Hello all, my name is Fred Kusumoto, and it's really my distinct pleasure to host the second of four webinars that HRS has been put together. If you missed it, on Monday, Prash, Saunders, and others really talked about risk factor modification and really the importance of taking care of all those little issues associated with atrial fibrillation early on and actually throughout the course of the management. That webinar will actually be available on HRS 365 at some point in the future, but that's past news. Let's talk about new news here. So I get to introduce the second session of this HRS webinar, and this is entitled What the 2023 AF Guidelines Tell Us About Rhythm and Rate Control in Special Populations. You know, and what's special, Andrew and I were just chatting before we came on. It's like everybody, everyone requires that individualized care. We have two speakers and a panelist. I'll go to each one to introduce themselves. Janice, you first. Hi, everyone. I'm delighted to be here. Alongside Fred, I was lucky enough to be part of the AFib guideline process. I think we're in for a treat. There are a lot that we'll be covering today. I'm coming to you from New York City, based in New York at the Icahn School of Medicine and I'm on Sinai. I look forward to speaking with all of you very soon. I look forward to taking more questions and discussing together. Onward to Cedillo. Hello, everyone. Thank you so much for this opportunity. I'm one of the EP physicians who just finished fellowship last year, and I'm currently an assistant professor at University of Wisconsin-Madison. Happy to be here. Andrew? Hi, my name is Andrew Kranz. I'm an EP in Vancouver and 18 months out from being the president of HRS. I chaired the secondary review process and solicited 15 people to help to fill the inbox of Amina and her team with comments to try to make sure we got it right. I'm really looking forward to this because it's such a transformative next step in the realm of AF management, and I'm looking forward to the webinar. Yeah. Thank you very much, Andrew. Like Andrew, I'm also a has-been. My name is Fred Kusumoto. I was HRS president a few years ago. Really, my honor, though, to really introduce this webinar and to moderate it. A couple of things. We're going to go through the two presentations. I'm going to have Andrew provide some input with regards to what his thoughts are and some overriding questions and things that he's put together, but I really look forward to a lot of input from all of you. This is your webinar. I mean, that's the beauty of these sorts of things, so please put in your questions. I will definitely make sure that they get addressed, and even if they don't get addressed, one of the nice things about our small community, in fact, HRS itself is that tight linkage that occurs throughout all, and I know that we can get those questions answered at some level at all. So, let's get started here. I get to introduce Janice Chute. Just so that you know, she actually also was the chair of the American Heart Association's scientific statement talking about atrial fibrillation in odd populations, particularly in the intensive care unit, that hospitalized patient. So, Janice, the floor is yours. Let's hear it. Thanks so much, Fred. I'll go ahead and queue up my slide. Okay, I think we are live. Okay, so I have the pleasure to be to be the part one speaker to proceed Sunil to help give us a bit of an overview in terms of what the 2023 AFib guideline tells us about rhythm and rate control in special population. From my part, we'll cover atrial fibrillation in pregnancy, in cardio-oncology, in cardiac surgery, and very briefly, acute medical and surgical illness. I think it will only do justice that we start with a quick overview of some of the ways that we think about recommendation and level of evidence. Very briefly, as familiar to the audience here, class one refers to strong recommendation where recommendation is indicated, is effective, is beneficial, should be performed, should be administered, should proceed. Class 2A is a recommendation that is reasonable, can be useful, can be effective, can be beneficial. Class 2B refers to a recommendation that may be reasonable, may be considered a softer recommendation where the benefit is likely greater than the risk. On the other side, these are balanced by class three recommendations separating into no benefit and furthermore, into a category of harm. These are distinct from the level of evidence. During the guideline development process, we evaluate the evidence separately, looking at the quality of the evidence where level A refers to high quality data, typically more than one randomized clinical trial. Level B, randomized with moderate quality evidence for one or more randomized clinical trial. Level B and R, non-randomized data. And level C, limited limited data. And level C, expert opinion. These are distinct from the class of recommendation. So for example, if something has benefited much greater than risk despite limited data that may still come as a class one recommendation. Similarly, if we have a recommendation that has abundant data, but the abundance of the data actually shows us that the benefit is less than the risk or the benefit or the risk is greater than the benefit, we could have very strong recommendation in class three and corresponding a strong level of evidence. And these two are to be interpreted in consideration of both parts, but not mutually exclusive. Fred. So Dennis, you might just go to presentation mode because we're seeing, you know, all of your slides. So why don't you give that a thought? Let's go ahead. There. So we're seeing the preview. So just if you go to the true presentation. Yeah, it also makes the text nice and big for those of us who are old who like to see a big, big letters. I was just squinting, Andrew. Come on now. You know, Sarah, I may have you actually drive for some reason in my share mode. It's going straight to even with this, I think it's still showing the presentation mode. Thanks for that pickup, Fred. Sarah, I think I'll have you tap in and I'll go ahead and stop share and let Sarah jump in to go ahead and queue up this slide for me to share. And then I'll drive alongside Sarah. Um, thank you, Sarah. So with that, we will go ahead and segue into the rest of the presentation. Thank you so much. So we pause briefly here. This is what was intended. I apologize that things were a little bit smaller earlier, but the gist of it essentially is looking at class of recommendation on one side and level of evidence on the other, considering them both as we go forward. So let's do go forward. Next slide, please. So first starting up what the AFib guidelines tell us about rate and rhythm management of AFib in pregnancy. Next slide. So regarding rate and rhythm management of AFib in pregnancy, the first thing is thinking about how we achieve acute rhythm control. Achievement of acute rhythm control is by cardioversion, whereby electrical cardioversion with direct current cardioversion receive a class one recommendation level B non-randomized pregnant patient with atrial fibrillation. DC cardioversion is safe to patient and fetus and should be performed in the same manner as patients who are not pregnant. So what does that mean? So the same manner refers to a general manner that we perform electrical cardioversion, which pulling from the rhythm control section of the guideline tells us that in general patients with hemodynamic instability attributable to atrial fibrillation, direct current cardioversion is a recommendation of choice with a class one. This also means that prior to pressing the button to deliver the energy, visual confirmation of energy delivery should be synchronized to the QRS. This also means softer recommendation, class 2A, biphasic energy greater than 200 joules or equivalent as initial energy may be beneficial and that initial unsuccessful in patient with initial unsuccessful attempt or longer duration of atrial fibrillation, optimization of electrophactor or energy escalation can be pursued. In general, DC cardioversion in pregnant patient is rapid, safe, and can be used in patient with and without structural heart disease. And this is a key part because there are certain therapies that are not suitable for patient with structural heart disease, whereas electrical cardioversion can apply to both. Moving on to the other side of the slide, the specific consideration for patient with atrial fibrillation include consideration for placement of the electrodes. First off, the general placement for atrial fibrillation electrode placement is predominantly anterior, posterior, and AP orientation, sometimes anterior, posterior, lateral orientation, but essentially the front part is anterior. And in a pregnant patient, one of the key thing is to minimize and avoid too much coverage of the breast tissue, which can increase an impedance in terms of the delivery. The pregnant patient should receive sedation as suitable for an obstetric patient, and there should be fetal monitoring during and directly after cardioversion. Next slide, please. Pharmacologic cardioversion is another form of acute rhythm control strategy. However, in this setting of pregnancy, the use is much more limited. In pregnant individual with structurally normal heart, again, we highlight here, it was structurally normal heart and hemodynamically stable. Pharmacologic cardioversion with aging with a history of safe use in pregnancy may be considered at a recommendation of 2B. And we will note here that quite often, women with atrial fibrillation in pregnancy often have accompanied structural heart disease, making this further difficult to apply. The specific IV medication that will highlight for our attendees today are the IV medication for pharmacologic cardioversion in our guideline, because this is a guideline chaired by American organizations. The recommendations and the medication listed here are limited to the ones that are available in the United States. First off is ibuterolide, with notable consideration for risk for acute T prolongation, TORSAD, non-sustained VT. And the second one, procainamide, with notable consideration for hypotension, AV block, prolonged QT, TORSAD, and hematologic disturbances. Again, this harbors back to the earlier message that if we were going for acute rhythm control strategy with cardioversion, quite likely the choice of that is electrical cardioversion. Next slide, please. In terms of rhythm control, we think of rhythm control strategy as strategy with PO antiarrhythmic medication to maintain sinus rhythm past the acute phase. The guideline has a two-way recommendation that in pregnant individuals with atrial fibrillation without structural heart disease, antiarrhythmic agent with history of safe use in pregnancy are reasonable for maintenance of sinus rhythm. And this implies that if a patient's already on it for pre-existing atrial fibrillation, we would continue on that. That would be reasonable. And also for patients who have received cardioversion for post-electrical cardioversion to continue to maintain rhythm, maintain normal sinus rhythm, this may be initiated post-cardioversion. The key PO medication I'll point out here are flaconide at the doses described here, fairly standard doses, and Sotilox. These two have notable experience for safety in pregnancy. The major side effects are listed here, and I'll allow you a moment to review both the elimination and elimination half-life. In specific side effects, I will point out for flaconide, the major concern, as we are in the general population, are for atrial flutter, AV block, QT prolongation, ventricular arrhythmia with proarrhythmic risk, again, contraindicated in a patient with structural heart disease. Sotilox, the clearance, the key thing is the clearance is the renal clearance, whereby the dosing is by creating clearance. Also, risk for a torsa, QT prolongation, AV block, and bradycardia. Next slide, please. In terms of rate control, this differs slightly from the general population. A two-way recommendation that rate control agents with a record of safety in pregnancy, such as Digoxin, either alone or in combination with beta-blockade are reasonable as first-line agent. I will point out that Digoxin level may be unreliable in terms of measurement during pregnancy. Digoxin may be administered with or without beta-blockade. Not all beta-blockades are equal in pregnancy. The two beta-blockade with acknowledged safety profile in pregnancy to underscore here are metoprol and propranolol. Atenolol is typically avoided, even in concern for intrauteral growth retardation. I will also note on the side, whereas in the general population, calcium channel blockers, such as verapamil, daltazan, can be used more liberally in the suitable population. In the pregnant population, this is certainly not the first line in pregnancy due to concern for uterine muscle relaxation, maternal hypotension because of the potent vasodilatory action. In terms of the fetus, there's concern for hypotension, hypocontractility, hypoxia, bradycardia. Next slide. Now, we will segue on to thinking about what the AFib guideline tells about management in cardio-oncology. Next slide. So, this is a category that's really becoming more and more acknowledged in the AFib community as a special population that deserves increasing attention. What the AFib guideline tells us about management in cardio-oncology is a class one recommendation where in patients with cancer and atrial fibrillation, multidisciplinary communication, including cardiology, oncology, and other clinicians ensure decision-making with the patient is recommended to optimize cancer and AFib treatment and to reduce the risk of drug-drug treatment and to reduce the risk of drug-drug interaction, QT prolongation, proarrhythmia, bleeding, and thromboembolism. And here, I underscore the key components are multidisciplinary shared decision-making, and importantly, with the various concerns related to drug-drug interaction, structure screening for potential drug-drug interaction, particularly those impacting cytochrome P450, CYP3A4, and CYP2D6 and P-glycoprotein metabolism. Next slide. The special consideration in cardio-oncology patient include the following. Here, we see that it's the patient impacted both by the cancer and the cancer treatment. Pointing out here are a couple of specific areas that I want us to consider. Number one, the assure risk factors, which include age, comorbidities, and these are substrate for atrial myopathy. In terms of cancer to the lower corner, the cancer consideration involved a location and the extent of the cancer, whether or not there's local invasion in the thorax and myocardium, the pericardial space, and the metastases. In terms of the interaction of the cancer and the cancer treatment in the bottom, we see that electrolyte abnormalities, emesis, enzymatic medication, dehydration, alteration, thrombosis, and hemostasis milieu are all part of the picture. In terms of patient's existing condition, there could be pre-existing heart failure, pre-existing bleeding issue. The chemotherapies themselves, some of the chemotherapies are associated with increased frequency of atrial fibrillation. Some of the chemotherapies are associated with heart failure. Furthermore, their drug-drug interaction concern for QT prolongation and potential need for interruption, the anticoagulation for procedural intervention. Next slide. This is a table from our guideline, and I will draw your attention and for your further reference later on as well. This summarizes the writing committee's effort to put together a table describing the medical cancer therapy associated with increased risk of atrial fibrillation. The medications, there are some medications that are associated with incidents about 1 to 10%, and then there are some that are associated with quite frequent incidents that are greater than 10%. These categories include anthracycline, which typically can be in the presence of cardiotoxicity, such as with LV dysfunction. Another category that's important to point out is alkylating agents, immunomodulatory drugs. The tyrosine kinase inhibitors, the TKAs, is a category that we'll chat briefly more in the next slide. With these, specifically, the older generation brutant tyrosine kinase inhibitor, ibrutin is one that we'll all become familiar with as one with particularly high risk for increased incidence of atrial fibrillation in these populations. We will see here that some of these increased incidents are in combination with another agent, so not monotherapy, but combined therapy in terms of chemo agents. Next slide. The concern for QT prolongation similarly follows the logic that a lot of these intertwine. There are specific cancer therapy listed here, arsenic, select TKIs, anthracycline, and sometimes worsened by concomitant bradycardia. There are also patient and cancer treatment-related scenarios where that further potential QT prolongation, and obviously, the concern is for prolongation of QTc, especially with antiarrhythmic medication. Next slide, please. Here's a salient example of drug-drug interaction. Ibrutinide, it's a brutant tyrosine kinase inhibitor that's primarily metabolized by CYP3A4. Therefore, in terms of drug-drug interaction, CYP3A4 inhibitors, well known to all of us, amiodarone, dronadarone, verapamil, daltazan, can increase ibrutinate levels. Therefore, concomitant use is typically avoided, and concomitant use is necessary, may require reduction of ibrutinide dosing guided by oncology team in a multi-disciplinary fashion. Ibrutinide also further inhibits peak glycoprotein metabolism, for example, increasing digoxin. There are also further implications for choice of beta-blocker for rate control. Next slide. This is a busy slide adapted based on a core figure from an excellent AHA scientific statement with the messages from the guideline overlay on top. These are the implication of the class-one recommendation we discussed earlier in terms of rate and rhythm control management, where we pull a sure decision-making, multi-disciplinary consideration, and structured screening. Specifically, broadly, we consider the presence or absence of heart failure or medication that could precipitate heart failure to further guide the medication choice. In terms of specific consideration, we also would consider drug-drug interaction, QT prolongation, and need for interruption anticoagulation, and remembering that anticoagulation should be considered any time that we're pulling the trigger for rhythm control strategy. Here, I will highlight pertinent to the drug-drug interaction, carvedola medication that's frequently used in our arena. It's actually not a preferred medication, it's actually not a preferred medication in many of these patients, as carvedola inhibits P-glycoprotein metabolism, critical to many of the chemotherapy agents, whereby metoprol then becomes the preferred agent. Non-dihydropyridine calcium channel blockers inhibit CYP3A4 metabolism, already highlighted in the example given above. Digoxin is metabolized by P-glycoprotein, therefore a potent P-glycoprotein inhibitor as a chemotherapeutic agent would dangerously increase the digoxin level. This is a key slide summarizing many components, and I will leave you with this to keep in mind, and as we segue to the next section. Next slide. So next, let's think about what the AFib guidelines tell us about management and AFib after cardiac surgery. Next slide. One aspect I want to highlight here is the extent of the recommendation provided. In this very section, the guideline provided recommendation across the continuum of care. It provided recommendation for before cardiac surgery, during cardiac surgery, in the post-operative period, and post-discharge. So let's take a quick look at some of these recommendations. Next slide, please. So first, upstream, in terms of prevention of post-operative atrial fibrillation after cardiac surgery, before cardiac surgery, a two-way recommendation is given in the guideline for patients at high risk for post-operative atrial fibrillation that short-term prophylactic beta blocker, amiorrorum, is reasonable. High-risk patients for post-operative atrial fibrillation are especially those patients with concomitant valve surgery, with specifically increased risk in those with concomitant mitral valve surgery, overdose with CABG plus aortic valve surgery, and overdose with isolated CABG. There are additional risk factors such as age, preoptodigoxin, rheumatic heart disease, chronic obstructive pulmonary disease, and increased cross-clamp time that are also risk factors. Of course, many of these also overlap with the candidacy in the patient who may be having mitral valve disease and mitral valve surgery. However, notably, looking back at the collective data over the decades, preoptoprophylaxis with beta blockers, amiorrorum, has shown mixed benefit, and studies are difficult to compare because of variable medication combination. A question that's often brought up is, if we were to provide short-term prophylactic amiorrum, what does that really mean? Next slide, please. This is a study, and in fact, the only randomized clinical trial in this arena. This study dates back to what was published in 2005. This is a study that enrolled 600 patients for non-emergent CABG plus or minus valve surgery. The intervention here, as a short course, was oral amiodarone, 10 milligrams per day, daily for six days prior to surgery and for six days after cardiac surgery. The primary outcome was incidence atrial tachyarrhythmia lasting five minutes or greater. The results are consistent across the different subgroups they examined. Essentially, the amiodarone reduced the proportion of patients who develop atrial tachyarrhythmia in the postoperative setting. These were monitored by way of telemetry and daily ECG. However, we should also point out that adverse effects related to amiodarone did occur. They were bradycardia related. The bradycardia related to amiodarone administration that required temporary pacing more in amiodarone. There were also some examples of QT prolongation. Currently, by way both in terms of a clinical practice pattern and also in terms of clinical management, amiodarone short-term prophylaxis is typically reserved for the highest risk patients, balancing the high risk that we discussed early and the potential for the side effects. Next slide. What about dream cardiac surgery? So, the guideline also includes a two-way recommendation that in patients undergoing CABG surgery, aortic valve surgery or ascending aortic aneurysm operations. Posterior left pericardiotomy is reasonable. This is based on a PALIC randomized clinical trial, a single center randomized clinical trial, looking at the effect of posterior pericardiotomy on the incidence atrial fibrillation after cardiac surgery. The key aspect to highlight here, number one, there is background beta blockade use, in fact. So unless the heart rate was particularly low, less than 65 beats per minute, with the need for epicardial pacing, have prior AV blocker receiving beta agonist, the patient would be on a beta blocker. So the effect was seen on patients who were predominantly on beta blocker. With this, the overall population had a reduction of postoperative atrial fibrillation, markedly so in the posterior left pericardiotomy group compared to the no intervention group, that the safety profile was good from the clinical trial. Next slide. In terms of the postoperative period, and this is key in terms of approaching the acute and rate and rhythm control in this population, the key thing I want to highlight here, the triage is still by hemodynamic stability, and this is going to be a core message. Remember, when we discuss this in terms of patients who are pregnant with atrial fibrillation, hemodynamic stability and instability continue to be the differentiating, the initial branching point. So in patients who are hemodynamically unstable in the postoperative period, that these patients should receive direct current cardioversion. In patients who are hemodynamically stable, the further decision is considering whether or not the atrial fibrillation is poorly tolerated or not, and that's in terms of both patient symptom, pulmonary edema, and other untoward cardiopulmonary effect. So in a patient whose atrial fibrillation is poorly tolerated, direct current cardioversion, potentially with or without antiarrhythmic medication subsequently is recommended. With the consideration of imaging to rule a left atrial appendage thrombus before cardioversion in those patients in whom the AFib has been present for more than 48 hours, who have not been anticoagulated. In patients whose atrial fibrillation is not poorly tolerated, this gives the clinician an option where either rate control, targeting heart rate of less than 100 beats per minute, and or rhythm control medication are recommended as the initial therapy. So a little bit of a balanced leeway. With the choice of the strategy according to patient symptom, hemodynamic consequence, and arrhythmia in the physician preference, and a lot of other circumstances of the patient. I will highlight here that the guideline makes further recommendation more subtle compared to the strategy ones we discussed to achieve the rate control beta blocker unless contraindicated, in which case a non-dihydropyridine calcium channel blocker is also acceptable. In terms of anticoagulation, when safe from surgical bleeding to anticoagulation for 60 days unless complication related to anticoagulation occurs, and to further evaluate the need for anticoagulation at 60 days. So next slide. So let's talk a little bit more about where all these recommendations came from. The key trial to highlight guiding the rate and rhythm control consideration in a cardiac surgery patient really comes from a CTSN trial. This was a randomized clinical trial that included 523 patients. The patients include a patient who underwent CABG, underwent VAL surgery only, or CABG plus VAL. These are hemodynamically stable patients with no prior atrial fibrillation, and these were included if they have postoperative atrial fibrillation greater than 60 minutes, or recurrent episode during the seven days post-op. Patients were randomized into rate control strategies, specifically targeting heart rate less than 100, hence the guideline part preserving the less than 100 beats per minute recommendation for rate control target. In the rhythm control strategy, where amiodarone is initiated, the dose specifically in the study was too low for up to three grams before discharge, and then maintain a less than 200 milligram per day for the initial 60 days, unless amiodarone related adverse event, but if AFib persists beyond the 24 to 48 hour marks after randomization to also pursue cardioversion. If the AFib persists for greater than 48 hours, anti-coagulate with Wolfrin, permitting low molecular weight heparin bridge, and for anti-coagulation for 60 days, unless complication occur. And this actually protocol from this study was part of the basis for the two-way recommendation from the guideline, where because the study was not an anti-coagulation study, this did not end up with a randomized level of recommendation for anti-coagulation. This was, as this was modeled after the protocol, it's a reasonable thing to do, but not specifically studied for. And from this study, we saw the result that the endpoints were comparable. The endpoints for this study was a primary endpoint for the number of days in hospital within 60 days, which we show here were comparable between the rate control and the rhythm control strategy groups, and the re-admission as a secondary endpoint, and I will mention that they are also comparable. Next slide. So following along the continuum, we provide a further recommendation that post-discharge the thinking doesn't stop. In patient who develop atrial fibrillation after cardiac surgery, who are treated with rate control strategy, and as 30 to 60 day follow-up, still it is reasonable to perform rhythm assessment, and if atrial fibrillation does not revert to sinus rhythm, remember this is a patient who has not been in anti-arrhythmic medication, unlike the rhythm control arm, and if the sinus rhythm is not reverted to spontaneously, to then consider cardioversion after adequate duration of anti-coagulation. And next slide, please. As a final segment of my discussion today, I will briefly touch on the area, thinking about what the AFib guideline tells us about management of atrial fibrillation identified in the setting of acute medical or surgical illness. Next slide, please. Key here, in fact, as a take-home message, as one of the top 10 take-home messages from the guideline, is that recommendations are made for patients with atrial fibrillation identified during medical illness or surgery, traditionally considered as the precipitant. The emphasis is now made on the risk of recurrence of atrial fibrillation after AFib is initially discovered during non-cardiac illness or other precipitant. Two things to highlight here, number one, figure 27 from our guideline, shown here, reproduced, demonstrates that, in fact, over years of follow-up, the proportion of patients subsequently found to have recurrent atrial fibrillation were quite similar between those with no precipitant and those with precipitant, similar to those, as we discussed, identifying the setting of acute medical or surgical illness. This goes against the prior paradigm where many of these atrial fibrillation were thought to be transient and secondary, but really hammering home that this may be the tip of the iceberg. Next slide. Accordingly, figure 28 from the guideline is an adoption of a larger figure that we had in the scientific statement that I will also call your attention to. But essentially, the key things to point out here is during the acute phase, treatment should emphasize acute precipitant resolution identification, as well as thinking about rate and rhythm control strategy in the management of atrial fibrillation in these patients, pointing out that sometimes it could be difficult to maintain rhythm when the acute trigger or the precipitant has not been resolved. Following the acute hospitalization, a key component of the message here is the emphasis on the continuum of care, where at care transition, there should be counseling regarding risk of recurrence, and there should be outpatient follow-up to further assess. Over the outpatient follow-up, rhythm monitoring may be considered. And as we talk about as a tip of the iceberg, lifestyle and risk factor modification may be implemented, risk stratification for continuation of anticollagulation should be considered, and assessed for need for continued rate or rhythm control strategy. Next slide, please. So the recommendation for atrial fibrillation identified in the setting acute medical or surgical illness include two pertinent ones. Number one is a patient-centric recommendation, that patient with atrial fibrillation who are identified in the setting acute medical or surgical illness should be counseled about the significant risk of recurrent atrial fibrillation after acute illness is resolved, so that they are not surprised. The second is an emphasis on the continuum of care. In patient with atrial fibrillation who are identified in the setting of acute medical illness or surgery, outpatient follow-up for thromboembolic risk stratification and decision making in aura anticollagulation initiation or continuation, as well AFib surveillance can be beneficial given a high risk of AFib recurrence. Next slide. So in summary for part one, in terms of rhythm and rate control management in special population, the key take-home messages are, number one, hemodynamic stability as initial triage remains consistent. Number two, drug safety profile, such as in the special population of pregnancy, is important. Drug-drug interaction demonstrated here, such as in the cardio-oncology population, would be key to consider. Furthermore, we highlight here today both in the setting of after cardiac surgery, as well as in the setting of acute medical or surgical illness, that management across a continuum of care is important. Now I'll turn over to my colleague here, Sunil, to continue on with part two. But before we get to Sunil, a couple things. First of all, Janice, congratulations on a true tour de force, really impressive, really emphasizing this notion of, you know, the continuum of care. I always talk about AFib, you know, in my sort of Star Wars, you know, people always think about these things, right? It's Luke Skywalker versus Darth Vader. It's not that, right? AF is trench warfare, right? A little this way, a little that way, but it's long and continuous, and it's really slow victory, slow losses, and so absolutely critical. So thank you very much for emphasizing that. It's interesting how the AF guidelines, as Sunil is getting things set up here, are so incredibly granular. You know, when you look at the original 2014 guidelines, there were basically two recommendations. There was a two-way recommendation for rate control. The only rhythm control guideline was for those patients in heart failure where the AF was thought to be associated with that specific tachycardia. And, you know, and that also got a two-way recommendation. Those are the only two when you really look about it. Now, as Sunil is going to show us, in fact, it's become a far more detailed, far more instructive, granular, providing guidance, right, to the clinician for us at the bedside. So Sunil, the floor is yours, so go for it. Thank you. Yeah, given that, you know, heart failure is such an integral part of AFib management, we'll review how, where heart failure shows up in the general AFib management guidelines and then move on to heart failure specific nuances in management of AFib. So, you know, this is just a rate control for, acute rate control for AFib management. And as was pointed out, if a patient was hemodynamically stable, you know, direct cardioversion is recommended and in decompensated heart failure. And if the patient's, if the patient's unstable, then you go proceed to cardioversion. But if the patient is stable and is not in decompensated heart failure, then you have your avianodal blocking agents, including beta blockers and non-dihydropyridine calcium channel blockers as a class one, and then digoxin as 2A and amiodarone as 2B for rate control. But if you do have decompensated heart failure, you really only have amiodarone as a 2B indication with the non-dihydropyridine calcium channel blockers actually causing harm. And you could consider magnesium for avianodal blockade as a 2A agent. And this kind of highlights that in the guidelines where, you know, if you're hemodynamically stable and you have heart failure, if you do not have heart failure, your EF is greater than 40%, you have your options with controlling rates with non-dihydropyridine calcium channel blockers or beta blockers, and then considering IV magnesium too. But if you are critically ill and are decompensated in heart failure, then you're pretty much limited to amiodarone and you cannot use your non-dihydropyridine calcium channel blockers. Now for long-term rate control, again, it's divided again based on heart failure and your EF, and if your EF is less than 40%, your non-dihydropyridine calcium channel blockers are contraindicated. But you can use beta blockers and digoxin is a 2A indication. But if your EF is okay, then you're okay to use beta blockers or non-dihydropyridine calcium channel blockers and digoxin. And that's the key take-home point here is not to use non-dihydropyridine calcium channel blockers in patients with lower EF. Now, as the increasing use of AV nodal ablations and what's the heart failure risk associated with that for rate control in AF, and we see that heart failure with AV nodal ablation can be attributed to RV pacing and the risk is correlated with baseline cardiac function. And that most of this data comes from the PAVE trial, which compared RV pacing to biventricular pacing after AV nodal ablation, and found that there was an improvement in six-minute walk tests and EF if you did biventricular pacing compared to RV pacing, but the benefit was primarily in patients who've had lower EFs as you would expect that. So again, if the patients have lower EFs, we would consider cardiac resynchronization therapy of some sort, but really the question is what if the patients do not have a low EF, what do you do then? Is RV pacing okay? And given that the risk of complications with IV pacing compared to conventional pacing can be higher, it is advised that RV pacing can be performed in patients with preserved EF undergoing AV nodal ablation, but you can, there's a 2B indication for considering a conduction system pacing, whether either with a his bundle or left bundle branch area pacing. Now rhythm control, this is also the general AFib guidelines for rhythm control, and we see that again, heart failure makes an important appearance here. With patients with reduced LV function or persistent AF burden, a trial of rhythm control is now a class one indication, and it's recommended to evaluate whether AF is contributing to the reduced LV function and at least attempt to improve the LV function. In addition, if you have AF and heart failure, rhythm control can also be useful improving symptoms in heart failure, as well as improving outcomes such as mortality and heart failure hospitalizations, as well as ischemia, which is a two-way indication. And importantly, pharmacological cardioversion with the butylitis contraindicated if you have a depressed LV. And this is the algorithm for that, where, so if you have a normal LV function and no structural heart disease or prior MI, you have all of your drug therapy options, including defedolide, dronadarone, fleconide, and propafenone is a 2A, amiodarone is a 2A, and sotalol is a 2B, but you do have a low EF and structural heart disease or prior MI, you have amiodarone and defedolide are 2A, sotalol is 2B, but, you know, class 1C or class 3 are harmful. But if you have a NYHA class 3 or 4 or decent heart failure or recently compensated heart failure, you know, dronadarone is quite harmful and is contraindicated, but if you don't, it's a 2A indication for dronadarone. Now we'll go over the guidelines specifically for the nuanced management of AFib and heart failure, but some of the take-home points are, irrespective of reasonable rate control, allowing AF to persist long-term can worsen your heart failure, and that an early and aggressive approach to rhythm control can reduce AF burden, improve ventricular remodeling, and halt any other occult arrhythmia-induced cardiomyopathy, which is now taken center stage in the current guidelines. And some of the data behind that is the sub-analysis of the East AFNet showed that early rhythm control could improve outcomes, which is a composite of death, stroke, and hospitalization for heart failure and possibly even ACS. And in Castle AF, when the AF burden was less than 50% at six months post-ablation was associated with significant improvement in mortality and heart failure hospitalizations. Now there's been other RCTs in heart failure and have shown that AF ablation improves outcomes, quality of life, compared to rate control or drug therapy, including, it's important to mention the AATAC trial, which compared amiodarone to ablation in persistent AF patients, which showed that ablation was superior than amiodarone for improving hospitalizations for heart failure as well as for mortality, even in persistent AF, which is important. Although historically, you know, we've trialed a lot of antiarrhythmic drugs prior to catheter ablation, the current data do support catheter ablation as first-line therapy, even before antiarrhythmic drugs in appropriate patients. And patients often, as we know, require both drug therapies as well as ablations. So it's really, you know, the current guidelines really indicate that you now have a class one indication for appropriate patients with heart failure to undergo catheter ablation. So specifically focusing on these guidelines, you can see that, you know, if you have a new diagnosis of heart failure and with AF, arrhythmia-induced cardiomyopathy should be strongly suspected and an early aggressive approach to rhythm control is recommended. And patients who are already on GDMT with reasonable expectation of procedural benefit, catheter ablation is now a class one indication to improve patient symptoms, quality of life, ventricular function, as well as cardiovascular outcomes. And as we've talked about, mortality improvement has also been shown. In patients with heart failure and AF, digoxin can be controlled for rate control, even as monotherapy as a 2A indication. And in patients with rapid ventricular rates where beta blockers and calcium channel blockers are contraindicated or ineffective, IV amiodarone is reasonable for acute rate control. And in patients with EF less than 50% with refractory rapid ventricular responses who are not candidates for other therapies, AV nodal ablation with biventricular pacing can also be useful. And it's important to note that in several patients with a rapid ventricular response in AF and with heart failure, you know, by the pacing may be ineffective due to pacing percentages being because of the RBR and the AV nodal ablation there can be beneficial as a 2A guideline to improve functional class, as well as reducing ICD shocks and improving survival. And AF induced cardiomyopathy of patients who've had recovery of LV function, long-term surveillance can be beneficial as a 2A guideline to detect recurrent AF because they could, you know, these are patients who clearly don't do well in AF and have heart failure and an AF in the future, even occult AF could lead to tachycardia induced cardiomyopathy. And in patients with AF induced cardiomyopathy refractory heart failure symptoms, undergoing pharmacological rate control, a stricter rate control strategy that is target heart rate less than 80%, sorry, 80 beats a minute and less than 110 during moderate exercise can be reasonable. Several trials that have shown that strict rate control versus, you know, less strict rate control is not, there's not been a significant difference, but this is, that's why this is a 2B recommendation. And those who undergo AV nodal ablation, conduction system pacing with either his bundle or left bundle branch area may be reasonable as an alternative, but to biventricular pacing to improve symptoms, quality of life and LV function. And I'm sure with more data emerging with left bundle branch area pacing will, so probably in the future become a higher grade, higher evidence-based guideline. It is important that you, there could be harm with heart failure patients if a non-dihydropyridine calcium channel blockers are used, which can lead to heart failure exacerbations or even mortality. And also important to note that dronadarone should not be administered for sinus rhythm maintenance in severe heart, NYHA class failure, class heart failure patients or in patients with decompensated heart failure, even if it's in the recent past due to early mortality associated with worsening EF. Now HEF-PEF, there's less data associated with it and there's a subgroup analysis from Cabana that showed that heart failure of past two patients, mostly who had HEF-PEF, had improved survival freedom from AF recurrence and quality of life when you compare it to medical therapy with ablation and a meta-analysis had shown that you could, ablation to be safe and effective and had lower hospitalization for heart failure and mortality rates which led to the 2A guideline where catheter ablation is reasonable as long as you expect benefit for the patient in terms of quality of life and improving symptoms. So this is a busy slide but this is the heart failure in AF slide that kind of encapsulates everything we've just talked about. So if you have heart failure with AF, you know obviously GDMT for heart failure is important, thromboembolism prophylaxis and risk factor modification for everybody and you know if cardioversion is indicated, especially if you're hemodynamically unstable, then you know electrical cardioversion, pharmacological cardioversion but if and in terms of rate control strategy if your LVEF is low then beta blockers are class one, digoxin and amiodarone can be considered but non-dihydroperidine calcium channel blockers are class three. Now if your EF is normal you have pretty much all of these options. For these patients you know I think it's important to consider increasingly catheter ablation for rhythm control as was just mentioned and the patients most likely to benefit from catheter ablation are if patients who have AF mediated cardiomyopathy that you suspect, earlier stage of heart failure, no significant ventricular scar and CMR, no or mild atrial fibrosis on imaging, paroxysmal or early persistent AF. Now these patients have still not had significant atrial remodeling and catheter ablation presumably can improve outcomes early on and prevent progression or at least slow it down and younger patients especially without significant comorbidities and I'll talk more about that as the other special population. Now patients who are less likely to benefit from catheter ablation are patients with advanced heart failure, significant ventricular scar, severe atrial myopathy, severe dilation and fibrosis, long-standing persistent AF, prior failed ablations, advanced age and multiple comorbidities and among the patients likely to benefit from catheter ablation now we can look at both HEF-REF and HEF-PEF and HEF-REF is a class one indication to consider catheter ablation now with HEF-PEF it's two way indication so both could benefit from it and if you after your ablation if you don't have any more clinical AFib long-term surveillance is recommended in patients who have had recovery of EF after ablation but in patients who have recurrent AF for HEF-PEF you could still consider repeat ablation for symptom control and decreasing heart failure hospitalizations or you could go to pharmacological rhythm control or rate control strategy after the ablation and but dronetarone is important to to realize is not indicated in severe heart failure or in patients who've had decompensated heart failure in the past four weeks and pharmacological conversion and maintenance sinus rhythm can be considered for all of these patients. In terms of pharmacological rhythm control and rate control strategy we talked about you know after you've been through all of these things and you know your heart your EF is still low and you have uncontrolled rate or rhythm and several therapies have been have failed I think AV node ablation and pacing is a two-way indication and the pacing can be a left bundle or a his bundle as an alternative to by the pacing if your EF is low if your EF is okay you could still consider traditional RV pacing or you know either of or a conduction system pacing you don't necessarily have to do biventricular pacing. Now if you have patients with uncontrolled rate with the biventricular pacemaker where your rates are limiting your CRT therapies then pacing the AV nodal ablation is a two-way indication to improve by the pacing percentage to improve outcomes. Now moving on to the other special populations we have what about patients with early onset AF. So we're talking about really young patients here so young patients are less likely to develop afib or associated strokes compared to other popular older populations with less comorbidities. Increasing consumer driven use of wearables is now increasing our detection of AF at a younger and younger age and when patients generally less than 30 years of age re-entrant SVT so whether you have you know forms of AVNRT or AVRT are found in about a quarter of these patients and then which frequently do lead to afib and targeting these ablation these rhythms re-entrant rhythms can frequently resolve their AF episodes completely. So which is why it's a to be recommendation that in patients with onset of an unexplained afib before 30 years of age an EP study and looking for re-entrant supraventricular tachyarrhythmias with targeted ablation may be reasonable due to high prevalence of these rhythms that promote afib in this population. In addition to the standard risk factors for afib and young patients have other inherited channel for cardiomyopathic disorders even if you have normal echoes so you don't have to have structural heart disease which people frequently think if you're young you probably need to have a structural heart disease to have AF but increasingly there's more and more data to suggest that there could be a genetic component to this or other environmental components to this that you could have normal echoes and still have AF when you're young. In addition to a standard workup so because of this genetic testing for rare pathogenic variations and advanced imaging modalities and surveillance screening could be considered it's a to be recommendation I think again more data is emerging in this field it's probably going to be there a fairly complex genetic predisposition as the studies would suggest so it probably won't be just a few genes and it would be it would be tough to identify that but it could be considered in younger patients. Now athletes so moderate levels of exercise is associated with a lower incidence of AF but high volume endurance athleticism find as greater than 45 mets hours per week has been associated with the high prevalence of AF especially in young athletes. Mechanism could be related to atrial myopathy or stretch or perhaps inflammation perhaps a genetic predisposition it's unclear and it's also unclear whether the changes are reversible but you know athletes often choose to continue their sports and aggressive rhythm control strategies are often sought because it could be limiting for them which is why it's a 2a indication that in patients who have AFib catheter ablation could be considered with the PVI you know without doing extra lesions as a reasonable strategy for rhythm control because of how effective it is and and now that it's become considerably safer over the years and there's a low risk for detrimental effect on their exercise capacity and most of these patients are young and athletic and they prefer not to be on medications and PVI could significantly improve their quality of life and there's data to support this where in one cohort perspective cohort study there was freedom from AF at three years at paroxysmal at 86 percent and persistent at 68 percent in athletes with AF with just PVI alone. It's important to remember that in some of these patients you can have sinus rate increases on average about 10 beats per minute after the ablation which you know these patients are often bradycardic at baseline and a 10 beat increase at baseline from there could could be symptomatic or they could feel them and they it's important to counsel them about this before a PVI is performed but there has never been a significant change noted with max exercise capacity in these studies. There was also a retrospective cohort study that showed that in patient at the 10-year follow-up these young patients after AFib ablation 83 percent had no recurrent events and significant quality of life improvement and the WPW and pre-excitation syndromes you know AF occurs in about 15 percent of patients with WPW and although the mechanism is unclear we suspect that the faster conduction properties of the atrial tissue which pathways often mimic can allow for rapid rates and can lead to ventricular arrhythmias and then sudden cardiac death so the risk for pre-excited AF is higher for those with either multiple pathways or a short integrated pathway refractory period less than 250 milliseconds which allows for rapid conduction and then predisposes them to VF and sudden death. So AF in young patients without evidence of comorbid conditions may be associated with an accessory pathway which should be evaluated for in an EP study and a pathway ablation is the definitive therapy for AF and SVT in these patients. For those who which is a class one indication for those who cannot undergo an ablation preventative pharmacological therapy could be considered at slowing pathway conduction but it can be complicated because if you know AV nodal agents could cause harm and could for you know preferentially promote conduction on the accessory pathway and promote ventricular arrhythmias and sudden death. So it's class one indication to uh in patients with AF and and a rapidly anterograde conduction based pre-excited AF with hemodynamical instability to be treated with a cardioversion and consider an ablation and also if they have a multiple accessory pathways that's another high-risk feature that where the patients have a class one recommendation for ablation. Patients with AFib with rapid anterograde conduction but no hemodynamic instability or having hemodynamic stability pharmacological cardioversion with ibutylide or procanamide can be considered and as an elective to as an alternative to DC cardioversion. And AV nodal blockers are contraindicated in these patients as discussed. Adult congenital heart disease. Atrial arrhythmias are a leading cause of morbidity in ACHD patients and patients greater than 50 years of age with CHD and AF are more prevalent. AF is more prevalent than having reentrant intra-atrial tachycardias but they can happen you know if they're younger where you know you would have reentrant tachycardias around previous scars especially surgical scars. In addition to standard risk factors for development of AF, atrial septal defects and RA dilation are independent risk factors for AF in these patients. And factors to consider when choosing medical therapy for these patients are sinus node dysfunction, AV block as well as ventricular function and other comorbidities. And adults are usually classified as having either simple, moderate or complex forms of CHD because before treatment's advised because the treatment can be quite different and individualized for a given ACHD for a given patient with specific anatomy. So simple ACHD and AF management is very similar to all other patients without ACHD where you could consider an ablation and medical therapies. But moderate or complex forms of CHD, antiarrhythmic therapy should be individualized since most of these drugs are pro-arrhythmic and can increase mortality in these patients especially 1C drugs. And it's also important to understand individual underlying congenital anatomy because access to these chambers may require specialized approaches and should be performed by operators with expertise and experience in CHD and in collaboration with a general cardiologist who follows the patient for long term with ACHD. Special attention is also required for appropriate periprocedural care and availability of ancillary imaging and centers that have that capability because often these patients require additional care surrounding these complex procedures. So ACHD patients with AF, rhythm control is generally preferred over rate control because most of these patients tolerate AF very poorly owing to their structural heart defects and class one antiarrhythmic drugs should be avoided in these patients. Amiodarone is an effective antiarrhythmic agent for maintaining sinus rhythm. However, we, as we know, therapy long-term with amiodarone is limited by their end organ toxic side effects and adverse effects, including acute adverse effects where patients may not tolerate them. Amiodarone induced thyrotoxicosis is more common in women with CHD and cyanotic CHD patients as well as those with Fontan physiology and should be more closely monitored and cared for. Amiodarone should be avoided in ACHD patients who have a low BMI due to increased incidence of thyrotoxicosis. Daphetalide may be a viable alternative to amiodarone in this complex population and can be considered. Droniderone is best avoided in these patients, especially with moderate or complex ACHD or significant ventricular dysfunction due to high risk for heart failure, stroke, and death. And EVI in these patients has a lower success rate than patients with normal hearts, as one would expect, and operators should understand the variations in systemic and pulmonary venous anatomy, including the superior vena cava, which could be a trigger for, there could be specialized triggers for AF in these patients that require additional lesion sets. Feature-related pathology in the right atrium of these patients, additional ablative therapies directed at atriotomy scars, CTI, as well as other right atrial triggers could be considered. And cryoballoon has also been shown to be safe for some of these patients. There's insufficient data on the role of safety and benefit of AF ablation in complex forms of ACHD. CVA preference, stroke risk in these patients is thought to be significantly higher. Some studies reporting up to 10 to 100 times higher than in normal hearts in smaller studies. And thromboembolic events are then an important management aspect of these patients and account for 4% of all-cause mortality in this population. So all patients with CHD should be on some form of thromboembolic prophylaxis. And CHADS-VASc score should not be used to predict thromboembolic risk in these patients. There's limited data for use of DOACs in patients, but in a survey, they seemed to appear to be safe and effective and are frequently used and can be used. A special focus on HCM, no substantiative changes from 2020 guidelines. AF is highly prevalent. CHADS-VASc score, again, to not be used in these patients, but just for our understanding, roughly it's an equivalent risk of a CHADS-VASc of three to have HCM. DOACs are acceptable alternatives to warfarin. Again, it should be individualized to a given patient if they failed the DOAC and maybe warfarin should be considered. Catheter ablation is an important option for these patients, but it is frequently encountered in clinical practice that the success is lower and these patients often need multiple ablations. Finally, sleep disorder breathing as another special population with increasing evidence being gained to treat AF patients with sleep disorder breathing. And it is a risk factor for developing incident AF with severity of sleep disorder breathing, increasing your AF risk. And it's independent of all forms of sleep disorder breathing. So even poor sleep quality has been associated with higher risk of AF. Sleep disorder breathing overall is prevalent in AF, generally thought to be greater than 20% of population with AF, but it's sometimes reported to be as high as over 50%, regardless of the type of AF you're studying. Sleep disorder breathing can include sleep apnea, which is often undiagnosed in our AF population. And it's also important to realize that conventional symptoms such as snoring may be absent and may require a formal sleep study to assess accurately. Observational studies that treatment suggests that treatment of sleep disorder breathing may reduce AF recurrence and AF burden, but, you know, thus far randomized trials have not been adequately powered to reveal this relationship or have shown that, you know, we don't know if treating sleep disorder breathing appropriately, although we've all had several anecdotes for patients where it has improved their AF burden. And, you know, and most of these studies, the patients who benefit most from sleep disorder breathing, such as those with severe sleep apnea or cardiomyopathy or severe obesity are often either excluded or many of these patients are not particularly adherent with therapies and can limit our understanding. And so there's a 2B indication that among patients with AF, it would be reasonable to screen for sleep apnea and consider sleep disorder breathing and treatment to help maintain sinus rhythm. Sunil, thank you very much. That was truly, truly outstanding and really, you know, shows how sort of rampant AF is, you know, in patients with heart failure, you talked about sleep disorder breathing and the special requirements, you know, in the setting of hypertrophic cardiomyopathy, WPW, et cetera. Now it's really my pleasure to turn this over to Andrew to talk about some issues, et cetera. But before I turn it over to him, I want to have this audience ask questions. There's a great question already about flecainide and what are the implications for the fetus that I'm going to ask Janice after Andrew is done, but Andrew, the floor is yours. Well, thanks, Fred. So kudos again to both speakers, really outstanding review of an extensive journey and process that we went on. I think, you know, I think the first comment is you might consider the pendulum was a little lean on recommendations and details back in 2014. And we've gone to the other extreme as the review lead. I remember getting a Word document that I said, well, I should read it this weekend. And it was 440 pages. And at that point, I was like, I send a message to my wife to say, don't expect much from me this weekend. And so one of the comments, though, is it's an extraordinary resource from the standpoint of it really is a compilation of review articles and recommendations. And that really is a sort of one stop shop for AF bringing yourself up to date. That's really good. Two comments I think to make just to sort of raise this in everyone's mind, including our speakers or the panel. So one is, especially when it comes to things like heart disease, true AFib is actually uncommon in congenital patients, but they have all kinds of atrial arrhythmias. And so what we're really talking about bundling wise here is a gradient of organization or complexity of atrial arrhythmias. And the most common one is sort of overt AFib, but it involves a whole range of different things. And it's important to keep in mind, because once you get into those areas where there appears to be atrial organization, and so on, there's much less specific data, and we for the most part lump it in. But that's something that happens in practice all the time when you're doing when you're obsessed with ECGs, like most of us are, that you see things that are not your garden variety AFib. I think the second thing that the specialty population, which is maybe self evident, but it's worth reminding us that these special populations are often best served by multidisciplinary clinics. And the reason for that, of course, is because they have much more going on than just their AFib. And one of the things that I have personal great value in is the pharmacists who are parts of those clinics, because they provide guidance on drug interactions. And a good example would be cardio-oncology. How do we do cardio-oncology without input from pharmacists? They're just fundamental to this. So they're really great team members in terms of that process. So what I wanted to do is reflect back to the panel and just, I have a series of questions, but they're specific questions. And what I want to do is reflect back to the panel of two cases that I saw recently that I think I'm keen to hear what other people would do. So the first is a lady who's in her mid-80s, she has borderline diabetes, hypertension, she's overweight, got a bad hip, and she's had atrial fibrillation for a few years. And then she's been cardioverted twice in the last month. And I'm reminded by my heart failure colleagues that heart failure is a BNP diagnosis, and you can have any ejection fraction you want. But she has what you might call low normal LV function, and her left atrium is about 50, the labia is 50, and she has moderate mitral regurg. And she is, when you go through the process of talking about rate and rhythm control, she's not terribly symptomatic with a rate control strategy. And she is resistant to the idea of an invasive approach to this, in part because she says, Doc, are you crazy? I'm 85 years old. I'm obsessed with my grandchildren, not my heart. And do you really, are you really recommending I do this? It sounds very aggressive and invasive to have ablation. And yet, I think the scales have tipped in the general heart failure population, if you think she's a heart failure population when she gets AFib, that favors us being invasive and aggressive. And then the second case is functionally the same thing. It was a lady in her early 80s, I saw an AFib clinic last week. And so this is a lady who's 81. And she's actually pretty well, other than reasonably controlled atrial fibrillation of being slightly overweight. And she gave a history of palpitations going back about three years that were usually quite brief. At one point, her daughter who was a nurse felt her pulse and thought it was irregular, and then presented in AFib for cardioversion, and was referred for ablation. And I kind of thought, wow, yeah, I could tell the referring in my mind, at least I thought, you know, maybe I'm overly conservative, but this seems crazy to undertake ablation. And I knew it was crazy because the ablation was spelled with an O, like when you go to a Catholic church and you oblate, right? And so I thought this is nuts, but it reflects the fact that the culture is moving in favor of this rhythm control strategy, so almost at all costs. And so then the question is, given everything we know, how do we apply this goal of heart health and heart failure prevention to an AFib population where there's a huge denominator of people with a low burden and a lot of comorbidities who aren't necessarily naturally inclined to undergo an invasive strategies to maintain sinus rhythm? So open that up as a sort of a general starter just to hear people's thoughts. Andrew, provocative as always. So really it gets down to some, as you're pointing out, atrial fibrillation is a multidisciplinary disease and all of these patients have multidisciplinary problems, especially age, as we all get older. So Sunil, I'll give you the first shot. So talk to us about someone, let's take Andrew's first case, someone who's older, right? Had some comorbidities, reduced ejection fraction, but not in the 20s or 30s or whatever, something that's moderately reduced. How do you handle that patient? An elderly patient is sounds like has a fairly complex AF substrate. It's not a, you know, she has mitral valve disease as well as a large left atrium who is not particularly symptomatic, it sounds like with rate control. So it may be reasonable to consider beta blockade as part of GDMT for both GDMT and rate control, maybe reassess her EF and if she's feeling okay, maybe that's all she needs or maybe considering amiodarone as a therapy. I mean, she is 80 years old, some frequent monitoring for rhythm control but again, she's also, there's concerns for possible bradycardia or if she's got underlying conduction disease, you know, that may complicate some of these decisions too. And, you know, I think at that point, would you consider giving a pacemaker to somebody just so you can give them some of these medications? I think it can get fairly complicated but I think avoiding an intervention for her is I think fairly reasonable, at least as a first attempt. So, you know, Sunil, you remind me of this story when I was younger and would read books to my kids and there's this book called, If You Give a Mouse a Cookie, you know, and you start to go and go and go and I call it the medical escalator where you kind of continue and you never know sort of when to stop. Janice, I'm gonna ask you sort of a corollary to that question before I turn it back to Andrew. You know, so how does AF burden sort of get into this, right? I mean, I have some patients, you know, that have persistent AF, that's kind of a different deal than let's say someone who has, you know, intermittent AF. You know, you're gonna think about the anticoagulation issue, which we're not gonna talk about here today because that would just be a huge sort of can of worms. But tell me about sort of the rhythm rate in someone who, you know, has some sort of moderate amount of AF burdens, you know, not like 2% or something like that, but it has a little bit more and you're trying to sort of tease out symptomatic, non-symptomatic. Do you treat those people? Is there a number that you choose? I mean, give us a little bit of sense for your thoughts. Yeah, that's a great question. And I think, you know, I think Andrew put it quite well in terms of some of these examples. I think a couple of things crossed my mind. So number one, I think, you know, for both of the scenario, I think about what does a patient want, right? So I think we also as a community moving toward increasingly patient-centered care and patient-centric data and patient-centric approach. And so I think key to what, one of the things that Andrew said earlier was actually in the first case, a patient doesn't want anything invasive. So I think that will likely guide the care, especially if you're considering invasive therapy, the patient has to be a partner in permitting that. In terms of atrial fibrillation burden, Fred, you're absolutely right. This is a hot area. There's a lot going on in terms of thinking about the implication of atrial fibrillation burden. One area of hot argument, which we won't get into is device detected. We're gonna leave that aside. So acknowledging that though, what else do we know about AFib burden? So when I think about it, especially, you know, there are a couple of things that crossed my mind. Number one is echoing the message that's clear in our guideline is a central figure that Fred has been instrumental with, which is thinking about AFib as a continuum. So really thinking about the burden developing low burden, lots of burden, progressively, you know, paroxysmal more burden toward persistent. And later on, if they choose permanent, and that's a choice of a form of permanent. But throughout the entire thing, are two things that are really important. One is what can you do to potentially slow the progression? And some of those are invasive, some of those are non-invasive. And then the second thing is what do symptom of, what I got to it, what do burdens mean? And then that related to that for some people, it's a correlation with symptom. And that beckons back to the consideration of a patient-centric care, what the patient want, what matters to the patient. So increasing a lot of the clinical trials are not incorporating patient symptom evaluation, being the AFib quality of life or AFib symptom severity. There are various indices, they are not being incorporated so that we can more objectively track people as symptom. In terms of AFib burden, a percentage is often discussed as 6%, insert people becoming quite symptomatic. But again, that's not black or white. I think the 6% can take many different forms and how is a 6% evaluated? Is it a patch-based monitor? Is it a loop recorder, as we were talking about before? I think that can vary very, very widely. So when I think about the burden, in terms of symptom, I'm thinking about what matters to the patient, and I'm thinking about what matters to the atrial tissue in terms of the atrial progression. So if we're thinking of strategies, they are less invasive. Rhythm control, rhythm control, remember, again, this doesn't apply to this population, the East AFib net 4 that Sunil alluded to, that was not based on an 80-plus octogenarian population. But certainly for that specific study, the rhythm control strategy was done with both ablation and rhythm control antiarrhythmic medications. So that is antiarrhythmic, still a form of rhythm control to potentially hold back progression. But what are the other things? So that brings back to Fred's other point earlier when he opened up by saying that we already had a very successful webinar that is by lifestyle therapeutic, lifestyle risk factor modification. And I think for Andrew's first case, we heard clearly there are several comorbidity and risk factors, including diabetes, including hypertension, including obesity. And I think probably worth mentioning that obesity is one that's increasing recognized and specifically more recognized in this guideline compared to prior ones, whereby we want to drive the BMI down to less than 27 or dropping 10% of the body weight. So these are things that this octogenarian can potentially consider alongside other strategies too. Yeah, it's such a great point. You know, and one thing I do like, Jose certainly held us to the fire to be really prescriptive. You know, it wasn't just lose weight and it was lose weight to blank or don't just exercise. That was exercise this much. And so it was really quite striking for sure. Andrew, sort of additional thoughts that you have for what you've done on these patients and what you decided to do. I'd be interested to hear in the questions we have. Yeah, so for the first case, I actually thought she was a great AFib ablation candidate because she gets unwell when she gets AFib and she's got enough underlying substrate that she's high risk for it to be a worse and a progressive condition. And that, you know, the fundamental shared decision-making thing is strike the relationship, let her suffer a bit with her AFib and she'll come around to the idea that she's a good candidate for ablation. And I don't mean that in a disrespectful way, but what I really mean is when you come across as the sort of dogmatic person, you've sort of abandoned that shared decision-making. We both agree this is a problem. I have a little different take on how we might try to fix this because I'm really interested in you in the longterm. So let's meet again in three months and talk about this some more. And between now and then you're gonna do A, B and C, which are things like see how increased activity and weight control and more symptom awareness and reporting and maybe some more monitoring informs that decision. And she gets her head around the question of whether doing more about this is necessary. The other thing in patients who are sort of stuck in AFib is always cardiovert them because then the question is how do you feel? Because symptom motivation is a huge motivator for people. For the second lady, I just said, let's keep an eye. And that brings me to my next question for the group. And it's around the groups that are the reversible AFibs. So no precardiac or non-cardiac surgery or intercurrent illness. And what I like most about these guidelines of all of the huge repository of wonderful information there and was this sort of concept of integrating burden, duration and CHAD score when you think about how you manage things including the stroke prevention. I know that's not our focus. But I guess my question in the reversible patients is what monitoring strategy would we use in those situations? And are you influenced for example by what their CHAD score is? And so for instance, I advocate for a lot of essentially wearable AF detections in people who I'm really worried about because loop recorders don't get dropped in easily in my environment. And I think these devices are reasonably reliable at detection of AFib. And then that draws to attention the need to continue anticoagulation or address what is likely an ongoing clinical issue. So I'm curious what people do to look for AFib when there's an element of reversibility. So Janice, I'm gonna turn this one to you first because right, you were the chair of looking at sort of AF in the setting of some sort of critical illness or surgery. Now they're in sinus rhythm. They've had their little spell of AF for like an hour or three hours, whatever the case may be. Now what? Give the audience some guidance. I mean, implantable cardiac monitors for everybody, you know, a watch for everybody. I mean, what do you do? Oh, you're on mute. Thank you, Fred. I think this is definitely something that we're toying with. And I think that the jury's still out in terms of how we do it. Let me try to share. I think, you know, sharing is not going easy for me today but what I'm trying to show the group here is in fact, actually one of the figures from the scientific statement. And this is exactly Andrew's point. I don't know. I hope this is showing up a little bit better. Essentially- It's beautiful. It turns out long-term follow-up that it's really looking at this multiple dimension, thinking about substrate for thromboembolic risk. And this goes back to the CHADS-VAS various consideration which by the way, in our guideline here, we are going beyond just CHADS-VAS. We're also looking at percentage annual thromboembolic risk. But thinking about the substrate for thromboembolic risk. And then on the other hand, thinking about AFib recurrence, you know, the burden, how likely. And then so both the patient and the actual AFib, how much AFib, how likely the AFib. And then integrating these to then think about increasing intensity of heart rhythm monitoring. Again, with CLD, you know, limited data, okay, at this point, where certainly what does that tell us? We know that with increased intensity of monitoring, you're more likely to pick up. And so what does this mean? In someone who's higher risk, you may want to have a more aggressive, a more intensive monitoring protocol versus someone who has a lower risk substrate, who is less likely going to have the recurrence of atrial fibrillation, then your monitoring may be more patch-based, more periodic. And the key thing I think is thinking about long-term management, really thinking about the substrate. So not just going away from just something that's transient and resolving and going away, to thinking about the substrate of the patient. Who is the actual patient? What kind of comorbidities and substrate that this patient has? That's super, Janice. So Sunil, tell us about how your clinic deals with all of these wearables. So let's say Andrew, you know, talks his patient into buying an iWatch or a Garmin or whatever the case may be. What is your workflow? How does this happen? How do you handle, you know, this sort of tsunami of data now, you know, being generated? Probably it's just going to get more and more. So, you know, in terms of, I think, you know, back this question about what do you do after, I generally leave it up to the patient. I discuss with them and say, hey, you know, again, I tell them based on the substrate that we know or we've seen during the ablation or other ways that I suspect you have a somewhat of a higher chance or a less chance for this to recur. But then I tell the patient, you know, we never know, you know, it's very possible that at some point in the future, it could be years from now, your first presentation of AFib could be after a stroke. You know, how do you feel about that? And what do we want to do about that? And do we want to continue to anticoagulate you the whole time? Do we want to do continual monitors every few months and you do your wearables at home? And usually, you know, discussing these options with the patient, they are, you know, that's personalized kind of discussion in therapies. They're very clear about, you know, I have an eye watch, I'm going to do this all the time. It tells me whether I have AFib or not, when if it's an indeterminate rhythm, they'd usually send it to their PCPs or some of the more patients who are more aggressive about their monitoring, they frequently do send it to us too through MyChart messages or one of those things. And it can bombard our messages, but we have a very good team of people, including nurses and nurse practitioners and other very highly trained group of people who kind of filter it through it for us. And only when it's unclear, does it really come down to us to really assess it. And often we can reassess it at a six month or a one year followup, unless they're truly concerned about it. But yeah. I'm a little mindful of the normal patient response of being terrified of stroke. Yes. And so then it is, I think, our role in a way to place that in the balance of the bleeding risk of prevention strategy and the overall, again, we sort of go to a burden and implications kind of thing, like Janice said very nicely. So you have to be a little guiding about that conversation. Because if you say, if you don't want a stroke, then we should do A, B, and C. And logic is thrown out the window when you say stroke, right? Absolutely. And including price, right? I mean, how long, I mean, these are not inexpensive drugs for anticoagulation. There's bleeding risk. There's, I mean, are they going to be on this for 20 years just because they're worried about a stroke that may never happen? You know, yeah. So obviously this is a huge topic. A couple of things though that I want to emphasize though here before we get to the question for Janice. The first is Sunil just emphasized, you know, the systems of care as did Janice and Andrew. I mean, having a system in place is so vital for all of us. And, you know, we have this fragmented healthcare system. It really is critical that wherever we are at our individual places to be advocates for developing a system for managing all of these aspects. The second I wanted to emphasize, you know, we've been talking about anticoagulation and AF burden and things like that. Cause you know, we're arrhythmia people, but you know, it's sobering to look at a study like suite AF where in fact, patients appropriately treated, got anticoagulation, et cetera, still had a significant risk for stroke. And it really gets to the point that Janice brought up of managing diabetes, managing high blood pressure, managing all of the other things that are so critical in this space. So Janice, in the last two minutes, blackened eye for, you know, you said it was good in pregnancy. So, but do we then have, what do we think about the fetus? So go for it. Yeah, it's actually a quite a tough question. So good in a reasonable way, Fred, I think, you know, good as a two way. So good in a reasonable way. So, you know, it's a good question. So the question from the audience, I thank you for that question. It's a tough thing to think through, is whether or not a pregnant woman being considered for blackened eye should have a fetal ultrasound, a fetal echo for the baby to specifically look at the baby's heart. The question's a very sophisticated question. So the reason where it came about is that for adults, we established that for adults with structural heart disease should not be on blackened eye, a 1C agent. And for the adult side, the reason why we worry about the pro-arithmetic effect are twofold. One is historical data from the cast trial in the ischemic population. Two is actually as a sodium channel blockade, thinking about the hypertrophy, in terms of perpetuating re-entry and in terms of ventricular pro-arrhythmia risk. So those are the specific structural issue that we worry about. Obviously, since then, we also extrapolate to scar, to the low EF assuming scar, et cetera. So this is a range of structural heart disease that we typically think about for the adult, and in this case, the mom. So what about the baby? How do we think about that? That's fairly tricky. So blackened eye has excellent safety profile in terms of anti-arrhythmic medication compared to most of the others. It is sort of a go-to medication for fetal arrhythmia by itself. And so it has a lot of direct utilization to treat the fetus that's having arrhythmia. In this setting of a fetus that's not having the arrhythmia, where the treatment is given to the mom, that's typically well-tolerated as well. Most of the scenario, if you think of a patient with atrial fibrillation, most likely, even when they're pregnant, you're quite likely going to see if that's spontaneously resolved. Especially in first trimester, you actually want to minimize initiating new medications anyways. So you will watch, and you will quite likely start digoxin to see if you rate control that. So by the time that you're escalating to thinking about adding de novo anti-arrhythmic, different from people who are coming in already on anti-arrhythmic, showing up to their OB known to be on anti-arrhythmic, where that's already in consideration, to add de novo anti-arrhythmic, something's kind of spiraling a little bit more out of control, there's a patient you're probably starting to worry about quite a bit. What, and then quite likely, you will, if you're so worried, you've probably done an electrical cardioversion with a lot of monitoring, with a fetal heart monitoring, and pending on the baby stage, you may end up already doing a fetal echo. So I think quite often we get that almost as information that's already folded in. If you're so worried about someone, the mom and the maternal fetus combo, quite likely the fetal echo ends up being part of picture, because you're not just reaching for this straight off the bat. The fetal echo, it's obviously, what the fetus kind of evolving over time. So it's not over, you're not going to be able to see the cardiac structure with a clarity that expect an adult echo at week four. So a lot of the structure of heart disease that you're screening for may not be feasible until sort of second trimester, midway through pregnancy. So I think there are a lot of consideration here, but I think the long and short to your question is, it ends up actually being a case that if you're starting someone, and I emphasize starting, not someone continuing on. If you're starting someone on fleconide, quite likely you're already initiating a good part of this multidisciplinary discussion that Andrew and Sunil and Fred have all emphasized, that you're working very closely with the OB, and quite likely there may be escalated monitoring the fetus already. So you will likely get that information. I don't think we have randomized clinical trials to guide us, nor do I think we'll have that anytime soon, because this will be considered a vulnerable population that's hard to study, but quite likely you will have this in your hand if you're dealing with the situation. Great, thank you. So we have one last question with regards to thinking about risk factors. I'm gonna take the question and refer you to the first session, which we'll really talk about sort of prevention, et cetera. The important thing to sort of remember is this though, there are a lot of these modifiable risk factors that have been associated with atrial fibrillation. You know, the evidence for looking at sort of treating that and its impact then ultimately on sort of, you know, incident AFib is a little less good. So that's, for example, for diabetes. You know, the ACCORD trial really didn't show that, you know, if you really aggressively manage the diabetes that that in fact is associated with a reduction in atrial fibrillation. So it's one of those things where, you know, while we know these things are risk factors, our treatment strategies, it's a little less, our evidence is clearly less robust than showing that some sort of treatment will in fact reduce then the incidence. So, but again, refer you to that session. And really, I just wanna take this last minute to thank Janice, Sunil, Andrew, for your time on this outstanding webinar. Really wonderful. For those who are attending, this will kind of get curated, taken care of, and then we'll go out to everybody. So really want to thank you all and thank you too for that kind words. We really appreciate it. And we look forward to having you be at our next webinar. Take care now. Bye-bye. Great working together. Thank you, everyone.

Atrial Fibrillation

2023 Guidelines

Rhythm Control

Rate Control

Pregnancy

Cardio-oncology

Cardiac Surgery

Acute Medical Illness

Heart Failure

Multidisciplinary Management

Antiarrhythmics

Beta-blockers

Patient-centered Care