those patients where we could restore sinus rhythm. So we now have hard clinical endpoint data for these patients. And when we look at a meta-analysis of 12 randomised studies in this area, we see that across the board, there's a reduction in heart failure events and a heart failure mortality. So it's very strong evidence we have now for catheter ablation, which has really developed over the last 10 years. And now the guidelines reflect this, both the American guidelines and to a lesser extent the European guidelines, now have a class one indication for patients with suspected AF-mediated cardiomyopathy, or with an expectation to derive clinical benefit from the restoration of sinus rhythm with catheter ablation. And particularly what we call tachycardia-induced cardiomyopathy, or what I like to call AF-induced cardiomyopathy, is now a class one indication in those European patients as well. So one of the things we also want to know about rhythm control is how it improves ejection fraction. This is something we're particularly interested in the Cameron-Moriah study we published back in 2017. So this is looking at patients with otherwise rate-controlled atrial fibrillation, and excluding those with other sorts of LV dysfunction, including myocardial infarction. And they all had MRI to assess the degree of scarring, and we showed significant improvements in the ejection fraction in those patients who underwent catheter ablation compared to medical rate control, keeping in mind that these patients maintained good medical rate control over the period of the study. And it really highlighted AF as an underappreciated cause of heart failure. And I make the point that even in the medical rate control, and we did see improvements in rate control over that time, but you can see that even with the best medical rate control, you can't match the rate control you get from sinus rhythm. So really sinus rhythm is the ultimate rate control in these patients. This is data from the CAMERA 2 study, which we recently presented as an ESC late breaker in London last year. In addition to improving the injection fraction, we see that there are significant objective functional improvements in patients. Patients both with and without scar had significant improvements in their VO2 max, which was not seen in patients who underwent medical rate control. Similarly, we saw that in tests such as the six-minute walk test. We saw significant improvements in quality of life as well in both those patients with and without scar. And we saw changes from baseline, significant improvements in the Minnesota living with heart failure questionnaire as well. In addition to this, we see reverse cardiac remodeling with sinus rhythm, so both in the ventricle and the atrius. So in the ventricle, we saw significant reductions in end systolic volume. This is measured by cardiac MRI. We also showed significant reductions in LA volume as well. In addition to just the structural remodeling, we saw electrical remodeling as well. A series of patients in our CAMERA MRI study returned for reassessment of their right atria with electroanatomical mapping. And we saw improvement in tissue voltage and reduction in complex fraction and electrograms as well, showing that in addition to reductions in size, the actual electrical substrate improved as well. More recently, this is work done by Dr. Louise Segan and our team back at the Alfred. We've looked at 235 patients with AF and heart failure who had coexisting functional mitral regurgitation. And those patients who underwent catheter ablation, 89% of those patients with at least moderate to severe MR improved by at least one or more grade of mitral valve regurgitation severity. So in addition to just structurally modeling, we see improvement in valvular function as well. And in addition to this, we do see some significant limitations just with medical therapy alone. So we're interested in what happens with medical therapy when you don't add rhythm control as well. We looked at the CAMERA 1 and the CAMERA MR2 cohort, particularly those patients when they were initially diagnosed naive to medical therapy and at the time when they were still in AF but now on guideline-directed therapy before the initiation of rhythm control with catheter ablation. And we can see that there was no significant difference or any very marginal improvement, which was not significant, improvement in ejection fraction until we established rhythm control with catheter ablation. This is an abstract we had presented here by Dr. Kenneth Cho, our PhD student, which was presented only two days ago. What about after the restoration of rhythm control? So we can see that rhythm control may not be that useful. Rhythm rate control may not be that useful before we restart rhythm control. What about after we've had rhythm control? Well, rhythm control in a certain population of patients, particularly those with AF-mediated cardiomyopathy, we'll hear more about this later on in this session, gives us potentially the opportunity to withdraw some of that therapy in the long term. And perhaps it's the maintenance of sinus rhythm that helps maintain the ejection fraction rather than ongoing medical therapy. So rhythm control gives us the option in certain selected patients to do that. How do we achieve rhythm control? I really like this study. This is a study from 2016 by DiBiase and colleagues, which really compared head-to-head the two main treatments at the time, which is amiodarone and catheter ablation. And I like this study because it's very elegant and it showed an improvement both in freedom of AF, but also these were secondary endpoints in reduced mortality and reduced hospitalisations. We always keep circling back to this study when we're asked by the non-EP, our non-EP colleagues, why can't we just put all these patients on amiodarone? Now when should we ablate? So there's always been a little bit of controversy about diagnosis to ablation time as a metric that we use. And perhaps in the unselected patients, there is a little bit of controversy as to whether it's something we should rely on or not. But I think in the heart failure population, we do have some data suggest that earlier intervention is better. This is a study we did of 210 patients with AF and heart failure, looking at those patients who had a diagnosis to ablation time of less than a year compared to those with greater than a year. And we saw that those who were intervened in less than one year had significantly greater improvements in ejection fraction, greater freedom from atrial fibrillation, and also reduced healthcare utilisation as well. What about who should be getting rhythm control? Does it apply to all patients or are there some special groups we should think about? We were quite interested in the group that had co-existing scar as well, particularly those patients who had scar from things such as myocardial infarction. This was the focus of the CAMRA MRI2 study which we presented at ESC last year in London. And those patients with scar were randomised either medical rate control or catheter ablation And there was a comparative arm of patients without scar who underwent catheter ablation. We could see that at 12 months, there was a significant improvement in both groups in the magnitude of improvement from baseline to follow-up of around 20%. The absolute value in the scarred patients was significantly less, but the improvement from the restoration of sinus rhythms appeared to extend to patients both with and without scar which we didn't see in the medical rate control group. What about older patients? These are patients with AF-mediated cardiomyopathy, 70 patients we looked at, and we saw that patients, even older patients, seemed to derive the same benefit. They all had same rates of normalisation of ejection fraction. And the freedom from atrial fibrillation also significantly improved. This is work done by Dr Louise Sagan as part of our team at the Alfred Hospital as well. And particularly we get physicians particularly concerned about the size of the LA in patients with heart failure, thinking perhaps rhythm control is futile in these patients. We looked specifically at this in the combined cohort of CAPLA patients and CAMRA patients and showed that with these 196 patients, it really didn't matter what kind of LA size you had at baseline. We saw that the improvement in terms of ejection fraction was equivalent between the groups and there was no significant difference even with freedom from atrial fibrillation based on the baseline left atrial size. So there are still patients who we do have to question whether we can successfully rhythm control these patients. We talked a bit about age, but I think frailty is a different thing to age. And patients, particularly frail patients, may not benefit from catheter ablation particularly. Those with persisting LA thrombus, some etiologies may struggle to benefit from catheter ablation. And those patients with permanent AF, where they've been in continuous AF for probably more than five to ten years, perhaps may benefit better from a CRT and AV node ablation strategy. And of course patient choice is always fundamental. Some patients just don't want to undergo procedures. And if it's an informed choice, that's entirely reasonable. So to conclude, I would say that rhythm control in patients with atrial fibrillation and reduced ejection fraction has a number of significant benefits over rate control, particularly with regards to mortality, hospitalization, functional capacity and quality of life, reverse cardiac remodeling, and also improved valvular function. And catheter ablation, in the absence of any contraindications, is preferable over amiodarone. And this persists despite age, increasing LA size, ventricular fibrosis, which do not necessarily preclude catheter ablation in these patients. So I'd conclude by saying timely rhythm control is recommended for managing all patients with AF with concurrent heart failure, reduced ejection fraction, in the absence of contraindications. And I'd like to think of rhythm control really as like the fifth pillar of treatment in these patients with reduced heart function. Thank you very much. We're going to wait until the end to do the questions. One of the reasons for that is we need to get Nasir Maroosh up here quickly to tell us about patient selection and ablation strategies in heart failure. Nasir? Doug, Kevin, ladies and gentlemen, thank you for being here on a Sunday, a sunny day in San Diego, end of the meeting. I thought we'll get maybe 10, 15 people, but maybe because Doug Packer has a chair, he attracts people that they put them in a chair in the session. Patient selection, ablation strategy in heart failure. How many of you in this room are heart failure docs, heart failure physicians? How many? One, two, three, three. How many do AFib ablations? Raise your hand. Obviously, a majority. So this is an AFib ablation meeting. That's why I want to start full disclosure. You heard a lot. Sandeep and his group, sorry, they told me how to use this, I don't know how to use it, but this is a nice slide to start with. The function before ablation and after, and you see the difference. That's for us in EP, when you see this difference within three months or six months or a year after, a huge excitement in terms of delivering ablation in the left atrium. That's what I want to talk about first. You've seen this slide. Castle AF, patient population like this, less than 35, EF, class two and more, they do very well with AFib ablation. You heard this extensively from Sandeep based on the castle. I want to look at, continue showing this data, becoming very important, we're talking about this a lot recently, the burden data. This is the castle data, see how we suppress the burden data over the whole study duration with the ablation procedure, and this is a major contributor to the outcome. We also, I think this is the paper from Johannes, where he shows that the 50% seems a very good cutoff, excellent cutoff for mortality benefit at three months follow-up on the ICDs. All the patients have the devices, so you can tell this is like the sustained improvement after 50% cutoff, and the guidelines change based on this paper and other papers that Sandeep showed, but that's mainly when this came out, the 1A indication for this patient heart failure. Now this, in the forest plot in castle, there was this group, less than 25% did not do as well as the others. So we went in and Christian Zones, who just here, just left back to Germany, we started the castle F transplant, which you heard about, based on that certain forest plot data. That's why we went in, looked at the sick patients, advanced transplanted patients, waiting for transplant, and this is the patient population, and that showed, as you can tell, and then Sandeep showed this Kaplan-Meier, an impressive reduction in mortality in this patient population. So all the data, for us in EP at least, very convincing that these patients, this patient here, with HFREF, needs an ablation. And I think this should not be debated today and now, and then we heard this was extensively. Now having said that, how we ablate, and I love the data from Sandeep looking at the LA function, because our heart failure colleagues, not only in this room, but in the world, they worry about the LA, they love the LA, they love the LA data, the reservoir volume, and so on. That's their number one indicator for improvements in their patients when they manage them. And then the tools we're using today, especially with PFA and our targets, should be very well carefully, you know, tested and delivered. And then if you look at, this is MRI data, blue means healthy tissue, red means the ablated tissue. And we do MRIs in our patients after ablation. This is the first PFA data. We thought we're not delivering enough scar until we realized this is different beast compared to our F energy delivery, and we adjusted our sequences at thresholds we deliver in the processing images. And you can tell how much scar we're causing with the PFA in this H here. And that's important, this patient that I'm talking about, the HREF patient with dilated atria and sick atria. This is a work from Christian Massad, who's sitting here, who started looking at the strains post-ablation. And we're lowering strain in these patients if we ablate a lot, and this is correlated very well with the amount of lesion you are delivering. So please and please, and this is another data from CalSat AF that nobody wants to talk about. We published this in New England Journal back then, that PVI in this patient alone, all PVI plus lines, where 48% of patients have this ablation, there was no different in outcome. So whatever you do, it seems PVI today and now, until somebody comes out with a decaf tube to see improved outcome to recurrence, we still today, PVI is enough to improve outcome in patients with HREF and beyond. And this is the data why this less ablation is better in terms of saving function, because that reservoir we're talking about in LA function, that the heart failure that I talked about, is very important. Keep it, don't destroy it, because you have the tools now to destroy it. If you look at the three days of data, last three days here, PFA is easy, 10 minutes, let's spend two more minutes and get the anterior wall and get the posterior wall, and the posterior wall definition has been extending with the PFA, used to be a box, now it goes down and goes up to the anterior wall, so be careful, please, where to stop and stick up with the PVI if you can. So this is a patient with HREF, today, PVI, PFA, should be the treatment, right forward. Now what about this patient here, the HREF patient, and that's a discussion, this is an elephant in the room. If you see this patient in the ER, if you send it to the heart failure specialist, they want three in the room, they will debate about what to do with them next. Okay, let's start this and that, and medical treatment, which is, I agree with them, today. If you send it to us, there's no EP in the world today. We'll see this patient unless it's sent to us specifically to ablate. We don't decide. We get them to ablate them. The majority of the patients are with the heart failure community. That's why, today and now, if you have patients, for example, coming shortness of breath to your hospital, AFib, paroxysmal AFib, persistent AFib, normal, you look at the ejection fraction, normal, LA size is normal, that's in the two criteria you look at. It's one A indication, you consider this is normal, heart AFib. Nobody looks into HFPEF in our specialty. Now if he comes with shortness of breath to a heart failure specialist, they would do the HFPEF diagnostics and so on and so on. A lot of our patients we see today are within this criteria. So if you look at the HFPEF population, AFib, we have two A indications, not one A like the HFREF. If you talk to the people with the heart failure community, and that's how they treat the patients today, not an ablation. They don't have data. In fact, if you look at our data, Tulane, over the last 10 years, 7% of the patients has been ablated to HFPEF AFib. Go with the guidelines data, AHA, 1% of the patients with HFPEF and AFib has been ablated today. That tells you a lot. The three guys in the room today that said they're heart failure physicians, they're not sending the patients to us yet for the EPs, for the ablationists. And that's why more data is needed. We have only retrospective data, you've seen it, you're going to hear about it at the end of the discussion. It was very convincing, by the way, for us in this room, and all of us are convinced that we should ablate this patient. But we need the trials. And there's a lot going on, and that's ours. I'm happy to announce the trials will be up and running. Everything set. There will be 55 sites worldwide. We're screening the first time in history, EPs are going to the heart failure, asking for their patient, not the other way around. So we're screening 4,000 HFPAF patients for AFib first. With patches, simple screening method, with certain criteria, high BMP, hospitalization, and so on, we're screening them. So the heart failure docs are part of our steering committee actually, they are the co-PIs, and they're leading this trial. This is a council led by heart failure, not by EP. And then we find these patients, we expect to find them, we are looking for one more percent burden or more, or more 24 hours episodes, and we're going to randomize these patients. Obviously, if we find them for an ablation, using PFA, obviously, Farapals or VariPals, and then versus medical therapy, EPs are involved only in this part of the whole trial. So now we're going to answer the heart failure physician to try to convince them that this 1% and 7% patient they're sending to us should be more than that. Obviously, it's a three years full up trial, looking for mortality, hospitalization, the heart failure docs likes BMP, and the quality of life and strokes. Take home message I want to send with your homework today, AFib with HFRAF, I think we have enough data, all of us convinced, even the heart failure community is convinced, ablation is the way to go, please do PVI first only, and wait, doesn't matter what kind of AFib it is, please. HFRAF, if you send it to me, I'm going to ablate it, I'm going to tell you right now, I'm ablating the patients. If you send it to the heart failure specialist, they're going to think about it. And our goal as an EP to work with them, to convince them is ablation is the way to go, and we need more trials for that. Thank you. our next speaker to the podium. Really, I love this talk in particular because we talk about patient-centeredness. And patients wanna know, once they get their ablation and their EF improves, what next? What to do with the vast array of medications that they're on. So thank you, Dr. Kaufman. We look forward to your knowledge. So, this is the question, when and if we should withdraw GDMT following AFib ablation? And what we know is that AFib and heart failure often coexist. Common factors promote both of these conditions and GDMT addresses some of these factors. We also know that heart failure patients do better after AFib ablation. And AFib can recur. And what should concern us as well is the fact that arrhythmia-induced cardiomyopathy can recur very precipitously when the arrhythmia recurs, even if the original cardiomyopathy took years to develop. And this we've known for a number of years. So when, if ever, is it appropriate to de-escalate GDMT? Well, when the EF has recovered perhaps, when we think the cardiomyopathy was purely due to atrial fibrillation, when there's no need for the other medicines like no high blood pressure, no other fast rhythms. Arrhythmia-induced cardiomyopathy is often considered a reversible entity. So why not reduce medication costs and side effects? But I do want to remind us that we've known for 30 years that pacing-induced cardiomyopathy, which is arguably the most pure form of arrhythmia-induced cardiomyopathy, causes inflammation, myocardial cell loss, and replacement fibrosis. So we do have to bear in mind this may not be an entirely reversible condition. So what do we know about withdrawing GDMT? Well, we know from the Swedish Heart Failure Registry that in the patients who over time were taken off some of their medications, there was a higher relapse rate, particularly those whose RAS inhibition or MRAs were discontinued, compared with patients who remained on their therapy. To a lesser extent, this was seen with stopping beta blockers, particularly in patients who had intermediate improved ejection fractions. But these were not randomized. This was observational from a registry. And maybe these patients were sicker, and they stopped their medicines because their blood pressure was low or something like that. So then we can look at another group of unselected non-ischemic cardiomyopathy patients with recovered ejection fraction SHRED-HF, where patients had randomized withdrawal of GDMT. And you can see that over the first six months, the treatment withdrawal group had about 40% of them had a recurrence compared to none of the patients in those who continued their therapies. Now let's look at arrhythmia-induced cardiomyopathies. We can consider the STOP-CRT, which was an interesting open-label pilot study that took 80 patients, had good indications for their CRT and a good response to their CRT. And it subdivided them into 20 patients who should continue their therapies. Group 2, withdrawal of Ras inhibition. Group 3, withdrawal of beta blockers. And Group 4, withdraw all of them. And interestingly, this being a study of human subjects, a lot of the patients, or some of the patients who were instructed to stop certain medications did not do so because they were worried about recurrent cardiomyopathy. And additionally, 28% of the patients had to have their therapies reinitiated due to other things like high blood pressure and supraventricular arrhythmias. That being said, over the two-year time period, there were very few events of recurrence of cardiomyopathy, which they defined as an increase of 15% or more in their end-systolic left ventricular volume index. So maybe there's a possibility here. Another study that looked at arrhythmia-induced cardiomyopathy looked at, again, a non-randomized withdrawal of GDMT in these patients with improved ejection fraction. And they found that Ras inhibition and beta blocker, if you stopped those drugs, there was an earlier time to relapse of cardiomyopathy, and to a lesser extent, the MRAs as well. And you can see here that the patients who stopped both their Ras inhibitors and their beta blockers did the worst. Those who continued them both did the best. And those who discontinued one or the other had an intermediate outcome. This still doesn't quite answer the question of what happens if you've had restoration of normal ejection fraction in a patient who's had ablation of their atrial fibrillation. So to address this, the most directly relevant study, I have to express my gratitude here to Dr. Louise Segan, a colleague of Dr. Prabhu, who worked together on this Withdraw-AF trial, which was presented in abstract form at the ESC Congress a few months ago and is not yet published. But I'm going to be showing some of their data that were presented at that meeting. This was a very interesting study where 60 patients who had experienced restoration of good ejection fraction after maintaining normal sinus rhythm for at least six months, 97% of them had had an ablation. And they had MRIs that showed no LGE. At that point, and they were very healthy, class one heart failure, euvolemic, they had to be on at least two heart failure agents in their recovered state. And they were, these 60 patients, randomized into two groups, which was the order in which they had a very careful staged withdrawal of therapy. So the first 30 patients had a weaning of their therapy over 12 weeks, followed by six months observed off their heart failure therapy, another CMR, reinitiation with up titration over 12 weeks, observed on their therapy another six months, another CMR. And then if they had been successful off of their medications, they were offered an extended monitoring period of 12 additional months off therapy with an echo at the end of that time. And the other 30 patients did the same thing but in reverse order. The primary outcome was failure to maintain an ejection fraction of greater than 50% following medication withdrawal. And there were a number of secondary outcomes as well, including functional status, biomarkers, quality of life, and so forth. I want to point out that these were really healthy patients. Very few of them had high blood pressure or diabetes. This patient population does not match the majority of my patients in Cleveland, I will say. But it is a very healthy population. And they were 100% of them on ACE inhibitors or ARBs or ARNIs, 100% were on beta blockers, and about 33% on MRAs, very few on SGLT2 inhibitors at the time of onset of this study. So interestingly, out of these 60 patients, only five across those two groups met the primary endpoint and had to resume their therapies on account of a drop in their ejection fraction. And 92% of the patients were able to successfully withdraw from medications. When it came to the secondary outcomes, there really were not any statistical differences. And what I find most interesting about this population is if you look at the five patients who failed, four out of five had new LGE on their MRI. And we don't know what happened on therapy. I don't have access to those data. But it's very important, I think, that we figure that out. Because did these patients develop a drop in their ejection fraction and new LGE because that was the natural history of this underlying disease? Or was it because they were exposed to this second insult when their GDMT was withdrawn? I really don't know. You haven't seen this slide, but in longer outcome therapy, when they were allowed to extend time off GDMT for another 12 months, 45 out of the 55 succeeders remained off of their heart failure therapy. And I'm told that the 10 who resumed therapy did so primarily for other indications like hypertension and supraventricular arrhythmias. So the summary and conclusions of the withdrawal AF investigators was that in patients with AFib cardiomyopathy following AFib rhythm control and ejection fraction normalization, withdrawal of heart failure pharmacotherapy was safe and feasible in the majority. That drops occurred in a minority with modest reduction in EF and without clinical heart failure or need for hospitalization. And that withdrawal of heart failure pharmacotherapy in this condition is safe and feasible with judicious ejection fraction monitoring and rhythm surveillance, which was done very closely. My conclusions are that in unselected patients with heart failure and recovered ejection fraction, and even in patients with arrhythmia-induced cardiomyopathy, withdrawal of GDMT often leads to recurrence of heart failure. In a highly selected group of healthy patients with recovered ejection fraction and no LGE, GDMT withdrawal can be attempted after ablation of AFib in closely monitored patients. And we await publication of a detailed analysis of these data. I want to know, by withdrawing GDMT, do we subject some patients to risk of potentially irreversible consequences, as might be the case if they're developing new LGE? Thank you. Thank you. So let's bring it up to the end here. Scott, let's have you go ahead and teach us about AFib ablation of HEPAF. Is it ready for prime time, or do we need more information first? Great, thank you everyone for being here. I'm Scott Brancato and I was asked to answer the question, is atrial fibrillation, ablation, and heart failure with preserved ejection fraction ready for prime time or do we need more evidence? Spoiler alert, the answer is yes to both parts of that question and you've already heard some of that from Dr. Maroosh's wonderful talk. My aim today is to highlight the current evidence and identify knowledge gaps and discuss treatment strategies in this challenging patient group. Heart failure with preserved ejection fraction or HF-PF affects about half of all heart failure patients and atrial fibrillation or AF is present in up to 60% of patients with HF-PF and patients with both of these conditions have worse outcomes than patients with either condition alone. And understanding the pathophysiology reveals why HF-PF and AF exacerbate each other and HF-PF diastolic dysfunction and elevated left atrial pressure lead to atrial stretch, fibrosis, inflammation, setting the stage for atrial fibrillation and atrial fibrillation results in a loss of atrial contraction, reduced ventricular filling, elevated filling pressures, which worsens diastolic function. This leads to shared mechanisms of atrial myopathy and neurohormonal activation and oxidative stress. Historically, rate control had been the primary strategy for AF management in heart failure with a goal of relieving symptoms and preventing tachycardia-induced cardiomyopathy. However, have we figured out, so far this talk rate control is not preferred and specifically does not address atrial remodeling, atrial fibrosis or inflammation or the critical role of the atrium in diastolic filling. What about rhythm control? Most people here are familiar with the EAST-AF-Net-4 trial, which demonstrated that early rhythm control reduced cardiovascular events compared with rate control. However, this trial wasn't designed specifically for HF-PF patients and we know that in the rhythm control arm only a minority of patients were ablated. However, a sub-study of EAST-AF-Net looked at about 800 patients that had both atrial fibrillation and heart failure. Over half of them had HF-PF and they found that early rhythm control reduced the composite outcome of death, stroke, and hospitalization, suggesting that early rhythm control may be beneficial in these patients. How can catheter ablation specifically help? Well, we know that ablation directly targets the triggers and the substrate that perpetuate AF. In HF-PF, the substrate is often fibrosed and inflamed and ablation directly targets the substrate and restoring sinus rhythm with ablation may improve diastolic filling, reduce left atrial pressure, and potentially halt or even reverse atrial remodeling. What's the evidence for that? So, as Dr. Maroosh had mentioned in his talk, it's really limited to observational studies, small randomized controlled trials or subgroup analysis of randomized controlled trials. Observational studies have shown mixed results. This is an example of a small randomized trial, sorry, a prospective trial that looked at cryo-balloon patients comparing outcomes in patients with HF-PF versus those without heart failure. Found a high atrial fibrillation recurrence rate with a high need for repeat ablation procedures and even persistent symptoms in patients in the HF-PF group post-ablation with no difference in their six-minute walk or probe BNP values. However, larger trials have found conflicting results. This is a meta-analysis that looked at over 2,500 patients comparing outcomes in HF-PF patients with those patients that had heart failure and reduced ejection fraction or no heart failure at all and found no significant difference in atrial fibrillation recurrence or repeat ablation as well as similar all-cause mortality and safety event rates. An even larger study that was recently published at HeartRhythm last year demonstrated a mortality benefit that was observed with catheter ablation. This was 15,000 patients from the TriNetX data set, they were all HF-PF patients and compared to antiarrhythmic drug therapy, those that had catheter ablation were noted to have a significant decrease in acute heart failure events as well as a statistically significant reduction in mortality. So those are the observational studies that we have to look at, some of them. What about randomized trials? Again, we are limited to small studies or subgroup studies. This is a small randomized trial published in 2023 that found that there was a small but it was a small, important randomized trial that found significant improvements in several parameters including wedge pressure, quality of life score, VO2 max, and interestingly, in the ablation group in this small study, about half of patients that underwent ablation no longer had a diagnosis of HF-PF about six months after ablation. What about larger trials? Well, the CABANA trial was not specifically designed for HF-PF, it did include a substantial subgroup of patients with heart failure and Dr. Packer and his colleagues published this in 2021. There were almost 800 patients in the CABANA trial with heart failure and about three quarters of them had HF-PF. And in this sub-study, they were noted to have a significant reduction in all-cause mortality, atrial fibrillation recurrence, and a clinically meaningful increase in quality of life. Other studies have shown conflicting results. This is a large randomized trial from 24 that looked at catheter ablation versus medical therapy, and while catheter ablation overall reduced mortality and heart failure hospitalizations, they didn't find that in the HFPEF subgroup, but it was really only a minority of patients that had HFPEF within this meta-analysis. The largest study that we have to look at was published in Heart Rhythm last year. In 48,000 patients, this was a Brazilian study that pooled randomized controlled trials as well as observational studies, and they found that in these 48,000 patients, there was a reduction in all-cause mortality, cardiovascular mortality, as well as heart failure hospitalizations. Well, what about the type of ablation? Does the type of ablation matter? Dr. Maroosh mentioned this in his talk as well, but we really don't have a lot of data about specific types of ablation. There are some small studies. This one looked at PFA and HFPEF patients in the MANIFEST study. There was a small group of HFPEF patients in the MANIFEST study that had a similar freedom from arrhythmia at one year of over 70%, which was a rate comparable to the patients without heart failure, and notably, no adverse events in the HFPEF patients, suggesting that PFA may be safe and effective in HFPEF. So we're left with some conflicting evidence, but I think the preponderance of evidence demonstrate positive outcomes. Now, there are limitations to all these trials, as we have talked about before, the observational nature and the subgroup analysis of RCTs. And why might it be difficult to demonstrate benefit in this patient population? I think it's essential to recognize that HFPEF is really not a homogenous entity, but rather a diverse clinical syndrome with a variety of phenotypes and different causes of HFPEF, so hypertension, obesity, inflammation, ischemia, age alone, all of those things can lead to the final common pathway that people experience that have HFPEF. So hopefully, future studies will be large enough to separate these phenotypes out. It may be that some people with a certain phenotype respond better to ablation than people with another phenotype, and we simply don't know yet. Where does this leave us with the guidelines? Right now, it is a 2A recommendation for HFPEF patients to undergo catheter ablation. The 2023 guidelines specifically talk about AFib management and heart failure, and they suggest trying to sort out who is likely to benefit from catheter ablation. For example, those in an earlier stage with no or mild atrial fibrosis, paroxysmal, younger patients, and for those patients, they gave a 2A recommendation for catheter ablation. Where do we go from here? Dr. Maroosh talked about CASEL-AF2. In addition to that study, there's an ongoing trial called CABA-HFPEF, which is being done out of Germany with Dr. Abdul-Parwani. It's a randomized controlled trial that aims to enroll over 1,500 patients with both AF and HFPEF to catheter ablation versus medical therapy, and looking at outcomes of death, stroke, and heart failure hospitalization, as well as quality of life, exercise capacity, and maintenance of sinus rhythm. And I managed to find this fun slide on social media from LinkedIn from Dr. Parwani's group. This was last month. They celebrated their 500th patient enrolled in that trial. It looks like a happy group of investigators in Germany, and so we look forward to hearing about the results of their study. So in conclusion, is AFib ablation and HFPEF patients ready for prime time, or do we need more evidence? Again, I think the answer is yes. I think demonstrated from the available studies that the predominance of data support the use of catheter ablation in patients with HFPEF. It may improve mortality. There certainly are ongoing studies, such as CASEL-AF and CABA-HFPEF, that will enlighten us further regarding this issue. Thank you. I think we have about 15 minutes for questions. If there's anybody in the audience that has one, then feel free to step forward. Otherwise, we have our questions ready. Lots and lots. Scott, I'm going to ask you a question first. You're going to have to help me understand what you mean when you say we need more information. Is it that we need more information before we're going to do HEF-HEF ablation? Or won't large randomized clinical trials like what Merge is doing, Cabana, HF, and Kata, HEF-HEF give the information? In other words, I think one of the problems is that you can do things in parallel or you can do things in sequence. And at this point, don't you think doing things in parallel would be better? I do, and I think that's what's happening. And I think we have enough evidence to move forward in that direction, but I don't think we can definitively say with absolute proof, because the gold standard of evidence hasn't really been met in this specific population, but it certainly seems that way. So I think we all have a lot of anecdotal experience with people doing better in sinus rhythm than they do in AFib, when they have high filling pressures. I think it's often subtle. You may not recognize a patient that has HEF-HEF until you bring them to the lab and you put a catheter in their left atrium and their LA pressure's 20 with VOA's to 40, and you know that that patient's going to do better in sinus rhythm. It's been my experience, at least. And I actually think it's perfectly true. I think that we do need to know more information, but I take it then what you're against is the idea of everybody going out and every HEF-HEFer they see ablating. You're for the clinical trial. Yes, for sure. I do think there may be a point of no return, you know, in people with advanced HEF-HEF from whatever, from amyloid or whatever cause. You get to a point where the atrium is so enlarged and so scarred, you know, what's a PVI really going to do in that patient? So, you know, I do think there needs to be patient selection still. I don't think we can ablate everybody with HEF-HEF. Okay. Any audience questions? Can you come to the microphone, please? Hello. So this is a question to Dr. Brunkard. So you were saying that the HEF-HEF population is very heterogeneous. I want to ask you if we want to get data about all these patients in a dedicated manner for the different clusters, what clusters would you choose to actually test of these HEF-HEF patients for ablation versus medical therapy? Yeah, I mean, that's a great question. I think that, you know, the easy ones would be the common ones, but there are probably patients that have less common reasons for having HEF-HEF that may respond differently. So amyloid I mentioned, for example, other infiltrative diseases. But hopefully these studies are large enough that we'll be able to separate, you know, some of that stuff out once the results are available. Okay, and the last question, I want to ask, do we have tachycardia used HEF-HEF, for example, just like with HEF-HEF? Do we have patients who we expect they are going to have a HEF-HEF that responds to ablation because it comes after atrial fibrillation just like with heart failure with reduced ejection fraction after atrial fibrillation? I'm not sure I understand that. I'm not sure I understand the question. Do we have patients who develop HEF-HEF after atrial fibrillation, after tachycardia, that might be responsive to catheter ablation more than any other patients? I think so. I think that, you know, again, those mechanisms exacerbate each other. So yes, I think the answer is yes. I think the mechanisms are problematic because in one case you go in one direction, in the other case you go in a different direction. So I'm not sure how well you're going to be able to parse that out. It would be good for the next trial. Thank you. Let's hear. Both you and Wani and Gerhard in looking at the randomization, are you going to exclude all of the patients in the ablation arm from guideline-directed medical therapy? The reason for asking the question is, you know, you could do a trial and it would be great if you had your guideline-directed on one side and an ablation on the other side, but you're probably going to get a bunch of patients coming into the trial who have HEF-HEF who are already on guideline-directed medical therapy. Do you just leave them on it or do you take them off of it so that you can truly look at the difference? Imagine you ask this question to a heart-failure doc what the answer would be. And we have to have them on that treatment. So the heart-failure doc wants them on that treatment. That's not our decision. The decision was made by them to keep them on their treatment, and everybody before the randomization have to be at least 2 weeks on that treatment before they randomize them. So everybody is on there. Yeah, and that's how we're doing Cabana-HF. Yes? In patients with reduced ejection fraction, we're talking more and more about prompt delivery of ablations and restoring sinus rhythm. How do you determine how prompt or how quickly you'll move to ablation after that sort of index hospitalization for heart failure? Well, in our institution, it has a lot to do with resources, and sometimes there's a waiting list to get in for your ablation. But certainly in the meantime, we're initiating GDMT. But I think if the plan is for prompt restoration of normal rhythm and ablation, we probably don't go as far with the GDMT while we're waiting. We don't have them on 4 drugs at maximal doses necessarily because we have the hope that they're going to experience such a major improvement once they have normal rhythm again. And sometimes if we have a wait, we'll be cardioverting them in the meantime too so that they're not waiting in atrial fibrillation. But I don't think there's any particular good reason to wait as long as they're euvolemic and fairly well compensated. One of the things that we did in looking at the intermountain registry that starts out with about 300,000 patients, but by the time you get them down to Hep-Pef, it's about 60,000. Then you can answer the question of, well, can you wait 6 weeks? Should you wait 6 months? Should you wait? And I think that's the question you're asking. So in looking at this, and we put out 3 or 4 papers here, where we parsed by less than 30 days, 30 days to 6 months, 6 months to 12, and 12 to 36. And we've looked at that for persistent and chronic and gender and that sort of thing. So it's a registry, so it's retrospective. But waiting a whole lot longer than 6 months is counterproductive, especially, and even in persistence, but especially in paroxysmals. So at least from the information we have thus far and in the studies that have been done thus far, I wouldn't be waiting out to 6 to 12 to 24 months. It just looks like there's a lot of data that look at 6 months as a cutoff, but 3 months is probably better. I think everybody is in agreement today that if you have the infrastructure to support it, you take the patient from the ER to do a PBI, and we ablate them as soon as possible. It seems that the understanding with early ablation or intervention, and you can simultaneously initiate the heart failure treatment, but the ablation, the effect is not going to go away on its own. If you have a safe way, which today is it safe and fast and efficient to ablate them with the PBI, with the PFA, I think more and more from the EP perspective and where the centers are like yours, very cohesive working together. People seem to be, I love the data from Doug, 6 months. 6 months is too long to wait. Within less than 6 months, it's much better. But most of us today are the way to the cath lab has been shorter with the current technology and the access to ablation, so it's a waiting time of 3 months. I would agree with that as well. I would just make the point that I think those patients with AF and reduced ejection fraction who are maintaining AF despite cardioversion, I think they're the ones that you prioritize. So when you've got minimal resources, I think you don't want to keep your AF and heart failure patients in AF. They're the ones you prioritize. So failing cardioversion, failing amiodarone in the short term, we'd be prioritizing those patients. A question for Betsy. So if you are in a resource-limited environment where you have a long time to wait for ablation, what is the antiarrhythmic drug protocol that you have at your institution? We end up using a fair amount of dofetilide in patients who have reasonable renal function and are willing to stay long enough to get started on it safely. That's our usual go-to. We use amiodarone in other patients who might have poor renal function. But, again, if they are going to have to go on amiodarone, we would really try to prioritize them for their ablation, try to avoid that. Yes. Great. Hi. Thank you, everyone. My name is Nikhil Alawalia from London at Bart's Hospital in London. My question is about atrial functions and perhaps for Dr. Maroosh. The studies we've spoken about and proposed that are comparing catheter ablation to medical therapy, but on the back of the APAF CRT trial and the HABA-CHF trial, which looked at CRT with avenode ablation in some groups of patients, do you think there are a subgroup of patients with atrial fibrillation and heart failure, perhaps the ones with longstanding AF, who may have less atrial reversible function or patients who failed one catheter ablation who may need to study ablation versus conduction system pacing plus node ablation? I mean, finally, what I'm excited about the most with the PFA technology is we can scale ablation in the same manner. The same catheter for everybody delivers very quick lesions. It's less subjective. So we can look at ablation first time. That's why these new trials with CasLAF2 ablating with PFA across the world, the same lesion set, will help us understand this better. But the reason I'm mentioning this will be a subset of patients. The work that's been done by Kisser and Sandeep will tell us that there's a population that we have to accept. We can restore sinus rhythm. I mean, that's fact. And we continue fighting this population. Maintaining rhythm and synchrony will be crucial. And this population, if the study I have to do today, I would take failing ablation patients and randomize them to what you're saying. And that study has to be done to convince the ablationists. Now we have ablations with an AP and the heart failure, and then ablationists that this is the way to go. But the study has to be done. I know there's one in Canada going on now head-to-head, but as initial therapy, not as a reduce. But if I have to design a trial now, I'm busy with CASEL, but I would design a trial for the redo ablations, patients who fail first ablation, bring them back, redo versus by replacing or his bundle placing with AV nodal modification. Thanks. Yes, please. So maybe a little bit more of a philosophical question for the panel, but what can or should we, as the EP community, do to get heart failure specialists on board with ablating? I think the evidence is there for HFREF, and it's a little bit more common, but particularly in the HFREF patient population. Take them to dinner. Yeah, you could do that. I think that one of the things about heart failure docs is they've gotten really excited about four-pillar therapy. It's great. They now have multiple options, whereas before it's kind of like Tomcat. Not Tomcat. Well, maybe something. You know, you can do natural lysine inhibitors, such as studies, or you could do SGLT2, and then GLIPS, and that sort of thing. So they have lots of things that they can do. But those lots of things take a lot of time. And I think that it is reasonable to say, as you talk with them, that based on what we know about ablation, you don't really have that amount of time. You do better if you do it quicker. And, you know, you're going to have to be doing some adjustments with guideline-directed medical therapy. But I think this is someplace where none of the trials that I'm aware of that we're doing are requiring that we spend a lot of time getting them on four-pillar therapy. So I think it's reasonable to go ahead. They just need the information. They need the information because otherwise they don't know yet. It's really not an either-or, right? It's an and. And so that's the approach that I've taken, is that we're going to do the ablation and you're going to manage their medications to optimize those. And then we'll see where the dust settles and maybe they can get off some of the medications and maybe they can't. Maybe it's a local culture thing because our heart failure people are constantly trying to get us to restore sinus rhythm in everybody, even if they've been in AFib for 12 years and their atrium is enormous. So I guess it may be local. And then a quick follow-up. Sorry. Sorry, I know we'll be around after, but I want to make sure we get to the last question. Thank you. What's your cutoff for how many years you're comfortable doing ablation if the patient has been in AFib for three, five, seven years or just one or two years? Everybody deserves a PVI. Everybody deserves a PVI. If people are in AFib for more, if they're long-standing persistent AFib within large atria, we've been sending for convergent. So we do hybrid. That kind of PVI. I think in those challenging patients, you do get a little bit of information from attempted cardioversion. So you can cardiovert these patients. Sometimes you can tell if it looks like PV initiated, reinitiation straightaway, or if it's purely that there's no underlying sinus node activity. So sometimes the cardioversion, even in these long, long-standing persistent patients, can be quite useful as well. If you asked me this question 10 years ago, it would be a different answer than today. With the PFA procedure of 25, 30 minutes, give them a shot and see what they do. You always can see the atrium shrinks, but they agree if the atrium is monstrous of 7 centimeters or 8, then surgical approach would be not a bad option. Okay. Well, very good. Thank you for being here, both to this session and to HRS. I think it's been a great four days. And to those on the panel, thanks much. Great talks. And we'll look forward to seeing you next year.

atrial fibrillation

heart failure

rhythm control

rate control

HFrEF

HFpEF

catheter ablation

pulmonary vein isolation

ejection fraction

interdisciplinary collaboration