Hi, everybody, and welcome again to our Conversations in Interventional Cardiology. My name is Sahil Parikh from Columbia University in New York City. I'm the Director of Endovascular Services there, and I'm one of the J-SKY Associate Editors. I'm really honored to be here representing J-SKY and our Editor-in-Chief, Alexander Lansky, and we're here to talk about a really important paper that was recently published in J-SKY entitled Novel Mechanical Aspiration Thrombectomy in Acute PE Patients, Results from the Prospective APEX-AV Trial. I'm really delighted to be joined by two really good friends and colleagues who are leaders in the field. Mona Ranade is an Associate Professor of Interventional Radiology at UCLA, and Brent Keeling is a Professor of Cardiothoracic Surgery at Emory, and we may be joined by our friend Dr. Ken Rosenfeld from the MGH, who I'd like to entitle the godfather of the PERT movement. We're going to talk a little bit about the paper and then talk more about the details and then broadly about the field of ulnar embolism treatment, but without further ado, Mona, can you share your slides and present the paper, please? Thank you again for having me, and it's my pleasure to introduce this trial to everyone. So we're here to talk about the acute pulmonary embolism extraction trial with the Alpha-Vac system. These are my disclosures. So look at the system to begin here. We have a large bore system, 18-fringe cannula that has a proprietary funnel that opens up to 33-fringe. This allows for improved clot removal, prevents any kind of clogging of large thrombus material. You have a ergonomic handle that serves as the vacuum source in this case. You have a volume-limiting switch that allows you to either go 10 mL or 30 mL for aspirations, and you also have a feature called a vacuum lock feature, which exerts constant negative pressure, so it allows for basically a single-handed operation. The way the catheter is constructed and the shape of the tip, along with the funnel being so atraumatic, it does allow for wireless navigation between the different branches of the pulmonary tree as well as from right to the left side. And you have a closed waste bag system that allows for up to 250 mL of blood products to be collected. It's also clear, so it allows you to see what you're getting and kind of assess the extracted material. The APEX-AV trial was a prospective multicenter, single-arm study. Dr. Brent Keeling and I were the co-national principal investigators. The study was initiated in collaboration with the PERT Consortium. We had 25 sites in the U.S. and about 122 patients enrolled between the time period of 2022 to 2024. So patients that were included in the study were patients with symptomatic acute intermediate risk PE that was diagnosed with an RV to LV ratio assessed on a CTA of greater than or equal to 0.9. And the primary efficacy endpoint in this case was a change from baseline RV to LV ratio assessed at 48 hours. And primary safety endpoint was a rate of any major adverse events. That included major bleeding. You had pulmonary or cardiac injury, clinical deterioration, or death. These were assessed in the safety—primary safety endpoint. So let's look at some of the features of what we saw in the periprocedural outcomes. You can see 94% of the patients underwent right femoral vein access. Majority of the patients were under conscious sedation for this procedure. The mean procedure time was about 37.2 minutes. The estimated blood loss in about 62.3% of the patients was less than 250 mL. One patient required intraoperative transfusion. Use of thrombolytics was at the discretion of the operator and was seen in three patients out of the 122. So when we look at the primary efficacy endpoint, the RV to LV ratio again assessed with a CTA at 48 hours, we saw that we have a 29.1% decrease, and this is comparable to the prior studies that have evaluated devices in this space. We have the primary safety endpoint looking at major adverse events. This was 4.1%, also comparable to the prior studies. What we've seen here is five major bleeds, two events were not related to the device, one clinical deterioration, one pulmonary injury, and there was no mortality. When we looked at the data further, we saw that majority of the adverse events were within the first 15 patients, and the rate of MAE is reduced to 1.9% after excluding the first 15 subjects. So we think that there may be more of a learning curve with the device, and clearly we saw an improvement in major adverse events as the device was utilized more. Another factor we looked at was reduction in clot burden. This was assessed by looking at the Modified Miller Index score. The clot burden reduction was CoreLab adjudicated, and we noted a reduction of 35.5% at 48 hours, and again you can see this in comparison with the prior trials. So the key takeaways, this is a safe device, we had 0% mortality, there was significant improvement in RV function, the 33 French funnel provides for what we think increased reduction in clot burden, and there was significant improvement in mean pulmonary arterial pressure. I did not mention this earlier, but we did see this and we saw it primarily in the patients that were considered to be hypertensive, which was marked by mean pulmonary arterial pressure of 25 or above. And again, this is an atraumatic tip, it provides ease of navigation between the different branches of the pulmonary tree, and the curve assists in this wireless navigation as well. That's all I have. Fantastic. Thank you for showing the data so clearly. So this is one of now several devices in the space. It follows a IDE clinical trial format that's seemingly now the de facto standard from the FDA. Brent is one of the co-PIs in the cardiac surgeon. Are there any other comments you have about notable findings in the trial? Is there anything that you're particularly interested in exploring further? Ooh, exploring further, a lot. But let me highlight a couple of things that maybe Mona kind of mentioned, but I find remarkable. One, there was no lead-in phase to the trial, right? And so I think excluding those first 15 patients, while not pre-specified in the protocol, was important, just to show that the major adverse events were really comparable to other devices. Secondly, I think, and Kenny might want to speak more to this, the collaboration between PERT and angio-dynamics, I think, is remarkable in this trial. And I think we're going to see more trials like that in the PE space. Hopefully they'll all collaborate with PERT, but I think that, you know, the collaboration between industry and some of our scientific organizations is going to continue to evolve in our vascular space, and we see that certainly in PE. I thought of a third thing, but those two, I think, are the ones that kind of stand out. The clot burden reduction, too, I think is important, and it's probably hypothesis-generating more so than anything else. Great. So, Ken, as I said, you're the godfather of the PERT movement, or the father, I don't know, it depends on who you ask. But as somebody who's been involved in the space for a long time, this sort of registry style of trial, looking at RB to LV ratio as a primary endpoint, has really become the de facto standard for approval of new devices in the space. Obviously, comparative effectiveness can't really be commented on too much, because these are not head-to-head trials, but how do you view this paradigm? Do you think this is really the paradigm going forward, and do you think that we do need to do head-to-head trials subsequently, or is this a class effect? Both, in answer to that. I do think there's a class effect, and first of all, I want to congratulate the PIs, Mona and Brent, for conducting a trial that actually was amazing in how rapidly it got done. I mean, how often do we see trials finish way ahead of time like this? I mean, it enrolled in lightning speed, and I mean, I think that was because of the dedicated PIs, the dedicated investigators, and maybe a little bit of collaboration with PERT that nursed it along and gave it some credibility. As far as the trial format and the outcomes that we're measuring, it was always selected by FDA as a surrogate, this RV-LV ratio, because we know people die from RV failure with pulmonary embolism, and that's what the original Ultima trial did with ECOS, and then subsequently the Seattle 2 trial, and now we have a class effect from thrombectomy, large vessel, large bore thrombectomy, which we're seeing in all the trials. I mean, I think, and I personally like it because we're getting these devices approved, I think, as long as they're safe, then we should be promoting this strategy for now, but of course, ultimately, we're going to need to do comparative effectiveness between the devices and see which ones are most safe and most effective. There's signals and signs along the way, and you guys have pointed out some of these. I mean, the amount of clot reduction seems to be more than some of the earlier devices, but again, they're not head-to-head, and there's reason to believe that there might be more clot reduction and less trauma because of the funnel and so on. It's kind of soft-tipped. I like that. It's also got some directionality that you can apply to it that allows you to go into different branches fairly atraumatically, so there's some theoretical things, but yes, I'd love to see ultimately head-to-heads. That's going to be a while, I think. Honestly, I think once we have a cadre of devices out there, then we're going to start seeing people do head-to-heads, and it's not going to be industry that's going to do it. It's going to have to be us that we say, or it's going to be through the registry, the PERC registry. You can see PERC on my background here, Pulmonary Embolism Research Collaborative, using our database. We already have 15,000-odd patients, and Brent, in fact, has written up a manuscript that summarizes the data for at least the first 12,000 or 13,000 patients, which is hopefully going to be published soon. The point is that, look, class effect, yeah, and by the way, I'm happy for that because we're finally making impact in inroads in terms of treating pulmonary embolism. I'm in the cath lab right now. I just treated a patient who had an absolutely massive PE and was transferred down here and actually ended up with an acute pulmonary embolectomy and didn't get it all, by the way. Got a lot less than we would have gotten. I ended up having, it was an interesting case, and I won't go into too much detail, but suffice it to say that she needed more work done, both thrombectomy and now balloon angioplasty two weeks later to open up more channels. But the fact that we can do this now is just incredible, and these patients, this 30-year-old patient would have died five years, eight, maybe eight years ago. So I'm happy with the progress. I think it's too much to expect us, and maybe I'd love to hear others' opinions on this. It's too much to expect us to do, you know, randomized trials so early, and, you know, we're too early in the field to really sort of do comparative stuff. And randomized trials, yes, but comparative stuff between the different devices, the catheters, is, you know, that'll happen. It'll happen. That's my own opinion, you know. Appreciate it. So Mona, I wanted to talk a little bit about the CT imaging data and the residual pulmonary vascular obstruction and the modified Miller index. How do you feel, as a radiologist especially, how do you feel is our ability, you know, at present to make those assessments with sequential CT scan, and do we need better imaging technologies to better understand this physiology, or is our contemporary approach the right way to go so that other trials follow suit? No, I actually do think that we've made a lot of progress in the way we've, you know, learned to image the pulmonary vascular tree, especially in the last couple years. The protocols are more refined. I think most of the practitioners even getting CTs for their patients are more, you know, more or less on the same page about getting CTs instead of VQ scans. I do think that some ability to evaluate perfusion, ventilation and perfusion, would be helpful in these patients. So I think as much as, you know, we want to associate the clot burden reduction as a good clinical outcome, sure it helps us right now, but I think in the future we're going to need more in terms of kind of getting an association of improved quality of life associated with better perfusion and better ventilation. So I think the field will move in that direction, but as far as imaging is concerned right now, I think this is great and I'm happy that more people are obtaining the CTs to initially make the assessment and then a lot of times that 48-hour CT is, you know, only done in a clinical trial space, but we do need that to generate, you know, sort of the data, at least for now. And I think it's, from a CT standpoint, I think it's good. We are able to tell the defects very clearly. And Brent, since you've had so much experience with the PERT database, I wonder if you might speculate about some of the future applications, maybe a pragmatic, you know, registry type of trial or database type trial would help us get to the, sort of the question that many of us have clinically, which is which patient is the best for which procedure? Any thoughts about how granular the data are that we've collected so far and how we might use that data or leverage it to answer that clinical question? I think it's a fantastic question. It's one that we talk about often. You know, I think that the most granular data we have for PE patients is probably through the PERT registry. I think that we can be more granular in how we do it and we're just kind of, we rebooted the database and so the last 3,000 patients or so have had kind of more granular data, more data points per patient. I think you're right in that we're really going to be able to drill down and figure out which patients, which procedure is most appropriate for which patient, whether it's large board thrombectomy or systemic thrombolysis, ECMO, surgery, what have you. I think we're going to be able to be a little bit more definitive in who gets what in the near future. That data is just going to be available to us. I think you kind of hit the nail on the head. Well, I appreciate it. Listen, it's a privilege to be with three leaders in the field like you guys. The readers of J-SKY are grateful for your submission to J-SKY on this pivotal trial. We look forward to recruiting more of these trials in our pages and certainly featuring more of this work at our SKY scientific sessions coming up this spring. I want to thank all of you for participating tonight and look forward to seeing you all soon.

pulmonary embolism

APEX-AV trial

aspiration thrombectomy

PERT Consortium

treatment advancements