Advances in LAA Closure and Occlusion
In this episode, Albert C. Lin, MD, associate professor of Medicine in the Division of Cardiology at Northwestern Medicine, discusses the treatment of LLA closures, including the devices that are impacting outcomes.
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Learn more about Albert Lin, MD
Albert Lin, MD
Albert Lin, MD is an associate professor of Medicine in the Division of Cardiology at Northwestern Medicine.Learn more about Albert Lin, MD
Transcription:
Advances in LAA Closure and Occlusion
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to listen as we discuss advances in left atrial appendage closure. Joining me is Dr. Albert Lin. He's an Associate Professor of Medicine in the Division of Cardiology at Northwestern Medicine. Dr. Lin, it's a pleasure to have you with us. And this is a really great topic and the prevalence that we've seen in AFib, I'd like you to discuss that with us and start by telling us a little bit about what you've seen in the trends.
Albert Lin: Let me first start by thanking you for this opportunity to discuss left atrial appendage closure with both you and your listeners. I would be remiss if I just launched straight into talking about left atrial appendage closure without at least reminding the listeners that we need to spend a lot of time and effort in trying to identify the patients who are at risk for stroke from atrial fibrillation. Upwards of 6 million Americans have atrial fibrillation at this point in time. It is a strong risk factor for stroke. If you have atrial fibrillation, you have four to five times the risk of stroke of an individual that does not have atrial fibrillation. It probably causes about half of the embolic strokes in the United States per year and can responsible for upwards of maybe even as high as 75,000 strokes a year.
We also know that the mainstay of therapy for stroke prevention in atrial fibrillation is anticoagulation. But if you sort of look at the trials looking at anticoagulation, we can see that of the individuals that would benefit from anticoagulation, depending on the series you look at, anywhere from about 30% to 50% of individuals are not getting the therapy with anticoagulation. And we know that that risk of not receiving anticoagulation therapy, which is remarkably effective at preventing stroke, increases with age. And that may be due to other risk factors associated with anticoagulation, such as the risk of bleeding. And that's sort of where left atrial appendage closure fits into this therapy for atrial fibrillation, which is a prevention of stroke, a method of preventing stroke without the use of anticoagulation long-term.
Melanie: And certainly, anticoagulation long-term is not ideal for some patients, whether it's adherence or, as you say, for bleeding. So in what ways are devices such as Watchman, which we're going to talk about and the Amplatzer Amulet evolving this treatment?
Albert Lin: Right. So the left atrial appendage closure devices have been a remarkable sort of evolution in therapy in trying to prevent stroke without the use of systemic anticoagulation. It is based upon the fact that about 90% of the strokes caused by atrial fibrillation involved thrombus arising from one specific anatomic location within the heart, which is the left atrial appendage. Left atrial appendage is a vestigial remnant of fetal development of the heart. It is very different from the rest of the left atrium, where the left atrium is quite smooth. The left atrial appendage has a lot of trabeculations in it, which causes even more stagnant blood flow when the patient's in atrial fibrillation. And the left atrial appendage closure devices, both Watchman and the Amulet device, which was just approved for commercial use late in 2021 take advantage of the fact by having a device that occludes the opening to the left atrial appendage, thereby preventing thrombus from exiting the left atrial appendage.
The Watchman device has clearly been shown in two clinical trials to be non-inferior to anticoagulation with warfarin in the prevention of stroke. And the Amulet device was approved by the FDA based upon a large clinical trial, comparing it to Watchman device and again, demonstrating that the Amulet device is non-inferior to that of Watchman.
So we see it in a group of patients that are at risk for stroke from atrial fibrillation, that may be at higher risk for bleeding, that there is now a therapy available for them to reduce the risk of stroke, probably as well as anticoagulation, certainly of anticoagulation with warfarin without the use of long-term anticoagulation.
Melanie: So, how is Northwestern Medicine using these devices? Tell us what you're doing with them right now.
Albert Lin: So we have a very active program. We were very active in the initial clinical trials for Watchman and we're early adopters of the Watchman FLX device, which was the second generation device that became available after initial approval of the Watchman 2.5 device. We are also involved in the clinical trials with the Amulet device and the pivotal Amulet IDE trial, which obtained FDA approval for the Amulet device. We have an active program screening patients for left atrial appendage closure. We are very active implanting both devices at this point in time. We thus far have winded to sort of follow the clinical data, which is we have reserved these devices for individuals that are really increased risk for complications from long-term systemic anticoagulation and so therefore have sort of tried to limit these devices to that group of patients where we think that they will have the greatest benefit from it.
However, there are unusual cases for instance, where we'll have to consider unusual applications of the device. For instance, we have implanted device in sort of a non-FDA approved indication, but in individuals that have persistent left atrial thrombus, despite anticoagulation, we have actually implanted some of these devices with cerebral protection in an effort to try to, in a sense, rescue them from failure of anticoagulation and persistent thrombus within their left atrial appendage.
Melanie: Well, Dr. Lin, as you're telling us a little bit about patient selection and ideal candidates, speak about some of the factors that play the biggest role in impacting outcomes. Are you using this procedure along with other adjuvant therapies? Tell us a little bit about your outcomes and why patient selection is important.
Albert Lin: In addition to the original indications for the device, which is by most criteria at this point in time, reserved for individuals that are deemed to be poor long-term anticoagulation candidates, probably the biggest factor in implant success is the anatomy of left atrial appendage. The left atrial appendage has variety of different anatomies. They are given colloquial terms such as a broccoli shape or a windsock shape, a chicken wing or reverse chicken wing. And a lot of these different anatomies can be somewhat more challenging than other anatomies. We tend to focus in on imaging the anatomy both by either CT or by a transesophageal echocardiogram prior to the implant, and then try to tailor which device that we implant either Amulet or the Watchman device based upon certain anatomies that we see.
The other thing that we like to do, which helps I think with the implant, is the use of intracardiac echo. While a lot of implants with left atrial appendage devices is guided by transesophogeal echocardiograms at the time of the implant, which we also do use. We also favor using the intracardiac echo, which gives us very good pictures also when we place the ICE catheter within the left atrium and image the device, including the imaging of the deployment itself through the ICE catheter, which then I think also helps tremendously during the implant.
Melanie: Would you like to tell us, Dr. Lin, about Northwestern Medicine and any involvement in clinical trials that are related to these devices?
Albert Lin: Yeah, we actually do have two clinical trials that I think are actually quite important for the evolution of the indications for left atrial appendage closure devices, both with Watchman and with Amulet. The first is the CATALYST Trial. The CATALYST Trial is a trial randomizing in a one-to-one fashion the Amulet device versus a direct oral anticoagulant, and also the CHAMPION-AF Trial, which is again another trial looking at randomizing individuals between the Watchman FLX device, which is the newer generation device in a one-on-one fashion against oral anticoagulation with the direct oral anticoagulants. I think both these trials are critically important because they are randomized against essentially the newer agents for anticoagulation, which has now taken over from warfarin as the leading medications being used for anticoagulation at this point in time. Since we don't have direct trials, other than some smaller trials published from Europe, this is going to be very important to sort of see where the left atrial appendage devices fit in the sort of armamentarium of therapies that we have for the prevention of stroke in atrial fibrillation.
And so therefore, you know, we highly encourage anybody that has patients that may be interested in a device that will allow them to get off anticoagulation, to at least consider enrollment in either one of these two. It is a randomized trial. And so therefore patients and obviously we don't get to choose whether or not they get the device or anticoagulation, but these are going to be two pivotal trials to sort of answer a lot of questions that we have regarding these devices versus the direct oral anticoagulants.
Melanie: Speak a little bit before we get ready to wrap up about the clinical implications from these clinical trials. How do you envision your research translating to patient care? What do you see happening in the next few years?
Albert Lin: This is a really interesting question. And I think some of this is going to be dependent on the data coming from these two clinical trials. One of the things that's been interesting about left atrial appendage closure is that there's been slight disconnect between the original clinical trials demonstrating non-inferiority against warfarin versus sort of the clinical indications that we currently use.
So when we look at the PROTECT and PREVAIL Trials, which were the randomized trials of Watchman device, the original Watchman device versus Coumadin, in order to enter the trial, you had to be a equally good candidate for either therapy, right? So you had to be a candidate that could tolerate anTIcoagulation and you had to be a candidate that could tolerate the implant of the device, where we've seen the clinical indications has really been shunted more towards individuals that were deemed to be poor anticoagulation candidates or poor long-term anticoagulation candidates. So this is not exactly the population that was studied.
What will be interesting with the newer trials is that if the device demonstrates non-inferiority to a direct oral anticoagulant in a population that can have either direct oral anticoagulants or left atrial appendage closure device, that does bring up the possibility that left atrial appendage closure may not be just relegated to the group patients that are deemed to be poor anticoagulation candidates, but may actually be opened up to a much wider audience in a sense, in which a patient could choose either systemic or anticoagulation for the longterm or a potentially one-time procedure to have their left atrial appendage closed and then thereby avoid potentially life-long anticoagulation therapy.
Melanie: What an exciting time to be in your field, Dr. Lin. Thank you so much for joining us today. That was fascinating. And to refer your patient or for more information about advances in left atrial appendage closure and occlusion, please visit our website at breakthroughsforphysicians.nm.org/cardiovascular to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. For more updates on the latest medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole.
Advances in LAA Closure and Occlusion
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to listen as we discuss advances in left atrial appendage closure. Joining me is Dr. Albert Lin. He's an Associate Professor of Medicine in the Division of Cardiology at Northwestern Medicine. Dr. Lin, it's a pleasure to have you with us. And this is a really great topic and the prevalence that we've seen in AFib, I'd like you to discuss that with us and start by telling us a little bit about what you've seen in the trends.
Albert Lin: Let me first start by thanking you for this opportunity to discuss left atrial appendage closure with both you and your listeners. I would be remiss if I just launched straight into talking about left atrial appendage closure without at least reminding the listeners that we need to spend a lot of time and effort in trying to identify the patients who are at risk for stroke from atrial fibrillation. Upwards of 6 million Americans have atrial fibrillation at this point in time. It is a strong risk factor for stroke. If you have atrial fibrillation, you have four to five times the risk of stroke of an individual that does not have atrial fibrillation. It probably causes about half of the embolic strokes in the United States per year and can responsible for upwards of maybe even as high as 75,000 strokes a year.
We also know that the mainstay of therapy for stroke prevention in atrial fibrillation is anticoagulation. But if you sort of look at the trials looking at anticoagulation, we can see that of the individuals that would benefit from anticoagulation, depending on the series you look at, anywhere from about 30% to 50% of individuals are not getting the therapy with anticoagulation. And we know that that risk of not receiving anticoagulation therapy, which is remarkably effective at preventing stroke, increases with age. And that may be due to other risk factors associated with anticoagulation, such as the risk of bleeding. And that's sort of where left atrial appendage closure fits into this therapy for atrial fibrillation, which is a prevention of stroke, a method of preventing stroke without the use of anticoagulation long-term.
Melanie: And certainly, anticoagulation long-term is not ideal for some patients, whether it's adherence or, as you say, for bleeding. So in what ways are devices such as Watchman, which we're going to talk about and the Amplatzer Amulet evolving this treatment?
Albert Lin: Right. So the left atrial appendage closure devices have been a remarkable sort of evolution in therapy in trying to prevent stroke without the use of systemic anticoagulation. It is based upon the fact that about 90% of the strokes caused by atrial fibrillation involved thrombus arising from one specific anatomic location within the heart, which is the left atrial appendage. Left atrial appendage is a vestigial remnant of fetal development of the heart. It is very different from the rest of the left atrium, where the left atrium is quite smooth. The left atrial appendage has a lot of trabeculations in it, which causes even more stagnant blood flow when the patient's in atrial fibrillation. And the left atrial appendage closure devices, both Watchman and the Amulet device, which was just approved for commercial use late in 2021 take advantage of the fact by having a device that occludes the opening to the left atrial appendage, thereby preventing thrombus from exiting the left atrial appendage.
The Watchman device has clearly been shown in two clinical trials to be non-inferior to anticoagulation with warfarin in the prevention of stroke. And the Amulet device was approved by the FDA based upon a large clinical trial, comparing it to Watchman device and again, demonstrating that the Amulet device is non-inferior to that of Watchman.
So we see it in a group of patients that are at risk for stroke from atrial fibrillation, that may be at higher risk for bleeding, that there is now a therapy available for them to reduce the risk of stroke, probably as well as anticoagulation, certainly of anticoagulation with warfarin without the use of long-term anticoagulation.
Melanie: So, how is Northwestern Medicine using these devices? Tell us what you're doing with them right now.
Albert Lin: So we have a very active program. We were very active in the initial clinical trials for Watchman and we're early adopters of the Watchman FLX device, which was the second generation device that became available after initial approval of the Watchman 2.5 device. We are also involved in the clinical trials with the Amulet device and the pivotal Amulet IDE trial, which obtained FDA approval for the Amulet device. We have an active program screening patients for left atrial appendage closure. We are very active implanting both devices at this point in time. We thus far have winded to sort of follow the clinical data, which is we have reserved these devices for individuals that are really increased risk for complications from long-term systemic anticoagulation and so therefore have sort of tried to limit these devices to that group of patients where we think that they will have the greatest benefit from it.
However, there are unusual cases for instance, where we'll have to consider unusual applications of the device. For instance, we have implanted device in sort of a non-FDA approved indication, but in individuals that have persistent left atrial thrombus, despite anticoagulation, we have actually implanted some of these devices with cerebral protection in an effort to try to, in a sense, rescue them from failure of anticoagulation and persistent thrombus within their left atrial appendage.
Melanie: Well, Dr. Lin, as you're telling us a little bit about patient selection and ideal candidates, speak about some of the factors that play the biggest role in impacting outcomes. Are you using this procedure along with other adjuvant therapies? Tell us a little bit about your outcomes and why patient selection is important.
Albert Lin: In addition to the original indications for the device, which is by most criteria at this point in time, reserved for individuals that are deemed to be poor long-term anticoagulation candidates, probably the biggest factor in implant success is the anatomy of left atrial appendage. The left atrial appendage has variety of different anatomies. They are given colloquial terms such as a broccoli shape or a windsock shape, a chicken wing or reverse chicken wing. And a lot of these different anatomies can be somewhat more challenging than other anatomies. We tend to focus in on imaging the anatomy both by either CT or by a transesophageal echocardiogram prior to the implant, and then try to tailor which device that we implant either Amulet or the Watchman device based upon certain anatomies that we see.
The other thing that we like to do, which helps I think with the implant, is the use of intracardiac echo. While a lot of implants with left atrial appendage devices is guided by transesophogeal echocardiograms at the time of the implant, which we also do use. We also favor using the intracardiac echo, which gives us very good pictures also when we place the ICE catheter within the left atrium and image the device, including the imaging of the deployment itself through the ICE catheter, which then I think also helps tremendously during the implant.
Melanie: Would you like to tell us, Dr. Lin, about Northwestern Medicine and any involvement in clinical trials that are related to these devices?
Albert Lin: Yeah, we actually do have two clinical trials that I think are actually quite important for the evolution of the indications for left atrial appendage closure devices, both with Watchman and with Amulet. The first is the CATALYST Trial. The CATALYST Trial is a trial randomizing in a one-to-one fashion the Amulet device versus a direct oral anticoagulant, and also the CHAMPION-AF Trial, which is again another trial looking at randomizing individuals between the Watchman FLX device, which is the newer generation device in a one-on-one fashion against oral anticoagulation with the direct oral anticoagulants. I think both these trials are critically important because they are randomized against essentially the newer agents for anticoagulation, which has now taken over from warfarin as the leading medications being used for anticoagulation at this point in time. Since we don't have direct trials, other than some smaller trials published from Europe, this is going to be very important to sort of see where the left atrial appendage devices fit in the sort of armamentarium of therapies that we have for the prevention of stroke in atrial fibrillation.
And so therefore, you know, we highly encourage anybody that has patients that may be interested in a device that will allow them to get off anticoagulation, to at least consider enrollment in either one of these two. It is a randomized trial. And so therefore patients and obviously we don't get to choose whether or not they get the device or anticoagulation, but these are going to be two pivotal trials to sort of answer a lot of questions that we have regarding these devices versus the direct oral anticoagulants.
Melanie: Speak a little bit before we get ready to wrap up about the clinical implications from these clinical trials. How do you envision your research translating to patient care? What do you see happening in the next few years?
Albert Lin: This is a really interesting question. And I think some of this is going to be dependent on the data coming from these two clinical trials. One of the things that's been interesting about left atrial appendage closure is that there's been slight disconnect between the original clinical trials demonstrating non-inferiority against warfarin versus sort of the clinical indications that we currently use.
So when we look at the PROTECT and PREVAIL Trials, which were the randomized trials of Watchman device, the original Watchman device versus Coumadin, in order to enter the trial, you had to be a equally good candidate for either therapy, right? So you had to be a candidate that could tolerate anTIcoagulation and you had to be a candidate that could tolerate the implant of the device, where we've seen the clinical indications has really been shunted more towards individuals that were deemed to be poor anticoagulation candidates or poor long-term anticoagulation candidates. So this is not exactly the population that was studied.
What will be interesting with the newer trials is that if the device demonstrates non-inferiority to a direct oral anticoagulant in a population that can have either direct oral anticoagulants or left atrial appendage closure device, that does bring up the possibility that left atrial appendage closure may not be just relegated to the group patients that are deemed to be poor anticoagulation candidates, but may actually be opened up to a much wider audience in a sense, in which a patient could choose either systemic or anticoagulation for the longterm or a potentially one-time procedure to have their left atrial appendage closed and then thereby avoid potentially life-long anticoagulation therapy.
Melanie: What an exciting time to be in your field, Dr. Lin. Thank you so much for joining us today. That was fascinating. And to refer your patient or for more information about advances in left atrial appendage closure and occlusion, please visit our website at breakthroughsforphysicians.nm.org/cardiovascular to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. For more updates on the latest medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole.