"Hi, good morning. My name is DJ, Lakkireddy. I'm the executive medical director at the Kansas City Heart Rhythm Institute in Kansas City.
What is the background to this study?
Well, historically, we figured that the success rates of ablation for non-paroxysmal atrial fibrillation has not really moved a whole lot in the last 20 years of doing the standard strategies of pulmonary isolation or the lines or the substrate modification. Going after the complex fractionated ATL electrograms.
Last 15 years of work that has been done by several predecessors as well as our group, we found that the left atrial appendage could be an important contributor for arrhythmia because of the volume effect that it creates. And so there is more tissue for the perpetuation of arrhythmias. There is more triggered activity as well as intra-atrial reentry tachycardias that can come from the left atrial appendage in several groups of people.
And so with that premise in mind, there was a pivotal registry that really showed us that there could be potential benefit of the exclusion of the left atrial appendage by tying it off in addition to the standard ablation that we do in these patients.
What are the findings to date?
And so that is what led to what we call the aMAZE study, which was finished, and we presented the results of which, while we found that the LARIAT was an effective tool to close off the appendage with complete elimination of the appendage in about 86% of these patients with a very minimal complication profile, but we did not find an additive benefit in improving the overall outcomes of ablation in these patients.
Thus, the primary endpoint for mace did not meet. While there was a trend towards an improved outcome in these patients, provided that there was a larger volume of the left atrium. So in those patients that have a left atrium that is larger than 130 cc, these patients really had a 20% absolute delta in further improving the overall outcomes of the ablation.
What that means is, in patients who have remodelled atrium where the atria are sick, eliminating the appendage perhaps plays a very important role. And that could be by reduction of the volumes of the overall left atrium and also elimination of the triggers and tachycardias, and also autonomic modulation that comes along with that.
So we requested the FDA that we should have a continued access protocol so that we can continue to enrol patients in this study, thereby improve our overall denominator in the study cohort. So we continued the protocol even after we stopped the study, and then we added more patients to it to really reanalyze the situation and see if we see any added benefit.
What this reinforced was the closure rate is excellent because operators really got really good at doing this procedure. So we now have a 95% closure, 100% closure in 95% of the patients, which is better than any other appendage closure device that exists out there in the world right now.
And then the complication rates also went down from 3.4% in the main trial to 2% in the continued access protocol. But the overall success of atrial fibrillation ablation with the addition of adjunct to LA ligation was not much different, clearly reinforcing that this appendage elimination is not for all comers that have the non-paroxysmal atrial fibrillation.
Which patients would benefit from LAA exclusion?
When you do a subgroup analysis and pulled up the patient both from the aMAZE main study arm as well as the controlled as well as the continued access protocol, we found that the additive benefit of appendage ligation still persists.
So it is refreshing and reassuring to know that in those patients that have non-paroxysmal atrial fibrillation with significant remodelling of the left atrium, as indicated by a large left atrial volume over 130cc, when you tie off their appendage, in addition to the radiofrequency ablation, you get a significant bump in the overall rhythm control at the end of twelve months.
Right. And thus it is safe to assume that this procedure perhaps should be offered as an adjunctive in those patients that have non-paroxysmal large atrium and they not only get the rhythm benefit, which is primarily what we are going to look at, but if you take the data from the percutaneous endocardial closure devices, where when you have effective closure translates into effective reduction in systemic thromboembolic events and the need for oral anticoagulation, I think it's reasonable to assume, even though this was not proven in a randomised control fashion, but again, science, every scientific nuance doesn't require a randomised control trial.
I think there is a lot of iterativeness to it based on the results from the other appendage closure device trials, where we can say when you are able to close the appendage successfully, you would perhaps have a benefit from systemic thrombolic events. However, there is no randomised control trial on that particular feature. Using the Lariat device, that's something that could be done, or this is something that I think one has to keep in mind.
What is the take-home message for practice?
So how does this really impact clinical care going forwards, a lot of the non-paroxysmal atrial fibrillation patients do have worse substrate because they have a larger atrium. Oftentimes it's more than 130cc. They're also at very high risk for systemic thromboembolic events, including stroke.
So by embracing a technique, you could potentially eliminate the or significantly decrease the risk of stroke, as well as improve the overall ability to keep them in normal sinus rhythm after a radio frequency ablation. So I clearly think that's a direction in which the field should move.
I think this data is being presented to FDA, so we'll see what comes out of that. But up until then, I definitely think this is an exciting area and this really requires further work.
What further research is required?
You can question that, oh, this really needs to be studied further in a further randomised control fashion. Or, I mean, doing these type of clinical trials is exhausting and they're very resource intense. And so I think the data that comes from subgroup analysis should be given some credence.
And so I personally believe that a device that has been in the market for more than 14 years and has a fantastic track record and a significant improvement in the safety profile of using this particular device, I really believe that there should be a specific indication in patients with large left atria with non-paroxysmal atrial fibrillation, they should be allowed to have a lariat ligation.
As a result of which, I think we can definitely move the needle on that. And then whether one should consider doing a stroke study using the Lariat is, I think, is off for grabs, because that's conceptually, this is not something that we haven't done yet.
Right. So if there is a way we can actually do a stroke study comparing the Lariat against the prevailing devices in the market, like the watchman flex or the amulet device, I think that would be a great way to really reestablish the role of this particular device, not just in arrhythmia, but also on the stroke front, which is, I think, is a major area that's currently being studied.
So what are some of the challenges that we have in the clinical research space? Again, large randomised clinical trials are expensive. One has to be cognizant about the incremental additive value that disruptive technologies actually bring to the table.
I think what we have to remember is the cost consciousness of what any of these new tools are going to bring to the table, and we should be able to tease out how we're going to use them, where exactly do they fit in, and what is a specific population? Who's going to derive the most benefit from any of these cardiovascular interventions.
So it's exciting times to be in cardiology. It's exciting time to be in the space of cardiac electrophysiology with a number of novel devices that are coming out in the left atrial appendage space with a number of novel technologies that are coming out in the ablation space, especially the pulse field ablation.
I think it's very exciting times. I would describe this as a major sandstorm, in a way, where you have a plethora of devices that are out there. Everybody is competing for a market share to really establish themselves as the leaders in this particular new technology.
So this reminds me of my fellowship days a couple of decades ago when there was a lot of excitement about ablating atrial fibrillation. So we now figured out how we ablate Afib, but we're also trying to figure out how to ablate it better and also really move the needle in the right direction.
So that's all I could say.”