Welcome to the 2021 Quality Summit. Thank you for sharing your time with us today. I have the distinct honor to welcome our speaker for today, Dr. Paul Verossi, who is presenting on the topic LAAO Procedure Decision Making and Patient Selection. Dr. Verossi is a clinical electrophysiologist and the Director of Cardiac Electrophysiology at the VA Eastern Colorado Health Care System, and he is a professor of medicine at the University of Colorado. He has been so generous in sharing his clinical expertise and guidance with the ACC over many, many years. He has been an integral part of the NCDR registry programs. Throughout the years, Dr. Verossi has been part of registry data set development work groups and a member of the steering committee for all three registries, the EP Device Implant Registry, the AFib Ablation Registry, and the LAAO Registry. He is currently serving as the chair of the LAAO Registry. Welcome Dr. Verossi, and thank you for sharing your time with us today. Thank you so much, Christina, and thank you to the organizers of the program to invite me here to speak to you about this topic. I'll be speaking to you about left atrial appendage occlusion procedure decision-making and patient selection. Over the next 35 minutes or so, we'll talk about a handful of topics, including understanding the stroke risk and non-valvular atrial fibrillation, and then the options of oral anticoagulation versus left atrial appendage occlusion that are really behind the decision-making that we're talking about. It makes sense to include some discussion about the concept of shared decision-making in left atrial appendage occlusion, especially because the Center for Medicare and Medicaid Service is mandating that this is being performed as part of the reimbursement rule. And then finally, putting things all together to discuss the evolving options for stroke risk reduction and non-valvular atrial fibrillation. So why would we even consider left atrial appendage occlusion? Why are we here? Well, from a big picture standpoint, non-valvular atrial fibrillation is common and increased with a fairly dramatically increased stroke risk, of which 90% or so is due to left atrial appendage thrombus formation. Anticoagulation along the mainstay of treatment for stroke risk reduction is very effective in reducing risk, but it's problematic in many people, as we will discuss. And then finally, occlusion of the left atrial appendage is an alternative to anticoagulation for which we've had emerging data over the past several years. Alan Goh, in this prescient manuscript from 20 years ago in JAMA, predicted a fairly dramatic growth in atrial fibrillation over the years, and this is exactly what we've seen. And this is partly why we're here talking about this, that we've had a dramatic explosion of patients who have this condition and that we need to treat to address their stroke risk. So how do we actually address this stroke risk? Well, we can stratify patients based on epidemiological data that emerged using the CHADS-VASC score, which is an acronym that stands for congestive heart failure, hypertension, age, diabetes, stroke, atherosclerotic vascular disease, and female sex. And based on how people stratify in here, you get a number of points in the scoring system. You'll notice that a number of these same factors are also involved in the bleeding risk stratifier, the HASBLED score, hypertension, prior stroke, being elderly are also the same factors that are included in the CHADS-VASC score. And the bottom line there is that this produces a dilemma. The patients who are at the highest risk for stroke are also often at high risk for bleeding, which makes the treatments of anticoagulation problematic in many patients. If we look at the data across the many, many randomized trials that have looked at warfarin antiplatelet agents and the DOACs, we can see that there's a large body of evidence to support the fact that warfarin is quite effective in reducing stroke risk. Antiplatelet agents work as well, but they're not quite as effective as warfarin. So warfarin is far more effective than the antiplatelet agents. If we look to the novel oral anticoagulants or the direct oral anticoagulants, such as dabigatram, also effective and actually seems to have a similar to lower stroke risk than warfarin. Similarly with rivaroxaban in a large randomized trial, the ROCKET-AF trial also reduced risk of stroke and seemed to have comparable, if not slightly lower risk of stroke associated with its use. And then in the Aristotle trial, apixaban, similar results, lower bleeding risk and seemingly lower stroke risk as well. And in fact, in the AVEROS trial, a comparison among patients who were deemed so high risk that they were unsuitable for warfarin, they randomly assigned them to receive either aspirin or apixaban. And what was remarkable in this trial was that while the risk of major bleeding was comparable with apixaban and aspirin, the stroke risk reduction was so dramatically greater with apixaban that now our guidelines as of late have really downplayed the use of aspirin at all in the majority of patients with non-valvular atrial fibrillation. So the bottom line for the oral anticoagulant options, we have the options of warfarin and the direct oral anticoagulants, and these have the advantages of reducing stroke risk fairly dramatically, and they're well tolerated by many, many patients. The downsides to oral anticoagulants are that it does require taking a medication. There are potential drug-drug interactions, and they can't be tolerated by all patients. There are some warfarin-specific problems, such as burdensome INR testing, and the fact that a stable INR between 2 and 3 really can't be achievable in everyone, even when patients are doing their best. And there are DOAC-specific problems, such as the high cost of the medications, and the fact that in the event of life-threatening bleeding, reversal is a challenge, although we have reversal agents such as Idarocizumab and dexamethalpha. These are expensive and not available everywhere. And then, of course, any anticoagulant carries a bleeding risk just by nature of the fact that their mechanism of action involves blunting coagulation. Bottom line here is that many patients will tolerate long-term anticoagulation. Some may tolerate short-term anticoagulation for a procedure, but some may not be able to tolerate anticoagulation at all, and until recently, they have not really had good options for stroke risk reductions, and we've just accepted that they've had to have a higher risk of stroke than others. Left atrial appendage occlusion is potentially an option here for us to address this risk and avoid oral anticoagulation, and those options include surgical approaches, endocardial device implantation, which with the Watchman device, the implants are amulet, occluder, and other devices that are currently in development. In addition, there is also the endocardial-epicardial suture ligation device with the Lariat. Surgical left atrial appendage occlusion via ligation with devices and other approaches has been employed for a long time, and only recently, such as at ACC21, the LAOS-3 trial results were presented demonstrating a stroke risk by about one-third, which is great news for our patients undergoing open cardiac surgical procedures. The Watchman device is an endocardial implant that's implanted via transeptal catheterization and was originally approved in 2015 on the basis of the PROTECT-AF and PREVAIL trials, which we will discuss, and then as of last year, the Watchman Flex device was approved, which is a shorter device with a larger array of sizes that can accommodate a much larger range of left atrial appendage ostea, ranging from 15 to 32 millimeters. Given the fact that it doesn't have the open tines at the end of the device, it's less traumatic, and now with the approval of the Watchman Flex device, the FDA has also approved a new DOAC-based anticoagulation regimen for the device. In comparing these two on the left in panel A, you'll see that there is, you see the open tines of the original Watchman device, and then with Watchman Flex, this is much more protected. Also, it's shorter in length, which means that it can fit in a wider range of appendages. Also, and I think operators like the fact that the device can be partially deployed in what we're calling the flex ball, that allows for a blunt, relatively minimally traumatic approach to placing the device in the appendage itself, which has its appeals interprocedurally. The Amplatzer Amulet Occluder is also an endocardial implant device that has a slightly different structure. It's a dual closure that involves both a lobe and a disc that covers over the surface of the ostium of the left atrial appendage, and which will appeal to many. There is no need for an oral anticoagulant afterwards, so no DOAC, no Warfarin at all. And also of note to a lot of us is that this device was just approved by the FDA on August 14th of this year. The Lariat device, which includes both an endocardial and epicardial approach, involving transeptal access by placement of a catheter with the balloon inside the left atrial appendage, and at the tip of that catheter is a magnet, and via an epicardial access-based approach, a second catheter with a magnet is opposed through the thin apex of the appendage, and then the Lariat is passed over the device to the base, and then it's suture ligated to close the device. We do not yet have a large-scale randomized trial proving efficacy for stroke risk reduction for the device. Bottom line, among these three endocardial approaches, both the Watchman and the Amplatzer device are approved for stroke risk reduction in non-valvular atrial fibrillation, but the Lariat device at this point is approved only for suture ligation of tissues. The Watchman device randomized trials include both the PROTECT-AF trial, which included just over 600 patients, showing both a comparable outcome in the primary endpoint and also the sub-endpoints of stroke and all-cause mortality. Similarly, the PREVAIL trial showed similar outcomes, although not statistically significant. There seems to be a slight reduction in benefit of the device in year two, which makes ongoing registry studies, such as those from the left atrial appendage occlusion registry, so important in understanding the real-world outcomes in these patients. After the publication of those two randomized trials that were really the basis of the FDA's approval of the Watchman device in 2015, there have been ongoing studies, including the Continued Access Protocol, CAP, and the CAP2 from the two randomized trials, plus the Evolution European Registry, a U.S. non-regulatory study for the initial experience published by Vivek Reddy, which we'll see in a moment, and then evolving data from the NCDR left atrial appendage occlusion registry. The Evolution Registry in Europe included a publication of about 1,000 patients in 47 centers in its initial publication, with about a 98.5% procedural success, 2.8% total adverse event rate, and a 9.8% one-year mortality, reflecting really the comorbidity burden and competing risks in this patient population. Vivek Reddy and colleagues published the initial experience in the U.S. prior to the fact that the LAAO registry was up and running, looking at the initial approval from March of 2015 through 14 months later in 2016, involving just over 3,800 patients in about 170 centers, showing a very high degree, greater than 90%, made 5% procedural success, and a very low rate of procedural complications. From the LAAO registry, we now have well over 80,000 patients in the registry being followed. And last year, Jim Freeman led the publication of the first couple of years of experience from the registry, and at that point, 38,158 patients, essentially many times the size of the randomized trials that had been published of left atrial appendage occlusion, with a fairly substantial burden of age and comorbidity, mean age of 76.2 years, Chad's VASC score on average of 4.6, so fairly high stroke risk, and a high bleeding risk as well of 3.1. Despite all of this, the real-world outcomes were quite good, with major adverse event rate in the short term of only 2.16%, which is lower than in both the EVOLUTION registry and in the randomized trials. Just a couple of months ago, Matthew Price, on behalf of the Steering Committee, presented the one-year outcomes at ACC21 from the LAAO registry, showing a one-year stroke risk of 1.53%, which is really quite striking. When you put this into the context, also thanks to Matthew for his contributions and leadership of this important study, if you place this in the context of looking at, both in blue, the risk of stroke untreated with anticoagulation, the risk if these patients were treated with warfarin in green, and the reference comparisons of the various trials that I've mentioned to you, including PROTECT-AF, PREVAIL, CAP, CAP2, and EVOLUTION registry, as well as our findings from the NCDR left atrial appendage occlusion registry, you see that we really have a favorable option for the use of left atrial appendage occlusion in the real world with regard to real-world effectiveness for stroke risk reduction. The AMPLATs are AMULET. This is hot off the press as of August 30th, 2021. D.J. Lacaretti and colleagues published the result of a randomized trial at the ESC just not long ago, comparing WATCHMAN versus AMULET in a trial of almost 1,900 patients, showed not surprisingly, given the fact that there is that disk over the surface of the ostium of the appendage, that there is superior short-term closure and non-inferiority for safety and effectiveness of the device over a couple of years of follow-up. So it's great that this is an option, and it was on the basis of this that the FDA approved the device. So if you consider back to the FDA's original approval in 2015 of the WATCHMAN device first generation, their original label included indications for patients with non-valvular atrial fibrillation increased stroke risk, where there is an indication for anticoagulation, and the patient is suitable at least for short-term warfarin at the time, and at the same time some reason to seek an alternative to anticoagulation. With the approval of the WATCHMAN FLEX last year, they added that DOAC is now a reasonable therapeutic alternative to warfarin in the treatment algorithm. The current treatment algorithm then for the WATCHMAN device post-implant includes either a direct oral anticoagulant or warfarin at implant until 45 days after the device is implanted and or left atrial appendage seal. From 0.81 to 100 milligrams at implant until seal, and then going up to full-dose aspirin. And then clopidogrel goes from the point that the DOAC or warfarin are stopped until six months out. With the approval of the AMULET device, there is no DOAC required, and aspirin and clopidogrel are used. Not to be left behind, the Boston Scientific and investigators are pursuing the possibility of whether the Watchman device can be safely implanted without the use of a direct oral anticoagulant. This is the basis of the ASAP2 trial, which is looking at exactly that question, planting the Watchman device without direct oral anticoagulant. And stay tuned, this is anticipated to be presented sometime in the coming years. When the Center for Medicare and Medicaid Services came out with its coverage determination for percutaneous left atrial appendage occlusion, it came out with similar sorts of indications and comments that the FDA included with some slight variations. They said that they would fund left atrial appendage occlusion in patients with non-valvular atrial fibrillation and increased stroke risk, and that a shared decision-making interaction had to be included in the process. These patients had to be suitable for at least short-term, but not long-term anticoagulation. They included specifications for the team implanting it that was trained in performing the procedure and performing a sufficient number of left atrial appendage occlusion procedures and ongoing other procedures with transeptal catheterization. They also mandated enrollment in the registry that ultimately they approved, and that actually is the left atrial appendage occlusion registry. Interestingly though, at the time that these sets of criteria came out, there were no suitable shared decision-making tools available to support this process. Shared decision-making can be supported by formal decision aids. Decision aids are formal tools that support the process of shared decision-making, including imparting the knowledge that patients need in a carefully constructed manner that is supported by literacy experts and graphic artists and other folks, and reviewed by focus groups of both patients and providers to ensure that they are of value to patients. Second, a process for eliciting the values, and then finally a mechanism for executing a patient-centered informed decision. These can exist in a variety of formats, including infographics, videos, interactive websites, and other sorts of constructs. Importantly, decision aids support but do not replace the formal shared decision-making interaction between a patient and an appropriately trained clinician. When we looked at the process of shared decision-making by polling LAO registry participant sites, we found that things were all over the place with how these decision-making interactions were being conducted. Some sites were having the referring physician document that shared decision-making had been conducted. Some sites were having a non-interventional physician in their own practice conduct that interaction separate from the proceduralists. Some places were having the procedural operating physician conducting that decision-making interaction, and there were other approaches that sites took as well. But the fact that there was such a variation in how this was being conducted and in the absence of tools really told us that there was a gap that needed to be addressed. So it's really been my pleasure to work with an amazing team here led by my colleague and friend, Dr. Dan Matlock here at the University of Colorado in partnership with the ACC to develop formal tools for exactly this purpose. And our team, again led by Dan, developed these tools and are available on the CardioSmart website for patients for low-risk, medium-risk, and high-risk for thromboembolic stroke risk in non-valvular atrial fibrillation. They include, I think, well-crafted and clear descriptions for patients about stroke risk using pictograms and various other sorts of things that can help to impart risk in a patient-friendly sort of way, both with and without treatment. Ways to compare the options with the various pros and cons, including warfarin, the direct oral anticoagulants, and for those patients with high risk of stroke, such that left atrial appendage occlusion is an option, including both patient-friendly visualizations of what these devices look like, what they involve, and the pros and cons of them are. The bottom line now is that we do have a growing range of treatment options with both oral anticoagulants and also with left atrial appendage occlusion for reducing stroke risk in patients with non-valvular atrial fibrillation, and we also have decision aid options to support these CMS-mandated shared decision-making interactions. Left atrial appendage occlusion does have a number of advantages, including providing an alternative to oral anticoagulants, and it allows stroke risk reduction in patients in whom oral medications are associated with unacceptably high bleeding risk. The disadvantage to the left atrial appendage occlusion procedures are that they require an invasive procedure with a highly specialized multidisciplinary team. There are procedural risks, of course, in all patients, some higher than others. The cost of the procedure may be prohibited in some. It may not address non-left atrial appendage-associated stroke risk, and it's not anatomically feasible in all patients, although with newer devices, as we've already seen with the Watchman Flex as opposed to the first generation device, this is improving and we are seeing a wider range of patients who can be treated. The bottom line here is that with the evolving options we have for stroke risk reduction among these patients, oral anticoagulation remains the mainstay in the majority of patients who can tolerate it, and then percutaneous left atrial appendage occlusion is an excellent option, including the Watchman Flex device in patients who can tolerate at least short-term oral anticoagulation, until we have evidence from the ASAP2 trial to say that we can do it without oral anticoagulation, and the Amplats or Amulet device is an option for patients who even may be entirely contraindicated for them to take oral anticoagulants, and then surgical left atrial appendage occlusion is an excellent option for patients undergoing cardiac surgery for other reasons. The bottom line here is that the MCDR left atrial appendage occlusion registry will be there to measure the ongoing safety and real-world outcomes as these options involve, and we will look forward to presenting those data to you. So in summary, over the last half hour or so, we talked through some explanations of the basis for the stroke risk in non-valvular atrial fibrillation, the treatment options, pros and cons of oral anticoagulation versus left atrial appendage occlusion, and the evidence underlying them. We talked a little bit about shared decision-making, and we talked about the evolving options for stroke risk reduction in non-valvular atrial fibrillation, and with that, I will thank you. Thank you very much, Dr. Varossi, for that valuable information, helping us understand a little bit more about the left atrial appendage occlusion procedure. We do have a few questions that have come in. I think we'll just tackle those. We have a little bit of time here. First question is asking, the procedure indication mentions the patient has to have the non-valvular AFib. In addition, has to have an increased stroke risk, but it also states the patient should have appropriate rationale to seek non-pharmacological alternative to oral anticoagulation. How should an appropriate rationale be interpreted? Is it appropriate that it's a patient choice, that they would prefer to have the procedure? Is that considered or deemed appropriate rationale? Well, I would say that this is kind of in the eye of the beholder. I think if we look at both the CMS reimbursement rule and the FDA label, I think that the wording of reason to seek a therapeutic alternative, what I would tell you is that from what we are seeing in the real-world experience from the LAO registry, overwhelmingly these patients are at very high risk for bleeding, and the majority of them do have some kind of bleeding problem. As time goes on, will it be increasingly the sort of thing that we may see larger numbers of patients where they simply don't want to be taking oral anticoagulants, where it's their choice? I suspect that we probably will, and I think that having the data to support the ongoing safety and real-world effectiveness of that is exactly one of the reasons why the left atrial appendix occlusion registry exists. Thank you. Another question that came in, have most patients who are eligible for ablation, they already had their ablation done when they present for the LAO procedure, or is LAO performed first or concomitantly with the ablation? How does it usually transpire? Well, I didn't bring up the AMAZE trial, but there is a trial going on currently with concomitant ablation and left atrial occlusion using the Lariat device that is looking at this happening simultaneously. Certainly, there are some places that are performing ablation and left atrial appendix occlusion simultaneously. What I would say is that in the majority of patients, these are separate issues. Addressing symptoms of rhythm control with either antiarrhythmic drugs or ablation is one domain of question, and addressing their stroke risk is a separate domain of issues. They're not necessarily in the same patient. They're not necessarily occurring in a given patient, both of them happening. They're just separate issues. In your experience, though, do you typically see patients who have already had an ablation when they present for the LAO, or is that not common? Not necessarily. I guess the way that I would say it is that in my practice, the majority of the patients undergoing atrial fibrillation ablation are people who tolerate oral anticoagulation just fine and may have a CHADS-VASc score of zero or one, and so don't need to take oral anticoagulation over the long term, but they're highly symptomatic from their rhythm aspects of the condition. Whereas patients undergoing the left atrial appendage occlusion are older, in their 70s and 80s, with having multiple bleeding problems and not necessarily so symptomatic from a rhythm standpoint, so they may not even need an afib ablation procedure, but they need to have the bleeding risk and stroke risk addressed. Yes, there are going to be some patients who may have both procedures, but they're really very different subsets of the group of patients with atrial fibrillation. That makes sense. Thank you. That's very helpful. We do hear a lot about afib ablation and heart failure. Does having heart failure impact patient selection for LAO in any way? Of course. I think that having congestive heart failure is a risk factor for morbidity and mortality with any sort of procedure. It does make things a little bit challenging. The bottom line here is that most people will tolerate the procedure for left atrial appendage occlusion if they have strong indications for it, and it's performed in the center with sufficient experience with the procedure. Most people will tolerate it quite well. It's a relatively short procedure in most places occurring in under an hour. It doesn't come with a very large fluid load, and it can be performed safely in most. Do you see currently after the procedure the patient has to stay overnight? Is that the case still, or are you seeing same-day discharge? Well, I suspect that it's definitely occurring in some places. I think in our university-based system, we're still admitting patients overnight for the procedure. We'll be keeping an eye on that and understanding what's happening in the real world. This is one of the places where working in something like the left atrial appendage occlusion registry is so gratifying. We get to actually see and understand what's happening in the real world. A next question that's come in. The procedure is indicated for patients with increased stroke risk and non-valvular AFib. Is it indicated for non-valvular AFib regardless of the AFib classification or AFib type, so it doesn't matter whether it's paroxysmal, persistent, and has no influence on that? Absolutely. This fits well with what we were talking about earlier that stroke risk reduction and rhythm control and the symptoms of the rhythm are often two separate things. There are patients who may have only infrequent paroxysms of atrial fibrillation, but with a high CHADS-VASc score may be at fairly substantially increased risk of stroke. So the way that we treat them in terms of addressing their stroke risk doesn't really necessarily change whether they're paroxysmal, persistent, or permanent AFib. Next question we have here. Are there any other patient risk factors that would prevent a non-valvular AFib patient from being a candidate for LAAO? Sure. Of course, you have to have a viable venous conduit from the femoral, either left or right femoral vein, to be able to get to the right atrium for the transeptal catheterization. I could imagine that if patients have a septal occlusion device in place such as PFO or an ASD closure device, and many patients may preclude being able to get across with transeptal catheterization for left atrial appendage occlusion. There might be certain left atrial appendage anatomies, such as those very small ones with less than 15 millimeters in diameter or greater than 32 millimeters in diameter, that would not allow the Watchman device. The amulet is so new that I don't have enough facility yet to be able to answer the limitations with them. And then weighing the potential risks, there may be individual patient factors that relate to risk that might make any of these procedures prohibitive. Thank you. And I think we have time for one more question here. Do you think we still have underutilization of this procedure? Is there a way to identify candidate patients more easily and more thoroughly? Well, I can say that we know that the group of patients with non-valvular atrial fibrillation and an increased stroke risk are being undertreated in general. We know that's true for oral anticoagulation. Some of that is a function of high bleeding risk. Some of it is just that we don't do a good enough job of ensuring that the right patients get the right treatments. It's hard to know really, I think, from our data in the left atrial fibrillation inclusion registry, whether there is undertreatment out there with regard to this device, although I suspect there is, because we really are only able to look at the patients who actually got their devices ultimately. I think that we'll need to look to other sources to be able to understand that better. But at the end of the day, I do suspect that there still is somewhat less utilization of all of these treatments and the remains undertreatment in patients with non-valvular AFib. Thank you. Well, I think we're out of time, and I want to thank you again, Dr. Varosi, for this wonderful presentation and sharing your time with us today. I know I've learned a lot. I'm sure our audience has as well. I also want to thank our audience for taking the time to be with us today, for all that you're doing to support optimizing patient care, and I hope you have a great rest of your day. Thank you. Thank you so much. I'll look forward to seeing the data evolve over the coming years with the left atrial fibrillation inclusion registry.

LAAO procedure decision making

patient selection

atrial fibrillation

stroke risk reduction

oral anticoagulation

surgical approaches

endocardial device implantation