Welcome, ladies and gentlemen, Dr. Chris Ellis, electrophysiologist at Vanderbilt, and joined by Julia Indyk. I'm an EP physician from University of Arizona in Tucson. Yep. And we will be co-chairing our session here, which is a group combined guideline or clinical practice recommendation statement from both the Committee of SCI and HRS. This document is not published yet and is still under discussion for the final wording on several of these topics, but we thought a very good session to go through the step-by-step how this paper is being put together and some of the more controversial things that we may have to decide about when it comes to wording in the final document. But we'll start first with Dr. Ed Cronin from Temple, oh, actually, sorry, Dr. Jackie Saw from University of British Columbia, who will be discussing how the guidelines were created. All right. I'll take it. So, I'm going to just swap. Thanks, Chris. Yeah, we swapped things around so that Dr. Cronin can speak on the technical part of it since he was on the technical panel. So I'm going to speak on how we developed the guidelines. Let's let the disclosures go on here. Okay. So SCI produces and endorses a number of guidelines documents in the space of interventional cardiology, and these documents are developed in oversight, overseen by the Publications Committee. So for the clinical practice guidelines for LAC, these are statements that include recommendations intended to optimize patient care, and they are formulated from a systematic review of evidence and assessments of the benefits and harms of alternative care options. So for this document, the SCI and HRS collaborated to conduct an original systematic review to formulate guidelines using the GRADE approach. And this guideline panel was coordinated and sponsored jointly by SCI and HRS, and so the oversight was provided by the SCI Standards and Guidelines Committee and the HRS Clinical Documents Committee. And both societies each vetted and appointed individuals to the guideline panel, and both societies also appointed an equal number of researchers to conduct the systematic reviews of these evidence, and this forms a separate technical review team, which they are non-voting authors. So these are the personnel involved. The guideline panel assesses the evidence and voted on the recommendations, so there were seven SCI members and seven HRS members. And a technical review panel identified and reviewed this evidence, and there were three SCI members and three HRS members appointed. And methodological support was provided by a nonprofit organization, the Evidence Foundation. So this guideline panel, with the support from the methodologists, formulated each clinical question using the GRADE approach, and each question utilized the PICO format. So we identified a specific population, the intervention, the comparator, and the patient important outcomes. And these outcomes were then rated numerically for their relative importance on a scale of 1 to 9, and only the critical outcomes of 7 to 9 were included in the final list of the PICO questions. And these PICO questions were then further reviewed by the technical review team. So it's quite a rigorous process. So SCI utilized the GRADE methodologies, right, which stands for Grading of Recommendations, Assessment, Development, and Evaluation. So the writing group endorses a number of the domains here listed, not just the quality of evidence, whether this is a randomized trial data or observational study, but also looks at the balance between desirable and undesirable effects of the intervention, the magnitude of benefits and the harms, and also taking into consideration patients' values and preferences, the feasibility of doing these interventions, the acceptability, health equity, cost, and also resource use. And if a decision is not unanimous from the panel, then it goes to a voting majority. So the guideline panel produces the recommendation of strong or conditional recommendation as well as the level of certainty of evidence. And the ranking of these evidence are listed here. So from high, moderate, low to very low. So high would be a strong, large randomized trial data supported by that, and the panel would be very confident that the true effect is similar to the estimate of the effect. So very low certainty of evidence would be when the panel has very little confidence in the effect estimate. In terms of the recommendations given, so these are either strong or conditional recommendations, and what implications means to patients, clinicians, researchers, and policymakers are the following. So for a strong recommendation, it means that most patients would want the recommended course of action, and a formal decision aid is likely not needed, and usually the strong recommendation is supported by credible research or other convincing judgments, and these recommendations can be adopted as a policy in most cases. For conditional recommendation, on the other hand, is more uncertainty. So for patients, majority of patients in this situation would want to suggest the course of action, but many would not, and so there would be different choices that may be appropriate for the individual patients, and this typically additional research would help strengthen these recommendations, and then from a policymaking perspective, this will require substantial debate and involvement of various stakeholders. So what this means, in summary, is if we gave a strong recommendation, that means the writing group is confident that the desirable effects of an intervention outweighs its undesirable effects, and most patients will be best served by the recommended course of action, then the document in this statement would write, the writing group would say recommend or clinicians should do this. For a conditional recommendation, the desirable effects of an intervention probably outweighs undesirable effects, so not all patients will be best served by the recommended course of action, and this decision is sensitive to individual circumstances, values, and preferences, and so the writing group would write suggest or clinicians might do this. So in terms of the clinical questions, so the writing group, the guidelines panel, started with 12 clinical questions that were structured in a PICO format, so this is really identifying the questions into population, intervention, comparative, and outcomes. So the 12 clinical questions are listed on the table on the left, and of these, we prioritize the highest eight ranking ones for inclusion in the document. So for instance, for LAC versus oral anticoagulation in a PICO format, we're looking at a patient population of patients with adult, with non-valvular AFib, and the intervention is LA occlusion, and the comparator is OAC, and then the outcomes that are ranked critical were stroke, periprocedural adverse events, pericardial effusion, quality of life, bleeding, mortality, and cost of care. And to address these PICO questions, formal search strategies were performed. The databases searched were Medline, OVID, and Cochrane, and overall, over 3,700 references were reviewed, and I won't go into the details of systematic review process because Dr. Cronin will go over this, but this really helps develop the evidence profiles for each of these PICO questions, and this process took six months. And following that evidence review, we conducted four two-hour conference calls in June and July last year to review these evidence, and not only reviewing these trial evidence, but also reached judgments on other factors, as I mentioned earlier, from the GREAT approach, which looks at patient values, resources required, feasibility, equity, cost effectiveness, and acceptability. And what this means in the framework, for instance, we're looking at LAC versus OAC, we will look at the desirable effects of the procedure, the undesirable effects, certainty of evidence, patient values, the balance of these effects, resources required, cost effectiveness, health equity, feasibility, et cetera. So for each of these PICO questions, we went through this framework of assessment. In terms of rules for quorum and consensus, so a quorum of 11 authors must be present on these calls, and the agreements on these recommendations must be unanimous. If it's not unanimous, then we would go into a formal voting. And at any time, anyone may send a message to the Evidence Foundation or SCAI and HRS to call for a formal vote as well. So if we go into the formal voting, the rules are strong recommendations require 75 percent agreement. Conditional requirements require a majority with no more than 20 percent preferring a no recommendation. And then these draft recommendations were circulated and then finalized by a survey. So this was the peer review process. So far, we've had public commentary and invited peer reviews between January and March. And we received approval from the SCAI Standards and Guidelines Committee in April. And currently, the document is under review by the HRS Clinical Guidelines Committee, and this will then go forward to the SCAI Executive Committee and then submitted to journal for potential publication perhaps in June. And I'll finish here. Yeah. Next, I want to invite my colleague, Dr. Ed Cronin, from Temple, who will talk about the LAC technical review, uncovering the evidence. Thanks very much, Julian. Bear with me as I catch my breath and catch my bearings, just running from another session. So I was at the honor of serving on the technical review panel for this guideline. Here are my disclosures. So why would we have a technical review panel? There's a few different ways you can analyze the literature when you're creating a guideline. The more conventional or traditional approach, or less formal approach, has been for individuals to be assigned a particular section, and they usually work in pairs, do a literature review, and construct an evidence table. And then the approach has been to look at the evidence table and say, what can I say based on this table? What can I say based on these data? What kind of recommendation can I draft? And then draft the wording, which then goes to usually multiple rounds of discussion and voting. You can also rely on an external systematic review, which could be commissioned specifically for that particular clinical document, as in the example in the middle, or it could be relying on an existing high-quality systematic review that wasn't specifically for that document. The GRADE process, as I think we've heard outlined, takes a slightly different approach. We kind of start the other way around, in essence, and the writing committee actually sets several PICO questions. So that's patient intervention, comparator, and outcomes. So very kind of specific questions. These questions are then given to the technical review panel for formal evidence review, which is more like a formal systematic review. Then evidence profiles are generated from this systematic review, and those are then sent back to the writing committee to formulate recommendations. So I'll just take you through, you know, what's involved with that using this as an example. So we screened evidence for eight different PICOs, and you can't read this slide, so I'll just highlight a couple of important figures. So we screened 3,615 records, so pretty time- and resource-intensive. We retrieved 178 full texts for review. And then at the end of the day, these are the numbers of studies that were included in the review. So 31 in total, although with some overlap, some contributing to more than one PICO question. One of the questions we found zero papers that was, you know, of relevant and of relevant design, et cetera. After identifying all of these papers, they're then assessed for risk of bias using some very, again, very kind of standard and standardized tools. As you can see, randomized studies tend to have a lower risk of bias. These are the randomized studies on the left. And the non-randomized studies, of course, are more kind of inherently liable to risk of bias. And this bias, again, is assessed based on formal categories, such as confounding, selection of participants, for instance, consecutive persistence versus non-consecutive, and so forth, missing data, et cetera, et cetera, and graded this way. And what we end up with at the end is this kind of evidence profile where you can see, you know, it's not just a list of studies, but more a systematic review, and in some cases, meta-analysis of individual studies giving us particular absolute and relative risks, et cetera, effects. Those are then graded by certainty as well and importance, which is very important, I think, but also very difficult decisions to make. So what's important, what's not important, you know, how many strokes per 100 patients are important. Of course, we're always going to say, like, every stroke is important, et cetera. And this process takes quite some time, obviously, and quite some work. Looking at it again, the certainty of evidence has to be graded, and this is, again, formal headings, such as inconsistency, indirectness, and imprecision. You can rate certainty up or down, again, according to pre-specified criteria. I think we found with the GRADE approach, it's very easy to rate certainty down and a little bit harder to rate it up, so you kind of tend to end up with lower certainty in most fields. So while we're doing all this task, you might ask, what's the writing committee doing? So as we're going through our 3,600 abstracts, I'm only joking, of course. They're working hard, too. Again, just to look at certainty of evidence, and I think this is key, just when you're reading this guideline to kind of compare it to the formats that we're more used to, the kind of AHA, ACC format, which HRS has also used historically to date. We're used to looking at class of recommendation and then level of evidence. So the class is an assessment of risk versus benefit, where interventions that have a benefit that greatly outweighs the risk are labeled as class one, and so on and so forth. And then we look at the level of evidence, level A, B, C, et cetera, where A is at least two randomized controlled trials of high quality. B and R, for instance, which is a common level, is randomized studies or studies not meeting the higher levels, et cetera. Whereas in the GRADE approach, it's a bit different. Certainty is classified as high, moderate, low, or very low based on how certain we are, how confident we are that the true effect is very close to the estimated effect that we've come up with. And then the recommendations are graded as either, as I think we've just heard, recommendations are graded as strong recommendations or conditional recommendations rather than, you know, class one, two, three, et cetera. So GRADE uses a more, you could argue maybe a more holistic approach where you integrate both the quality of evidence, the balance between risks, harms, burdens, patients' values and preferences, and resource use. I would say it's not necessarily, you know, better or worse, or I wouldn't necessarily think of it that way, but just a different way of doing it from the kind of ACCHA format that we're all very used to. So lastly, I'd just like to acknowledge the technical review panel. Some members are here today, especially, you know, support from Sky, from Chelsea Arma and Scott Firestone, from HRS, from Angela Fix, who's here, I think, as well, and we were guided throughout this whole process by the Evidence Foundation, especially Emily Sonnerth, Rick Morton, and Niamh V. Faltheater. Thanks very much. All right, great. Now we'll actually get our recommendations, proposed recommendations. So Dr. Gerald Naccarelli from Hershey, Pennsylvania will present those to us. Thank you. So Iíd like to thank the organizers for allowing me to present the overview of what we found. So youíve seen some historical perspective that there were large guidelines published several years ago, of course, by the time theyíre published there are several years of data. The approach that was used was a little different as already presented to you in the previous two recommendations and you could see the large number of people that were involved here. Sorry. Okay. Youíve already seen this, Iím going to skip over this because I wasnít sure it was going to be covered and weíre going to get right into some of the questions that were asked. I think what youíre going to find a little bit is in life thereís no certainty. So the first question that was asked was in adults with non-valvular atrial fibrillation should left atrial appendage occlusion be performed rather than no oral anticoagulation? And the recommendation of the panel was for patients with non-valvular atrial fibrillation and contraindications to anticoagulation. The guideline panel suggested that left atrial appendage occlusion over no anticoagulation. It was conditional with very low certainty of evidence. You know, thereís some remarks here, you know, some patients may wish to avoid the procedural risk of a left atrial appendage occluding procedure while most would likely wish to reduce the risk of embolic stroke. Clinicians obviously need to discuss the risk of the procedure versus the ongoing risk of thromboembolic events associated with no treatment. Obviously the procedure may be inappropriate in certain patients, for example those with less than one year life expectancy. One of the frustrating things despite all the work that was done as from the previous presentation is thereís really a dearth of controlled prospect of randomized data to help the panel, you know, to make more than a conditional recommendation with a very low certainty of evidence. The next question we approached was in adults with non-valvular atrial fibrillation, should left atrial appendage occlusion be performed rather than OAC? And our recommendation was for patients with non-valvular atrial fibrillation who have decided to pursue treatment. The panel suggests either left atrial appendage occlusion or oral anticoagulation. Again this is conditional with a moderate certainty of evidence. Obviously thereís some remarks, you know, itís going to be patient-centric. Patients with contraindications to oral anticoagulation as listed would reasonably prefer treatment with a left atrial appendage occluding device over chronic anticoagulation. And again, there may be certain subgroups of patients, for example, with short life-term expectancy that it would be inappropriate to do an invasive procedure. Just as an aside, thereís three randomized trials of patients addressing this issue and you can see the data is somewhat encouraging although somewhat mixed. The reduced risk of all-cause mortality, the hazard ratio was .76, no significant difference in stroke, 1.05, major bleeding .88, reduced the risk of hemorrhagic stroke, that was the largest reduction obviously without anticoagulation, and a non-significant increase in the rate of ischemic stroke, so a little bit of the good and the bad, you know, depending on which way one goes. There were a lot of imaging questions that were raised on the routine imaging thatís done prior and post-storing and post-procedure. So the next question was in adults with non-favoritrile fibrillation who undergo LAAO, should CT or TEE be performed prior to the procedure versus no imaging prior to the procedure? And the panel suggested that obtaining pre-procedure TE or CT instead of omitting the procedure. Again, I think this is pretty routine, however, based on the data it was a conditional recommendation with very low certainty of evidence. What about the role of intracardiography guidance rather than using TEE during the procedure? Again, the panel suggested that either ICE or TEE imaging during the procedure is rational, but again, a conditional recommendation and with low certainty of evidence, again, based on the lack of strong clinical trials to look at this. Additionally, there may be some clinical caveats, patients who prefer to avoid general anesthesia and the invasiveness of TEE might prefer intracardiac ultrasound. Next question was for patients, should clinicians prescribe post-procedural OAC versus antiplatelet therapy? The panel suggested either OAC or dual antiplatelet therapy for patients undergoing the procedure. This is, again, a conditional recommendation with a low certainty of evidence. There are patients with more significant contraindications to therapeutic oral anticoagulation and they may be reasonable to select dual antiplatelet therapy. We decided not to make any recommendation about the use of single antiplatelet therapy versus any other antithrombotic regimen because of the knowledge gap. The next question was about follow-up TEE or CT imaging be preferred over no follow-up and the panel suggested that post-procedure TEE or CT, again, conditional recommendation, very low certainty of evidence, although as you're going to see, this is pretty routinely used at this point. Regarding the question of what to do with patients with post-advice leak of any size after undergoing the procedure, should oral anticoagulation be preferred over no oral anticoagulation, the panel actually makes no recommendation regarding the use of oral anticoagulation in adults with a PDL after occlusion because of the knowledge gap. There's like a single study where the rate of PDL of any size at 45 days was 41 percent, so this is a problem, decreased to 32 percent at one year, no difference in clinical outcomes associated with the presence or severity of PDL, no difference in the composite of stroke, systemic embolism, and cardiovascular and unexplained death. So given some of the knowledge gap, although this is an important clinical question, the reason for that may be lack of recommendation. What about patients with device-related thrombus after going to procedure? Should indefinite oral anticoagulation be preferred over no oral anticoagulation? The panel suggested oral anticoagulation rather than no oral anticoagulation. Again, this is a conditional recommendation with very low certainty of evidence, and they made no recommendation about the optimal duration of oral anticoagulation and the timing of repeat imaging to assess for PDL and DRT because of knowledge gap. Of note is DRT resolution was not significantly improved with the use of oral anticoagulation. You can see the hazard ratio is 1.13, crossing the confidence interval of one. The rate of major bleeding, not significantly different, although higher with anticoagulation. So small sample sizes in the presence of confounding variables leads us to a low certainty of results for this important question. So there's a decision pathway, I think, of what people are doing. This is kind of a figure in the paper, and it basically, you know, shows that if you have non-valvular atrial fibrillation and you're able to tolerate an OAC, whether you can get in this pathway or not, versus those that have a contraindication. And it basically shows, you know, right now this is what's pretty routinely used in just about every lab, you know, with pre-procedure imaging, intra-procedure imaging, post-procedure imaging, looking for leaks in thrombus. And then post-procedure antithrombotics based on PDL, again, we're making no recommendation right now for device-related thrombus. We're suggesting oral anticoagulation with conditional recommendation and low certainty, and with no complications, whether to use dual antiplatelet therapy or oral anticoagulation, again, a conditional recommendation. So we're going to present some cases that may bring in the real world, I think, as we discuss in the panel. We'll probably make some more editorial comments. Thank you. So next, we're going to have two presentations that are going to emphasize cases. So while guideline is something that tells you how to do something right based on evidence, it's almost not as binding as a rule, but it's almost next to a rule. So what I'm going to do in my talk is really not follow the guideline. And how there are a lot of cases that we do in the real world that actually fall outside of the fringes of the guidelines. So here I have a total of three cases, which I'll try to quickly wrap through. And I'll try my best to get through this. So up until the next set of guidelines come through, this is kind of what we have from the 2023 AAPIB guidelines. You have patients with moderate to high risk for stroke, chastise risk of more than two. Those who have a contraindication to long-term oral anticoagulation due to a non-reversible cause percutaneous LAO is reasonable is a class 2A indication, right? So these are basically long-term anticoagulation contraindicated patients. And then you have a subset of patients in those who have a high risk of major bleeding in oral anticoagulation. Percutaneous LAO may be reasonable alternated to oral anticoagulation. This is a class 2B indication. So this is a definite major positive shift towards the utilization of LA closure devices. And then if you look at the 2023 practice guidelines for cardiac surgical exclusion, it's a class 1A indication because they're already there. Basically taking out the appendage or clipping it and all of that is relatively straightforward. So it's a lot less restrictive and a lot more open than what we actually see in the percutaneous elective procedures that you see in these cases. So let me present you a clinical vignette one, 65-year-old male with a history of persistent AFib, chastise risk of four, tachycardia associated to cardiomyopathy, large atrium, 150 cc, failed to enter with drugs, presented for catheter ablation, gets a successful ablation. And then there are triggers localized to the base of the LAA, which were mapped and ablated, focal ablation of the left atrial appendage base. There were more triggers deeper in the LA body that were not targeted, and the patient was sent home. Obviously, what do you expect? The AFib comes back, right? So what should we do next? Option A, perform a LAO with an endocardial device and stop the river oxaban, and continue antiretroviral drugs. Actually, this patient has something else going on, too. That's what. Hold it down again. Sorry. All right. So this is what happened to this patient, and this patient actually had significant amount of GI bleeds. And what also makes it more kind of complicated is the patient had critical medial ADL disease and a PTCA with additional anti-platelet therapy was added to it. And his bleeding complications really became more obvious after all of this got added on, and there was evidence of AV malformation in the duodenum requiring – gosh, this moves a little more sensitive. So is it a choice of subcutaneous octetide to help shrink the AVMs? Do you want to stop the flecainide and start on class III agent? Consider a lariat LAO ligation or an atroclip to really address the potential arrhythmogenic source. Consider a redoablation and concomitant LAO with an endocardial device, right? So how many of you would choose D here in the audience? How many of you would choose E? Okay. So, I mean, between the two, they seem to be reasonable, but then, again, you really have this active AV malformation issue, and that's a nuisance. I mean, once you have AV malformations in the gut, there is no predictability to where the new AV malformations are going to happen. We have some temporary success using octetide to really transiently shrink the AV malformations that sort of buys you some time, and then you can work through your potential appendage occlusion strategies, whether it's an epicardial or endocardial. In this case, I decided to go with a lariat. This is something that I'm relatively familiar with and I'm pretty comfortable with, and so here is I'm going to show a skinny lariat technique. This is a new approach. So what we're trying to do here is you do a transeptal puncture and epicardial access routinely through anterior approach, and then you put a pigtail into the left atrial appendage, and that pigtail basically lifts it up. So within the pericardium, you have an appendage with a pigtail in it that really lifts it up, and you pass the lariat loop over it. In the previous iterations of how we used to do this, you used to have two magnets, one endocardial, one epicardial. These two magnets used to attach to each other, and then you use that as a railing, and then you pass this little lasso over it in order to go and capture the left atrial appendage. With a skinny technique, you essentially took out all of those magnet business and you really minimized the potential for complications, and thereby you could actually get over the appendage relatively easily, close it off, tension it. Once you are happy with what you got, you basically cut the suture, open the fob, and then your procedure is basically done and the appendage is closed. You leave the drain in place for 24 hours, and what you hear is basically a small nubbin that really endothelializes nicely, and then you're done with the procedure. Patients usually go home after 48 hours. So this really addresses the arrhythmogenic issues. So this is the data from the AMAZE clinical trial. Excellent closure, even though AMAZE didn't meet its primary endpoints. The subgroup analysis clearly shows that for those patients who have a large left atrium body, the addition of the appendage exclusion with the laminate actually is very effective and helps you with almost 15 percent drop in the recurrence rate. So that's something that is outside of the guidelines. I have an 88-year-old that has permanent atrial fibrillation, chaste vascular five, large atrium, multiple fibrillations, large appendage thrombus with repeated showering strokes. So we tried pretty much everything that one can actually try. I mean, apixaban for three months, then dabigatrin for three months, warfarin, and even subcutaneous enoxapirin. In all of this, it took about 12 months for this patient. So we're constantly trying to stick to the guidelines here, and the guidelines are not really working, and the patient is really continuing to have showering embolizations. In the meantime, there is no new functional deficits, but again, she enjoys a robust quality of life. So after a long discussion, the family, patient, extended family members, we decided we're going to go after this clot. I'm going to skip to this. So what you see here is a hunkering clot. I did a little bit of MacGyvering here. I wanted to protect the patient from the embolization that happens during the process of the clot retrieval. We took a Watchman device, cut the base of it, and we crushed the anchors. And we used it as an umbrella that goes and says, again, don't try it in your garage. And we deployed this right in the ascending aorta, about the level of the coronary, so that it actually acts as a second layer of protection. And then we did deploy the cerebral protection device into the carotids. And we used two transeptal sheets, one for the amyloid delivery and one for the suctioning of the clot from it. So you should have your second sheet ready to go in the event if there is a problem here. So what we did here is we got the amyloid device loaded up, ready to go. We took that sheet very close to the appendage of the clot. You have to remember, most of these clots are actually pretty fibrinous and concretous. They don't just come off just like that. They're not fluffy clots, right? These are the organized, almost near-fibrotic clots are the ones that don't come out that easily. So you have to really go in. And you've got to get onto the clot. And then you can use manual suction to really get that clot in. And it takes a few attempts, right? So once the clot is completely suctioned out, it really opens up. You can deploy the device. So we were ready to go in with this. So you can clearly see that the clot is clearing out here. We deployed the amyloid device nicely. And we are able to get this patient off of anticoagulation. In the end, this is what we sucked out of that appendage. It's almost like a 20cc worth of clot that was present inside of that. So we'll move to the next case. Here is another interesting case. Patient had a post-Watchman peridivis leak, right? And there was a debate about whether we should do a coil, a plug, or what else, right? And a lot of us here have been used to the idea of doing coils. We also do radiofrequency ablation to create a little bit of endothelial denudation and allowing for the tissue growth to happen. In this case, we took a very creative approach, where we used, actually, the skinny technique of Lariat, where we went epicardially. And I was able to, actually, this is a case from Rudy from Wisconsin. So we talked about this particular case. And he was able to basically take the Lariat over the Watchman device and get onto the neck and tightened out the suture very nicely until the leak completely disappears, right? And then once you deploy the suture, you basically tension it, release it, and then all of a sudden, you have achieved complete closure of it. So it's a much more elegant way of closing a PDL in this type of scenarios than otherwise. So I just wanted to share these three cases. And yes, these are completely out of guidelines. But again, this is kind of sometimes you have to step out of guidelines to take care of these patients. Thank you. Thank you, DJ. Our final speaker will be Jacqueline Joseph from McGill University. And she'll also be presenting us another case. Or three. No, no, no. Three. Just one. OK. Oh, that was incredible. Wow. What nice cases. So I'm going to go a little bit more toward the guideline. All right. We're going to talk about device-related thrombus, which is really the elephant in the room. Thank you again for the invitation to speak today. These are my disclosures. Okay, to scan your�to submit your question. I think we have a polling question. That�s why. So this is a 78-year-old female with persistent atrial fibrillation, hypertension, and a previous TIA. She had recurrent upper GI bleeds on rivaroxaban, and then had the same issue when tried on apixaban. She underwent an uneventful left atrial appendage occlusion, and she was given DAPT for three months and then aspirin alone. And that�s her four-month post-implant TEE, looking pretty good. And then she had a TIA recurrence at 12 months, and we repeated the TEE. And you can see here a lovely device-related thrombus sitting there. So polling question. Now, how would you treat this patient now, and when would you re-image her? A, oral anticoagulation for three months and then re-image. Don�t forget, she had these upper GI bleeds, so you�re kind of taking a little risk. And then DAPT lifelong, OAC only for six weeks, then re-image, DAPT lifelong. Lifelong oral anticoagulation with re-imaging at three six-months. DAPT for three months. You can just see the number of potential options here. Lifelong DAPT or none of the above. Just a poll. Maybe just spend � I don�t know if anybody�s using the poll. So I�ll just move on. I don�t know how to see the end of that poll. But anyway, okay, so you get the idea. So the questions we have are, what�s the incidence of DRT and its relevance on clinical outcome? How should we treat these patients? And what�s the optimal time to re-screen for the resolution of the device-related thrombus? And so when we look at healing and endothelialization after left atrial appendage occlusion, it�s really misunderstood. But in total, we have an acute prothrombotic state that�s triggered by direct exposure of the device to the circulating blood, an endothelialization process, and then this long-term kind of stable phase where we develop a neo-endothelium over the device. And, you know, there�s not much study to this, which is surprising. One nice study coming from Quebec City looked at platelet activation and coagulation activation, and this is day seven, so baseline day seven, 30 and 180 days. And you can see that early on there�s this high level of coagulation around day seven before it tapers off. So that�s something to say for what potential anticoagulation we should be giving these patients. And, in fact, this is a really nice report by Dr. Ellis here, but this was a report of two patients, and they didn�t have any clinical events. The first patient on the top, an amulet device, this patient underwent a heart transplant two years later, and so they looked at the actual device. And here below was a Watchman device. The patient had an unrelated death eight months later, and then they looked at the device. We�re going to go a little bit deeper into what these look like. So this was the Abbott amulet device. This is just where the device was taken out, so that�s not really related. But when you look at the endothelialization process here, you can see that that attachment hub is not really covered, and there�s a lot of bare areas that are not covered with endothelium going forward. And when you look even closer, electron microscopy, you can see these areas where there�s not a uniform layer. You see all these disruptions where clearly potential thrombus may form, and here is showing these blood cells appearing even on this specimen. Similarly, with the Watchman, there was, you know, areas that were not covered at all with an endothelialized area. So this is something to really consider, you know, in certain patients when you�re taking them to left atrial appendage occlusion. And so when we look, and this is a very busy slide, but I�m not going to go through it all. All I want to say is that when we looked at the guideline to see whether we should apply oral anticoagulation for the treatment of device-related thrombus or no, we really looked at these four or five studies, and however, there was one recent study that just came out by Dr. Laccaretti, which is also important to consider. And we�re going to go through just the big trials, the big three of these to understand how we should be treating these and how we should be looking again if there�s resolution yes or no. So the first one was by Samal and Jack in 2021, essentially looked at 37 centers and collected their cases on DRT, a total of 237, and they matched those to kind of the timing, similar timing, similar patients around the time that they implanted these devices. And you can see that the DRT diagnosis, 65 percent were made within the first six months, but 36 percent were diagnosed after six months. And again, there was � when we looked at what those patients of DRT received post-implant, there was really no difference between DRT or controls, between what they received, SAPT, DAPT, oral anticoagulation. Most patients were, in fact, on SAPT or DAPT at the time of the DRT diagnosis, makes a little sense. And obviously management, most patients were put on an oral anticoagulation if they were capable of taking one. And finally, the long-term management, so these patients who normally don�t, shouldn�t have to take a blood thinner now all of a sudden are taking blood thinners, 19 percent were on an oral anticoagulation long-term. And of course, the outcomes are sobering, twofold increase in major cardiac events, 15 percent death if you had a DRT versus no DRT, 17 percent ischemic stroke, 7 percent major bleeds, and 25 percent had continued presence, so no resolution of that DRT, at least in this follow-up. Again, not randomized data, but a large registry. The second trial, the Euro DRT, sorry, European and Canadian DRT registry included 156 cases. This is just looking at what anticoagulation was given. Overall, patients were on DAPT, but when they were diagnosed with DRT, they went on to oral anticoagulation. Again, a higher mortality, less resolution, not that much resolution, sorry, 20 percent, no resolution of DRT in follow-up. So again, another large registry of these patients. But what was, in patients who didn�t have resolution of their DRT, they had, as compared to those who had resolution, you can see the much higher rates of stroke and death in these patients. So this is really an area that we really need to focus on the new, when we�re developing new anticoagulation devices, this is something that we really need to pay attention to, and it would be nice to talk about this during the panel discussion. And finally, this beautiful study came out looking at the DRTs in the Amulet IDE study comparing Amulet with Watchman, and you can see, well, what they did very nicely is on the imaging, they risk stratified patients on the imaging to high risk, so these were huge device DRTs, doesn�t matter Amulet or Watchman, they were big ones, versus low risk. And so high risk classified was pedunculated morphology, if it was mobile, if they were large, three millimeters or more, and if there was no continuation, so it wasn�t necessarily laminar on the left atrial wall. And then the total incidence of DRT was 3.3 with the Amulet and 4.5 with the Watchman 2.5, so a little bit older version, and the majority of the high risk DRTs occurred over 45 days after implants. The outcomes, not surprising, the risk of having a DRT was much higher for any MACE, and most high risk DRTs were unresolved, despite treatment. But very importantly, patients with low risk DRTs had no clinical events, and these ones resolved quite nicely. Again, big slide, but this is really important. What I want to kind of present here is that each patient has their own healing process. I don�t think you can give a recommendation, a general recommendation. I think that it has to be personalized. Unfortunately, there�s no clear guideline that you can give. You can see early, you know, the ones who have an early DRT, those pretty much resolve, and same thing with the Watchman. Early, those resolve. The ones who are late, those ones have developed a high risk of cardiac death and stroke. And there�s many risk factors that we can look at, clinical risk factors, so on and so forth. And then overall, and this is, you know, these are all the different gaps, you know. The orange boxes are really the gaps where we still need a lot of evidence. We have no evidence, not much evidence for. And I think where we�re heading now, so oral anticoagulation versus DAPT, we don�t have too much of a recommendation as was discussed previously. Timing of follow-up re-imaging, it�s not clear, but I think we probably need an early imaging and a late. And then when we do detect the DRT, as per our guideline, we do favor oral anticoagulation versus no oral anticoagulation. And the next subset might be, based on the study from Dr. Cohn already, is whether we can re-stratify these patients to high or low risk on the imaging, and therefore decide whether we give them either oral anticoagulation or perhaps if they�re a low risk DRT on imaging with a high bleeding risk, perhaps only a short course of anticoagulation or conservative management. And then again, the timing of follow-up imaging still remains to be determined. And so that�s where we received, where we went ahead with the recommendation already mentioned. And I think I�ll stop here for sake of time, but those are my conclusions of the presentation. Thank you. Okay, great. So we definitely want to open this up to discussion. I want to take a step back just for a second on the big picture, lest you think that clinical guideline recommendations don�t actually apply to cases you�re doing. This is a perfect example where the guideline like we have three specific blind spots that we made no recommendation on, and we actually just touched on like all three of them. You know, bare devices that don�t endothelialize, probably it�s not safe to stop anticoagulation, but there�s no, we have no data to tell you which patients you need to remain on anticoagulation like indefinitely and which ones don�t. Patients with peridevice leaks, again, we made no recommendation because there�s no real convincing data that you have to treat every leak, at least not from what our current studies show. And then the other is single antiplatelet therapy. No recommendation hasn�t been compared really well enough to adapt or oral anticoagulation. And when you bring up back to the DRT questions, you know, it makes you concerned. Maybe you could stratify some way patients you knew would be safe to use for single antiplatelet therapy, but certainly in my practice, and I think I would ask the panel and others, you know, we do routinely a TEE in the early healing period, which is generally sort of six to 12 weeks after implant to decide about early cessation of anticoagulation, but we always bring patients back for a one-year imaging. And it is not surprising to find DRT on a one-year follow-up in the absence of any clinical event. And so then the question is, well, what, you know, so would that just resolve on its own? Do you have to treat everyone or do you have to aspirate the clot off and, you know, clean the device and start over again? It�s a tough question. But I want to start just with the panel. What�s your usual post-implant imaging follow-up regimen? Because even that, we didn�t have a strong consensus on how best to follow these after implant. Maybe start with Jackie. Sure. Go for it. I mean, you just hit the nail there, right? It�s�there�s no consensus. I mean, we do�I do generally a CT follow-up at three months, and we don�t routinely do another repeat at one year unless there are features on that first scan. So if there�s, you know, incomplete, there is still contrast getting in, then we would repeat that or other features like deep implant or imperfect implant. Yeah. I mean, we sort of do a first CT, mostly CT. We used to do T�s before, but now just it�s a convenience issue. Barring renal issues and contrast allergies, we go with the CT between six weeks to 12 weeks because most of the times it�s probably hard to get them in accurately right at six weeks. And then we routinely do a 12-week for the very same reason. I think that observation study where they had this 25 to 30 percent of non-resolvable DRTs actually come from DRTs that happen for a long period of time, and then you incidentally happen to bump into them because you did a CT or a T for something else, and then all of a sudden there is this hunkering clot on it that�s actually fibrosed. And those are the ones that are extremely difficult to get rid of, as you have seen it with the non-appendage closure device-related thrombi that you see. So I think if a patient�s device is screened at 12 months and is nicely endothelialized based on flow patterns and contrast through, the risk of DRT in those cases is relatively lower than those that are not properly endothelialized. So I think 12-month CT, in my opinion, is an important strategy. I don�t think I have anything to add. Remember, a lot of these imaging recommendations came from the trials, and then people just continued that because it kind of worked, right? So 45 days, and so I�m seeing in practice that sometimes the one year is not being done. People are doing the 45 days, six, seven weeks, and then if they�re okay, they�re just letting them slide. Now, I�m not sure�you know, we have cases that were presented here where that�s a problem, you know, but again, we�re not seeing it as clinical. The question I was going to ask DJ is how many sites now are kind of skimping on that one year, but I agree with him. I think the advantage right now with what we know is if you can get that one year and things look really good, you may not be home free, but you�re almost home free, and you feel really good about things. So I like the approach that he�s taking. I find the CHAMPION trial is actually doing a good job with this. A four-month�so they�re giving anticoagulation for three months, and then at four months, they do a T or some kind of imaging, I forget, and then at one year as well. I think that�s properly done, and all trials going forward probably should consider some type of�you know, because we�re just getting�we don�t know what the true incidence of these are and what the clinical relevance is sometime. And I think it�s�I just want to say one thing, though, I forgot to mention, is that it really shows that we really need to develop newer materials and newer�for left ventricular appendage occlusion, and this is a really good thing for companies to do. I think it�s a very important step. Ed, did you have a comment? So I�d provide a little counterpoint, actually. We do a 45-day TE, and if that�s fine, then we don�t do anything further. And I would say the rationale for that is all that we�ve discussed, we don�t really know what to do with these patients. Many of them can tolerate indefinite oral anticoagulation. The clinical significance is unknown, so we don�t look unless there�s a reason to look. One of the social Q&A questions came up, and this, I think, is important along the same topic, just to wrap it up on it, is do you use CYP2C19 phenotyping to guide post-implant drug regimen, that is to say, tailoring the regimen to the patient�s degree of plavix resistance and that type of data? Well, we routinely don�t do that, but I do agree that the incidence of the plavix resistance is much more higher than what we think it is. There�s actually a shift in thought process in the post-procedural regimens, that there are a considerable chunk of us that are slowly moving towards a half-dose DOAC approach, which I think is much better, less bleeding risk, and as it is clearly shown in both non-randomized and observational and randomized trials, that a half-dose DOAC actually probably is a better choice, lower risk of bleeding, and much better risk of DRTs. I think that strategy should be seriously thought about. Certainly need more data on that. We have a question from the floor. Quick question. I�m sorry. Dan Leskowicz from UVM. I came in a little late. You may have talked about this. The latest iteration of the Watchman device uses a charged fabric, the idea that it�s going to be coated with albumin. Was that discussed? Are there any data suggesting that this has any meaningful impact on device-related thrombus? I mean, that�s probably a hot topic. There is the HealFlex registry, which certainly has that as a single-arm study, just looking at DRT rate, but it may not necessarily be reflective of the patients that we�re worried about, but I would say at this point it�s not. I�ve seen plenty of DRTs on a Watchman Flex Pro. It�s not, like, inevitable or, you know, impervious to it. There is the ongoing Simplify study, which is randomized patients to aspirin alone, DAPT for six months, and or half-dose DOAC, right, for three months, I think. So we will get that answer, I think, including DRT incidents. The paradox of that was, after we switched to the coated Watchman Flexes, I had my first DRT on my third case. It�s like, okay, I mean, I don�t think it�s got to do anything with anything, but I think it�s more of a patient mainly than other things. What do you think, Jack? I think we have a lot of moving parts, and I think one of the frustrations, the process that we took to look at these questions was very detailed, and what was very frustrating was because there�s case series, non-randomized trials, second-generation devices, ongoing trials, ongoing trials that stopped because they weren�t enrolling because people said, �I�m too busy to enroll because I�ve got to do three of these devices tomorrow.� And the same thing happened with AFib. If you think about everything we did, it�s kind of what happened with AFib ablation. Cabana was about 20 years too late. But there�s a lot of moving parts here. You raised the clopidogrel question, right? That�s an argument maybe just to not have that, but we don�t use the other antiplatelet drugs. They weren�t ever used in any of the trials, so people kind of just kept doing what was proven from the trials, which I think is actually a good idea, right? But now people are doing more and more things that were different from the trials, and now you�ve got new devices, and whether the new device is better or the same, who knows, right? And then you see, I think DJ nicely labeled, you can see the anticoagulation is, it�s like whatever they feel like doing that day, you know? And if you�re not in a trial and you�re not collecting that, it�s really hard to make a recommendation. Thank you for an awesome presentation. I favor, not I, but looking at the data, it seems that actually like you already mentioned as well, the lower DOAC seems to be, you know, a half dose seems to be doing better. What I struggle with is patients that are on Warfarin, whether they can�t take DOAC or they can�t afford it, how do you approach that? If you�re stuck with DAPT, what do you do? If GI problems related to angio-dysplasia is an issue, then these are the cases I had a lot of luck with Octeotide. It actually works fantastic. We have a large series of over 400 patients that we�ll be publishing soon here. The Octeotide really shrinks off these AV malformations by working at the vascular proliferative factors, and I find it very, very useful. Within two weeks of starting the Octeotide, a lot of these AV malformations shrink all across, and that really gives you a breathing room to do whatever anticoagulation or anticoagulatory strategy that you require and helps you to get over. I had anecdotal cases where I have put patients on one year-long of Octeotide, and most of the insurance companies now actually cover it. If it�s not a GI issue, if it�s a cost issue or kidney problem, you know, renal function, do you� You can still use Warfarin. So you would discontinue with Warfarin pretty much? Actually the original device, right, was 45 days of Warfarin and then dabbed. Thank you. So I think we�ll probably wrap it up there. It�s 12.15, and thank you for your participation.

clinical practice guideline

left atrial appendage closure

interventional cardiology

GRADE approach

Society for Cardiovascular Angiography and Interventions

Heart Rhythm Society

patient care optimization

evidence reviews

anticoagulation strategies

device-related thrombus