Dr. Douglas N. Gibson provides an update on alternate treatment options for patients with elevated stroke risk who are poor candidates for long term oral anticoagulation.
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at this point, we're going to move on to an update on the left atrial appendage inclusion space. This is a technique that we use for stroke prevention and patients currently that are not candidates for oral anticoagulants, shin was gonna take a tour through this and highlight some of the major develops developments and some of the future directions that became more clear earlier this year. So these are my disclosures. So currently this is a gets a class to be indication for stroke prevention in patients that are considered poor candidates for long term or atlantic coagulation. So that's the current guideline level recommendation for this therapy. Again, this is a very significantly moving targets. So I expect that class recommendation to go up and we're also broadening out to studying this in patients who are reasonable candidates for or atlantic coagulation. Yeah, so the major advance in the recent history is the availability of a device called the Watchman flex. This is the second generation watchman. I think this video sort of illustrates appendage inclusion in general and the watchman flex in particular. So it's the procedure that is performed through a single venous puncture generally takes under 30 minutes. Now we gain access to the left atrial appendage via trans septal approach. They can see the different shapes of appendages. We engage the appendage of the pigtail catheter and then generally what we do first is take some measurements based on the angiography and trans esophageal echo images. We take a contrast injection to get the lay of the land at this point will will choose the size of the device. And then here comes the deployment of the watchman and the major events. There is the distal end of the watchman no longer has sharp times on the end of it. The back was also ordered together, allows you a lot of uh flexibility in terms of repositioning um and adjust and improvements in safety as well. You can see that the back end of the device is a little more forgiving and still very careful with it, but a little more forgiving on the back of the appendage, there's extra anchoring features which will go over and greater seal rates, primarily shortened procedure, times, improve safety and improve efficacy is what we've seen as a result of this so far. Somebody get the device deployed. Little anchored teens are here we tug on the device to make sure it's seated. We evaluated with eco, make sure that we like what we call the release criteria and once it's already uh that's all verified by about three different people in the room. We left the device go. So this is the old watchman on the left versus a new watch one on the right. They, I think one of the more important features is that they counter sunk, the threaded insert, the place where the core wire attached to is right at the central face of the device that used to stick up above the face of the device. That's where we most commonly saw a device related thrombosis and in the new watch, when the counter sunk, that I mentioned that the clothes in the back end, they added extra anchors for anchoring. So the old watchman used to have 10 anchors and the new watchman has 18 anchors and they increased the metal frame of the device. It's a more robust device and that in addition to the increased amount of fabric probably results in the greater seal that we saw. This is a close up of the face of the device, showing that the threaded insert has been counter some of the lower right image on that screen shows that there's very minimal if any metal sticking up of the face of the device. That translated into a real reduction in device related thrombosis, which to me I think is the major achilles heel of this field still even ongoing today. So this is the case example just to illustrate some of the futures of it. It's 76 year old had an enlarging abdominal aortic aneurysm which is what patient was primarily referred for, where the patients referring. Cardiologists wanted this patient off oral and regulation patient was also very unstable on their feet because of peripheral neuropathy and several important falls. And um it was a daily user, wanted to be a daily user of nonsteroidal anti inflammatories which combined with oral anticoagulants in significantly increased bleeding risk. So a couple of good reasons to have it done these are the baseline images and and this is a little bit of a nightmare appendage which will become clear on the instagram, you see later. But a fairly large appendage with minimal depth. And that's one of the advantages of the Watchman flexes. You don't need as much depth going forward. So we always assess the size of the, of the left atrial appendage based on trans esophageal echo views which you see in front of you. Mm uh it turned out in the right lower image. There's there are two lobes that we couldn't really fully appreciate on trans esophageal echo until we got in around the angiogram and and the two lobes of the bifurcation between them made this case somewhat difficult. So here's the angiogram you can see in the upper left, we'll get a better picture of it. But it's a very depth challenge case with the uh except ation. You can see the two lobes there on the puff of contrast. And the separation really prevents the device from opening up entirely. And once again, it was a depth challenge case with a wide Austin. Mhm. So because the back end, the device is much safer, you have more flexibility in terms of gaining depth and maintaining that depth during a deployment. This is something I don't think I really would have been able to do with the watchman 2.5. And looking at the follow up images here, this is deployment and you can see that the shoulders land very close to the Austin where the Austin is an angiogram. After we deploy it, we give it a ton test to make sure it's satan stays in position. And I think here's the impressive feature of this. We got a good closure with the shoulders right at the Austin. I I don't think that would have been possible with the watchman flex. If so it would have been a very, I'm talking about the watchman 2.5. It was possible with the watchman flex. Uh if I was able to close that with the watchman 2.5 it would have been a very nerve wracking case with more risk. So the Washington flex was approved based on the U. S. I. D. Trials and you can see that the safety performance was very good. The primary complication rate was 0.5%. This is a bit surprising with the ischemic strokes resulted in those complications. I would expect things you know maybe like pericardial effusion or perforations, that sort of thing. Aesthetic strokes. I think what's going on there, we have not seen an ischemic stroke with the Washington plantations because we don't interrupt or atlantic coagulation. I think I know the details of at least one of these and what happened. It was a very difficult deployment. five or six attempts. The patient had their anti coagulation interrupted going into the case. And it was the next day that the patient had a stroke. The fairly minor stroke. The patient made a good recovery. But I think if that patient would have continued on the Orlando coagulation straight on through, that might not have been the case. Have some other data to suggest that uninterrupted maybe a little bit better. And we've seen that in our other a thermal ablation related literature that perhaps not interrupting anti coagulation is a better way to treat these patients. So here's just a slightly illustrating the improvements in safety that prevailed. Trial was the most recent U. S. I. D. Trial for the older version of the watchman. The nested registry is what happened. That's a national registry that tracks complication rates. You can see the complication rate came down as operators began to do this in high volume. Um And then with the Washington flex, he even made an improvement upon that. So the 1.5 complication rate is a subset of the national registry that was analyzed in the Washington flex improved on that safety. This is I think one of the more impressive features if you looked at at one year post implant, the closure rate was 100% and and that the closure, that closure rate does matter. The device endothelial realizes by end of thallium tracking in from the edges of the device. So if you had a leak, perhaps the end of thallium wouldn't be able to bridge that gap leaving the device uncovered with endothelial in and perhaps creating a risk for ongoing device related thrombosis. So that's a very impressive result Compared to about a 20 of the great with the Old Watchman. So D. R. T. This is I think what I was most excited about having a place a fair number of these devices and D. R. T. Is still seeing uncommonly but common enough to be very annoying. And you can see the D. R. T. Rate for this. Uh Watchman flex was about 1.7% overall with the old watchman. The D. O. T. rate was about 3.7 in the trial. So a dramatic reduction from the I. D. Trials to clinical practice that the R. T. Rate comes down and we expect that to occur with the watching flex as well. Um Only two of those D. RTs and watching the flex I. D. Was correlated with a clinical events. So most of those D. R. T. S. Are discovered based on screening studies and we treat them and patients do well overall without clinical events. Yeah. So the other sort of burning question is the space is evolving is how to do X. Factor into this. So the Watchman flex trial was done with postoperative doapp treatment. So as we play some watching device uh based on the results of the watching flex I. D. Trial, you are able to prescribe dough acts which patients are much happier about as well as as clinicians just a safer more easily managed type of therapy to treat them with afterwards. Um And the other broad area of interest is how does how does the appendage occlusion space compare with jokes? And and despite doc's being an improvement I still haven't found any meaningful increase in the number of patients that need protection from stroke. We're actually getting these medicines prescribed either warfare or does back. I think the doctor will make a dent in that. But there's still, I think it would be a large patient populations that need protection from stroke would go uncovered despite the advent of dough axe. Yeah. So uh Dr Eddie and a group out of Prague did a study comparing appendage inclusion and and the appendage inclusion in this trial called the Prague 17 trial was done with either the Abbot amulet device or the Washington device. There was a very small percentage of Washington flex devices in this trial. But it was a basically a more open trial in terms of how you close the appendage and it was directly compared to dough ax. Uh, and primarily that meant eloquence. Most of the patients treated with the attacks were on eloquence. So this a couple interesting things about this trial. First of all, they selected a sicker patient population ran into the gates. Any, any patient that has a history of bleeding requiring intervention that automatically sex CeleXA sicker patient overall. Um, the second enrollment criteria, if you've got a cardiac symbolic event while taking into coagulation, I'm sure that subject sub selects a patient at very high stroke risk. And then you can see the chads and has led scores, you know, respectable numbers. The average numbers enrolled were much higher than those as well. So the study outcome, it was a composite and, and that's a valid source of discussion related to these studies. The use of composite endpoints. But as you can see here, these are endpoints that are all important as you evaluate your patients clinically. Um, I think people tend to want to focus specifically on the ischemic stroke rate, which is not something I get to do as a clinician. When I'm evaluating these patients, I do have to taken into account there bleeding risk as well as their ischemic stroke risk as well as the hemorrhagic stroke risk. So there's a composite endpoint you can see there. And I think the criticism is that this is a way to make the device look not inferior by combining endpoints instead of focusing on one or perhaps two important endpoints. I expect that discussion but all in all, I think all of these outcomes are important and they're clinically relevant to what we see when we're evaluating patients two. So how did the results come out? You can see? So the cumulative incidence of the primary endpoint is on the horizontal, inside the vertical axis and time is on the horizontal axis and the curves are tracked very closely with each other. So the event rates are very comparable. This was designed as a non inferiority trial and it met that non inferiority endpoint. Yeah. So this was an intention to treat trial. So a very good well done trial. And we looked at specifically stroke and tia and this is all stroke and tia. And you can see that the curves track very close to each other. We also looked at cardiovascular death again very comparable in terms of death. I think that one of the more surprising aspects of this trial was bleeding. And so you can see that no acts. I think this is a testament to the fact that the no X. Are safer and you can see bleeding events uh in the left atrial appendage closure space we're not dramatically lower um slightly lower but not dramatically thing. The other question that we always you know, I think it's a good question to ask intellectually is excluding the procedure related bleeding once your appendages closed. Has that timeframe onward compared to left atrial appendage conclusion has actually compared to or atlantic coagulation. Um And we would expect really this one that strongly favor left atrial appendage closure because you know again, you're excluding the procedure related bleeding events. And you're just asking the question from the safe discharge from the hospital outside the procedure window, how does appendage closure compare with oral anticoagulants? In one group is on anti coagulation, one group is not and and these obviously there's a strong trend for left atrial appendage closure, but it was not significantly different at that point. And this was playing as a five year travel. These are about three year results. So as time goes on, they will be more and more bleeding in the blood thinner groups. So that based on that trend, there probably will become significant at some point. It's just not quite there yet. Yeah. So the other device that's on the near term horizon is the Amulet device from Abbott. This is a slightly different technology aimed at closing the appendage. You can see there, it's got a disk that sits over the face of the of the Austrian uh gives you closure more approximately into the left atrium. There's very little pouch left behind if this is done properly and then the anchoring unit there further inside the appendages called the lobe. So it's a disk in lobe shape. You'll hear this referred to this. This trial has completed its U. S. I. D. E. Enrollment there under its undergoing follow up. So we would expect the U. S. I. D. Results here in the not too distant future. The data that we have, the largest set of data is from a european observational study. So these were patients again with a defibrillation who have an appropriate indication for appendage closure underwent an ambulance. You can see the t. follow up was only at 1-3 months in the I think a lot of senators in the U. S. We also do a transit off to echo follow up looking for D. R. T. At one year as well. That will become important here to second. I'll show you so good numbers of patients enrolled. Good numbers of patients implanted. There was some drop out but not meaningful here. The primary endpoints, so relatively low complication rates, both early and late And then. I think here's the here's the important strides slide. So ischemic stroke 2.2 per year. And the way you analyze these trials before you have the randomized prospective trial which again has been completed in the US. is you look at what's the anticipated stroke rate versus the observed stroke rate Based on a similar Chad's ask patient population to expect perhaps a 6.7 incidents per year of stroke and after an annual it device That reduced to 2.2%. So the there's one other thing the D. R. T. Rate I think was somewhat impressive in this trial. You can see the D. R. T. Rate is 1.6%. Um That number is unexpectedly low and I think that's because they didn't do the one year follow up trans esophageal echo. They didn't want an echo at 123 months afterwards. I think if they added that one year number of the D. R. T. Rate would be comparable with what we're seeing with the older version of Washington. But that remains to be seen when we're awaiting the U. S. I. D. Try trial results and we'll get to see what that number is. Something go got to go back one slide here. So there are some very significant studies in progress where I mentioned that the annual latest we're awaiting those results. There's a trial called the catalyst trial. Now the major thing that's happening in the field is we're branching out to study patients who are reasonable candidates for all and a coagulation and Abbott and boston Scientific both have a trial that covers that patient population called the catalyst and champion trials. So again one of these is an omelet versus doc again in an oral anti coagulation eligible patients. And the other one is a Watchman flex versus does back again in oral anti coagulation eligible patients so that those who will be very interesting sets of data. Very important, large trials will go through some of the m points and the powering of that here in a second, the option trial is a post of a fibrillation trial that's comparing watchman flex and domack patients again and in patients that are able to take or atlantic coagulation. That again, is a very large trial with three years of follow up. And and again, asking the question, how do these patients do with appendage closure vs. Orlando coagulation? So, just to take a look quickly at the catalyst trial, you can see that these are, you know, kind of breaks down the number of a fib patients that we have as you follow the follow it down. Oh, I see intolerant perhaps 35 of patients. And those are the ones that go to the current appendage closure programmes. But the osc tolerant, you know, a good number of those patients. Uh And the question is are they better served with oral, anti coagulation or independent conclusion procedure. I think this is one of the more interesting things. These studies are powered well enough to to use ischemic stroke as a primary endpoint. So you can see that one of the primary endpoints and the catalyst trial and also the champion trial as well. As they specifically asked the question, you know, is the ischemic stroke rate different uh comparing organic organization with appendage closure. That sort of gets to the fundamentals of the question of how important is left atrial appendage. We really feel that that's the most important driver of stroke in patients that they fit. But it would be nice to have more data showing that by closing it. You do the same good job that you do with or atlantico regulation. Okay so again in conclusion the punished closure is a safe and effective alternative to Orlando coagulation at this time for patients that are poor candidates for two or Atlanta coagulation. Future studies again are certainly going to expand our knowledge base and in particular expand our knowledge base in the region of patients that are candidates for Atlanta coagulation and answer the question for us. You know, what should we be doing treating them with Orlando coagulation indefinitely or appendage closure. So thank you very much. That's my twitter twitter handle at the bottom. And um let's see if we have any questions in the chat room. Otherwise we get ready to move on to the next speaker here. Any any of the moderators have any questions about anything or anybody see any questions that need burning questions that need to be addressed. Maybe a quick question duck. Um What is your current practice of post watchman? If somebody comes in with a fib and you need to cardio verden. Yeah so uh no cardio versions within the first month. And then I've been pretty liberal about recommending transits off to echo uh screening the D. R. T. Rate is not insignificant and I don't actually do those cardioversion my partners do and I would hate to get them stuck in a situation where there is it for the patient as well. They're you know they're thinking about the patient primarily. I don't want a bad outcome for them. Also the guy who's doing the cardioversion, I don't want that person to get burned by having A. D. R. T. That was unbeknownst to them. So I think in general most of our people are doing t guided cardio versions or at least you know maybe a ct examination ahead of time to make sure now we're pretty careful program. And so most of our patients have had some uh good follow up after a watchman. So generally we can just look back to the previous T. E. And if that looks good and it's only a couple months later then those patients will just go ahead and get cardio burden. Is that what you guys been doing? Yeah I think looking for. And if the leak is I think Rockfish recently published that less than five millimeters that's okay. Safe to go ahead and just cardioverter and no need to anna calculate. I think the biggest question that always comes up is do we need to and accumulate them a post cardioversion for a month or is it okay? You know not all thomas comes from the left atrial appendage. Are we obligated to or can we just safety cardio rhythm? I think I still do that now. These are this is an interesting group of patients. Some of them are very high risk for bleeding. So it's really an individualized decision application is relatively lowest bleeding and we have the option and generally because of the atrial stunning of advise that they take anti coagulation for a month or some of these patients will come back for ablation as well. And we do the typical post ablation two or three months of or atlantic regulation but super high risk. And they really really really need to be car diverted. There's an occasional patient in there that we won't coagulate, but I would say that's that's extremely rare.
