PAUL FRIEDMAN: Hi. My name is Paul Friedman from the Department of Cardiovascular Medicine. And it's my pleasure and privilege to introduce my colleagues, doctors Chris DeSimone and Abhishek Deshmukh, who'll be covering updates in the management of patients with atrial fibrillation in 2024. There's a lot happening in this field, and we have no better two individuals to give us this update.

Chris is a consultant and director of research in the Division of Heart Rhythm Services within the Department of Cardiovascular Medicine. For the Department, he serves as marketing director; and in the Division, he is the director of research. He holds the academic rank of Associate Professor of Medicine, and his clinical interests include complex ablation procedures.

He comes to us via Upstate New York, where he did his bachelor's degrees in both biology and biochemistry. He also got his PhD and his MD degree before coming to join us here. His research interests include avant garde animal studies, assessing the mechanism of ventricular fibrillation, one of the leading causes of death, which he's on a path towards hopefully helping us eradicate it. And to that end, he has over 250 publications.

He has 50 patents that have been filed or granted, and is actively involved in the development of new technologies. He also has received many honors, including the Mayo Brothers Distinguished Fellow Award, the Mayo Clinic Cardiovascular Medicine Outstanding Research Fellow Award, and a number of Mayo Clinic Experienced Provider Recognition awards, as well as a President's Discovery Translation Award, and the Earl Wood Career Development Award.

He will be joined by Abhishek Deshmukh, who is an Associate Professor of Medicine who joined the staff in 2016 and directs our ECG and Physiologic Monitoring Lab, which has been a hub for much of the artificial intelligence work that the Department is doing and is also a source for externally-facing services that Mayo Clinic is offering to other hospitals. He has a very active research program using large data sets and advanced analytics with risk prediction for heart rhythm disorders and has published over 380 manuscripts.

He also serves on the ACC/AHA writing committees and has been coauthor on three guidelines, including those for management of post-TAVR conduction disturbances, management, and evaluation of patients with ventricular arrhythmias and sudden cardiac death risk, as well as stress cardiomyopathy. He's co-director of the EP fellowship training program and has received Teacher of the Year awards. He also directs several Mayo CMEs and has mentored trainees from around the world. He's also a co-inventor and is involved in algorithms distinguishing rhythm disorders.

I could spend the whole time talking about my colleagues. They're terrific. But I'll stop here and let them teach us about atrial fibrillation. So Chris, Abhishek, thank you.

ABHISHEK DESHMUKH: Thanks a lot. I'm Abhishek Deshmukh. We'll talk about managing patients, what you are going to see in your clinic from right today, afternoon, as we are done with this. These are our disclosures.

So our learning objective is to discuss a case-based approach to explore contemporary management of atrial fibrillation in routine clinical scenarios, and this is going to appeal to an internist, rheumatologist, cardiologist, endocrinologist, because all of us see atrial fibrillation; summarize some recent large trial data that may guide clinical decision-making in atrial fibrillation; and discuss best strategies for management of atrial fibrillation and heart failure.

So we'll show you four cases of all patients who are 68 years of age, and you'll appreciate how AFib can present different. So this is a 68-year-old female with paroxysmal atrial fibrillation, had multiple visits to the emergency room for atrial fibrillation with rapid rates. This is the ECG, which shows atrial fibrillation. CHADS VASc score is 3; EF is normal; and has been treated with beta blockers. But despite being treated on beta blockers and the rates are well controlled, the patient is still quite symptomatic with atrial fibrillation.

So how should we manage this patient? Should we do rate-- should we increase the rate-controlling medications, rhythm control with drugs, rhythm control with ablation, or no change? And all of us will have our own opinion about how we are going to deal with this patient. But we'll just maybe tease out how an electrophysiologist would approach some of these nuances.

So when we think of pillars of AFib management, it's really based on number one thing-- we really want to avoid a patient with atrial fibrillation getting a stroke. So the first thing we do is to assess and do risk stratification of stroke risk in those patients. Second is optimize the risk factors because atrial fibrillation can be seen and caused by several of these risk factors, and we have to do our best how we can optimize these risk factors to reduce the recurrence of atrial fibrillation.

And after we are done with this, we really want to treat the patient. So we want to prevent stroke, we want to prevent the risk factors, and we want to treat the patients from their AFib burden to see how we can make them feel better and then live longer. And that can be done by either rate control or rhythm control. So how do we approach this?

So the factors which favor rate control versus rhythm control is important to understand and really based on, it depends on the patient factors. There are some patients who prefer rate control. They may be younger, but they may feel older. So those older patients prefer rate control, longer history of atrial fibrillation, and they are really not very symptomatic from atrial fibrillation. Those are the patients who would develop-- who would favor rate control.

Rhythm control would be patients who want rhythm control. Patients who feel younger; they may be older, but they feel younger, and they want to feel better. So those are the patients who should go for rhythm control. Shorter history of AFib and more symptomatic would be the group of patients who would favor rhythm control.

And then there are certain physical exam findings and anatomical changes. If the rate is easily controlled, or the atrium is severely enlarged, there is less LV dysfunction, or less valuable regurgitation, those patients tend to do better with rate control. But if the rate control is difficult to accomplish, smaller atria, more LV dysfunction, more mitral regurgitation or tricuspid regurgitation, those are the patients we should aim for rhythm control.

So these are two easy approaches, rate control and rhythm control. But majority of our patients fall in the middle where, you know, the symptom burden may be variable, left ventricle may be enlarged, EF might be low but not severely reduced. And then how we can tease those things out when we evaluate these patients, we would summarize as we move along with this talk.

But the main thing is, regardless whether you approach rate control or rhythm control, the decision of anticoagulation does not change. And every patient should have an independent risk assessment for stroke prevention. So historically, the AFFIRM trial taught us that if you do rate versus rhythm control, there is really no difference in mortality, no difference in stroke risk, and less hospitalizations actually in patients who had rate control.

So from that, we kind of learned that there is no difference in rate control versus rhythm control. But the caveats to that was there was no AF ablation when the study was done, and strokes occurred when anticoagulation was stopped, regardless of the rate and rhythm approach. So if patient is in sinus rhythm, anticoagulation was stopped, and those are the patients who got strokes. So again, important that the decision of anticoagulation doesn't really depend on rate and rhythm control, and everybody should get this stratification for stroke prevention.

So from there, how do us as electrophysiologists think of atrial fibrillation? So the way I think about atrial fibrillation is like lighting up a piece of wood on fire. You need to have a matchstick or a lighter or a trigger to start that fire, and that comes from the pulmonary veins, which initiate these triggers. You need to have some autonomic changes that suddenly these triggers start to occur much more frequently, so that piece of wood is like catching fire. And you need to have a good piece of wood to keep that fire going for a longer period of time, and that would be atrial substrate. And with all the comorbidities the patients bring, those are the patients who are going to have more persistent and longstanding, persistent atrial fibrillation.

And once we understand this concept, then we want to see who are these patients who would benefit actually from rhythm control and more specifically, from an ablation intervention to see if we can reduce the burden of atrial fibrillation. So the idea is to target these triggers initially, which are causing atrial fibrillation.

This is what we do in an AF ablation. This is the left atrium. This is the pulmonary veins. We put catheters in the pulmonary veins, and we are trying to do a pulmonary vein isolation, PVI, trying to isolate these veins that we stop this firing from entering into the heart. So you may have a best piece of wood, but if there is no matchstick or lighter or trigger to start that fire, that piece of wood is not going to catch fire by itself. And this is how the end result looks like when we do a pulmonary vein isolation procedure.

So coming to this patient, we did an AF ablation, we did this pulmonary vein isolation. Patient did well, significant improvement in symptoms, quality of life, dramatic reduction in AFib burden. And regardless of this, the anticoagulation kept going on, so that in case the patient has recurrence, the risk of stroke is going to be lower.

Let's look at some of the trials which have highlighted this early rhythm control approach. A key game-changer trial for us was this EAST-AFNET 4 Trial, where about approximately 2,789 patients within one year of diagnosis of atrial fibrillation were randomized to rhythm control with either drugs or ablation versus rate control. And the primary outcome was mortality related to cardiovascular death, stroke, heart failure, or acute coronary syndrome.

So this was done in 11 countries in Europe and randomized into early rhythm control with drugs or ablation or usual care. And if you can see, a lot of these patients were on flecainide and amiodarone, and that was the agent which was used much more frequently in Europe to treat atrial fibrillation. And in the usual care, not many people were on antiarrhythmics, and some patients ended up getting an AF ablation at 8% and about 20% at two years of time.

What did it show? I'm going to tell you in a bit. But one thing to remember is to look at the fine print of any table, one of these studies, and see what is going on. More than 3/4 of these patients were on metoprolol. Last check, metoprolol was rate-controlled. So it's important that we have to control the symptoms and control the rate when we are treating patients with atrial fibrillation.

So these patients were on beta blockers. And what it showed, with early rhythm control, there was a significant decrease in composite of CV mortality, stroke, heart failure, or acute coronary syndrome hospitalization. So clearly, early rhythm control won in this study.

Now, how do we accomplish rhythm control is either by drugs or ablation. And this was an early AF trial, which randomized 303 patients to either getting antiarrhythmics versus AF ablation. And all of them had a loop recorder to find out how much AFib they get after the ablation. The primary endpoint was documented atrial arrhythmias. And ablation significantly reduced the risk of having atrial fibrillation compared to antiarrhythmic medications.

And the key was, it was much better in patients who had low baseline AFib burden and patients who are younger and healthier. So again, in symptomatic patients, in the right patients, ablation is going to significantly reduce the rate of AF recurrence compared with antiarrhythmic medications.

So when we think of atrial fibrillation, it's kind of a continual disease and it's kind of a spectrum. Initially, it starts off with paroxysmal AFib. That's all the firing which is happening from the veins. And then as the substrate progresses, the patient is going to have more and more atrial fibrillation.

And the symptoms also change, depending on where the patient is. If it is earlier, you're going to have more symptomatic. If it is kind of late-stage, more permanent AFib, they are going to be less symptomatic. So where we really want to target these patients with atrial fibrillation is early during the paroxysmal phase because that's what AF ablation is going to do, is to treat these triggers which are coming from the pulmonary veins.

And we don't have a good sense how to ablate the substrate yet. That's why as early as we ablate, those patients tend to do well. It's almost like thinking like cancer. You know, cancer treatment is going to work out much better if they're in stage 1 compared to stage 4 of their cancer.

What some of these studies have also taught us, that if you oblate early paroxysmal atrial fibrillation, there is going to be slower progression to persistent atrial fibrillation, less recurrence of AFib, and reduced burden of AFib. And why this is important, that even if the patient has recurrence after initial AF ablation, as long as they are still in that paroxysmal or the trigger phase, they are going to do much better after a repeat ablation. So really important to think through this.

So from here, we looked at one patient with the symptomatic patients, 68 with atrial fibrillation. Now we'll talk about how we can analyze a patient who has somewhat equivocal symptoms. And Chris can tell us more about it.

CHRISTOPHER DESIMONE: Thank you, Abhishek. Thank you all for coming today. So really what we want to do, now that Abhishek's laid the case for patients with symptoms or no symptoms in a rate- and rhythm-controlling approach, we want to extend that because we want to make patients feel better if they have symptoms. If they're not, we're less reserved on pushing for catheter ablation.

Remember as we move through these cases today, we want you to appreciate that not every patient should get a catheter ablation. We want to help massage who should get catheter ablation. I'll walk you through some of these.

So this is a case, 68-year-old gentleman, and he had, quote, "asymptomatic," persistent atrial fibrillation. Otherwise healthy. Five years ago, he had an aortic valve replaced, and he's very active. He walks several miles most days. He enjoys tennis, and he enjoys golf. Now, I really press patience-- and I challenge you to do the same-- I really press patience on what their symptoms are, what they could be.

He was really denying symptoms, but then I finally had him give up to me that he's noticing issues with hills during golf. His tennis game is struggling. He's not like Roger Federer, like he used to be. It's just not as good.

At routine exam, he was found to be in AFib by his primary care provider. So AFib was diagnosed on exam. ECG confirmed. Despite his asymptomatic status, he was sent for cardioversion back to normal rhythm. Now, he immediately reverted back to AFib, even in the recovery room. So he didn't have a good chance at, do I feel better in sinus rhythm versus atrial fibrillation or not? So he's unsure given the brevity.

His echocardiogram showed he had an enlarged left ventricular size. And his ejection fraction was mildly reduced, about 48%, so not in the normal range. And compared to his echo post surgery, which was five years ago, the LV size increased, the ejection fraction was reduced, and the left atrium was severely enlarged.

So certainly on these points, when you're kind of on the fence as the patient having symptoms or not, and how can we make them feel better, we move to objective testing-- echocardiograms, exercise testing. His exercise tests showed no ischemia but a limited exercise capacity, 6.5 METs, much less more than what he was describing to me or who I would accept in a patient who came to me like this.

So, what to do now? Number one, he's asymptomatic. You do a rate control and an anticoagulation approach. Number two, restore sinus rhythm with drug, an antiarrhythmic drug. And after he's been loaded with an antiarrhythmic drug, perform cardioversion. Three, restore sinus rhythm with an ablation strategy.

The question really comes down to, again, is he really asymptomatic? Because that's going to dictate how aggressive we want to treat his atrial fibrillation. So objective data, as I mentioned-- get an echocardiogram, look at the ejection fraction, look at the volumes-- what we're trying to do is assess the structure and function of the heart objectively-- and do an exercise test.

So I convinced him to come into the hospital for loading with sotalol. And you could see, his echocardiogram, he's got big ventricles. His EF's a little bit down. Some valves are leaking. And we cardioverted him sinus rhythm and repeated echocardiogram the next day. And he told me, there's no difference in my symptoms whatsoever. And there was no change in the structure and function of his heart.

I said, just bear with me. Stay on the antiarrhythmic medicine, and keep yourself in sinus rhythm for the next couple months. So three months, he returned. His pumping function was better. His LV size diminished. And he told me he noted a marked difference in his symptoms. His exertional capacity clearly increased. He was golfing like Tiger, he was playing tennis like Federer again, and he felt overall better. And he was very appreciative of this.

His echocardiogram showed LV improved, as well as his ejection fraction improved. And when he did the exercise this time, there's no challenges here. He had an excellent capacity of 11 minutes.

So I continue to monitor him. Again, we never cure atrial fibrillation; we always monitor it. It's treating it just like diabetes. We continue to follow him at six months intervals. And our backup plan is for catheter ablation if he has breakthrough atrial fibrillation while on an antiarrhythmic drug agent.

So it's not so much of ablate this person, everyone gets an ablation. It's more of some patients need drug therapy to control their rhythm, others require ablation. Some patients require ablation and a combination of antiarrhythmic drug.

The CABANA trial looked at ablation versus antiarrhythmics. And this was spearheaded here at Mayo Clinic by Dr. Packer. And this study randomized 2,200 patients with symptomatic atrial fibrillation. And they randomized them 1-to-1 to rate rhythm control or catheter ablation and followed them up for four years.

The primary endpoint was a composite of death, stroke, bleeding, or cardiac arrest-- all heart events, not things that we tell patients we could help you with, with ablation or rhythm control, usually. Not surprisingly, there was no difference in the primary endpoint. But there was a significant decrease in atrial fibrillation-related hospitalizations in the ablation group compared to the medical therapy group.

So a takeaway from this was that even though ablation versus antiarrhythmic drugs did not have a significant difference in the composite outcome of death, stroke, bleeding, or cardiac arrest, but atrial fibrillation is much better at reducing atrial-- sorry. Catheter ablation is much better at reducing atrial fibrillation, especially atrial fibrillation-related hospitalizations, compared to antiarrhythmic drugs or rate-controlling drugs.

And here I'm showing this Kaplan-Meier curve, showing there's no difference in the heart incomes, but you could see a clear difference in recurrent atrial fibrillation in the ablation group compared to the drug group.

I just want to take a step back and reiterate again, we do ablations for a living, but really, our real love is to help patients feel better. We want to ablate the right patients, and we want patients to get ablations if they need so early. And really, as long as they're in rhythm control, that's a good approximate for how they're feeling.

Now, ablation is not a cure. It doesn't eliminate the need for anticoagulation, and it does not improve mortality. Patients don't care about Kaplan-Meier curves and randomized controlled studies. Patients want to feel better. And no doubt, as a substudy of the CABANA trial showed-- and many subsequent trials-- that quality of life is markedly improved with ablation compared to antiarrhythmic drugs.

So, when to consider a patient for atrial fibrillation ablation? Number one, if they're symptomatic. And again, I challenge you to prove that to yourself and to the patient if you're on the fence about any symptomatic status. If they have a recurrence or breakthrough, despite being on an antiarrhythmic drug, very reasonable to escalate the care to a catheter ablation approach.

Again, you have to tell your patients this, and we'll tell them this-- ablation is performed to treat atrial fibrillation, not to cure it. And also, objectively, if we note a change in cardiac structure and function-- and this is going to lead into our next patients-- then we should do something to act. Minimum rhythm control, but it seems like the studies that are coming out are suggesting catheter ablation.

Now, remember, as Dr. Deshmukh already mentioned, this is like dealing with cancer. So think of atrial fibrillation as cancer of the left atrium. The earlier you intervene, whether it be with rhythm-controlling drugs, catheter ablation, it's all going to be much easier if you take care of that cancer at an earlier stage. So think about it as time-dependent. This is what the data is showing us. So the earlier intervention leads to better outcomes. Much easier to treat patients with paroxysmal atrial fibrillation than it is to treat patients with persistent atrial fibrillation.

There's also "do-nots" for ablation. So do not ablate a patient who cannot be on anticoagulation. We give them anticoagulants to take and IV heparin during the case. They need to stay on blood thinners for a minimum of three months after the ablation procedure.

Similarly, along a same vein, do not offer ablation to patients who only want to do this to get off anticoagulation. Irregardless of how effective the ablation is, CHADS VASc score is the determinant of whether or not patients should be on anticoagulation.

Don't oblate patients who expect or are asking us to be curative. You know, sometimes you'll hear patients, oh, I had an ablation, but it didn't work. It's not that it didn't work. The ablation procedure itself worked on that day. It's just that the atrial fibrillation came back because maybe the veins reconnected or there was a different trigger. So just keep that in mind. And never ablate a patient without managing-- aggressively managing risk factors, as Dr. Deshmukh noted earlier.

Well, let's move on to case 3. Again, another 60-year-old, male, admitted for atrial fibrillation with rapid ventricular rates. Now, this gentleman was otherwise completely healthy, but he came to us in the hospital after several weeks of dyspnea, fatigue, and having a poor appetite. So he really wasn't feeling good. ECG showed atrial fibrillation with rapid ventricular rates. And we did an echo guided cardioversion. And we do that when patients have not been on anticoagulation to rule out a thrombus in the left atrial appendage.

On that echocardiogram, we noted his left atrium and LV were severely enlarged, his ejection fraction was 25%, and he had severe mitral and tricuspid regurgitation. We started him on amiodarone, beta blocker and ACE inhibitor, as well as a DOAC for anticoagulation for stroke prophylaxis. Now, he felt great for about a week but came back into the hospital with similar symptoms. We found that he had AF recurrence.

Now, amiodarone is a drug that won't work right away. It usually takes a couple of weeks to build up into the system. So we had him continue his amiodarone loading and planned for another cardioversion one week after additional loading of amiodarone. And follow-up at two months showed a normalized ejection fraction, a normal LV size, and the valve function had improved. But patient had what seemed to be early signs of thyroid dysfunction from amiodarone, so he was sent for catheter ablation.

In three months post-ablation echocardiogram, his EF improved, the leaking of the valves went away, and his heart dimensions got smaller, which is a great thing. So all of what he was having driving his symptoms, as well as changes in the structure and function of his heart, were all related to the patient's atrial fibrillation with rapid ventricular rates.

So resolution. He comes to us very happy in sinus rhythm, markedly improved symptoms. His ejection fraction was 63%, as I'd mentioned, normal heart structure and function. And we continued him-- despite him being in normal rhythm, we continue him, given his elevated chance [INAUDIBLE] anticoagulation. And for his heart failure symptoms, on beta blocker and ACE inhibitor.

The CASTLE-AF trial. This actually shows a signal that ablation can improve mortality in heart failure. This trial randomized patients with a dejection fraction less than or equal to 35%, New York Heart Association class II to IV symptoms, and all patients had to have an ICD or CRT in. And the reason the investigators did this is they wanted to be able to measure atrial fibrillation burden before and after.

So these were randomized 1 to 1, ablation versus a rate- and rhythm-controlling approach. And the ablation group had a reduced all-cause mortality or hospitalization for worsening heart failure. And in addition, they had a reduced AFib burden, an improved six-minute walk, an increased ejection fraction.

So the takeaway here is ablation in patients with heart failure was associated with a significantly lower rate of composite endpoint of death from any cause or hospitalizations for worsening medical heart failure therapy compared to medical therapy itself.

Now, let's look at the K-M curves. Death or hospitalization from worsening heart failure. You see that the curves start to separate early, 9 to 12 months, and they stayed persistent through follow-up. Death from any cause takes a little bit longer. But as you see, about three years or more is when those curves start to separate, and they stay fixed in separation.

So now let's talk about which heart failure patient should get an ablation. Those that will benefit from ablation have an element of tachycardia-mediated cardiomyopathy. Basically, they have atrial fibrillation and they're in rapid ventricular rates for a long time. Could be weeks, could be months. They'll benefit if they have paroxysmal or early-stage persistent atrial fibrillation, if they have early stage heart failure, and in younger patients who, for the most part, have less comorbidities.

Who would have less benefit from ablation? Obviously, those patients that had advanced heart failure; severe atrial enlargement because with that, enlargement has more stretching in fibrosis and scarring and much more difficult substrate to treat, like Dr. Deshmukh said, outside of the pulmonary veins.

If someone has longstanding or persistent atrial fibrillation-- again, that cancer's been there for a long time, and it's spread, and it's really tough to treat. And of course, if patients have advanced age or multiple comorbidities, they are not that patient that we want to decipher and cipher for them to get a catheter ablation or rhythm-controlling approach.

I'll turn it over to Dr. Deshmukh, who's going to talk to us about a different patient and how we could do something not solely rate-related or rhythm-related or catheter ablation, but someone that falls in that middle he was describing.

ABHISHEK DESHMUKH: Thanks, Chris. So, so far, we have seen three patients who are 68. And you know, the treatment still, which had the same theme, antiarrhythmics, ablation. But you know, everybody's AFib is different, but the treatment for everybody's AFib remains the same. And as we tease through all the 68-year-old patients, we need to also look at pragmatically who is your mother and who is your mother-in-law.

[LAUGHTER]

So I'm going to not talk about my mother-in-law, but sort of a mother-in-law case here. So 68-year-old female; again, comes in with AFib with rapid rates; admitted for heart failure and AFib and rapid rates; and keeps on getting admitted to internal medicine, then cardiology, and keeps on bouncing back through different services; several hospitalizations because she comes in with a lot of snacks and cookies. CAD, COPD, CKD, pulmonary hypertension, obesity, and all the other comorbidities you can think of.

So we learned that if you are unsure, the best idea is to give them amiodarone and cardiovert again. So we did that. This was an echocardiogram, so heart is enlarged, and all these valves are leaking. We cardioverted thrice on full amiodarone, and the patient did not maintain sinus rhythm, EF remained low, and the LV continued to be enlarged.

The blood pressure was softer, 80 to 100 systolic. And if the blood pressure is on the lower side, it's that much harder to up-titrate the medications, beta blockers, ACE inhibitors, and what we need to give to treat this patient. And she was on very low doses of these medications and really not getting enough benefit out of these medications.

So how do we manage this patient? Would this patient be a good candidate for an AF ablation? Remember, she's been through a lot already. So these are the patients where we think about doing an AV node ablation and cardiac resynchronization therapy.

So what cardiac resynchronization therapy is that you have a heart with four chambers. There's one pacing lead which goes in the right ventricle and one pacing lead which goes into a ventricular branch of the coronary sinus to pace the left ventricle. And the idea is that the right ventricle and left ventricle pacing can be controlled by a pacemaker, and then the patient can pace by ventricular. So that's cardiac resynchronization therapy.

And the idea behind doing AV node ablation is to give infinite amount of beta blockers, meaning you just block the AV node. Because you can't give that much of beta blockers, you can ablate the AV node, and then the patient doesn't have an underlying rhythm. And then the pacing kicks in to cause a cardiac resynchronization therapy.

So these are the patients who are a little bit on a sicker side that they were studied. 133 patients with symptomatic AFib and at least one heart failure hospitalization; randomized to CRT plus AV node ablation versus rate control; the primary outcome was all-cause mortality.

The study was actually stopped at 29 months because there was a significant reduction in mortality in patients who got CRT plus AV node ablation; and the benefit was similar, even if the EF was lower or more than 35%. So really key thing in that right patients who have advanced AFib, permanent AFib with heart failure, CRT plus AV node ablation was superior to medical therapy in reducing mortality in these patients.

So this is how the device would look like. You would have one lead in the right ventricle, another lead in the coronary sinus, and an AV node ablation was done and the patient was paced. So again, a different flavor or for more sicker patients who may not be a candidate for ablation or who have failed ablations or who have tried antiarrhythmics and multiple cardioversion doesn't work out.

And this could be a good exit strategy. Again, the aim for these patients is that once you do that, then with their heart failure, you can further up-titrate their medications to make sure they keep on feeling better and living longer.

CHRISTOPHER DESIMONE: All right. So let's wrap up some golden nuggets for you to take home. Number one, early rhythm control should be the norm. Number two, do not leave a young patient in atrial fibrillation without at least one attempt at sinus rhythm. You're setting that patient up from being in paroxysmal to persistent or even permanent atrial fibrillation and making their life much tougher, as well as ours, at keeping them in normal sinus rhythm should we need to in the future.

Number three, ablation is more effective than drugs in reducing AFib recurrence. Number four, ablation in heart failure confers a mortality benefit in the right patient. Like Dr. Deshmukh just showed you, cardiac resynchronization therapy with a pacemaker and AV node ablation, very valid option in those that are sicker heart failure patients that are more advanced. And finally, all patients with atrial fibrillation deserve serial stroke risk assessment and anticoagulation if they merit, and all require risk factor modification.

And with that, we'll leave our emails up here. We love nerding out about atrial fibrillation ablation, and we would love to answer any of your questions. Feel free to email us at any other time. And we'd like to thank Dr. Mueller and Dr. Issa for the invitation to Grand Rounds, and Dr. Paul Friedman for the amazing introduction to us. And thank you all for your interest and engagement.

MODERATOR: All right. Thank you so much for a wonderful and engaging presentation. So just a quick reminder to everybody-- if you would like to ask questions, use the Slido app. So you can go to www.slido.com. For today, [INAUDIBLE] coded MAYOMGR2. Once again, that's MAYOMGR2. We also have a number of questions that are up here. So if you see a question that you really want asked, up-vote it and I will be more likely to ask it.

So first question that we have here-- can you comment on the use of metformin to improve substrate, like reducing atrial remodeling and reducing risk of atrial fibrillation?

CHRISTOPHER DESIMONE: Nothing that I'm aware of that suggests metformin would try to improve or reduce any atrial myopathy. But I will say, if it's anything to improve risk factor modification, which it certainly would be, if you're aggressively controlling your diabetes better, then I would say that's probably a good thing. I just haven't seen it shown in any studies.

MODERATOR: One of the sort of mantras that has come up here has been that early prevention and early management is key. With this in view, does that change the way that you look at perioperative atrial fibrillation or secondary atrial fibrillation? Like that patient that may not have ever had atrial fibrillation and got sepsis and then is in AFib for the first time.

ABHISHEK DESHMUKH: In the world of AFib, once you have AFib, you always have AFib. You know, it can be primary, secondary, tertiary, or any other AFib. So if you have AFib, it still boils down to the pillars of AF management, which would be stroke prevention, risk factor modification. And then the third step would be rate versus rhythm control. So even if you have postoperative AF, we still consider anticoagulation in the right situations, depending on the CHADS VASc score.

MODERATOR: Next question here. So one of the great presentations we recently had was a presentation on the use of AI to predict atrial fibrillation. And so with the advent of these tools, would you ever consider antiarrhythmics in a high probability patient who has no proven atrial fibrillation?

CHRISTOPHER DESIMONE: So I think great question. And definitely Dr. Friedman was the pioneer of this area. We're lucky to have them here. So the data are amazing, the AUC curves that it predicting atrial fibrillation. And I would say Dr. Friedman would say, we're not there yet, but that's fodder and food coming up probably soon over the next few years to see if an AI ECG will be actionable.

And with that amount of prediction, I would say if this is so-- the fidelity of that test, the ECG, and the augmentation and the better types of extraction this could get is, why not, if we could save a patient from a stroke? Because that's the most important thing, if we find that early. You know, some patients might not have been on anticoagulation, and that might have prevented a stroke. We see a lot of patients, unfortunately, that present with a stroke and present with atrial fibrillation. So that would be game-changing, paradigm-changing.

MODERATOR: Next question here. Can atrial remodeling be reversed?

ABHISHEK DESHMUKH: A great question. So atrial remodeling certainly can be potentially reversed by various factors. Number one would be a risk factor modification. Clearly there is data that you can remodel the left atrium.

The other extreme is like really avant garde athletes, you know, whose heart rate is 40 beats per minute. They're really proud on that heart rate. But if we map their heart, they have a lot of atrial fibrosis and scarring. And a lot of these young patients have atrial fibrillation. So if you detrain them, there is enough data to suggest that reverse atrial remodeling can also help to reduce atrial fibrillation. So certainly that can be modified.

CHRISTOPHER DESIMONE: And I'll just add one point to that. So you've seen that in some of the patients we showed you today, right? Their left ventricles got smaller. Their left atriums got smaller. The heart's pumping more effectively in sinus rhythm compared to atrial fibrillation. So definitely, definitely, that's what we aim for.

As Dr. Deshmukh was saying, sometimes it's already too late. But if we intervene early enough, we love getting repeat echocardiograms three months post ablation and see that left atrial size diminished. That tells us there's positive remodeling.

MODERATOR: And the next question here-- what's the role of left atrial appendage occlusion and when do you recommend it?

ABHISHEK DESHMUKH: So left atrial appendage occlusion is to occlude of the left atrial appendage to reduce stroke. And right now, the class II way indication is that if a patient is not a candidate for anticoagulation because of bleeding, then those will be the patients who would be considered for a left atrial appendage occluder device. Having said that, there are a lot of studies going on right now to see, compare left atrial appendage occluder devices versus DOACs to see whether there is any superiority.

MODERATOR: Next question here. Can you have too many cardiac ablations?

CHRISTOPHER DESIMONE: Amazing question, for whoever asked that. You can. Now, this is kind of-- it's not a cookbook way of going about things and saying, OK, once you've hit one, you're only going to have one more for the rest of your life; or, we've done five, can't have any more.

Some patients have come for us all over the country, all over the world, some for their seventh, eighth, or ninth time AFib ablation. It's all dependent on the patient's substrate itself. And we're really not well at predicting that, meaning we don't know until once we're in there. And once we're in there, we're able to use a few signals.

One is the pressure in the left atrium. If you ablate too much, you run the risk of something called stiff left atrial syndrome. Basically, you've made all your healthy myocardium in the atria fibrosis and scarred, and that's not a good thing. And then we've given you another problem. So too much ablation, yes.

However, you could go in and see that even after three or four ablations, you still haven't isolated the pulmonary veins. So even if it's their fourth or fifth ablation, I don't count it for it to be a true ablation until we've had sustained isolation of the pulmonary veins. So I would say definitely can have too many ablations. Concern is risk for stiff left atrial syndrome, but patient-by-patient basis.

MODERATOR: And sort of a follow-up question to that. Can you comment on the potential arrhythmogenic risk of developing fibrotic and scarred myocytes in the setting of an ablation?

ABHISHEK DESHMUKH: Yes. The idea of ablation is to really kill those cells so that the cells don't conduct any electricity. So we are building kind of like a fence across these pulmonary veins so that the firing shouldn't enter. It's like an electrical fence. But if you oblate more extensive in the left atrium beyond the pulmonary veins, you know, ablating other parts, there is a real risk that you can create more fibrosis and scarring in the left atrium.

And what is a fibrotic muscle? It doesn't contract. So the same thing. You might ablate the left atrium so much that it doesn't contract. And really, you know, God gave us left atrium to send blood from left atrium to the left ventricle. And if you lose that action of the left atrium, and that's what Chris said, they develop stiff left atrial syndrome and more shortness of breath and pulmonary edema type symptoms.

MODERATOR: Next question here. So this is more a clinical question, or like more a specific question about some patients. Why would a patient who had an AV node ablation and was 100% paced still need a beta blocker?

ABHISHEK DESHMUKH: Good question. So AV node ablation is treating the rate, but imagine beta blockers in setting of heart failure have much more pleiotropic effect. So even if they are AV blocked, you still need to give beta blockers. Because remember, in heart failure patients, they can have AFib; they also get ventricular tachycardias and their beta blockers will have a role of suppressing that.

MODERATOR: And the next question-- are there procedural options that can help to reverse atrial fibrillation outside of an ablation?

CHRISTOPHER DESIMONE: So-- can you say it one more time?

MODERATOR: So are there procedural options to help to reverse and treat atrial fibrillation outside of ablations?

CHRISTOPHER DESIMONE: Yeah, I would say we can technically say one. This would be called a surgical maze procedure. So that would be at the time someone has a mitral valve repair or something where they had to open up the chest. And they kind of do a more widespread version of what we would do percutaneously because they're-- but again, that's still procedural based. The non-procedural base would be drugs, of course, and then electrical cardioversion. I don't think there's anything else we could think of.

ABHISHEK DESHMUKH: I can add one very simple tip to that, but it's very hard to do. There's enough data has been shown that if you lose 10% of your weight, it's going to be as good as getting an AF ablation. The challenge is hard to lose that 10% of the weight and easier to do an AF ablation. So if you need one procedure, that would be to lose 10% of the weight.

MODERATOR: So follow-up question to that. Are GLP-1s options for atrial fibrillation prevention?

ABHISHEK DESHMUKH: It's a great question, and we actually have a paper, a study coming up at one of our upcoming meetings where we have shown that GLP-1 agonists do help to reduce the burden of atrial fibrillation, likely from weight loss.

MODERATOR: So next question. So there seems to be sort of an old mantra out there that everyone with atrial fibrillation deserves a shot at cardioversion. Do you agree?

CHRISTOPHER DESIMONE: I do agree. And the reason being is because you don't know how well that patient's going to feel or how much better they're going to feel if you get them back into sinus rhythm, number one.

And number two, think about it; structurally and functionally, the physiology of the heart is meant to have adequate filling in the atrium and adequate pumping into the ventricle so that you can have appropriate ventricular diastole. But if you interfere with that, you lose that atrial kick, and many, many patients depend on that. So yes, I do think everyone deserves at least one chance to get out of atrial fibrillation.

MODERATOR: And the next question here, how much is antiarrhythmic drug efficacy potentially affected by medication interactions?

CHRISTOPHER DESIMONE: It's a good question. So a lot of patients that are on QTc prolonging agents or a lot of patients that have kidney failure or kidney issues, it depends a lot on what type of dose we could give them and the safety, because a lot of these drugs, especially the class III drugs, which block predominantly potassium channel, they prolong the QT. So that could have a big effect.

So these drugs could interact with each other. And because they interact with each other, they increase the QTc more. So that's an issue. Some drugs are more metabolized by the liver, so patients with liver issues have issues with that.

But I would say it's a good thing that you have to have a good assessment of what medicines they're on so that you could reduce the efficacy because you don't want to go too strong so that you create another problem.