Wonderful talks. I think a really good overview of the key areas and recommendations in this document. And I can see there are a few questions that are coming in. I'll try and address these questions through each of the panelists. One of the very important questions that was raised here is, you know, we've seen a remarkable reduction in complication rates over the past decade with this procedure. And so the question is, you know, we've always considered that you need to do this procedure in a hospital where there is surgical backup. So is this feasible now, given that our complication rate is generally less than 0.5%, certainly less than 1% peri-procedurally? Can we do this procedure now in hospitals without surgical backup? Or if local transfer is available within an hour? And I'm going to ask Dr. Wisnett to answer this one. Thanks, Jackie. You know, when I saw that pop up, I wanted to go back to the document and see if we addressed it. My sense is that all the guidelines have still suggested that this be done in hospitals with surgical backup. I think that even though complications are rare, they do happen. And I feel like it should still be done with a surgical backup, is my own opinion. But I'd welcome the thoughts of others. Jackie, can I chime in here? Please go ahead. There is clearly a relationship between complications and learning. So I think one of the emphasis on the document was that people early in their learning experience should have more readily accessible access to cardiovascular surgical backup than an experienced operator. And I believe the recommendations from the document that it is advisable that cardiovascular surgical backup be readily available. And I don't think there was an assistance that would be on site, but just be readily available. Jackie, I think there's an important point about this to remember. The left atrial appendage occlusion at the present time is an elective procedure. We don't do a lot of urgent emergent left atrial appendage occlusion device procedures. Occasionally we do, but because it's an elective procedure, we just need to make sure that from the patient's standpoint, we give them the resources to make this be as uncomplicated as possible. And those patients that develop a major complication, to be able to say, we do have some help that is quite close to help bail us out of this procedure that was elective and has now gone south. And the concern is that this goes out to places that do this in patients that are not potentially as well screened and evaluated, like we heard about with CTs and all the other things that we have available. That's been the concern. Absolutely agree, Dave. I think we are all patient safeguards and we want to make sure that this procedure is done safely as being a preventative procedure. So in our document, we've suggested that for physicians who are early in their learning curve and starting to program, they should be in a center that have on-site cardiovascular surgery. And some previous documents by the Europeans have suggested that on-site surgical support is optional if you have to transfer within an hour. And obviously, this is a controversial area, but what we want to make sure that if you're embarking on a procedure and you probably should have surgeons on-site available with more experience, if you have an off-site surgical backup within an hour, that's probably reasonable. I think the key is being safe for all patients, as we've addressed. Vicki, I would ask the panel, all these implanters, who has had tamponade and a perforation among the panel on the call right now? I know I have, but when I talked to the case years ago, I did have a proctored case that we had to have emergency surgery. David, Brian, nothing? Well, you know, Cliff, Jim? Yeah, I definitely have. Yeah. I mean, the rate of embolization in the current era is well below one in a thousand. The rate of perforation, at least in our data from the registry, is still about one in 250 cases. And I would agree, we actually just submitted a paper on the volume-outcome relationship, which is what I was kind of talking about earlier. And I think there definitely is a relationship there, but there's still some risk of perforation, even in inexperienced hands. So, you know, I think it's something that needs to be taken pretty seriously. I think the recommendation among the panel that generated the paper is accurate. When you're early in your experience, you really do need that on-site backup. But as you gain experience and confidence, just readily available may be sufficient. So the history of that goes back to the very first panel days. As you may or may not know, there were three different panels for the Watchman device. They were all for the same indication, the protocol, the device. And with the very first panel, at that point in time, the incidence of pericardial effusion was 5%. People looked at that and said, again, this is an elective procedure. Why are you screwing around? I don't mean that to do something. We then did two more experiences that said that as the volume increased, and as we got better, the patient selection got better, the rates of pericardial effusion have dramatically decreased as Dr. Freeman has talked with us about. So there's clearly a volume, procedural volume outcome experience with that. You also need to remember that not all perforations in, at least in the early experience, related to problems with the left atrial appendage. We looked at, in the PROTECT trial, those patients that had pericardial effusion and did a root cause analysis. And some of the time you can't tell. Some of the time, the pericardial effusion comes from a failed transeptal that you didn't originally realize it was perhaps because it was a small left atrial appendage. You couldn't get it. You couldn't get the transeptal done safely. And so it's not just because we perforate the left atrial appendage itself. You can have perforations from transeptal procedures just on the way. Yeah. We in our EP lab, we've seen perfect transeptals in the middle of the fossa, but you can occasionally have a potential space between the two layers of the fossa as it comes together. And so even though it's a well-done transept, you can get some flow into the pericardial space. So I think the point is just that even in experienced hands, there still can be some risk and you want to cover that, but certainly amongst new implanters, definitely higher risk and having a surgical backup there is a good idea. I have an important question for Dr. Wang and that relates to imaging. One of the more controversial questions that we get a lot is, we know that we need to do the first imaging between 45 to 90 days and that we can do it with TEE or CT. What about a second imaging? What about delayed imaging? Should we be doing it at one year and should we be selective in the types of patients who would require that or should we do it in all comers? That's a great question, Dr. Saw. And the biggest problem is we don't have the answer. Nobody's ever studied it. No clinical trial ever paid for the cost of a post-procedure one-year TEE or post- procedure CT. And it's honestly very hard to convince a patient to even get a 45-day TEE. It's just uncomfortable. We are probably missing some device-related thrombus, but then we don't know if they're clinically significant. And that's a big thing. We don't know what is endothelialization, what is not. Even if we had a one-year imaging and we saw something on a device, there's no way that we can, by imaging without pathology, tell you if it's endothelialization or if it's truly an atrial surface clot. And then with the clinical relevance of that, we don't have any data for it. Well, our current recommendations would be is that if you have a 45-day imaging and you see a device-related thrombus, cite specific recommendations for anticoagulation for that specific patient scenario. But we do recommend that they get a repeat imaging within a month to see if there's any clinical improvement or not to decide next interventions. If there's improvement, obviously that's great. If it's gone, even better. If it's not, then the question is, is it endothelialization? If it gets bigger, obviously something needs to be done then. So there is an important lesson to be learned from the experience with selection of 45 days. It was important because the 45-day window was chosen because at that point in time, you were going to go off of warfarin. That point in time, however, they were still on warfarin. And so people have said that you should do your follow-up imaging at a time that you have the patient on optimal medical therapy, whatever your optimal medical therapy is going to be. But don't do that 45-day study when you're on agents that you're going to then change the next week or two weeks from now. So do it when they're optimally treated for the long term. And some people have said then that should be six months, not 45 days. I agree entirely with Dede that the issue is we will never know what the best strategy is in terms of things like device-related thrombus or potentially even leak because we don't have, by protocol, all patients undergoing the study. At the present time, we do follow-up studies in somebody that's had an adverse event that tells us that they've had an adverse event. It doesn't tell us what those patients that have never had an adverse event, what they look like. I have a question for Dr. Kavinsky. I've been asked this numerous times. And that is with regards to the requirement of recommendations about 12 LA procedures over a two-year period to maintain the skill set. And I think we all probably think this is actually pretty low in number. Maybe I just want to hear opinions about how this came about. And do you think there will be an update to that recommendations soon? Especially we have more than one device currently on the shelf. So this was done by consensus because, as you might expect, there's really not a lot of data-driven recommendations here. The 50 procedures, structural procedures, is based on consensus recommendations from other types of percutaneous procedures like ASD closure, BFO closure. Those numbers were looked at. And then the procedures that involved access to the left atrium through an attack septum were considered qualifying procedures, as well as all the ablations in the left atrium. So the 50 number was garnered off previous documents referring to procedural volumes necessary for doing these procedures. Now, when it came to ongoing experience, there was a careful, there was a lot of discussion on balancing necessary experience against access to care. So there was a careful desire not to exclude people. Therefore, in the interest of not excluding people, the bar was set pretty low. So, you know, 25 cases over a year with 12 involving left atrial appendage closure over two years. So you only have to do six a year. Now, there were people who felt that that was way too low, and there were people that felt it was reasonable. So, you know, this was a consensus decision. Again, not that data-driven, but everyone sort of agreed with it. And this is persistent. So perhaps not the most satisfying answer yet. You know, so many of these numbers that we put for training requirements are fairly arbitrary. And, you know, the SCIA has come out with a new training document which has some volume requirements to it. And I think, you know, they use some of the numbers that we generated to make their recommendations. And I would ask Dr., could I ask Dr. Wong a question? Being the interventional imaging person that she is, does she envision herself doing intracardiac? What does she view as the role of intracardiac echo for guiding left atrial appendage occlusion procedures? And does she envision the sort of the imaging specialist doing ICE themselves? Didi had to drop off. Oh, I'm sorry. So maybe you can answer that question. Well, currently when we do ICE imaging, I do the procedure with myself and my fellows, actually. So we don't have an imaging echo person in the room. And so it's really, you know, that also means that we need to be very facile with understanding the images. And we've been using ICE images for ASDPFO closures for a number of years. So extending to LA closure, we felt very confident. But I think there is a clear learning curve. And there's more technical requirements for doing ICE guided LAC and also understanding the images. So I think for beginners doing ICE guided procedures, they need to correlate their findings on TEE with ICE images as well for at least five to 10 cases. And that is indeed the recommendation from the document, right? That when they start out, they should do both. Yeah. And I think that is absolutely for safety reasons and, you know, to really understand the anatomy well. But should you have an echocardiographer in the room? I think that, you know, obviously for simplicity and efficiency of the procedure and run the lab, if we can minimize having an additional person in there, I think that will be optimal. But I think if you're, when you're starting out learning and you don't really understand the images as well, I think you should have the echocardiographers in there. Yeah, I was just, I was doing that question to be provocative for her. I think in terms of procedures, as we move more and more towards same day dismissal, yeah, it is much easier if you've had ICE rather than you've had general anesthesia. So do you think, David, that ICE will become the imaging intraprocedural standard for this procedure? I think so, actually. I think that there will, Dede talked about, and Jackie can talk about this, the use of CT ahead of time to make sure that you've got a good target to make sure that the patient is well hydrated, all of those sort of things. I think we will see more and more emphasis on pre-procedural imaging, whether that be with CT or TEE, and then the procedure guidance be with ICE. Absolutely agree. I think because currently the technology of ICE is not as good as TEE at this point. So for procedural guidance, I think knowing the anatomy upfront with baseline imaging, be it CT or TEE, is very important. Since we're getting past the hour, I want to ask the final question to Dr. Holmes. I think this is the toughest one, and that's addressing future studies and controversies that's remaining in this area. So what other studies do you think we should embark on to really expand the indications for patients with non-valvular AFib in this field with transcatheter early closure? What other randomized trials that are needed? Sure. That's a great, really good question. I think that if people were to talk about the two current issues that raise the most concern, that would be device-related traumas, number one, and would be periprocedural leak, would be residual leak. If we were to bring along a device that says the problem is that the left atrial appendage develops clot, and that can then embolize, but what we need to do is to bring along a device that is called left atrial appendage occlusion, well, that's what we should do. We should then occlude the left atrial appendage. If you then call a device that occludes the left atrial appendage as occluding some of the time. And Jackie, you've talked about device leaks. Device leaks are not benign. And so I think the future is going to be for this procedure is to number one, make it safer and easier. Number two, it's going to be mitigate the issues of device-related traumas, which while infrequent, occurring in 3.4% range, as well as device leak, those will be the trials that then will subsequently lead to a wide increase in the number of procedures. I would add also, I think something like along the lines of the LAOS-IV study where you're doing left atrial appendage occlusion and some anticoagulation or long-term anti-thrombotic strategy that's more intensive than aspirin could be a really interesting study. And there are several studies dealing with that, that will be half dose of the DOAC sort of forever along with left atrial appendage occlusion. And that might then take care of the issue that thrombus from the left atrial appendage only is the cause in 90% of embolic strokes. Yeah. Yeah. It gets rid of the residual risk question. So, and then I do think that similar to like the PCI literature, there'll probably be a lot of studies looking at post-procedural anti-thrombotic strategies, and that'll be a moving target over time as we get less thrombogenic devices with coatings and things of that nature that mitigate the risk of DRT. So, I think there'll be a lot of intensive investigation in that space. The field still has some unanswered questions. It's a tremendously explosive field. It will even become more relevant for the huge number of patients, because we're under-treating a lot of patients that don't have the benefit of left atrial appendage occlusion. So, there's going to be lots of room for everybody on this call and all of you listening on the call for new devices, for new strategies, for new answers. I think you both, everyone's hit the point there that, you know, there are still a lot of remaining questions, a lot of clear controversies, and we look forward to new devices with new iterations and coatings, et cetera, to minimize DRT, minimize period device leak, and improve the safety of this procedure, which I think, you know, that would all help with the data available in ongoing randomized control trial, really bring this procedure to a class one recommendation. And so, with this, I really want to thank everyone, the panelists for being involved, excellent talks and discussion. We've gone just past the hour. I'd like to thank Sky for the opportunity to create this document on behalf of all the writing group committee, and I hope this document will be helpful for all the proceduralists and imagists who are dealing with this procedure. Thank you so much.

left atrial appendage occlusion

LAAO procedures

surgical backup

complications

intracardiac echo

patient safety