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Different Facets of AFib Management (COMPASS Webin ...
Different Facets of Afib Management (COMPASS Webin ...
Different Facets of Afib Management (COMPASS Webinars Episode 1)
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This webinar is a component of the HRS COMPASS Early Rhythm Control Project, supported by Sanofi and Biosense Webster. Thank you for all the people registering and attending tonight. I'd like to take a moment to introduce our moderator for the webinar, Dr. Luigi DiBiase. He is the Section Head of Electrosurgery and the Director of the Ritual Services and Professor of Medicine at the Albert Einstein Montefiore Hospital in New York. In addition, Dr. DiBiase serves as a Senior Researcher at the Texas Cardiac Arithmetic Institute in St. David, Austin, Texas. So thank you, Luigi, for moderating tonight, and welcome. Thank you, Dr. Natale. Thank you for the introduction, and I'm very excited for this episode of the COMPASS event, as you said. And I welcome everybody that is joining tonight, and I would like to introduce a group of speakers with our old friends and all experts in the field. The first speaker will be Dr. John Allison, which is the newest electrophysiologist at the Texas Cardiac Arithmetic Institute. His interests include novel ablation technique and complex device management. After him, we'll have Dr. Devi Naeem, who is the Director of Cardio-Electrophysiology and Research at the San Bernardino Medical Center Arrhythmia Research Group in Johannesburg, in Arkansas. Her clinical practice focuses on cardiovascular disorders, cardiac ablation, pacemaker, defibrillators, and epithelial appendage occlusion therapy. She has also served as the Chair and Vice Chair for the HRS Membership Subcommittee for the last five years. Welcome, Devi. Next, I don't think needs any presentation because we all know him and we learn from him, is Dr. Natale. He is the Executive Medical Director of the Texas Cardiac Arrhythmia Institute in Austin, Texas, as well the EP National Medical Director for the HCA. And the spreading innovative advance in the a-fib and ventricular arrhythmias. His many scientific achievements are well known, being the first EP in the nation and the world to perform his pioneering procedure. He's also a prolific author and educational speaker. After Dr. Natale, we'll have Dr. Mohanty, which we all call Mitra. She's the Director of Research at the Texas Cardiac Arrhythmia Institute in Austin, Texas. Being a prolific researcher, she has been actively involved in the beginning and implementation of many completed and ongoing trials at the Texas Cardiac Arrhythmia Institute and is well-published in peer-reviewed journals. She has been a member and fellow of HRS since 2014. We also were supposed to have tonight Dr. Amin Allamad, but unfortunately he is not going to be here. He's supposed to be a panelist and Dr. Allamad is currently serving on the editorial board of the Journal of Cardiovascular Electrophysiology, the Arrhythmia Journal, Arrhythmia Journal Case Report, and he's an Associate Editor for the Journal of Cardiovascular Electrophysiology. In addition to private practice, Dr. Allamad continues to be involved in many research grants and programs. His area of interest is ablation of atrial ventricular arrhythmias, as well as the evaluation and development of new technologies. Now that we have completed the introduction of all the presenters, I would like to have the first speaker, Dr. John Allison, to start his presentation. John, welcome. Thank you, Luigi, and thank you, Andrea and everyone at HRS for this opportunity to talk to you all. So this evening, we're going to talk about early AFib management and evidence of ablation versus drugs. This is obviously a very extensive subject with a lot of evidence behind it, but I'll do my best to hit the highlights in the available time. So here's what we know. Electrophysiologic and structural remodeling can precede the emergence of AFib, and electrical remodeling may be reversible early on, but structural changes may not be completely reversible. This is a sheet model where they create an aortopulmonary shunt to increase left atrial volume and pressure as part of an early AFib model. Section A at the top is the baseline. Section B is after the shunt has been created, and we can see early myocyte diameter increase and myocyte death. Panel C is after reversal of the shunt when pressure and volume have returned back to baseline, and myocyte diameter doesn't change much. And panel D, we see that in graph form that after shunt reversal, myocyte diameter doesn't change, but interestingly, left atrial size here in red returned back to baseline after the shunt was reversed. Electrophysiologically, after the shunt was reversed, the action potential distribution also returned back to baseline. And in humans with hypertension and left ventricular hypertrophy that are treated with Losartan or Atenolol, we actually saw a reduced incidence of new AFib in those treated with Losartan, which is likely related to the beneficial remodeling effects of ARBs, and this is when both patients had equal blood pressure at the end of the study. We also know that atrial fibrillation is associated with increased mortality, independent of other risk factors, and the majority of deaths are not related to stroke. This is data from the Framingham study that shows that AFib increased mortality in age, sex, and risk factor matched patients. The first panel on the left is patients 55 to 74 years old, and the panel on the right is patients 75 to 94 years old. And here's data from the RELY trial, which was Dabigatran versus Warfarin with 18,000 patients, and it shows that a vast majority of deaths in patients with AFib are not stroke-related, which makes us think that in the contemporary anti-coagulated AFib population, we should be looking for other interventions to reduce mortality, which was the basis of the original hypothesis that early rhythm control of atrial fibrillation is going to improve patient outcomes. Unfortunately, the initial rhythm control trials didn't support this hypothesis, but it's probably because the failure of the prior rhythm control trials was due to a failure to achieve rhythm control. In AFIRM, only 63% of the rhythm control arm was in sinus rhythm at five years, and in fact almost 40% of the rhythm control arm crossed over to rate control by the end of the trial. And in RACE, only 39% of the rhythm control arm was in sinus rhythm by two years. Poor patient selection also played a role. This is a study that looked at several of the major first of the early rhythm control trials, and we can see that almost all the studies looked at persistent AFib, and none of them improved patient outcomes. Patient outcomes did tend to improve with improved patient selection and better tools. There were some initial heart failure trials looking at rhythm control with drugs, notably Diamond CHF for defetalide and AFCHF for amiodarone that were negative, but in ATAC, which was RF versus AMIO for persistent AFib and heart failure with EF less than 40%, the primary outcome, which was recurrence of AFib, was met, as was the secondary outcome of all-cause mortality and unplanned hospitalization. And obviously in the seminal CASL-AF trial, which was RF versus medical therapy for paroxysmal or persistent AFib and heart failure with EF less than 35%, the primary outcome of death or heart failure hospitalization was met as well. And of course, that brings us to one of the major trials of the last couple of years, which is EAST-AFNet4. We all know this was early rhythm control with catheter ablation or antiarrhythmics versus usual management for paroxysmal or persistent AFib that had been diagnosed less than a year ago. It involved 2,800 patients that were randomized one-to-one, and the primary outcome was met, which was compositive cardiovascular death, stroke, heart failure hospitalization, or acute coronary syndrome. Here's a breakdown of the choice of early rhythm control. At the beginning of the trial, 92% of the patients started with antiarrhythmics as their form of rhythm control, but by two years, 20% had undergone catheter ablation. And by the end of the trial, 82% of the early rhythm control arm were in sinus rhythm versus just 60% in the usual care. This is the same data in graph form. There have been six major randomized control trials looking at catheter ablation as first-line strategy for treatment of AFib. The first three, RAFT, Mantra, and RAFT2, all looked at RF as a first-line treatment for atrial fibrillation. Unfortunately, the results were modest and were marred by safety concerns. Of course, mapping technology and force-sensing catheter improvements have likely improved the safety outcomes of RF. Over the last couple of years, though, we've also seen three major trials looking at catheter ablation with cryo as first-line treatment for atrial fibrillation. Stop AF first was about 200 patients with paroxysmal AF randomized one-to-one, cryo versus antiarrhythmics, and the primary outcome, which was freedom from AF, was met. And it was notable that a third of the patients in the antiarrhythmic group ultimately did undergo ablation due to the side effects of medications. In early AF, this was 300 patients with paroxysmal AFib or randomized one-to-one, cryo versus antiarrhythmics, and similarly, the primary endpoint of first-documented atrial tachyarrhythmia was also met. And cryo first was a little over 200 patients with paroxysmal AFib that were randomized one-to-one, cryo versus antiarrhythmics, and the primary outcome was greater than one recurrent atrial arrhythmia. And in all of these trials, the definition of recurrent atrial arrhythmia was actually very strict, and it was 30 seconds of a sustained atrial arrhythmia on some sort of ambulatory monitoring or in-office EKG. These trials were not specifically designed as early intervention trials, but we can see here that all were studied solely paroxysmal patients. The mean time to diagnosis from AFib intervention was more or less one year, and left atrial sizes are not particularly enlarged. This is a meta-analysis of the six trials that we've just discussed, examining catheter ablation as first-line strategy versus antiarrhythmics, and the primary endpoint, which was freedom from AF, freedom from, sorry, freedom from atrial arrhythmias was superior in the ablation arm. The secondary outcome of symptomatic atrial arrhythmia or hospitalization was also superior in ablation, and the adverse events marker also crossed the line of unity, so it was not significantly different. Obviously, I think I'm speaking to people who all believe in early rhythm control, but we all know that a major barrier to early rhythm control is actually getting these patients into clinic and being able and seeing them early in the course of their disease, and I think that's why we all await the results of the ER to EP study. It's an ongoing, currently recruiting trial. It's an observational cohort study, and it's 400 patients, there'll be 200 prospective treatment pathway patients, and 200 patients in a historical cohort. The model of the study is that patients come to ER with AFib. If AFib is the primary problem, then they'll either go down two pathways. They're either going to be admitted, and an AFib care navigator will be contacted who will help guide rate control, rhythm control, antiregulation, and cardioversion, and eventual discharge, or if they're okay to be discharged, then they'll be started on anticoagulation if needed, antiregulatory rate control if indicated, and there will be an internal referral to the EP team through the EMR and a text message with patient details, as well as a call to the AF care coordinator. In the preliminary data, 100% of the ER to EP group, of the treatment group, was evaluated by EP during the study time, versus only 50% in the control group, and 46% of those in the treatment group underwent ablation, versus only 40% in the control group, and this was statistically significant. We can also see that the time to EP evaluation, time to ablation, and time to oral anticoagulation was all significantly reduced in the ER to EP group, although we should also note that the time for all of these in the control group was probably significantly lower than real-world practice. And here we just see that, you know, this particular treatment pathway decreases time to ablation, decreases time to antiarrhythmic drugs, decreases oral anticoagulation, decreases heart length of hospitalization, and decreases the number of hospitalizations. In conclusion, electrical remodeling of AFib may be reversible if AFib is treated early. Failure of the initial rhythm control trials was due to a failure to control the rhythm. Early rhythm control with either catheter ablation or antiarrhythmics reduces cardiovascular morbidity and mortality. There is more randomized control trial data to support early catheter ablation, particularly cryo, versus antiarrhythmics to achieve freedom from AFib, but there are no major trials to date to support that catheter ablation will reduce morbidity and mortality compared to antiarrhythmic drugs. Thank you. Thank you very much, Dr. Allison. As you know, this night and this symposium is supposed to talk about the different phases of atrial fibrillation management. You clearly told us that we should intervene early, and we can for sure discuss this later. As a reminder, the disclosure of all the speaker and panelists have been displayed at the beginning when I was introducing the speaker and are available to you online. It's my pleasure now to introduce the second speaker, Dr. Devi Nair, and we are going from early ablation to when to consider left fetal appendage occlusion. Devi. Thank you, Luigi, for the introduction, and thank you, Dr. Natale and HRS, for this opportunity. I'm just going to get this started real quick. Okay. So in the next 10 minutes, we'll discuss about LA closure and when to consider LA closure. So when we look at atrial fibrillation, there's at least, as far as we know, 2.5 million patients in the U.S. who are at high risk of stroke with atrial fibrillation, and it is a major unmet need when it comes to stroke prevention in this patient population. So about 40 percent of patients who are indicated for oral anticoagulant do not take one, and we've had multiple registries that have shown the same, and if we look at the NOAC clinical trials, there's at least a 2 to 4 percent per year rate of main bleeding, and at least 30 patients continued usage within two years, and I'll elaborate on these slides. If we look at stroke, stroke is probably the most devastating complication of atrial fibrillation. AF increases stroke risk at least four to five-fold. There is incidence of all-cause stroke, and patients who have AF is at least 5 percent per year, and if we look in the setting of AF, at least 15 to 20 percent of all strokes are due to AF. The other difference is if we look at proportion of strokes that are attributable to AF, that is seen to increase with age, and you'll see in this graph, as the patient age goes up, the proportion of strokes from AF go up as well. Why do we care about stroke in the setting of AF? Because strokes that happen in the setting of AF are associated with greater mortality and morbidity, especially they're more disabling strokes, probably because they're more larger infarcts, you get more hemorrhagic transformations and higher mortality. If we look at oral anticoagulant use overall, over the last many years, we've seen that the total oral anticoagulant use has gone up tremendously, but if you look at kind of the differential between oral anticoagulant use, the total oral anticoagulant use is pretty much the same. What we are seeing is a decrease in warfarin use and an increase in the NOAC use. So the actual patient population that's taking oral anticoagulation still continues to remain low. This is a database analysis of the commercial insurance payers by Yao and his group, and you'll see that patients who are mostly on COAX rather than vitamin K antagonists like it used to be, and most of these patients are at high risk of stroke and have a high bleed risk. There have been multiple analysis that have been published that have shown very poor endurance to oral anticoagulation as well. Multiple papers in the AHA journal, Circulation, and JAMA articles that have shown a decreased use or decreased endurance to oral anticoagulation, oral anticoagulants, but also patients who are on sub-therapeutic doses of oral anticoagulant. This is, again, the analysis from Yao and his group looking at the use of DOACs, and you'll see that endurance rates, even with drugs like epizoban and dabigatrin and rivaroxaban, are extremely low in this patient population that is at a higher risk of stroke. This is looking at rates of major bleeding in some of the major trials. These are some of the DOAC trials, and you can see they range anywhere from 2 to 4 percent. Now, looking at the bleeding risk, if you were to take a patient that has a CHADSVAS score of 4, the annual bleeding risk is probably about, or stroke risk is about 4, and say if this patient has a HAZMAT score of 4, you're looking at maybe an annualized bleed risk of about 8.9, but what we have to keep in mind is that the patient's 10-year bleeding risk is much higher because these bleeding risks compound over time. So, when we look at a younger patient, we're looking at what that bleeding risk is going to be over time as well. This is an impedance analysis that looks at ischemic stroke rate and compares it to the baseline CHADSVAS score, and on the top line here, you can see the ischemic stroke rate if a patient is not on any anticoagulant or not having any therapy. You can see there's a very exponentially increasing rate of stroke as the CHADSVAS score goes up. Now, this solid line shows ischemic stroke rate on oral anticoagulant, and you can see that the oral anticoagulants substantially decrease stroke rates in this patient population. Now, here we've put together all of the BAC trials, whether they are FDA trials or non-FDA registries or NCDR database, and what you see, these rates, the ischemic stroke rates in these trials also kind of go along the ischemic stroke rate with oral anticoagulant thing, showing that definitely, you know, if you have a patient that cannot take any therapy, they should at least get some alternative strategy as it definitely decreases stroke risk. Now, when we talk about left atrial appendage closure, we're looking at, say, local therapy versus systemic therapy, so appendage closure is directed towards the left atrial appendage, which is known to be the source of thrombus that causes stroke in NBF patients in at least 90% of cases. So when we look at sites of thrombus within the heart that causes or within the body that causes stroke in these patients, majority of these strokes happen because of thrombus within the appendage, and hence, we direct our attention towards left atrial appendage closure, and the two current commercially available devices are Watchman and Amulet device. Now, if you look at the potential LAC patient populations, if you think about total AF population, it's about a million, and at least 95% of these patients have non-valvular atrial fibrillation, and from there, if you look at the patients who have high risk of stroke, which is a CHADS of two and above or a CHADS VASC of three and above, that's at least 75% of patients. Of this, at least 5% of patients in this group cannot take any kind of oral anticoagulants, and they are usually patients who have, say, cerebral amyloid angiopathy or things of that sort, and at least 60% of these patients can tolerate oral anticoagulant and should be on one because it definitely reduces stroke risk in these patients, but there is about 35% of patients who are truly intolerant to oral anticoagulant therapy and have a meaningful reason to be not on an oral anticoagulant therapy, and this is your current approved left atrial appendage closure population. So this is a consensus memo that was sent to CMS by HRS, ACC, SCI, talking about who are the potential patients that are candidates for appendage closure. Now, LAC is not just for patients who are at risk of bleeding. It is also for patients who have multiple other issues, and we will elaborate a little bit on this consensus memo. So the way I categorize these patients are, number one, they are patients who are bleeders. So these are patients who have had, say, spontaneous bleeding, whether it's intracranial or recurrent GI bleeding or recurrent GU bleeding and cannot be on long-term anticoagulant because every time they go on an anticoagulant, they bleed, or they could be patients who are considered to be, say, future bleeders. For example, patients who have a pretty high HASP blood score compared to their stroke risk, or patients who are at, say, high risk of fall and have, say, significant issues with ambulation or gait and are on an oral anticoagulant. You can talk about patients who have risks with occupation. So, for example, patients who are farmers who use heavy machinery, there are a lot of occupations that put patients at high risk of bleeding. Lifestyle is another thing. There are patients who might not want to be on a long-term oral anticoagulant because of their lifestyle issues. Again, all that we, or every care that we give patients is for improvement of quality of their lives. So if it does impede, if the lifestyle change impedes their quality of life, it is definitely something to be brought into that shared decision making. The non-compliant patient is another patient. We saw the non-adherence rates of oral anticoagulant. And, you know, the non-adherence could be because of many, many reasons. It could be for a patient that's on warfarin, it could be struggle maintaining INRs, whether because it's a diet issue or whether it's polypharmacy, or it could be because of the cost of the medication or other reasons why the patients have to discontinue oral anticoagulant. Now, regarding indications for LAC, there are, obviously, the current indication is a patient that cannot tolerate oral anticoagulant therapy or is not a candidate for long-term oral anticoagulant therapy. But there are ongoing and upcoming trials that are looking at the indications such as the option trial that look at the patients who are, say, a fibrillation patient or trials that are looking at LAC as a first-line therapy. So this is an option trial that finished enrollment and is currently on follow-up, is looking at left atrial appendage closure as first-line therapy in patients who are post-AF ablation. So these patients either got LAC concomitantly or sequentially after an AF ablation. The champion trial, also just finished enrollment, is a trial that's looking at patient, looking at left atrial appendage closure as first-line therapy in NVAF patients randomized to Watchman Flex versus oral anticoagulant. And these patients will be followed for five years with multiple primary and secondary endpoints. The Catalyst trial is another trial that's looking at the AMLUT device as the first-line therapy in NVAF patients for stroke prevention. And again, currently, enrollment's happening in the Catalyst trial. So in summary, left atrial appendage closure is currently indicated in NVAF patients with high stroke risk who are unable to take long-term oral anticoagulants. There are multiple appendage closure devices available with different efficacy and safety rates. There are multiple trials that are ongoing that are looking at optimizing therapy, looking at new technologies, and looking at expanding treatable patient populations. With that, thank you very much. Thank you very much, Devi. There was a great presentation and we went from, we need to update early, when to use anticoagulation or closure device and possible options. Next speaker is our host, my mentor, and it's a pleasure for me to introduce again, Dr. Natale. He's gonna talk about of a complication of cardiac ablation in the era of Poolsfield ablation as a new possible energy source. Dr. Natale. Thank you, Luigi. So those are my disclosure. As you heard before, Dr. Allison mentioned about potential complication with cardiac ablation, mostly driven by what we call collateral damage. So PFA is the next energy sources that hopefully will be available to everybody in 2024, maybe if we are lucky at the end of 2023. What is the difference between what we're doing today and Poolsfield ablation? So what we're doing today is either cryo or radio frequency. They both have similar complication rate, although clearly RF require more operator skill, but they both can cause pulmonary vein stenosis, atrial hysterectomy, fistula, and phrenic nerve palsy. And also with RF, clearly there is pericardial irritation that at least 20% of the patient experience after ablation that require treatment. PFA instead is a non-thermal energy sources that affect primarily cardiac cell. So as a lower risk of collateral damage by altering their membrane and causing apoptosis through irreversible electroporation. And this is a sort of an example of the cartoon of what to expect. So affect primarily cardiac tissue and the tissue exposed to the field is the one that become eventually apoptotic. The one thing that we learn is that there are several way of delivering this energy. And I think that's something up to us to learn which one is better, both because the waveform is better because the device is better designed, but each single system require sort of assessment to have an idea of the success rate. These are three of the four devices that are undergoing testing in U.S. for the FDA. All three that you see here have finished enrollment and they are in the follow-up stage. The one in B probably will be the first one to have FDA approval. And then A, the second one and C will be the third. This is an example of the sort of a larger single point device. This is the difference with what we are doing today in comparison of the size of the electrodes and also the size of the lesion. It's sort of a large single point as you see here where lesion has to be delivered overlapping one to another to avoid the reconnection. What is similar to all this technology is the safety. And this is really what is exciting about this. That for many, many years, we have implemented strategies to reduce the risk of what we call collateral damage. With PFA, all of that will go away. So there's no risk of pulmonary vein stenosis. There is no risk or virtually minimal risk of phrenic nerve injury, and there is no risk of esophageal injury. We'll talk a little bit about artery. Clearly with RF, we learned that lesion caused to the artery can cause occlusion or stenosis that require intervention. We'll see what we've seen so far with the PFA, but overall better than radiofrequency energy. Those are some data showing large ulceration obviously in experimental model by using radiofrequency energy that were not seen with PFA as you see in this screen. And then also with histology, there was no evidence of ablation lesion in the outer layer of the tunica muscularis and in the vessel with PFA, whereas there was a transmural lesion in lesion delivered with radiofrequency energy. Also when MRI was used to look at the extension of this lesion clearly, in here you see comparing thermal lesion which include both cryo and RF versus pulse field ablation, and you see that there is no evidence of enhancement in the esophagus. There was some enhancement in the aorta, but certainly in the lower extent than seen with RF and cryo. This is another of the system that also had completed the testing in U.S. and soon to be approved in Europe, and this is an example of the lesion. So the caveat with PFA is what you see here, this is the delivery. With single lesion, you see that all the recordings appear. That does not mean that you have chronic lesion. And so that's something we have learned. And in most of the study, we had to apply energy at the same site multiple times to maximize the effect, the chronic effect of this energy source. This is again, some data from our lab where we measure temperature while delivering PFA towards the esophagus, and you see that there are very small amount of temperature increase that certainly do not raise any issue. And in some early study in Europe, we also have used endoscopy and we haven't seen any sort of red flag for lesion that raise concern. This is some data looking at, in animal at stenosis of the pulmonary vein, RF versus PFA, and you see that with RF, clearly there is a narrowing that was not seen with PFA. And the same is true in patient. Those are the pulmonary vein dimension before and after. You see there is no, virtually no changes. And again, some data in some of the early clinical study from Europe showing a very low rate of complication. None of those are driven by the effect of collateral damage. So you see no pulmonary vein stenosis, no esophageal fistula, no pericarditis, no pulmonary edema. Obviously there are procedural related complication like perforation because of the transeptal or stroke because you are doing procedure in the left atrium, especially when uninterrupted, when we're not using uninterrupted strategy. One important issue in our experience with what you are doing today, the most common site of reconnection is in the area facing the southwest, 91% of the time because of our data in a large number of patients. And what is the difference? That in those area, our lesion duration is shorter because we move away because of the esophageal temperature increase. All of this is gonna go away with pulse regulation. It is an example of a chronic study that has been done in Europe. We remap in showing almost close to 100% permanent isolation of the posterior wall because we don't have to worry about delivering in tissue facing the southeast. Also the superior vena cava, this is some example of delivering in the superior vena cava without any issue with the friendly nerve, which you know right now that can happen with radiofrequency energy. And also with cryo when we deliver from in the right pulmonary vein. So clearly all the problem we worry about for many, many, many years are going to go away. Another important effect is the chronic lesion. With PFA, we have sort of a really true anthral chronic lesion, whereas we've seen that with the balloon system, both cryo and laser, the chronic effect is more in osseous isolation, although the acutely seems to have a more anthral effect. So that's important. Also here you see PFA being used in anatomical variant. This is an example of persistent superior vena cava, which we know is an important target in patient atavit. And you see cases where the basket was delivered in that structure, which is quite big to achieve isolation. Now some clinical data from Europe showing a short learning curve in validating the safety. Here a large series from 24 center in New York including 1,758 patient, showing again that all the issue that we're worried for many years do not happen. So no PV stenosis, no superficial fistula, no cranial nerve paralysis. There was some transient cranial nerve in less than 0.5% that was resolved. Obviously, as I mentioned, the complication rate that still happen are the procedural release. So vascular access, pericardial tamponade because of transeptal and stroke. I have to say that the way we are doing the procedure today, especially in United States where access is obtained by ultrasound guidance, transeptal is also guided by intracardiac Keiko and most of the center use an interrupter. I think even some of these complications that you see here will be minimized. So this procedure will become extremely safe in hands of experienced people that use sort of the state-of-the-art technology. So the one issue that is still up that has to be studied more is the risk of stroke. Many years ago, with radiofrequency energy, we show that that can result in microbubbles detected on transcranial doppler as you see here. We've seen this also to happen during pulse field ablation. However, we have done a study that was just finished in Europe, in Brussels with one of our ex-fellow in the group of EP there, showing that despite the microbubbles are detected during pulse field ablation, there was no stroke seen at MRI. So as long as you manage your transceptal sheet properly so that you don't have air embolism, pulse field ablation doesn't seem to be a problem as RF was in increasing the risk of thromboembolic event. A big issue, actually the number now are higher than this is that the duration of this procedure, it is way shorter than as you see here, than sort of a match population undergoing RF. And this in summary, especially include about a waiting time of 20 minutes that was required by FDA study to assess early reconnection. So the one issue that I think we are sort of learning about is sort of this coronary spasm. As you see here, this is a case reported during mitral response line. And this is a case during right atrial response line performed with the flower, which is the catheter designed more for left side use. This is a study done by Vivek where they actually inject contrast in the coronary artery immediately after delivery of energy. And you see here that there was a coronary spasm. In all these cases, the coronary spasm was clinically silent. So there was no ST elevation, but clearly there was coronary spasm on the angiogram and coronary spasm was reduced by injection of nitroglycerin. So it never resulted in a persistent narrowing, which is what we have seen with radiofrequency energy. So this is something that we're gonna have to learn more about, but at least that does not cause permanent narrowing. So it does not have long-term consequences for the patient. It's an acute effect that I think we're gonna have to deal with. I'll show you a case from one of our fellow that I mentioned is now in Brussels. This is a patient that is having right atrial isthmus with the flower catheter. So this big sort of electrical field, and you see here the ECG before, and after delivery, you see that now there is a little bit of ST elevation that get worse and then some PBC, then more ST elevation with the wider of the QRS and by germinal PBC eventually resulting in PF. It was cardioverted and very quickly the ECG normalized. And by the time the coronary angiogram was done, all the coronary artery were normal. Here's the RCA and here you see the LAD. They're all normal without any issue. So as I mentioned before, it's something that happened, we're gonna have to learn about, but at least does not cause a permanent narrowing as we've seen with radiofrequency. So here's the adoption of this new non-thermal energy source for atrial fibrillation is gonna significantly reduce procedural duration, improve lesion durability if properly used and completely eliminate the risk of collateral damage, which is really the most exciting aspect of this new approach. However, obviously, I mentioned before at the beginning, the efficacy could change based on the device design and the way from use to deliver the energy. This is something we're gonna have to learn device for each single device. Thank you very much. Thank you very much, Dr. Natale for this very educational and complete presentation on this such a new topic. Next speaker will be Dr. Mohanty. She will talk about lifestyle changes and anticoagulation in patient with atrial fibrillation. Okay, let me see if... PFA, where did it go? We can last the screen now. No. Give us a second. No, this is not. Not this one? No, it's yours. Current date on PFA. So all windows. There you go. Sorry. I'll just click on one. Hi, I'll just quickly say thank you to Dr. Natale and the HRS Compass Program for this opportunity. In the next 10 minutes, we'll discuss about anticoagulation and lifestyle change in atrial fibrillation. So first, why anticoagulation is relevant in AFib as Debbie has already said, it increases the risk of stroke by five times and the main stroke prevention strategies are drugs or the left atrial appendage occlusion or exclusion because LA is recognized as the major source of cardiac emboli in patients with non-vulvular atrial fibrillation. And you can see that in this schematic over here in this illustration, kind of how the blood clot goes to the brain and causes the stroke. And there are two main types of drugs, oral anticoagulants that are used. One is warfarin and the others are the direct oral anticoagulants, which we are seeing DOACs. And the DOACs were approved for stroke prevention in atrial fibrillation between 2010 to 2015. So now we look at the questions on management of anticoagulation in AFib. The first question is whether the periprocedural anticoagulation should be continuous or interrupted. The next is post-ablation anticoagulation. That is two questions there, to stop or to continue after successful ablation. And the second is anticoagulation following left atrial appendage closure. So first we will quickly look at the periprocedural anticoagulation. This paper was published by our group in 2010 where we collected data from nine centers. The patients were divided into three groups based on the ablation catheter used and the anticoagulation strategy during the ablation procedure. So you can see that only group three was on warfarin, the other two were off. And the periprocedural stroke TIA, periprocedural is within 48 hours of the procedure, occurred in 1.1% in group one, 0.9% in group two and none in group three. So it was statistically significant, but the major bleeding was comparable between the three groups. So the conclusion was the combination of an open irrigated catheter with uninterrupted warfarin was associated with no stroke events without increasing the bleeding risk. Next, we did the randomized compared trial where patients were randomized to either discontinued warfarin or continuous warfarin during the procedure. And the inclusion criteria were INR within last three, four weeks of ablation to be between less than three or less and charge to score was one or more. And we saw that in this group, in this study also, we saw that the combined stroke TIA events were 4.9% in the off warfarin group, whereas it was 0.25% in the on warfarin group. So we concluded that this was the first randomized trial showing that performing a catheter ablation with uninterrupted warfarin resulted in lower peripheral stroke and minor bleeding events. This is a meta-analysis that was done on six randomized trials that compared uninterrupted DOAC versus warfarin. And here, as you can see in the bar diagram, uninterrupted DOAC strategy was associated with lower major bleeding events than the warfarin. And the other endpoints like minor bleeding events, thromboembolic events and silent infarcts were comparable between the groups. So based on all these evidences now, the guidelines recommend uninterrupted anticoagulation during the ablation procedure. Next, we'll go to the next question, which is can anticoagulation be interrupted after successful AF ablation? Now here, there is a meta-analysis of 10 studies where more than 11,000 patients were included, and they saw that there was no significant difference in thromboembolic events between the two groups. One group was off OAC, one was on OAC. So you can see that there was no significant difference in thromboembolic events. However, the risk of major bleeding in off OAC group was significantly lower compared to the on OAC group. So their conclusion was it may be safe to discontinue OAC therapy in patients after successful AF ablation. However, there is an increased risk of major bleeding was observed in patients on OAC. This is our study where we looked at thromboembolic risk in atrial fibrillation patients with left atrial scar post-extensive ablation. So group one received limited ablation, which was PVI plus postural isolation plus isolation of SVC. Group two received extensive ablation, which is limited ablation, all of these, plus ablation of non-PB triggers from all sites except left atrial appendage. And we noticed 19 TE events were reported. Group 1 had 1.02%, 9 events. Group 2 had 10 events, which was 0.61%. So there is no difference between the two groups. The median time to stroke was 14 months in Group 1 and 14.5 months in Group 2. And the mean scar area was detected as significantly higher in Group 2 versus Group 1. So these are the examples of electroanatomic maps showing limited versus extensive ablation. And we concluded that differently from the cardiac MRI detected pre-ablation scar, scar resulting from extensive ablation was not associated with increased risk of stroke compared with that from the limited ablation. In the previous study, we did not have LA isolation. So next we looked up in patients that received LA isolation and the thromboembolic risk in them. And we saw that LA electrical isolation is associated with significant risk of stroke. As you can see, 16.7% in patients that were off OAC with impaired LA function. Those who were on OAC, the stroke rate was much lower. That was 1.7%. But the patients who regained LA function, that was normal at six months TE, they were all off OAC without any events. So LA isolation is, in fact, associated with significant risk of stroke that can be effectively reduced by optimal uninterrupted OAC or LA occlusion. By the way, 84 of the 90 patients received that had stroke received LA occlusion. And at the median follow-up of 12 months, only one event occurred in a post-watchman case that was on OAC. So now there are two randomized trials that are ongoing or kind of very, very recent. One has been just recently finished and the other one was terminated. We don't have results of the ODNAF trial yet. We will find out how it works out with dabigatran versus no anticoagulation, probably by the end of this year. So can anticoagulation be interrupted after successful ablation? The answer is oral anticoagulation can be discontinued. In closely monitored arrhythmia-free patients, and when we say closely monitored, we kind of refer to the wearable devices that are showing to have high positive predictive value. So patients can be closely monitored and OAC can be discontinued. However, in patients with LA isolation, either lifelong OAC therapy or LA closure should be updated for thromboprofile access. Now we go to the next question. Antithrombotic therapy following left atrial appendix closure. How should we address that? This is our study, which we published recently in 2021, where patients were given either half-dose NOAC long-term or the standard antiplatelet therapy, like aspirin plus clopidogrel. And as you can see in the bar diagrams, after successful Watchman implantation, long-term half-dose NOAC, represented by the orange line, significantly reduced the risk of composite endpoint of device-related thrombosis and thromboembolism and major bleeding events compared with the standard antiplatelet-based antithrombotic therapy. These are three randomized trials that are ongoing right now. One of them is ours, and there are two others. Probably in the next three years, we will have some definitive answer as to how to address anticoagulation in post-LA occlusion patients. Next, we will go to lifestyle changes in atrial fibrillation. There are four areas here. One is the BMI, either underweight or obesity. Then the other one is physical activity and alcohol and smoking. Let's look at obesity first. Obesity is a well-known risk factor for initiation as well as persistence of AFib. Now the question is, does obesity influence arrhythmia outcome following AFib lesion? The answer is yes and no. Now there are three studies that I have kept here. All three studies, major studies, they showed that obesity is associated with reduced efficacy of the ablation procedure. Then we are going to the next slide. We have four studies that showed long-term ablation success was not different in obese patients compared to non-obese patients. So we don't know yet, but then the Garfield Registry, which is a registry with 42,000 patients, they kind of separated them based on the BMI. They saw that patients within two-year follow-up, there was a USEP relationship between BMI and all-cause mortality. There is patients that were underweight with BMI less than 18.5% and extremely obese that were more than 35 kg per meter square, whereas had increased risk of mortality and new or worsening heart failure. So the next question will be, does weight loss impact arrhythmia outcome in AFib patients undergoing catheter ablation? There are four landmark studies that were conducted by the Australia group that showed the impact of weight reduction on atrial fibrillation and ablation outcome. The fifth study, REVERSE-AF, was also conducted by the Sanders group from Australia. There is one important thing they reported. They said that in patients that lost at least 10% or more weight had the lowest rate of progression from paroxysmal to persistent and the highest rate of reversal from persistent to paroxysmal AFib. They also saw that more than 10% weight loss was associated with 45% patients not requiring any ablation and further 37% requiring only single ablation. So the most important question here is, is it easy to achieve 10% weight loss and is it possible to sustain it? The answer probably is no, because as you see here, this paper says that the physical activity, AFib patients engage in significantly less average physical activity and worsening of symptom severity is associated with more reduction in physical activity. So if the physical activity cannot be maintained, then the weight loss to achieve it and to maintain it becomes really difficult. Then we will show you one study from our group. This we presented in AHA 2017, where we showed how challenging it is to enroll patients and keep them compliant through the study period. Because of symptom severity, most of the patients refused and then some were not motivated or they had other comorbidities like arthritis and other stuff for which they were not fit to do physical activity and then advanced age. Then the next thing is, this is a paper from Cleveland Clinic Group. They showed that when the patients have morbid obesity plus sleep apnea plus diabetes plus high blood pressure, then only when all four comorbidities were controlled, patients have least arrhythmia recurrence compared to those who had zero to three comorbidities controlled. So not only weight loss alone is not sufficient, the other risk factors have to be modified to achieve the maximum benefit. Then with the last studies from our group, we saw that in patients with long-standing persistent AFib, weight loss did not cause any change. It has no impact on arrhythmia recurrence as you see in the Kaplan-Meier curve. So that is one group that did not benefit from weight reduction. Now there is a USEP curve that was showed in another study where Kaplan-Meier analysis showed BMI less than 18.5 or more than 30 with significantly more AFib recurrence. So the both underweight and obese patients not only have more risk of mortality, they also have more risk of AFib recurrence. So does BMI matter? Yes, it does because obesity and underweight both are known to be associated with increased risk of AFib. However, weight reduction does not benefit all, especially the long-standing persistent AFib patients. Now I will quickly cover smoking and alcohol and their impact on AFib. This is a meta-analysis on smoking and the next one is a meta-analysis on alcohol intake that showed both smoking and moderate alcohol consumption were associated with increased risk of incident AFib. Now we are doing a randomized trial where we are going to look at impact of post-ablation alcohol intake on arrhythmia recurrence quality of life and cognition. It just started, we have enrolled nine patients only, so most likely in next one or next two years we will have some results, good results for all of you. Now the last one is the lifestyle change, physical activity. Although moderate exercise is known to be beneficial, there are reports shows that extreme levels of exercise may be associated with higher risk of AFib. I will show you one interesting data that we published. We saw a very nice differential association of exercise intensity with risk of atrial fibrillation in men and women. There was a protective impact of moderate physical activity in both men and women, but when vigorous physical activity was associated with significantly increased risk in male whereas it benefited women. So with this I will finish today's talk and say no matter what your DNA says, a good diet, regular moderate exercise, not smoking, limiting alcohol and some other surprising lifestyle decisions can change that destiny. Thank you. Thank you very much Mitra for this nice presentation. I think as long as the time is concerned we have some time for some question and discussion. There is a patient from the audience. I start with Dr. Natale. Dr. Natale, what do you think or do you know what would be the complication rate of PFA in inexperienced operators? Well, you know, as I said, that's why I showed those studies. So would they still have risk of complication because of the procedure? So the access, transcendental access, vascular access, those are not going to disappear especially in the hands of people that do not have a sort of a system. I mean, what I mentioned is in our lab everything is driven by ultrasound, both the eyes. So I think that procedure is going to become bulletproof pretty much. But, you know, some of the complications they show in those registry from Europe, they are really driven by, you know, procedural problems. So transcendental access, vascular access, and the stroke in Europe, very few centers do uninterrupted like we do. So when the center do uninterrupted, they are not going to see stroke with this approach. I mean, we've done a very thorough study in Europe with the transcranial dopamine and brain MRI. And I think, you know, if people have stroke, it's probably because of the management of the transcendental shift of the air embolism. It's not because of the PFA per se. Thank you very much. For Davy, again from the audience, and I encourage everybody to send your question here. What's your protocol, and everybody can comment after, about a patient that has a Watchman and has to go on cardioversion? Would you give anticoagulation before and after, and yes or no? And second, what do you do if you have to cardioverse a patient that has a DRT on the Watchman? Thanks, Luigi. Those are great questions. So no, I believe that we do not have a good understanding of DRT rates in our current LAC population because we don't image often enough or enough in that sense. So because of the worry with the current generation devices and that risk of DRT, I like to image. So I usually will start them on anticoagulation at least 48 hours before if they are stable enough to wait for two days. But if they're not, then I'll do a TE-guided cardioversion. I like to image. If they've not been imaged recently, I like to image them to make sure there's no DRT, make sure there's no leak or any of that before I cardiovert them, and I tend to keep them on anticoagulation after. Now, for a patient that has DRT, that's a different story. I actually will anticoagulate them, reimage them, make sure that there is no DRT before I will do any kind of cardioversion. Dr. Natale, anything different? I think we kind of follow a different protocol. In our center, if the patient had a recent imaging, there is no leaks, which I think is sort of one of the concerns, and no thrombus. I think we have done cardioversion without reimagining them. But as David said, if you don't, then you need to check because there are patients that develop thrombus on device. So that's something that is real and we need to sort of make sure it's not the case. So it depends on what kind of follow-up. Unfortunately, we see a lot of patients that get implanted, and after 45 days, they have no further follow-up. So those are people where sometimes we found clot because they were reimagined a year after. So clearly, at this stage, until we have a better grasp, at least in our lab, we're very strict about imaging them at least three times over the year following implant. And in people that are perceivable, as Iris Kimita mentioned, that we use a half-dose. With a half-dose, so far, I think we have only one patient and we have several hundreds that have something to look at thrombus, a very sturdy device. It was not mobile. And the patient did not have a stroke. Whereas we have a few patients that stop after a while the half-dose and within several months, they don't stroke. So we know that half-dose really protect these people as Mitra showed in the study that we published. Thank you. Let's go for John. John, how early is early? Meaning the continuous question we have, I think we agree that early ablation is better, but how early? One episode of AFib, 10 episodes of AFib? I mean, what is your definition of early ablation? I don't know that it's based on the number of episodes of AFib you've had, but more just we know that from the time of diagnosis, the earlier you get to it, the better. And so within a year, we've clearly seen that it's benefited patients with morbidity and mortality as far as rhythm control goes, whether it's with antiarrhythmics or catheter ablation, no matter how many episodes they've had. Like I said, in East AF Net 4, it was both paroxysmals and persistence. They just had to have been diagnosed within the year. But just for the audience here, you have a patient go to the emergency room in paroxysmal intrapubulation in normal heart, no little comorbidity, hypertension, I would say. And it's the first time he's diagnosed with AFib. Would you offer an ablation already or would you just wait? I would definitely offer them rhythm. I mean, I think rhythm control is the key. We don't know whether catheter ablation is going to improve their outcomes other than recurrent atrial arrhythmias. We don't know if it's going to improve their cardiovascular morbidity and mortality. So I would offer them rhythm control with either antiarrhythmics or catheter ablation and kind of give them the option of the pluses and minuses of either. If they have a structurally normal heart, no coronary disease, and they're going to tolerate flecainide easily, that might be the best thing for them, especially if they're adverse to some minimally invasive procedure like ablation. But then some people, they say they don't want to take medicines every single day, and maybe that's not the right option for them. But I also think that, as Andrea mentioned, I think the conversation is going to change drastically when PulseField becomes widely available and the safety of catheter ablation increases significantly. I completely agree. I also say that you mentioned in your presentation that also IFIB is progressive. So one episode means it's the first episode of something that will progress at some point. So we need to inform the patient that you have an arrhythmia that most likely will progress. For rhythm control, ablation is superior to medication in any trial. So I think we need to give this option to the patient by explaining the difference in the outcome in maintaining the risk of developing IFIB between males and females. Mitra, in your presentation, you talk about different exercise tolerance in the risk of developing IFIB between males and females. What do you think are the plausible explanations of that? Okay, Luigi, this is a very good question. There are some possible explanations, and I will tell them one by one. The first one is, when you say vigorous exercise, that's a broad range of intensity and duration. And there is no standardized definition of intense exercise. So most likely, the studies that reported women to have a protective effect and men having more risk for IFIB, probably the women had shorter duration or less intense exercise. That is one possibility. Second is, during exercise, the sex hormones are released, which are protective for women. Third is, they have a lower blood pressure and lower sympathetic tone in general, which kind of favors. So these are the plausible explanations. There is also one thing called threshold effect. That is, after a certain level of exercise, one cannot tolerate. Probably that threshold effect is different between men and women. That is why they respond differently to the exercise intensity. Thank you. And before we go to the conclusion, Devi, you mentioned a new trial that will, and probably, if positive, we will be able to offer a left-fetal appendage closure as a truly alternative to anticoagulation to our patients. Do you think the introduction of factor 11 will change this possibility somehow? I know there's not much information about what's your personal opinion. I mean, I think we have to think about the future. I think I'm definitely eagerly looking, waiting to see the results of the CHAMPION and the CATLAS trial. And if positive, I think it will change the shared decision-making that we have with our patients during AF management. Factor 11 is going to be interesting, if you ask me. I think, I mean, at least currently, there's a suggestion that there's very low bleeding rates with the factor 11. And if it does show good ischemic stroke control or stroke reduction, then there is a possibility that patients might be more adherent to it. But again, cost is still going to be an issue. It's still once-a-month administration. So there are going to be adherence problems. I think one is going to have to worry about need for temporary interruptions, things like that. So there are a lot of things that we have not thought or put into place. So it'll be interesting times. I think the future of Orlando Coagulans and future of appendage closure is yet to be seen. Thank you. Time is our enemy. We are at the end of the hour and at the end of this webinar. I would like to thank HFRS, the COMPAX project, the host, Dr. Natale, all the speakers, Devi, Mitra, and John, and of course, all the attendees to this event. I would like to also remind all of you that this webinar will be available free of charge on the HRS 365 platform in the coming week and will remain available for at least three years. Again, thank you very much to all the panelists, the speaker, the attending, and hope to see you soon in person at the HRS in New Orleans. Thank you very much.
Video Summary
This webinar focused on early rhythm control in atrial fibrillation (AF) management. The speakers discussed the benefits and risks of different treatment strategies, including catheter ablation, antiarrhythmic drugs, and left atrial appendage closure. They highlighted the importance of early intervention in AF and the potential for catheter ablation to improve clinical outcomes.<br /><br />The speakers also discussed the role of anticoagulation therapy in AF management. They emphasized the need for uninterrupted anticoagulation during ablation procedures to reduce the risk of stroke. They also discussed the impact of weight loss, smoking, alcohol consumption, and physical activity on AF outcomes. They concluded that weight loss and lifestyle changes can have a positive impact on AF recurrence and overall health.<br /><br />Overall, the webinar emphasized the importance of individualized treatment plans for AF patients and the need for ongoing research to improve outcomes in this population.
Keywords
early rhythm control
atrial fibrillation management
catheter ablation
antiarrhythmic drugs
left atrial appendage closure
early intervention
clinical outcomes
anticoagulation therapy
stroke risk
weight loss
AF recurrence
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