So we're going to then talk about patient selection criteria and then future directions, terribly important part of discussions like this. As we know about patient selection criteria, we know that when it was approved, it was approved as transcatheter left atrial appendage occlusion was appropriate for patients with non-valvular atrial fibrillation and a high thromboembolic risk who are not, who are not suited for long-term oral anticoagulants and who have an adequate life expectancy, minimum greater than one year. That's terribly important as we see older and older patients and quality of life might benefit from LAAC. There should be patient-provided discussion for shared decision-making, and that's terribly important in this era where the patients are central to all of our discussions. We know that depending upon where we live in the world, there are different indications for use. In the United States, we've just talked about that. The patients have a CHA2-RAS score that are increased risk for stroke. Recommended for anticoagulation, but deemed unsuitable for it. The European Union, on the other hand, has been slightly different. Their indications for use was that WatchmanFlex, and this relates to the flex, but we now have other technology available, is intended to prevent thrombus embolization from the left atrial appendage and reduce the risk of life-threatening bleeding events in patients with non-valvular atrial fibrillation who are eligible for anticoagulant therapy or who have a contraindication to anticoagulant therapy. In the early days of the procedure, the majority, the vast majority of patients treated in the European Union were felt to be inadequate and unable to be treated with oral anticoagulant. We lived in China. These were the indications, at least for the Watchman left atrial appendage closure device intended to prevent thrombus embolization likely to be formed in the left atrial appendage and reduce the risk of life-threatening bleeding events in those patients, again, with non-valvular atrial fibrillation who are eligible for anticoagulant therapy or who have a contraindication to anticoagulant therapy. So that was the whole gamut of patients who could be treated in China. Those that could be treated with them, anticoagulants. Those in whom could not be treated with anticoagulants. And so these indications have varied by the geography of the patient and the physician. This then led to the criteria that were accepted in 2019. ACCHA HRS focused update on atrial fibrillation. Watchman was included in those AF guidelines. We need to remember it's a 2B indication. Level of evidence was B, non-randomized. And the recommendation was, again, can be considered in patients with atrial fibrillation and increased risk stroke. Contraindications to long-term anticoagulant. We need to remember the bottom line, the red line that says new clinical data and FDA approval have necessitated this recommendation. We anticipate that, indeed, the new strategies and the new randomized clinical trials will increase that to a 1. But it will depend upon the information that comes out of those randomized clinical trials. So these were the 2019 ACCHA HRS focused guidelines. We can see that these are then the European guidelines, the 2020 guidelines for the management of atrial fibrillation. Again, stroke prevention, patients with atrial fibrillation, contraindications for long-term anticoagulant treatment, specifically anticranial bleeding without a reversible cause. They also include the data that we know that came out of the recent surgical trial. But we will focus on the transcatheter approaches where it's, again, class of recommendation is a 2B. Level of evidence is B, very similar to 2019 ACCHA heart rhythm. As we think about those specific societal recommendations, we need to realize that they include special groups of interest. And this would be pretty much important information as we think about the field going forward. We could identify, or we could all identify patients in our clinical practices, those that have had prior JR bleeding, those that have had prior intracerebral hemorrhage, those that have had a history of stroke on oral anticoagulants. Those patients, which is an increasing group of patients who have cerebral amyloid angiopathy, the group of patients who fall. We know that falling risk, falling accounts for one in seven emergency room visits, at least in the United States. Those people that come in after having a fall. In patients with non-valved atrial fibrillation on an anticoagulant, a fall is a real risk. And finally, another special group of interest for us to consider as we expand the indications and the interest in these technologies would be that group of patients who have left atrial appendage thrombus. You can see it on TEE. Whether they have an anticoagulant on board or not, we do see patients like that. That when we do the echo, we say, there it is. What are we going to do about it? Let's talk about then some of these specific groups. The first is recent data that was just published early this year, 2022. It was performance of left atrial appendage in those patients who have intra-atrial thrombus. It's a multi-center registry. 126 patients with left atrial thrombus on pre-procedural imaging. What are you going to do with patients like this? The strategy would be to say, if you're not on an anticoagulant, we'll start one. However, some of these patients are already on an anticoagulant. Are you going to double it? We're not going to do that because we don't do that. Are you going to change to another oral anticoagulant? We do do that. Or could we go ahead with direct left atrial appendage occlusion in this registry study, which is a multi-center registry from around the world, actually? Endpoints were a composite of bleeding, stroke, death at 18 months, and procedural success. So it's perhaps the highest risk of patients. There is something there in the left atrial appendage. This was where the thrombus was. Location, as you can see, we can see it could be in the body. It can be in the apex. And typically, that would indeed be the case. There were some patients who had a thrombus at the ostium or over the ostium. Those would be patients that we typically wouldn't treat. But those patients that had an apical location for the thrombus, there are some patients in whom we're going to treat those patients. We'll be nervous about it. We'll be apprehensive about it. But there are some patients in whom it's terribly important to be able to treat those. And so the patients in this registry were either treated with direct left atrial appendage closure, seen on the right, most of the time those patients that had an apical location. We can see that it was organized in most of the patients. So as you get a sense from looking at the echo images, you can say, well, it seems like it's been there for a while, and it's organized. We can see that it was mobile, however, still in almost a quarter of the patients. So it's a very high-risk group of patients. And those patients that had persistent atrial fibrillation and who had persistent thrombus, we can see most of the time, it was also in the left atrial appendage apex, but not all the time. We can see that you're able to tell that some of those were acute, and some of those were more subacute. But this is just a registry experience of a large number of patients. What are we going to do from a clinical standpoint? This is what they found. Captain Meyer's survival estimates for major adverse events, bleeding and stroke. And we can see in the solid line are the group of patients that are treated with direct left atrial appendage occlusion. It's terribly important for the audience that the strategy used in this is called no touch. This is a strategy where you try to avoid doing anything in terms of movement of guide wires or any other sheath manipulation in the left atrial appendage itself. You position your sheath at the ostium, and then you forward advance the device, keeping everything out of that apex, where in this series, most of the thrombi were there. But you can see when you use this no touch technique, that indeed the patients, it's a small number of patients with left atrial appendage occlusion closure did better over the course of 18 months. Is it perfect? It's not. But they did better. What did they conclude in this group of patients? And you can see the authors from around the world in the presence of left atrial appendage thrombus. Most of the time, we're going to go ahead with anticoagulant therapy. But there will be some patients in whom we clinically decide that that is not the best strategy, and we can't continue with that because it hasn't worked. Direct left atrial appendage closure was feasible. High procedural success. And in contrast to what I might have thought, there's an absence of peri-procedural embolic compilations. The no technique works. However, over the course of follow-up, they have more device-related thrombus. And so we're familiar with that, and we'll need other strategies to deal with that. But in that patient group that are the highest risk, they have current left atrial appendage thrombus. We can deal with that using a low touch approach. The next group of high-risk patients that we are concerned about are the group of patients that have ischemic stroke despite an oral anticoagulant. And it's only non-valvular trepidation. This is a registry. It's a large registry of 5,300 patients with a recurrent recent ischemic stroke with information on oral anticoagulant prior to and after the index event. The specific aims are terribly important here. Are patients with an ischemic stroke or TIA on an oral anticoagulant at increased risk of a recurrent event? And the second aim is, can we change the oral anticoagulant and improve the outcome? So if they're on apixaban and they have a stroke, we then change it to Xarelto. Maybe they're going to do better. We'll have to just see in this study. This is the cumulative incidence function curves for the main outcome of recurrent ischemic strokes. We can see in yellow are those patients who are naive and those patients who have been on prior oral anticoagulant. And changing an oral anticoagulant from one to another when they've had a stroke on the oral anticoagulant does not work. And so just by virtue of changing it, it doesn't seem to matter. These authors, next slide, found that, indeed, in those patients with atrial fibrillation who have an ischemic stroke, despite prior oral anticoagulants, are at higher risk for recurrent ischemic stroke. That's similar to those without prior oral anticoagulant. And so in this group of patients, atrial appendage closure in this high-risk patients is a better strategy. The next group is an interesting group. It's the patients that have had intracerebral hemorrhage, the Nordic country study, patients with atrial fibrillation and prior intracerebral hemorrhage. They were then compared using a propensity-matched scoring system, using a primary endpoint of a composite of all-cause mortality, ischemic stroke, or major bleeding. And the following slide is one of those things that you don't need any statistics for. This was the result in those patients that had standard care in orange versus those patients that had left atrial appendage occlusion following an intracerebral hemorrhage. You don't need any statistics to look at that. You can say, you want to be in the group of patients that have the orange outcome. What are the ongoing trials? Well, the ongoing future trials will be left atrial appendage occlusion versus DOAC, left atrial appendage occlusion device versus left atrial appendage occlusion device number two. It'll be oral anticoagulants versus DAP or SAPT. It'll be half dose DOACs plus or minus SAPT. Ongoing trial will look at ICE versus TEE. Ongoing trials will look at MRI versus CT versus TEE for procedural planning. The ongoing trials are going to look at other issues, but the potential goals going forward will be to number one, achieve class one guideline indication, document the superiority over DOACs, document ideal optimal post-implant medications and strategies to make the procedure safer, make it easier, expand the patient base, or expand the user base. We have the future laid out for us, and it's incredibly bright. Thank you.

patient selection criteria

left atrial appendage occlusion

thromboembolic events

geographic variations

indications