Okay. Thank you. All right. So, let's go through some data that's happening right now. So, these are the trials I'll be discussing today, some of the completed and ongoing prospective single-armed device trials. These ongoing randomized trials listed there, I'm not going to be discussing registries or cohort studies, nor the planned RCT STORM-PE. Okay. All right. So, these are the ones that have been completed, the non-LYTIC single-arm studies that have been completed, FLIR and X-TRACT-PE. These were the first of their kind for thrombectomy devices. FLIR was the first to come out, X-TRACT-PE to follow. RESQ-PE is the first sort of device in the CDL world, although it has a mechanical component. You know, we've been talking about low bleeding rates. We've been talking about, you know, smaller doses of LYTICs, and I think that's what this device is able to use. Very promising, less than 1% major bleeding rate, but let's remember it's only 109 patients, so the sample size is not quite there in terms of where we need to be to understand the true bleeding risk of this and other devices. If we look along these single-arm trials, you'll see that they're all doing the same thing from an RV to LV ratio standpoint. I'll remind everyone these are single-arm trials. There's no control group, so we don't know how they're doing compared to anticoagulants alone. So these are associated RV to LV reductions. These are not causative RV to LV reductions. We have to remember that. The primary safety events you can see since Seattle 2, all of these are achieving lower bleeding rates, and I think that's, you know, probably a consequence of not using LYTICs. We're getting smarter about using LYTICs, although these bleeds may have other consequences than just bleeding when we're talking about thrombectomy devices, and I agree with Peter that we really need to understand the safety of all of these devices much better before we're routinely using them in clinical care. Right now the APEX-AV trial is enrolling. I am on the CEC for this. This is another thrombectomy device out of many thrombectomy devices, about nine more coming up. So this is something to be looking out for. My argument is that while this is very exciting and the innovation is incredible, we're sometimes putting the cart before the horse, and we need to know whether thrombus extraction is the right thing to do in the first place before figuring out exactly how to do it. Okay, so PURELESS. This is sponsored by NIA Medical. It is comparing the flow treatment versus catheter-directed lysis. So this is not a randomized controlled trial. It's a randomized trial of two techniques for CDT, an important but not the ultimate question that we need to ask right now, ask and answer. The primary endpoint is a WN ratio of this composite. I'm still learning about WN ratios, so I'm not going to pretend to talk about it right now. And they're looking at these other endpoints as well. But it'll add to the body of knowledge. I do think that that's a fair statement. But really this is kind of the crux of what I want to talk about, which is that after ulcerative colitis, and actually canary, which came out recently with about 94 patients, interventional trials have not included this control group. So we don't know how any of these devices are doing compared to what is the standard of care right now for intermediate-risk PE, and that is anticoagulants alone. So compared to PROMPT, anticoagulation, close monitoring, advanced supportive care that you've heard about, our growing knowledge about how to deal with a sick submassive PE patient, we don't know if our catheters are really changing RV to LV ratio in a positive direction, death, deterioration, long-term quality of life. So we're really way behind when it comes to these clinical outcomes. If we think about it, there are really two reasons we have not been able to say that catheters should be routinely used for intermediate-risk PE. The first is, compared to systemic thrombolysis, we've randomized precious few people. So greater than 1,500 patients have been randomized in trials of systemic thrombolysis. And at this point, less than 100 have been randomized in CDT trials. Insufficient clinical outcomes data, the RV to LV ratio, we've got to get away from this metric. It's inadequate. It doesn't show a great correlation with morbidity, especially reduction in that particular measure hasn't really shown a great clinical correlation yet. We need clinical outcomes to really be correlated with what we're doing and compared to anticoagulants alone. So in that light, there are two trials that I think are worthy of discussion. The first is, and they're kind of complementary, I alluded to this in the last two sessions ago. The first is the HiPytho trial sponsored by Boston Scientific. It's looking at short-term outcomes in intermediate-risk PE patients. And then I'm going to spend most of the time on PE-TRACT, which is looking at the longer-term cardiopulmonary health in the year following PE. HiPytho, ECOS versus anticoagulants, including patients with intermediate high-risk PE, but they have an elevated risk of decompensation, having two out of the three factors you see here. So they are enriching the intermediate-risk population to see if they can hone in on those patients who do the worst with anticoagulants alone and if the catheters make a difference. 400 patients, so a good large trial follow-up is a year. They are looking at longer-term outcomes, but that is a secondary or exploratory outcome compared to their main composite of PE-related mortality, recurrence, and clinical deterioration, I think, within the first seven days. It's currently enrolling, and I think enrolling fairly well globally. I'd like to remind everybody that post-PE whatever is common. In this particular case, peak oxygen uptake is reduced in a good number of patients, up to 50%, and this was a surprise with the Kahn study in 2017, just an observational study seeing 100 patients that almost 50 of them had a reduced peak oxygen uptake, and we're seeing that in multiple studies, that at least even in negative thrombolytic studies, at least a third of them have residual symptoms following PE. So this is where PE-TRAT comes in. This is now funded by the NHLBI, and we are about to enroll our first patient in July of this year, hopefully. So the design of this study is to randomize 500 patients to catheter-directed therapy plus anticoagulants versus anticoagulants alone, the primary endpoint being peak oxygen uptake at 3 months and NYHA class at 12 months with these secondary and exploratory endpoints, fatal and non-fatal clinical deterioration at 7 days, 6-minute walk distance at 12 months, QOL, thrombus burden, bleeding, recurrent VTE, health economic analysis. And I'm going to make the argument that PE-TRAT is the most important PE trial going on right now. It has independence. It is the only non-industry-sponsored clinical trial with that rigor that comes along with NIH funding. It has the protections against bias. So this is the only one that's really truly motivated by finding the correct answer for PE patients and not having one approach win. I mean, if we're trying to convince people who don't do this procedure, we need this level of evidence for them to believe us. We're all the believers in this room. Well, let's prove it to the people that don't believe us yet. True randomization against anticoagulants alone, a large sample size, and a comprehensive clinical assessment of CDT. Let's go on a little imagination trip. So imagine you're able to, after PE-TRAT, confidently advise an intermediate risk PE patient that you will have a better chance of having better exercise tolerance if you get this therapy. The risk is you may not be able to tell them that, but at least you'll know. Individualizing care based on subgroup analyses. Knowing whether CDT actually reduces the RV-to-LV ratio and PA obstruction at 48 hours compared to anticoagulants alone. And then, along with that, whether that even matters. Knowing exactly what's going on with patients who have persistent dyspnea, you know, three to 12 months after their PE. Because we're not just looking at the peak oxygen uptake. We're looking at all CPAP parameters. So this will give us a lot of insight. The health economic analysis is huge for public health. We are collecting blood biomarkers to look for associations. Clot biology, hopefully, because there is a mechanical thrombectomy component to this. So if we can actually get clots from patients, we can learn a lot about clot biology. Which CDT technique preliminarily, again, we're not powering for this, might have the highest net benefit, efficacy versus risk. So this is a difficult trial to enroll into. You have a weak PE. You have a sick patient. We're developing innovations around this. Hopefully, this will help future PE trials. Spec sheet for novel devices and pharmaceuticals. When we know which patients actually work that this therapy might work for, we can innovate around that. Actually defining this post-PE syndrome, which is a bit nebulous right now. Better risk stratification, to Sunjum's point. And guidelines with level one recommendations, finally. So we're building a large community across the country, greater than 200 physicians. We have a lot of societal partners. Where we are now, we've engaged over 50 sites, a lot of site activation. We are hoping to enroll the first patient by July, aiming for 15 sites activated by the end of the summer. So in conclusion, I would say, yes, there is a long pipeline of pivotal device trials. And they're important in their own right, but they should be considered only phase one and phase two. They're single-armed. They don't have a control group. They cannot be taken from that point to use without very, very serious study. We have three complementary randomized trials seeking to address unanswered questions. Peerless is CDT versus thrombectomy to some degree. Hypitho is CDT better than AC in the short term. And then let me emphasize one more time that CDT in the long term is being assessed by PE-TRACT. I will put forth to you that this is the most important trial. And we have many interventional cardiologists in our network. Please do support this trial. If you're interested in joining, email me. There's still an opportunity to do so. But absolutely, PE-TRACT needs your support. This is not an interventional radiology trial. This is a PE trial for interventionalists and non-interventionalists. Thank you. I appreciate the time.

thrombectomy devices

pulmonary embolism

device trials

bleeding risks

catheter-directed therapy