Hello, everyone. My name is Julie Mobaid, and I am the product manager for the LAO registry. And today's session is reviewing the data post-LAO anti-thrombotic therapy. And I'm happy to introduce Dr. Homsi. He is the professor of internal medicine at the Ohio State University Wexner Medical Center in Columbus, Ohio. And I'm going to invite him up. Thank you. Thank you, Julie. It's not easy to say my name. So I'll make it simple. I tell my patients, say Homsi. Good audience. I love that. At this time, you're still awake? Let's sail through that. What's really important about, think about, anti-thrombotic, it's difficult to say that after Watchman or Amulet. It doesn't make sense to you. You should not give it, right? Because you give it because you don't want to give it. What kind of dichotomy? Let's sail through that. Well, think about it for a second. This is what we're going to try to accomplish in the next 45 minutes, and we'll open some discussion. I like the discussion. You know, we talk about, like, energize your thought and see what you can do. So really, what we need to know, why understand the option for post-procedural medication? Why we have to give medication? What medication? Is it vitamin K antagonist? Is it aspirin? Do we have anti-platelet? Doac? Have Doac? Noac? Have Noac? Nothing? God knows. It's so much confusing. By the end of this, it's a God help, you know. But there are some good green light at the end of tunnel. We're going to share that at the end, you know, which is going to be so beautiful. But let's go through that. Then we're going to review and understand the data. Why is so much difficult to understand that? Because each study was done with a different design. And each study has a few patients, a few hundred, not a big study, you know. And then in the end, we'll talk about what's going on, ongoing study, how to adjust in all the study. And we have some data that just came out. But for people who doesn't do the procedure, let me explain that to you as simple. It's called percutaneous endocardial left atrial appendage closure device. The surgeon used to do that easily when they do mitral valve procedure. They go in, they get atrial crypt, they clip it, they suture it, they cut it, whatever they can do, depending on the surgery and how they do it. And they did really well, you know. But for us, we thought for a long time, if patient cannot, doesn't need surgery and had non-valvular atrial fibrillation, could we close that device? So many devices, by the way, has been tested. Plato, one of the study, one of the device was close to be there, but they run out of money. Then Boston Scientific start to adapt a different iteration of Watchman 2.5. It's funny name, but I call the first generation. Let's go about, think about this. So what we do usually, we go from the groin, get an IV in the groin, 1416 French, and we pass the catheter up, put an intracardic echo. Everybody hear me? If you don't hear me in the back, just do this. He adjusts the audio. But anyway, then we do transeptal, and we're good at it, you know. The electrophysiologist, we live in left atrium. As you heard Dr. O'Meara earlier, he talk about ablation. We live there. Interventions tried to fight us with that, but they are good colleague. We like pick on them and pick on us. And then we go inside, and this sheet actually, the device is inside the sheet. And what we do, we go literally inside the appendage, and then unsheathe it and open up. And they have barb and hook it there and test it. It's called PASC right here to be sure that it's really secure, it's in the right positions. Multiple, you know, condition has to be verified before you release. How you release? You unscrew it, and then that become loose. And that what left is here, and this is the sheet and it's way out. But think about for a second, look at this appendage here, how much is fibriculated, how much area of, you know, circumstance to get clot. In 1991, one of the surgeon actually went through this process to think about, and he did meta-analysis of all the surgery and said, which one would benefit from anticoagulation or ligation at that time, surgeon. They found that non-valvular heart disease, because we have non-valvular heart disease, 91% of the clot come from there. So the number 91 came from that study in 1991. You know, 91% from there. Now if you have rheumatic heart disease, that's inflammatory disease, it's going to affect the atrium. So even if you ligate it, you're going to help, because 53% come from the appendage. I want to give you this idea, it's beyond the scope of this talk, but to give you this one in concept, why we close this, we think that we got it, 91%. The other cohort you should be careful with is amyloidosis. Amyloidosis, they don't do well because they have a lot of scars. So patient with amyloidosis, I said no. And there are questionable people who has HOCM as well. Okay, let's stick with non-valvular heart disease. So this is the first iteration in 2015, approved in 2018. We have this device called the Flex, and mainly what they do, they flex the feet. So feet were free, looks like strawberry, now it's more like marshmallow. And it's closed here. And look at the front here. You see this one here? This is what we're going to talk about. This is called the healing process. When you put that foreign object of titanium and nickel and this mesh, what's going to happen? It's a foreign object. You're going to attract febrin. You're going to attract platelet. So yes, for a short period of time, we can do it. So the indication for Watchman is to do this procedure if the patient can be on anticoagulation short-term. You have to look at that on the guideline. It has to be. Otherwise, you don't do it. Now, Amulet here on the bottom was indicated, was done, European did a lot of study on them, and they use dual antiplatelet therapy. And they have more experience than us because we don't use that much. So let's go to the first the first objective of my talk. Sorry about that. Here you go. Understand the option for post-procedure medication. So if you look at the data from all study we have, the concern is now we worry about we have a clot on the face of the device. That's called device-related thrombus, and it's only about two to five. It's not that much, but guess what? We try to close the device so the clot would be behind the device, not on the face of the device, all right? And then if you have that on, that's scary. Imagine like you get a call from TE at 45 days. Hey, that comes again. Look at this one. I see the kind of wiggling on the face of the device. Not a good news for that day. It's low, but you don't want to deal with that. Then you have to put the patient back on anticoagulation, and think of the patient has AV malformation in his gut, and he bleeds. It becomes so complex. The thought of this, I think because you have thrombogenicity, is that the patient has a lot of risk. There are multiple risk factors from the patient or from the procedure, and there are many studies that have evaluated that, and mainly you have to look at this and be careful when you select patients. So patients have cardiomyopathy, or patients have prior stroke or TIA, or patients have permanent AFib that has more scar and more remodeling, or has chronic kidney disease above age 80s, 85. Guess what? Most people, they get this in the 80s. And hypercoagulable disorders. If you have venous thromboembolic phenomena like DBT and PE, vascular disease, or somehow iatrogenic pericardial effusion during procedure, that means you attempt multiple times to put the device in, and you end it with complication. What about the left atrial appendage characteristics? If you have a large appendage, sometimes you might have leak. We'll talk about leak tomorrow. Or you don't have a good device to fit in. Or you put the device too deep, and that make it more, you have more sluggish flow close to the, say, for the device. We'll show a picture of that. Or you have history of left atrial thrombus. Patient have it, you postpone it, you give an anticoagulation and have it tell you about the mechanic, or we have peri-device leak. Or you have patient is not on anything. You don't give him anything. So here is an example of amulet here at a good position and Watchman. But look at this one here. The disc is inside what's called the landing zone. This is called the landing zone. And that's what you should keep it here. You should keep the blood vigorous and closer to that area. And if you see this, this is the left formality vein that our previous speaker was talking about ablation. So there is a ridge between this area, between the appendage and that area, and should not go from the tip of the ridge to the face of the device more than 10 millimeter. If you do that, you have problem. That same thing with surgical. If the surgeon leave a stump of 1.1 centimeter stump, you should be anticoagulation because that put the patient at risk of clot formation. So the reason we came up with this idea about like, do we have to do anticoagulation or not? It is because of an early animal study, but we'll talk about that in the next few slides, that how this device or the process of healing and endothelialization of the face of the device. The endothrombotic therapy is used to prevent device red thrombus, but two to five percent, not much still, you know, you should prevent from that. It depends on the healing process and it depends on how good the healing process completed, how much endothelialization, and go through three processes, three phases. First, you're going to have prothrombotic state simply because you have a device state that's going to attract what? Attract the fibrin, attract the platelet aggregated. Then after that, you're going to have the endothelialization process and then new endothelialization process, which shows a few picture here. But the key for that, you should prevent from the thrombus, a fibrin formation, and that's the reason they suggest to start anticoagulation and antiplatelet therapy. This actually an old study by Schwartz and group back in 2010. They took nine canine dogs and they look at this dog. They give them aspirin, 325 milligrams, big dose. Warfarin, 6 milligram, and titrated kebiner between 2 and 3. They were really anticoagulated after the procedure. Before that, they crack their chest, look at the chest and look at the appendage, and they went through the groin. They want to be sure that this device is really sealed and looks beautifully sealed. And then they sacrifice the first group. Here we go. This house of dog, the dog look different, his heart, even though it looks like this is AP, looks like right, left, left, right, and it's vertical heart. But this is the x-ray and the same dog here grows looking from the atrial side. You see a lot of redness here. You see some kind of layer of fibrin. And when you look at under microscope, low or high, you see this black dot and these are the fibrin are deposited there, all right, even though patient has been given warfarin and aspirin. Now let's look deeper here in patient 45 days. Because of the prevention of anticoagulation, antiplatelet, now we have this glistening white panacea from smooth muscle, which is closing this area here and here and creating this endothelium. But the problem is the first veneration is this metal. You see this one, this is a big hop. And if you look at the right side under big magnification, what you see, you don't see a lot of industrialization. And that's the reason we abandoned this and we went to WatchmanFlex. WatchmanFlex has smaller exposed metal. So by giving the anticoagulation, we have even anticoagulation with warfarin with therapeutic target, still have some fibrin, but we're able to have endothelialization. Here also they included in their paper about four human being who died and had Watchman. And they have the same process of seeing that it's sealed. You see the the endothelium at the top, subendothelium or neo-endothelialization at the bottom. And you have a closed area and the clot is inside there. And you see a very smooth transition and good healing process. The author concluded one thing here that dog are different than human and the dog, they heal faster. Again, the dogs here didn't have atrial fibrillation. Oh, there are a lot of circumstances you have to keep in mind. Why we do like 45 days? Because of that. The reason we do 45 days TE because of this. It's sealed well, look nice, so do it 45 days. That's the first data we have. Now to go one step further to evaluate the activity on the coagulation and platelet activation to prove it in laboratory. So we were looking at markers and here it's about 43 patients, 27 Watchman and 16 Amulet or Amplexor. And what they did, all of these patients, they have anti-platelet therapy, no anti-coagulation. They give them either dual anti-platelet therapy or a single anti-platelet therapy. And they look at this marker, prothrombin or thrombin for coagulation and look for the soluble P selection or the CD40 as a marker for activation of platelet. Remember, we go back, all of us remember this, the cascade intrinsic and extrinsic. Prothrombin is a step before creating the fibrin here. So if you are really activating the clotting factor, you're going to activate prothrombin and that will degregate to 1, 2. And thrombin also will be attached to antithrombin. And these are the medicine that we use. All this factor 10 antagonists because it gets the common pathway for 7, 2, 9 and 10 is where it's the vitamin K antagonist and the bigger trend is called Pradaxa inhibitor thrombin. So when they tested, they found that significant increase of the marker of coagulation. Now remember, this patient are on not anti-coagulation, just anti-platelet. So look at the baseline. The baseline is here. They said it's significantly higher. It comes down to 30, not yet back to baseline. 180 days, still high. That's the reason now we think we need to stay longer time on anti-coagulation. Same thing for thrombin, antithrombin, still high and doesn't go back to the baseline, up to 180 days. When we look at the platelet activation, we didn't see any big difference. If you use in red, do anti-platelet therapy or in single. And really, the data showing that you inhibited the platelet. So good. We need to use anti-platelet. Now to test the idea about the impact of anti-coagulation, this is really eloquent study just published recently about looking at half dose, low dose. We were thinking about if we give anti-coagulation, could we give lower dose? And this intention of the study was really not the intention not to tell you that we have to block the coagulation cascade as much as to prevent from bleeding. But when they analyzed it, they found that they have three groups. They give lower dose at 10 milligram of rivaroxaban, which is Xerolto, and 15 milligram and the one anti-platelet therapy, aspirin, low dose aspirin, and clopidogrel. And you can see the prothrombin fragment 1 and 2 is significantly inhibited even with R10, which is 10 milligrams, so half dose. At that time in 2020, we start talking about half dose anti-coagulation. Why not? We can enhance the healing process and utilization and no bleeding. And it showed the same impact on the prothrombin as antithrombin is it day number 10 or day number 3. So let's go ahead and review. So we understand now we have to use antiplatelet and anticoagulation, hopefully different dosing, to prevent from or to enhance the healing process. So let's go back and look at the clinical data. Now I'm going to review our data at Ohio State University. Since 2016 until 2023, our actually NCDR employee at Ohio State, Nancy, did that for me, so shout out to Nancy here because she gave me all the information. And what you see here, we do a lot of DOAC and aspirin, a lot. Next comment, warfarin. And that because of change of practice, because first we started with warfarin, aspirin, then switched to DOAC and aspirin. And few people we do, you know, different regimen like DOAC and Plavix or do antiplatelet therapy or DOAC alone, but we do not keep the patient without anything. We give him something. That's opposite to, sorry, here you go. And if you look at the incidence of drug, sorry, device-related thrombus, it's the lowest on the DOAC, four out of 400, almost 480, two on warfarin out of 210. So we have lower incidence of DOAC and aspirin related to device-related thrombus. Now our practice in the United States, we are part of the U.S. continent, but if you go across the Atlantic Ocean, they are different. European, they use a lot of antiplatelets. So if you look at evolution, this evolution study, this is 1,000 patients, all of them, most of them are 80% that cannot be on anticoagulants by other specialists, either GI or urologists say cannot be, or neurologists, they have a bleed. So most of the time, they use a lot of, you know, DOAC, 60% they use DOAC. So same thing with Amulet. Amulet started in Europe and they have more experience than us, you know. But if you look at the U.S. data here, up to 31,994 use either vitamin K antagonist or DOAC. Now let's look at the earliest data. I'm going to look at, again, look at this data here. In red is warfarin, in blue is Plavix, and in light blue is aspirin. So the design of the first study, PROTECT-AF, 463 patients, you give warfarin by itself, alone. Then you start doing antiplatelet therapy. Of course, you don't echo TE here, and then you do antiplatelet therapy for four months and a half. At six months, you continue on aspirin. That study actually, when it went to the FDA, did not approve it, and they asked for more because they have more complication. So they went back and they did PREVAIL. And in PREVAIL, they did change of the anticoagulation and give aspirin as well as vitamin K antagonist for four or five days and continue the same activity after that, four months and a half, and lifelong. What we found in this group, that 3.74% of this patient has clot, not in the PROTECT, not in PREVAIL, also for continuous acquisition because they analyzed almost 1,700 patients. So it's a high incidence with the vitamin K, and we were concerned about it, how we deal with this. And we found that if you have a clot on the device face, it was associated with increased risk of stroke almost three and a half fold. That's huge. That's high. And what other thing they noticed here, which is really interesting here, and people start making a lot of analysis, that 86%, almost 87%, all ischemic stroke, they found no device with thrombus. Now, think about it. Do you think the last thrombus went up to the brain and caused a stroke? We don't know, right? But that was concerning. And the other thing we noticed, also the compliance. Everybody knows how horrible it is to take the vitamin K antagonist, and about 40%, less than 40%, they use the vitamin K antagonist. Other thing we noticed, also, they have higher adverse event as well as major bleeding. So we started looking at DOAC. And when we look at EVOLUTION, the 1,000 patients, they were 10.9% of this patient, they took DOAC after the procedure. And EVOLUTION was registered, actually. It was not a study. Just collect the data there. And it was not a study. And they collected, and they found that 59% of patients received full-dose DOAC. And look at the incidence of DRT, 1.3, compared to 3.1 with that. And they have lower incidence of bleed. We said, OK, yeah, low numbers, but we see lower device with thrombus and lower bleeding. So we went one step further. We said, let's look at this study and compare the DOAC with aspirin. It was a higher number, 285 patients, which is like one-to-one, three months follow-up between that and DOAC. And we found that you have more complication or early death in patient has 3.7 compared to 1.1. Sometimes it becomes a little dicey how you describe that. But you have more complication, more death, more mortality in patient. Again, you have to analyze this data in a very cautious way. But you come to this point here, major bleeding with that is 7.4 compared to 3.2. And DRT device-related thrombus was none on DOAC and 2.6. Again, all the studies are small, but you have to analyze in caution. So we are really feeling that DOAC is the medicine to go and use. Now when we tested the Watchman Flex, and really, Watchman Flex did not change anything about the fabric. The fabric on the face of the device is the same. But what we did, we have changed on the morphology of that and the end of the device. So we prevent from more concern of perforation or pericardial fusion. So this is not a randomized study. It's almost 400 patients. And what they did, they give everybody DOAC and all the operators, they were well-skilled operators, great operators. You have to analyze it again. And they give DOAC and low-dose aspirin for 45 days. Again, four months and a half, they did Lavix and aspirin, then aspirin indefinitely. There was no device-related thrombus. And they have two on the DAPT. And they have five on single antiplatelet therapy. So that also gave us more hope and interest in DOAC. Now this is another study. Look at, really, this is published in 2021. Again, as I said, after we got the information about low-dose of rivaraxaban 10 and 15, they designed a study to look at bigger size, about almost 600 patients here. They give them full-dose DOAC, aspirin, same like the WatchmanFlex. But instead of this, we're going to give half-dose DOAC and just aspirin for 45 days and continue on half-dose DOAC. And they found zero device-related thrombus and lower rate of major bleeding. That was interesting also. This study actually is just published recently in JAMA. And this was a European study. And it has the same intention to look for half-dose DOAC alone for three months and compared to DOAC. I'm sorry, compared to that, Plavix and aspirin. This study was designed to have about 160 patients. Unfortunately, because of COVID, they couldn't do it. And they have to, after it got 60% of the enrollment, which is 90 patients, they stopped enrollment. And they published this data just recently. And what they look at, look at a couple of things. How effective and how safe. So in the arm of, and this is at three months, just to look at the data at three months. In the half-dose apixaban with 2.5 milligrams twice a day, at three months, they found to have two bleed. In the DAPT, they found to have 10 bleed. Now 60% of the patient have GI bleed. So if you look at the percentage, you can look at 4.6% compared to 21.7, significantly lower. So half-dose DOAC could also be effective. Now if we look at the data from DAPT, which has been used in Europe a lot, and most of the study come from Europe, you can see of this study called ASAP, this 150 patients were declared not suitable for anticoagulation by their physician, non-cardiologist, said you cannot give them anticoagulation. And they came and they had Watchman and they gave them DAPT, the one anti-plate therapy, for six months. Then after six months, continue aspirin indefinitely. BRAC 17, three months, DAPT, and then aspirin indefinitely. Now in Prague 17, they were two-armed. They have Watchman and Amulet, and they have DOAC, aspirin, and DAPT. And inflexibility is almost the same like ASAP. And when you look at the incidence of device with thrombus, it's high. It's close to the one we've seen with aspirin, with aspirin and Warfarin. And the incidence of stroke was also high. Now the big question after you get to six months, what do you do after that? Do you continue on aspirin or not? There's concern, as all of us we know, the U.S. task forces now, they're saying you don't need to take aspirin if you don't have car disease, if you don't have stent, if you don't have any intervention or history of stent thrombosis. You should not take it because of high incidence of bleeding. The problem after six months, there's one-third of patients, they have device with thrombus. It's seen after six months. So how do you reconcile with that? Do you stop the aspirin? Do you do something different? Do you balance bleeding from stroke benefit? This will going to be really known by aspirin left at appendage occlusion trial. It's ongoing. And literally what we're going to do, there are different arm on that study. We'll show it later on. But one of them, we're going to stop at six months and see what the outcome. Imaging is going to be very important, and we touch on that tomorrow. Could we use imaging for our advantage to stop the anticoagulant or anti-placelet? And if we look at this data, actually, from evaluating the healing process of the left-handed appendage occlusion device. Now we have Amulet and we have Watchman. Nowadays, we don't have Watchman 2.5. They look at, under CAS-CAN, something that's called hypoattenuated thickening, HAT. And there's three stages, or three grades. First one, grade zero. When you see this two dot next to the hop here, you think there's a thrombus there. This is not thrombus. Actually, the fabric is under the fabric, and we'll show a picture later on. And the illustration will show you here that this is because of the design of the fabric. So when you have sub-fabric HAT, that means that's natural healing and there is no need for anticoagulation or restart anticoagulation. If you have thickness less than three millimeter or more than three millimeter, but connected from end to end, you have continuity from atrial side to other atrial side. That could be also healing process, normal healing process. The question here, we talked to our imaging colleague, could you evaluate the tissue characteristic of the face of the device and tell us, like, you have tissue, clot, endothelium? Not yet. They are working on that. There's nothing yet to tell you, because if they can't tell you, we have this, how many Hounsfield units is the blood, this clot, you know, how sometimes we use it for other like coronary disease, see if you have active inflammation or not. They don't have it yet, but they're working on that, if they can define, if they put this and characterize this area to be, you know, endothelium and healthy tissue. But for now, we think if it's this continuous from one side to other side, this is called HAT-1. Now, if you have it, if you have more than three millimeter here, and you have this continuity, that concerning, that's a clot, either on the flex or the amulet. The thickness, again, if it's irregular or if it be done collated, that's really concerning, and this is scary when you see this stuff, you know. So the thought is if you have grade one and grade zero, they'll tell you this might be benign endothelialization, but if you see two or three, you better start patient back on endothelialization to resolve this issue. And this is what HAT-0 is. The design of the device, the fabric actually doesn't go down on this folded area here, it cover this area here, from here to here, and it depend on the compression. If you have 8% compression, maybe it look flat, but if you compress more, it become more elongated, you know. And how you measure it, look at the face of the device, and the widest area of the device touching the appendage, then you can see this area in between, this is normal HAT here, and you don't have to worry about it. And this is a gross picture showing it's healed from a patient who had the CT before, and when they analyze it under microscopic area, they didn't see anything on the face of the device. So if your patient have HAT-0 or HAT-1, you could consider stopping the anticoagulation and deplete it. If you have two and three, then you have to re-initiate and re-evaluate every three months to see if you need to, if you have no thrombus in three months, you can make a decision, with shared decision, to de-escalate, or if a patient still have, or you can continue on that, and that discussion with the patient. Sometime if you have the thrombus for a long, long time, it could organize, become really difficult to eradicate, you know, and there are some case report, it lasts forever with different anticoagulation. This is a case here, a patient who has a 77-year-old guy who has aortic stenosis, was mild, and he has a Watchman device, and you see on the TE, this is left atrium, this is the mitral side, or mitral annulus here, and this device, and you see this big, huge mass here. Patient underwent aortic valve surgery, and when they took this out, was very organized and very fibrotic, would not go away, you know, so aggressive anticoagulation has to be done earlier, otherwise it would be difficult to eradicate. So if you conclude and you try to say, how I do it until I have more information and understand what I do, usually DOAC should be chosen over vitamin K antagonist. And you have to avoid combination with anticoagulation aspirin if the risk of bleeding is higher. Why is this? At pinnacle, FLEX, which is the study we studied, the Washman FLEX, and Amulet, you see a lot of bleeding because you have dual anti-plate therapy here, or you have DOAC and aspirin. So this bar is too high. Can we get rid of it? And maybe the answer is low-dose DOAC. Let me walk you through this ongoing and impending trials. And they are really a good design trial. And there is a concern on that. I come to that in a second because they have a new device introduced. It might affect the outcome of the study. It's called Washman FLEX Pro. We'll talk about that in a second. If we look at the guideline, it will say you have to be on anticoagulation for short-term to be eligible for the left artery appendage occlusional device. Now a patient cannot be on that. So they have multiple studies, like here we have the stroke, close, or clearance. This patient has intrascribal hemorrhage and were announced not to be on anticoagulation. So you're going to go in and put the device in without anticoagulation, ASAP2, the same thing, and compare. So this patient has central nervous system bleeding or neurosurgery contraindication for an intervention, including anticoagulation. Here it's novel indication. Somebody asked earlier about could you do Watchman and ablation. Yes, this is called the option study. It's been submitted. We are looking at it. Possibly the CMS will approve it. I think October 1st will be the deadline you can do PVI, ablation, and Watchman at the same time. Champion AF and Catalyst AF, they're comparing Watchman compared to DOAC and emulate with Catalyst to DOAC. Loess-4, this is a study, actually, we are going to close the appendage and people has high risk and continue anticoagulation or with different protocol, either full dose, half dose, or lower dose. These studies are still ongoing. Again, you see different design. This study is interesting, FADE-DRT, and you see this purple here. This is genetic tailored antithrombotic therapy. So they can start with three arm. First arm is standard, Warfarin, and then do antithrombotic therapy for six months, then after that, aspirin by itself, or they can test with Warfarin, see if the patient has any genetic deviation of achieving full anticoagulation, and maybe change the anticoagulation and continue with aspirin, or give low dose DOAC. Again, we have a lot. This is the study we talk about aspirin, lifted appendage occlusion device, that after six months, they can stop or continue and see if we have any late thrombus on the face of the device. Multiple studies, just single antiplatelet or dual, which could be reasonable with the newer iteration of the Watchman. We're doing this study at Ohio State School, Simplify. So we're looking at this device, which is just approved and due as just the second quarter of this year. Watchman FlexPro, same device you've seen, but it has fluoropolymer on the fabric. And what fluoropolymer actually is taken from the drug-releasing stent. What it does, it absorbs albumin, and when it absorbs albumin, albumin doesn't have ammonia acid. Ammonia acid actually attracts fibrin. So if you have more albumin on the fabric, you have less thrombus. That will decrease thrombogenicity, decrease inflammatory response, and enhance industrialization. This actually was tested in vitro and in vivo by Walid Saliba, actually, and this was published late last year. And what we see here, they look at two things. They took a piece of the device, five by five millimeter, and put it on a special flow loop. The blood will go through for half an hour. And when they did that, they didn't treat and they didn't give any anticoagulation. And they look at two things. They look at how much albumin absorption. The highest albumin absorption, the lithrombus formation. And they look also on a platelet adhesion quantification as well. This is in vitro. In vivo, they look at two things. They look at canine models and pig model. The canine model, none of the animal got anything, no antiplatelet, no anticoagulation. This people has the device. So this will be revolutionary. I think this is going to make a big difference, in my opinion. So first, what they did, at three days, 14 days, 45 days, they look at the inflammation assessment. And they look at, under microscopes, see if you have any thrombus. Then three days and 45 days, look at industrialization. They did TE, and they look at gross inspection, and look at if you have any thrombus. Now in porcine model, which is interesting, if anybody has worked on the pig, the pig in the left atrium is so big and doesn't look like human. So the one closer to the human is the right atrium. So they implanted the Y2FX Pro in the right atrium appendage. And they look at multiple expression of the endothelial and vascular tissue. They look at VECAD and P120. If you look at the in vivo here, and look at the Y2FX Pro in blue here, and Y2FX here, and you can see you have less inflammation, if you look at this here specifically, compared to dense inflammation this day three and day 14. So you have less inflammation on that. Thrombus, you see smooth surface of the device. You have big thrombus and irregular and very concerning HAT3, maybe. So in day three and day 14, you have less thrombus, less inflammation. When they look at day 14, 28, and 34 with the TE, they found even they have some thickening here, but resolve over time. And when they look at the gross picture of the dog after they euthanized the dog, they have no thrombus. If you compare to Watchman, you have thrombus. There were six patients. Actually, day number one, you have one thrombus here you see. But day 28 and 48, you have none. Again, remember, these dogs have nothing. No aspirin and no anticoagulant. If you look at Delta D-dimer from the beginning, from seven days to 15 days, you have less thrombogenicities compared to Watchman FLEX, seven days and 45 days. When they look under a microscope, this is really fascinating to me. I look at this five by five, and after they're exposed to the blood, and the greener you get, the high albumin. And the high albumin, less adhesion, we'll show a picture later on. If you're in the Watchman, you don't see any albumin uptake, I mean, minimal. And if you define how much albumin the areas cover, it's close to about 50%, and they give you mean intensity, and all of them are significant compared to Watchman FLEX. When you look under microscope, either electronic microscope or gross microscope here, you can see the red color here is the plated aggregation. You see a lot of plated aggregation with Watchman FLEX, but not with Watchman FLEX Pro. And if you look deeper on the knot, you see minimal, maybe a few plated here and there, but you see more plated aggregation on the face of the device. And the area for plated binding, again, it's significantly less. Same thing with the, if you look at the expression of indeternalization, we found higher expression. This can be a CAD P120, and the whole surface percentage-wise on the Watchman FLEX, almost 84%, and more than 60 compared to the Watchman FLEX. Now when we look at the gross pictures of the device on both Watchman FLEX and Watchman FLEX Pro, we find better defined and glistening and clearer. And then we took three areas, one at the peak, one close to the hub, and one opposite side, and we see a lot of expression of vascular and adherence cells compared to other cells. So we have better healing, better indeternalization. And that will summarize all what we have on that process. We have better protein absorption, actually better albumin absorption, less plated binding, less inflammation, faster thrombus resolution, and better indeternalization. So I think this device, especially with simplified study, we're going to give aspirin alone, give dual anti-platelet, low half-dose anticoagulant. I wish I'm on the steering committee to give nothing, but they said no, next phase. But that would be good if you don't give anything. There are two devices that are in trial. This called, the confirmed trial is called CLASS, and this is really interesting. They have two sides, and it's made from a special fabric, no metal here. And it has foam, and what the foam actually expand over time and fill that area to prevent from pre-device leak, and also prevent from DRT. And they have canine data, and they have complete seal and no thrombus. Again, this is ongoing study. Also we have this laminar device, which is interesting device. This has a ball and locking mechanism. This is actually, it goes inside the appendage. You roll it, you fold it, then you lock it. It's interesting. Yeah, you have to eliminate everything there. They have, again, nine dogs and 15 human, and they have good sealing and no DRT. We are comparing these two devices to the Watchman Flex Pro, and we're going to see what the outcome will be. Everyone was excited about Factor IX, this should be here, sorry. Factor IX tagulin, when we have the study came out, phase one, phase two, that it has less bleeding, less thrombus formation, and we're excited about it. But unfortunately, OCEANIC AFib trial just got terminated because Factor IX has more stroke than epixaban. This would be our last slide. So I think until we know more about our patient, we need to look at, on the right side, what the indication for the LAA closure. Is it major bleed on ortho-calculation aspirin? Our patient has stroke. We have to balance bleeding and stroke. And what comorbidity? Look at the nine clinical comorbidities that could cause the device-related thrombus. If the atrium is enlarged, do we have cardiomyopathy, do we have peri-device leak, or we have other problems covering the whole lobes. And then, I think, until that time, if we can give anticoagulation, I think it would be reasonable to give aspirin and Doac for four or five days, then maybe aspirin and clopidogrel, which is Plavix, for six months. Then after that, continue indefinitely. If you can't, the other option is you can get Doac for three months. And instead of testing patient device at four or five days, we test the device here. So instead of 45 days now, we're doing TE here. If we decide to go three months, we'll do TE here. And at the end of, if we find on the TE that the device looked good, or without any device-related thrombus or peri-device leak, then we discontinue aspirin after six months, and we continue for one year. If you cannot give anything more than just a really short period of time, and you cannot give it, so you can choose any of these objects. I think I'm in favor of half-dose Doac. That's my own bias. Aspirin for six months, we don't know yet. I'm not comfortable with it yet. It's not a bad idea to get a full half-dose Doac or aspirin. So nobody knows. The jury's out. But we'll know more when we have more information coming through. But in the end of the day, really, you need to balance between what the risk for the patient is. Is he a bleeder? Can I take it? Or he has high risk of stroke? If I have a patient who has high risk of stroke and has stroke before, I would give him half-dose Doac. If a patient is a bleeder, and I have a good evaluation of the device, and the atrium is not enlarged and not fibrotic, and he is doing good, he's not in atrial fibrillation, I would feel comfortable to stop the endocagulation at one year. With this, I'll conclude. I'll be happy to take any questions. Thank you. Actually, we just have one question. I'm going to ask who reads, well, there's some coming in, but who reads HAT? Radiologists? Yeah, usually radiologists. The radiologists will tell you about this, but you have to educate the radiologists. I mean, I remember we have one of our, the head of the CT at Ohio State. He's from Hopkins, well-trained, great guy. And he called me and said, we have thrombus on the device. I went down and said, oh, this is HAT 0. I said, what HAT 0? So I have to show it to him, you know. And we are talking about, like, define that layer. Is it the thelium? Is it fibrous tissue or others? So you have to educate your radiologists. When is the best time to do TEE after implementation? 45 days or more? I mentioned that in the end, you know, if you decide to do DOAC longer than 45 days, and some people, they do that. A patient has risk of stroke. So, again, balance between bleeding and stroke. If you have the luxury to continue longer and you decide to give DOAC and aspirin beyond 45 days, I will do three months. If you have a patient who is a bleeder and you worry about he's going to bleed, so you give him half-dose or full-dose DOAC and aspirin at 45 days, you look at the device. And then you decide to switch to DOAC, to adapt or not. So it depends on the strategy. If you feel that you have to go with your post-procedure longer than 45 days, do three months. 45 days, if you think patient cannot tolerate longer, anticoagulant. That is all the questions. Okay. Thank you very much. Thank you. Appreciate it.

antithrombotic therapy

left atrial appendage occlusion

Watchman

Amulet

DOACs

antiplatelet therapies

thromboprophylaxis

Watchman FlexPro

post-procedural therapies