All right. Thank you. Clearly a lot to cover in one hour, but I appreciate SCAI SHOCK incorporating PE into the meeting this year. All right. So I thought since it's a lunchtime session, let's see if we can be a little interactive. So I'm going to have you guess the trial. This is a 1,006 patient randomized trial for acute pulmonary embolism. The inclusion criteria was RV dysfunction and a positive troponin. The average age was 66. The average systolic blood pressure was 130. And the heart rate was 94 beats per minute. Any guesses on what this trial was? PAPO? Yes, yeah. So the treatment in this was single bolus tenecteplase versus anticoagulation, the PAPO trial. And really showed, I think as Shripal illustrated earlier, there was benefit to thrombolytics, although it came at a cost of increased bleeding and intracranial hemorrhage. All right. So second trial, 115 patients total. The inclusion for this one, though, was a systolic blood pressure less than 90 or a drop in blood pressure greater than 40 for 15 minutes, a vasopressor for cardiac arrest for less than 30 minutes with recovery. The average age in this was 64. The average systolic blood pressure at the time of enrollment was 97. Heart rate was 100. And the majority of these patients were sky-shock C or greater. So this one was the non-randomized, what we call the flame trial, of large-bore thrombectomy versus standard of care. And again, showed that there in this non-randomized study compared to performance goals in the context arm that patients that underwent large-bore thrombectomy did quite well. And so as we walk through history, we've seen this evolution with MI. We've seen this evolution with stroke. And it's been really exciting in the last decade to see this evolution of knowledge as well as clinical trials for pulmonary embolism. And we've gone from heparin to systemic TPA, some of the catheter-based therapies, to now growing data. And we're finally entering the era of real modern era randomized clinical trials. The bulk of the trials so far have been really catheter-based single-arm studies. There's a variety of devices that I've shown here. In the interest of time, I'll skip over this. And there are several more that are in the pipeline that are currently undergoing relatively small single-arm studies, really to show more the feasibility and the safety of some of these devices for acute pulmonary embolism. Where we are now, really large for randomized clinical trials that are ongoing. The first one is called PE-TRACT. This is the only one that's NIH-sponsored. And it's a randomized clinical trial of catheter-based therapy versus anticoagulation. And one of the nice things with this is that follow-up will include VO2 functional testing. Really, the entry criteria for this is intermediate risk PE with an RV to LV ratio greater than 1. The next trial is we go in order of the higher the risk of the patient. The STORM-PE trial is a randomized clinical trial of the Penumbra device versus anticoagulation. It's really designed for intermediate risk PE. And for this one, it's an RV to LV ratio greater than 1 with a positive troponin, or BNP. Then the next two trials are really looking at, even within the intermediate risk, kind of that higher end of the risk stratification. And HYPO is looking at randomizing patients to ECOS, which is ultrasound-facilitated catheter-directed thrombolysis, to anticoagulation. And in this group of patients, they're slightly higher risk. RV to LV ratio greater than 1, positive troponin, heart rate over 100, and systolic blood pressure less than 110. And then the final trial, which recently started, is called PURELESS-2. This is a randomized clinical trial of large-bore thrombectomy with the Inari device versus anticoagulation. And this trial is trying to capture even that higher risk end of intermediate risk PE, where they have an RV to LV ratio greater than 1, a positive troponin, BNP, or lactate, but then need to have at least several other criteria, including tachycardia, systolic blood pressure between 90 and 100, and either hypoxia or ongoing respiratory distress with a high respiratory rate or a fair amount of oxygen. And so here's the same type of patient. And as we enter this era of randomization, this happens across the board in clinical trials, especially with devices, because now you have the option of using a device on clinical grounds, or you have an option of enrolling a patient in a trial. And we all want to do what's best for our patient. Yet we have to be careful that we continue to enroll patients to really be able to fully understand the impact these devices can have. So let's take patient one, who's a 65-year-old female, comes in with shortness of breath, has bilateral PE, an RV to LV ratio of 1, a positive troponin, heart rate's 101, blood pressure's 110. They're relatively comfortable looking in bed. They can have a conversation with you. But says, when I get up to walk to the bathroom, I get short of breath. You've then got patient two, who comes in with syncope and shortness of breath, has a large bilateral pulmonary embolism. RV to LV ratio is a little larger. Now, in addition to the positive troponin, you see the heart rate's a little faster, blood pressure's a little lower, a little bit more oxygen. Now, this patient looks comfortable laying in bed. By the end of our conversation, you can tell she's dysthmic. You don't even have to get her out of bed walking to realize that. And then you've got patient three, who, again, comes in with syncope, has bilateral pulmonary emboli. That RV is even a little bigger, and is a little more tachycardic. Blood pressure's a little bit on the lower side, needs a little bit more oxygen. And really, you can tell, is tachypneic just laying in bed? All three of these are intermediate risk PEs. We have to sort out how we're going to enroll these types of patients moving forward. Because if we only enroll patient one, that may skew the results and give us a different outlook going into the future than if we enroll patient two or patient three. Now, as we get into high-risk PE, we've seen this evolution as well. Like any new technology, we first have to understand, is it feasible? Is it safe? Our techniques, our ability to do these procedures in the highest-risk patients has gotten better over the last handful of years. And we've seen this evolution from really institutional data. This is where we pulled data from a few centers to show that treating these patients with large-bore thrombectomy was feasible and safe. And then you move on to larger database studies, and then prospective registry-type studies. And we're now finally ready for randomized clinical trials. And folks for a long time have asked, why hasn't a randomized clinical trial been done in this space? Well, we had to get there first. We had to perfect our technique. We had to perfect the devices in our understanding. And I think now we're finally ready to enter this era for high-risk PE of really doing a true randomized clinical trial. And so recently, it was announced that the PERSEVERE trial is getting ready to launch here. It'll be in acute high-risk pulmonary embolism, 200 patients randomized to either large-bore thrombectomy with a flow-tripper device or standard of care. And patients will be followed for three months with a primary composite endpoint of mortality, cardiac arrest, bailout, bleeding, or need for ECMO. Now, we don't have all the details, and I think at some point in the near future, this will come out with a more formal presentation and an announcement. The key inclusion criteria really is going to be high-risk PE. Now, what exactly that means or how that's going to be defined, we're not allowed to reveal just yet, but again, it will be coming soon. And I think this now will really be the nice fifth true randomized clinical trial, not only in intermediate-risk, intermediate-high-risk, but now really high-risk pulmonary embolism as well. So I think this is a very exciting time for pulmonary embolism. The PE field has had amazing evolution in a relatively short span of just 10 years. We've progressed from small IDE studies to retrospective studies, to registries, to prospective, to now really randomized clinical trials that are not only looking at short-term but intermediate and long-term outcomes, so we can really study this disease state from the time of the PE out to several months down the road and see how patients do. All of these trials, in my view, are really complementary to each other. This is going to answer a slightly different question, and hopefully being able to put all that together in the end really advances this field. But we need to continue to enroll. Just because we have access to the devices doesn't mean we should not enroll in these trials moving forward.

acute pulmonary embolism

clinical trials

thrombectomy

anticoagulation

catheter-based therapies