Hello, everybody, and welcome to a clinical conversation at Interventional Cardiology sponsored by SCI. Very excited to present to you new data on what I view to be the most exciting area of interventional cardiology right now, new clinical research in pulmonary embolism therapies. I am Jay Geary from the University of Pennsylvania, and I'm joined by an all-star team from around the country of endovascular specialists and non-invasive specialists for PE today. You're going to hear first from the primary investigator of the real PE study, Peter Monteleone, coming from Ascension in Texas, and then you'll hear from Greg Piazza from Brigham and Women's Hospital in Boston, who's the lead investigator of Optalyse 3D. Finally, we'll be able to have a good and robust panel discussion of all this new information that we're chewing on from June Lee, who is at University Hospitals in Cleveland and is the head of the pulmonary embolism response team there, Rob Lookstein from Mount Sinai Hospital, he's the head of IR there, and Eric Shosemsky, who is the director of vascular medicine and intervention at the Beth Israel Deaconess Hospital in Boston. Well, the activity is supported by an unrestricted educational grant from Boston Scientific, and we'll go ahead and pass it along to Peter Monteleone to take it away on an update of the real PE2 study. Thank you all so much for the opportunity to be here and to talk about this new exciting work that we had the chance to present just recently at the American College of Cardiology meeting. What we're going to be talking about is called Real PE, and this is the second edition of Real PE. So Real PE has given us the opportunity to look at the contemporary real-world safety, comparing ultrasound-assisted catheter-directed thrombolysis to mechanical thrombectomy. Now the original Real PE, we published in October of 2023, it's available in JSCI with a QR code there to the top right for folks that might be interested in taking a look. And we can't really talk about Real PE2 without talking about Real PE1. So very quickly, what Real PE does, the results are as interesting as the methodology. We utilized a novel tool, the Truvada data set. The Truvada data set has been working in multiple fields of medicine and science in order to answer some of the complex questions that we get best from real-world, quote-unquote, big data. At this point, Truvada includes more than 30 member health systems and over 120 million patients. It's about a third of all United States medical records, and it's real-time available data. It includes semi-structured data, unstructured data, as well as more typical, commonly available claims data. It gives us a really powerful look into the electronic medical records of a huge number of patients. When we performed Real PE1, we looked into two different versions of Truvada's data set. We looked at every patient going all the way back to 2009, and we also looked at what we called at the time a contemporary data set between 2018 and 2023. And we looked at every patient that was treated with ultrasound catheter-directed thrombolysis with the ECOS catheter, or mechanical thrombectomy using the Inari flow-treater catheter. We identified those patients treated based on the mandated unique device identifier codes, and we looked for utilization of those devices being utilized in patients presenting with pulmonary embolism. And it gave us the opportunity to look at these cohorts and make comparisons based on their Truvada-available data. This is real-world data, so there were certainly differences between the patient cohorts in this initial version of Real PE. So you can see age differences with a slightly older cohort being treated with mechanical thrombectomy, both in the contemporary as well as the total cohort. Also some ethnicity differences with Black patients and Hispanic patients being differentially represented. When we looked at medical history as well, there was a difference in cancer, which some of us may clinically expect with treatment with mechanical thrombectomy versus ultrasound-assisted catheter-directed thrombolysis. We saw more cancer patients treated with mechanical thrombectomy. Now, Truvada gave us the ability not just to look at claims data, but also do some direct assessments from the electronic health records within the Truvada member systems. One of the things we really keyed in on was this question of bleeding, which has been such a big question in treatment of pulmonary embolism, whether with interventional therapies or just with conservative anticoagulant therapies. It's certainly a major, major problem and issue. And so we looked and compared these patient groups in Real PE1 and said, what's happening to their hemoglobin values, comparing their pre-procedure test to their nadir within seven days after the treatment? We looked at transfusions administered, and we gave that raw data, but then also pooled it with modeled data about billing claims and codes to get ISTH as well as BARK3B of bleeding outcomes. And what we saw is across the board, surprising to some, ultrasound-assisted catheter-directed thrombolysis had lower rates of bleeding by comparison to mechanical thrombectomy with Floetriever. We saw it by all measures. We saw it for strict hemoglobin decreases straight out of the medical record. We saw it for the diagnostic bleeding codes. We saw it for transfusions utilized, and we saw it for both the ISTH and BARK3B modeled outcomes. And it was true for both the contemporary as well as the primary total data sets. We performed multivariable regression in Real PE1, and it showed us that there was, in fact, a unique association with mechanical thrombectomy in these patient cohorts for bleeding associated with mechanical thrombectomy. And it was actually even more robust in the contemporary cohort. Now, that was all Real PE1, and that was October 2023. And there were some major obvious quick questions that came from that. The first was, well, times have changed. You know, we're oftentimes using blood return now when we're doing mechanical thrombectomy. And the second was, well, you know, though it's valuable to have real-world data, there's pretty fundamental differences between those groups. And so that's what led to Real PE2. Real PE2 is the first step in answering these questions. Now, one of the important things to say out loud is the Truvada data set is not a stagnant data set. This is growing every day as patients are being added more and more, including patients with the most up-to-date contemporary therapies. So rather than saying we're going to go back to the exact data set from October 2023, we pulled the most up-to-date data set for Real PE2. And the goal here was to do a comparison, comparative analysis using exact matching between these patient populations and look at propensity score matching, not just at a contemporary data set by a randomly selected date, but after FDA approval of the FlowSaver blood return device with FlowTriever. And so we looked at similar outcomes, seven-day safety events, 30-day readmission events, again with a focus on major bleeding. And you can see how the populations have changed. So on the top right, you'll see Real PE1 that even the contemporary cohort stopped in May of 2023 and went back all the way to 2018. For Real PE2, we started with when FlowSaver was FDA approved and made it onto shelves. So we're looking between 2021 and May of 2024. You can also see the total Truvada population continues to grow. So 82 million at the time of Real PE1, 107 million patients that we're pulling from from Real PE2. And you can see the total pooled numbers of patients that we identified, again, from unique device identifiers and then exact matching performed among those patient cohorts. And the results were similar with exact matching. You can see the total numbers here of the patients that were analyzed, and the odds ratio between this updated, more contemporary group using exact matching demonstrated the same findings. Both ISTH and BARK3B bleeding was higher with mechanical thrombectomy with the Artinari device as opposed to ultrasound-assisted catheter-directed thrombolysis with the ECOS device. Really interesting, especially when we think of where this is taking that first step towards propensity matching and giving us real valuable data coming from what's happening in the real world. Now, an obvious question that gets asked about real-world data is, well, this isn't an RCT. And it's not. And it's not claiming to be a randomized controlled trial by any means. You know, the excellent work by investigators, including represented on our panel here on the peerless analysis, did do a randomized controlled trial looking at mechanical thrombectomy versus all-commerce catheter-directed thrombolysis. It was surprising for some that they actually didn't demonstrate a bleed by preventing use of thrombolytic using mechanical thrombectomy. There was no difference between those groups for major bleeding in peerless. Now, peerless, again, was expert controlled operators. These are really the best mechanical thrombectomy operators you can find in that that's being represented in a clinical trial. And even there, there was no difference. And so it lends some interesting credence to what we're seeing in real-world data about potentially when these therapies are unleashed into the real world, what we're seeing in terms of bleeding rates comparatively between the groups. It's not a perfect study. So again, you know, there's no unique device identifier for all of these patients with Flosaver. That now exists. It's something we consider using in the future when we're trying to identify these patients treated with blood return. It's also not a randomized study. But as we gain these tools that let us look at huge subgroups, this is going to be a commonly asked type of question and methodology to answer it. And finally, there's more matching to be done. You know, it certainly would be very interesting to start pooling in HasBlood variables and other variables to let us do direct comparisons between bleeding risk in these patient populations. So a really interesting next step in the pathway of device safety analysis and protocol-driven care. So in short, we were able to look at big data and see these differences between bleeding risks with more bleeding with mechanical thrombectomy with Inari versus ultrasound CDT with ECOS. It showed that with exact matching by all measures, direct and modeling, we saw those differences. And I think it's a really interesting methodology to ensure safety of devices going forward in the future, especially with exploding therapies, which, as Dr. Geary mentioned, this really is one of the most exciting fields going on in cardiovascular medicine. So with that, thank you all so much for your time. Thanks so much for that great summary of this new data set, Peter. And next, Greg Piazza, my friend and the director of ASCO Medicine at Brigham and Women's in Boston. Thanks so much, Jay. And we're going to talk about Optalyse 3D, which we presented at ACC just a few weeks ago. And to really get into it, we got to take a step back, much like Peter did to look at Real PE. We've got to go back to Seattle 3D. So we did the Seattle 2 trial, and that was a single-arm study really focused on safety endpoints. But we did look at surrogate markers of efficacy before and after the ultrasound-facilitated catheter-based fibrinolytic procedure. And what we observed was there was a very nice improvement in RV to LV diameter ratio, a surrogate for PE mortality. With most patients in the study actually normalizing their RV to LV diameter ratio. What was interesting, though, was when we looked at the degree of pulmonary angiographic obstruction, or the modified Miller index, we noticed that there was about a 30% change in the proximal angiographic obstruction. So that got us thinking, how are we getting such improvement in RV to LV diameter ratio, such RV and loading when we're leaving 70% behind of the proximal thrombotic burden? And so that got us postulating that maybe the mechanism of action or the target of ultrasound-facilitated catheter-based fibrinolysis is more distal than we can see on a conventional CT scan. And we, at the same time, pioneered an imaging technique, which was initially designed to help identify parts of the lungs in patients with emphysema that had a mismatch in perfusion that might benefit from being resected to improve that mismatch in these patients. And it was a technique that really allowed us to see down to one millimeter cross-sectional area vessels, very tiny peripheral pulmonary vessels. And so we thought we could apply that to the Seattle 2 dataset and identify if there was a small vessel change. And so what we can see here is the first thing we did was we construct the volumes, RV and LV volumes, and we could calculate a ratio. What we want to see when we're unloading the right ventricle with any catheter-based technique is you want to see RV volume decrease. And here's an example where pre and post we're getting about 30 milliliters off of the RV, and we're also seeing re-expansion of the left ventricle. That's what we'd like to see. Looking at a recreation or a 3D rendering of the pulmonary vasculature, we can see here as I'm highlighting, this is before the procedure. Typically there are pulmonary vessels that go all the way out to the pleura, really small 1-millimeter cross-sectional area vessels. They should go all the way out through the periphery to the pleura. But there's a lot of dropout here in this patient with pulmonary embolism. So orange and red vessels are small 1-millimeter to 5-millimeter cross-sectional area vessels. Blue-green are your more proximal vessels, what you might see on a CT. If we superimpose these, we get this vascular action map. Anything in royal blue is a pulmonary vascular segment that was not being perfused before the procedure and afterwards has an increase in blood volume. We can see all of this blue is in the periphery. We're actually getting peripheral change. In this study, it was a little bit difficult to tell whether this was a pulmonary artery change or pulmonary venous change, but needless to say, a peripheral, very distal pulmonary vascular change with increased blood volume. We then look to see, okay, what matters the most to unloading the right ventricle? Does the change in RV volume correlate with proximal thrombus resolution, or does it have to do more with the distal? What we actually see here is looking at small blood vessels, vessels that are smaller than 10-millimeter cross-sectional area. We can see that the more of this change you get, the more unloading of the right ventricle you get. If you look down here, we're looking at large vessel fractions. These are huge, really proximal pulmonary vessels, and you don't see a correlation with RV unloading. That really suggested that at least for ultrasound-facilitated catheter-based fibrinolysis for this type of CDT, we want to see a distal small vessel change. Now, in PIRLIS, which, as Peter mentioned, gave us a lot of excellent data on overall safety of these different techniques, CDT and large-form mechanical thrombectomy, it was interesting because one of their more subjective endpoints that showed a difference was the change in clinical deterioration and or escalation to bailout therapy. If you look more detailed at the data, it's actually driven mostly by escalation to bailout, which had a criteria of the investigator feeling that thrombus resolution wasn't achieved, and so a second procedure was selected, and this was seen more often in patients undergoing CDT, which the CDT arm did include patients who underwent the ecosonic procedure. If you take out the patients that had escalation to bailout because of inadequate thrombus removal, then there's not really a statistical difference. But what's more important is with CDT, at least ultrasound-facilitated catheter-based fibrinolysis, in Seattle 3D we showed that really the proximal change in thrombus burden doesn't tell you the story. We're looking really for a distal pulmonary vascular change. So that brings us to Optalyse 3D. You'll remember Optalyse PE was a trial looking at four different dosing arms, a little bit more of an accelerated ecosonic procedure, and looked at RV to LV diameter ratio change, modified Miller index, to see if there was a difference or any loss of efficacy as you decreased the dose. What we did was use this 3D reconstruction technique to look at the different dosing regimens. We grouped low-dose and high-dose to see if there was any loss of efficacy in this distal pulmonary vascular change, but we also wanted to see if we could tell exactly what blood vessels were actually showing the change. Since when we did Seattle 3D, our technique has improved where we can segment the small arteries, the small pulmonary arteries from the small pulmonary veins, and able to look at what's actually happening. What we saw with ultrasound-facilitated catheter-based fibrinolysis is not that we really see much difference in the pulmonary arteries, even out to the distal branches. What we're really seeing is a change in small and medium-sized pulmonary veins. That becomes really important, as we're going to talk about in the middle, because getting blood volume to the pulmonary veins is exactly what you want in PE therapy. The goal of PE therapy is to improve gas exchange, and the only way you can really prove that you've improved gas exchange mechanistically is to show that you're getting blood from the pulmonary arteries across the capillary bed to the pulmonary veins. Seeing that small pulmonary venous change is very important. We saw that there really wasn't a difference in this small pulmonary venous change between the two low-dose regimens and the two high-dose regimens. We also did an exploratory cohort looking at large-bore mechanical thrombectomy using Flotriver and then a heparin cohort—10 patients, intermediate, high-risk PE—and essentially didn't find the same change in venous volumes, suggesting that this might be a unique aspect to catheter-based fibrinolysis, in particular with ultrasound facilitation. What are the implications here? The goal is to get blood from the pulmonary arteries, as I said, to the pulmonary veins. If you can get blood volume into the pulmonary veins, you know they've gone through the capillary bed, you know they've perfused the alveolar capillary unit, and that's exactly what we're seeing here. Showing an increase in pulmonary arterial blood volume even peripherally is great. It's showing that you're getting blood volume across the proximal pulmonary angiographic obstruction and relieving that, but it is not proof of the concept that you got increased perfusion of the alveolar capillary unit. Getting blood volume and increased blood volume through the pulmonary veins is proof of that. It seems to be that when it comes to this type of CDT, what we really should be looking for is that pulmonary venous increased blood volume, almost like myocardial blush that we used to see when we do angiograms that we still look for good perfusion, but it's actually that pulmonary venous change that really tells you that you got adequate thrombus resolution with ultrasound-facilitated catheter-based fibrinolysis. So lots more work to be done on this, but actually giving us a little bit more of a clearer picture of what we're actually doing with this type of CDT. Thanks so much. Wonderful mechanistic presentation and study there, Greg. Thank you for leading it. To first start off with engaging the panel here, let's start with the REAL-PE study, and I'm going to toss it first to June. June, you were an investigator in PIRLIS, and Peter did a nice job of presenting some data from PIRLIS to try to put REAL-PE in context with PIRLIS, which was a randomized trial that was looking at a variety of outcomes that included bleeding with large-bore mechanical thrombectomy versus catheter-directed thrombolysis. The question for you, June, is when you were enrolling in PIRLIS, what did you notice in terms of who was being enrolled, and what do you notice about that, and how it played a role in what we may have seen there? So, great question, Jay. Thank you. I think, as investigators, we all know that we try to enroll patients into studies and trials as unbiased as possible, but I think intrinsically there is some bias. It's sometimes from the operator, sometimes it's actually from the patient, because they are seeing commercials, they're talking to their friends, they know the technology that's out there. I think one of the things that we used to think about, actually, when we enrolled in PIRLIS is whether or not a patient is already at high bleeding risk, and that was one of the criticisms of PIRLIS, is that the patient cohorts that were ultimately enrolled were probably a low-bleeding-risk cohort, and that was one of the things that we remarked upon is that, yeah, overall there's a low bleeding in both arms, and perhaps it's intrinsically because the patients that, inadvertently, we cherry-picked, that got included in the trial were actually a low-bleeding-risk cohort. And that may explain some of the differences between PIRLIS versus what we're observing in real PE2. Fantastic. And then, so the bottom line from your perspective is that perhaps there was a little bit of a low-bleeding-risk there, it randomized into the trial, and I think Peter kind of alluded to that a little bit, actually, in his presentation, that maybe there was higher bleeding-risk patients that were in real PE2, but then real PE2, obviously, we're looking at as observational data, and we've got, arguably, certainly one of the most preeminent national experts in analysis of that observational data here, and Eric Krzyzewski, who's worked extensively in this arena. So how do you contextualize this discrepancy between randomized trial and observational data in this case? I appreciate that, Jane, and nice work, Peter. I think, you know, there's important considerations here. You know, sometimes we enter into observational comparisons when there's a dearth of randomized data, and we have to be careful with some of those assumptions, and, you know, we do whatever we can to control trial and measure confounding. This is a little bit of a different situation where we have now a randomized trial to put next to an observational study. So I think it's not uncommon. We saw this for other vascular trials, like BASCLI, where you're going to get generalizable data, real-world data that doesn't look like the randomized data, and to June's comment, some of that is definitely due to the unmeasured confounding, and we know all our practices for thrombectomy versus thrombolysis. So to me, I think it's a really important study, though, to remind us that there isn't one device for pulmonary embolism, and we've talked a lot about this as a group, but, you know, both of these strategies are really effective. As Jane mentioned, both of the endpoints, in particular, bleeding in the Pearless trial were quite low for either end of BASCLI or strategy. And so when I look at Pearless 2 now, I say, we shouldn't be shying away from catheter-directed thrombolysis if that's the right strategy for any of our PE patients, and similarly, mechanical thrombectomy is going to have an important role, and particularly, you know, in patients that may not have made it into Pearless, like those who do have higher bleeding risks or thrombolysis contraindications, which are hard to measure in real-world evidence. So, you know, I don't leave us with a tasty nugget of data here outside of the fact that these are complementary data sets, and I think it just reinforces what we've said all along, which is these are really complementary devices that should be used in PE strategies and toolkits for any program in this space. Yeah. So I think a summary there is that, obviously, we know observational data has—with administrative data especially—has risks of confounding, and there was big attempts made to match on that, but it's impossible to totally obliterate it. And secondly, you mentioned adjudication of endpoints sometimes can be a little complicated in administrative data compared to trials, but all that being said, the thing that is a common thread between both studies, Pearless and RealPE2, is that the patients in both cases did undergo some selection. In one case, they're selected for a trial, in another case, they're selected in clinical practice. And June alluded to the selection and to the trial. In both cases, if you were selecting patients, whether you're selecting them for randomization or selecting them directly for catheter-directed lysis, you seem to be—I wouldn't even say surprisingly, let's just say low bleeding risk—I think that we're happy about the concept that this represents a valid therapy for those patients we select for it, and perhaps the bleeding risks are, in this era, are quite a bit lower than what we would have probably thought about a decade ago. Next I wanted to go ahead and engage Dr. Lookstein on Greg Piazza's presentation as somebody who has read a lot of studies with, you know, chest CTs for PE over the years. You're looking at proximal clot, you're looking at distal clot, you're looking at it in the acute setting, you've read studies in the chronic setting. So there's a big debate out there now that what's going on, because both Seattle 3D and Upplace Reader are telling us that maybe we're clearing this distal circulation a little better. Large, more mechanical thrombectomy, we all see the results on the table. Sometimes we're clearing proximal clot right in front of our eyes in a fairly dramatic fashion. How do you think through this, you know, seeing what you've seen as a radiologist over all these years, reading so many studies and then treating these patients also as an interventional radiologist? Jay, thank you for the question. I want to also congratulate Peter on, you know, great data and obviously Greg. I want to echo a couple of Eric's points that I think we take away from all of these studies that all of these therapies appear to work very, very well. And I think that we're not at any kind of state to say that one technology is superior to another. We're still very early on here. I have mild to moderate concerns about the safety observations that are being seen in the real world registries, which I hope we can talk on later on in the panel. As it goes into Optalyze 3D, I think that, you know, in the last five to six years, there's been so much enthusiasm about mechanical thrombectomy, almost to the detriment of the potential benefit of either systemic or local fibrinolytic therapy and what the not only the immediate benefit is, but what the long-term benefit is of an acutely symptomatic patient. I think that Greg's data really, you know, sort of gives, should give all of us pause that maybe we've been too enthusiastic about pushing aside fibrinolytic therapy. I, for one, believe that fibrinolytic therapy is incredibly powerful for the acutely symptomatic patient and I think it's going to continue to have a role moving forward. I think all of us as clinical scientists have a lot of work ahead of us and, you know, Jay started off the session by saying it's one of the most exciting fields in cardiovascular medicine. And I would echo that there's such potential to try and identify which acutely symptomatic patients are ideally suited for a solo thrombectomy treatment course, which acute symptomatic patients are ideally suited for a solo fibrinolytic therapy course. And I think just to be a little bit bullish about the future, I think there's going to be a role for combination therapy and, you know, hopefully by the end of this decade we'll be talking about trial designs about offloading the obstructive thrombus in the right ventricular outflow track in the main pulmonary arteries, but recognizing the real potential benefit of clearing out the distal circulation and how it impacts the patient's quality of life. I think Optalyze 3D really demonstrates that there is a very powerful effect on the distal vascular bed in the pulmonary artery. And I think that this needs to be not only validated, you know, hopefully prospectively, but also with the other disruptive technologies that have either been recently FDA approved or are in pre-market IDE studies right now. So, again, we're very early on in this space. I don't think we should abandon fibrinolytic therapy at all. I think it's going to continue to have a role, and I think we all have a very, very sincere obligation to try and find out which patients are ideally suited for either thrombectomy or fibrinolytic therapy, and possibly even, again, identify which patients would be best suited by combination therapy. There's, I think, a couple of different points were raised there that I'd like to expound upon. The first is this concept of what we're trying to accomplish with either of the therapies, and there's early benefits where we're focused with most of the clinical trials that are going on, but then we're also thinking a little bit longer term. And when we think longer term, when you look at cardiopulmonary exercise testing down the line, you do see a couple of different types of etiologies for the dyspnea that come out in the best available studies that have been done in the natural history of the disease. And they fall into three categories. The first is subclinical RV dysfunction. So, you actually have cardiac output that doesn't rise to the degree that it needs to, even though the echo at rest might look okay. The second, I think Greg did a nice job on that slide of showing problems with impaired gas exchange, which leads to essentially increased dead space ventilation is basically what that is. And that comes out in CPETS. And then the third is deconditioning, which is a different topic for a different talk. Obviously, we all agree that rehabilitation is important in these patients. I think Jay's making some really good points about what happens next, and in particular the long-term sequela of palmar embolism that we really haven't explored. So, any ideas in terms of how we get a better understanding of what happens after discharge to our patients? You know, we know really well that we can get patients to survive better with these interventions through hospitalization, but we don't yet have that data that tells us what happens after discharge and whether any of these strategies are improving long-term sequela or heparin alone or anticoagulational or whatever it might be. What are your thoughts? It's such an important question, and I think if I had a little magic eight ball, maybe I'll be able to tell you the answer to this. But you see a patient come into their ER with pulmonary embolism. How do you decide which therapy is the best for the patient? I don't think we really have that answer right now in 2025. And really, in terms of talking about long-term outcomes and quality of life measurements for the patient, these studies are still ongoing to understand what is the mechanism of improvement in patients that receive anticoagulation alone versus catheter-directed thrombolysis versus a large-bore thrombectomy or medium-bore thrombectomy. So, we don't have that answer. How do you pick that patient? I think Dr. Piazza really showed a really elegant study with the perfusion improvement in the venous architecture, which I think is very interesting. And maybe to Dr. Lookstein's point, something that is a combination therapy in the great future might be attractive to help improve both large debulking as well as the small arterial compliance. And just to follow up a little bit on that combination therapy piece, one thing that comes up, and it ties it back to Peter's presentation, is we do still worry about bleeding complications to some extent in both arms. I mean, we're seeing equivalence in peerless. We're not quite seeing equivalence in real PE2, but you still had some complications happening in both arms. And does combination therapy worry anybody? Because now, you know, your large-bore mechanical thrombectomy is, by its very nature, a large access site, and now you're adding on. We think maybe it's the best of both worlds efficacy-wise in the lungs, but is that necessarily the best thing for the whole body, and how are we going to judge that as a question? Yeah. I want to make a comment, Peter, and hand it to you, but I just want to say, you know, we use low-dose thrombolytics and vascular procedures all the time, and that's with arterial access. So, you know, I was thinking the same thing, Rob, as usual, as the presentations were going on, was maybe we got something here where we can combine these to really benefit patients and really limit the amount of thrombolysis. So, you know, Peter, I'd love to hear how you position this as you also deal with all these different vascular beds, but I feel like we probably, at the lower end of TPA dosages, can keep this relatively safe, as long as we're not doing too much trauma to the pulmonary vasculature. Yeah, I think the concept is fascinating, especially when you start seeing kind of biomechanical data like what Dr. Piazza has pointed out. You know, to Dr. Lookstein's points, these technologies are all being unleashed into the world very quickly. You know, they're being studied in controlled trials by expert operators in places with protocols that are very good at it, but at the same time, they're simultaneously popping up in larger and larger numbers, and we're all hoping that guidelines are going to help advance that and escalate that care even further. And so it's going to be an interesting process to see as more and more of these technologies are being adopted by operators that maybe don't have so much experience with large-bore access that are doing it for the first time in a patient that they're bolusing with heparin on the way out of the room. You know, I think we start to see some of these real-world trends that we see. And Rob, there's a bunch of clinical outcomes trials that are going to get published theoretically over the next couple of years. They all seem to be enrolling very briskly, which is great news. But those clinical outcomes trials, I don't know if they necessarily get to the nuances we're talking about on this panel. What do you think about that? I agree with you. I think there's a tremendous amount of work to be done. I think we're all patiently waiting for the results of a handful of pivotal randomized control trials evaluating endovascular therapy versus optimal medical management currently. Until those are completed and published, we're still sort of cautiously advancing everything forward. To go back to my previous comment, my one concern is that it appears in the real-world setting we're seeing a slightly different safety event than we're seeing in either single-arm trials or the randomized trials to date. Until we identify who is clearly going to benefit from an escalation over just optimal medical therapy, I think we all need to be a little bit more cautious about liberally advocating for the use of these technologies, especially in somebody or a patient that doesn't have an imminent perception of cardiovascular collapse or imminent mortality. Obviously, I'm referring to intermediate risk patients here. Obviously, all of us are aware there's multiple randomized trials going on. We really just need to all be a little bit more cautious, make sure these trials enroll rapidly, make sure they undergo appropriate peer review and they have appropriate safety monitoring. Up until that day, I just think we all just need to be very, very respectful to the patients that we serve and make sure that we are judicious. We're using shared decision-making in our practice in New York in the absence of these pivotal randomized trials. We're having, obviously, very respectful and constructive conversations with all of our patients, but we're trying to enroll every single patient we see, both on the floor and the emergency room, in these randomized trials in the hopes that we will have level one evidence in the near future. That's a great final word from you, Rob, and I really appreciate it. What I heard from that is what you mentioned last, that given that we don't truly know the risk-benefit ratio for these therapies, especially in intermediate-risk patients, it is extremely important for us to enroll the full spectrum of eligible patients in these intermediate-risk trials and not take it as a foregone conclusion, despite the dissemination of the therapies, that they necessarily have net clinical benefit. We really need to enroll fully, and that's a great message to send, Rob, I appreciate it. Thank you all for joining us during this Sky Clinical Conversation. Hugely appreciative of this multidisciplinary panel of experts, and most importantly, from the very exacting work that Peter and Greg led with these two late-breaking clinical studies.

pulmonary embolism

thrombolysis

mechanical thrombectomy

ultrasound-assisted

Real PE study

Optalyse 3D

clinical research