Thank you for having me here today. It's really a pleasure. So CDT, after talking about BPA and hearing about thrombectomy, I think sometimes CDT does get forgotten or at least slightly overlooked. And if you look at what we do use, there are a variety of catheters. There are the standard catheters, Crag-McNamara's, Unifuse, and Fusion catheters, and then there are the more specialized catheters like ECOS and Thrombolex and Fusion device. What's nice about coming after the BPA discussion is so many of the now advanced skills, which are becoming more common, can be used to make a PE, an acute PE procedure, more intelligent. Typically when we do a CDT case, it's a dual access, depending on the device being used, it's five or typically six French, a dual common femoral vein access. A number of people around the country are now advocating for IJ access. I would say we in our lab don't do that. If you are going to do something like the Bashir catheter, it's eight French rabies bilaterally, but we do do angled pigtails or a seven French swan for Rosen wires when we are doing catheter-directed lysis. In terms of the technical elements of preparation for those who aren't that familiar with this, prepping your hookups well in advance, having long venous tubing available, always remembering to order your TPA ahead of time, especially if it gets produced by your pharmacy, and then just really having your algorithm as to what you are going to do afterwards in terms of the nature of your drip. For us, it is we get 400 units of heparin, one milligram an hour per catheter. We try to keep it under 12 milligrams total whenever possible. We check PTT, CBC, and fibrinogen somewhere between Q6 to every eight hours. That's our deal. But what we did learn from the BPA world, and we've started to get better at, is using our various views to anchor our wires. I remember many of the initial PE case when we would do a CDT, and in our minds we would plan to land the distal catheter one place, and sure enough, at the end of the case, we walked away. It was 10 centimeters more proximal, and we said, it's okay, it's lytics, and it will probably work. But what we have learned here is that by really targeting A8 and A10 segments and using multiple views, we really can anchor those wires quite well, get the distal tip where it needs to be, and really do effectively lyse the segment. I made Vlad, I stole this slide from him, because I thought it's a great example of wiring in the LAO50 position to target a specific branch on the right side, to target the A8 segment. Similarly, going LAO50 is extremely helpful in the left lung, again, just to really anchor a wire to get an appropriate distal position. This is what the specialty catheters look like. Really, because for the Bashir catheter using A8 French rabies, you do require support to truly get them more distally, and on the screen left, you can see the ECOS device. So just thinking about, broadly, CDT, I think it's maybe making a comeback, and so it's nice to lead off this way. For the early trials, I won't belabor them, but Ultima and Seattle-2 really led to the introduction of the device to market in 2014 and 2015, but with the moderate bleeding seen in Seattle-2, it created a tremendous gap in the PE marketplace, and hence entered thrombectomy and all the enthusiasm that the crowd feels towards that. But really, simultaneously, what developed was a real push to enhance CDT in and of itself. So that means refining our technique, decreasing our dose, and reiterating our devices. And then came Optalyse, and then came Knockout. Now, what's really interesting about that is the push towards shorter duration therapy and lower dose has really kind of created, potentially, another window. Optalyse with its four arms, and you can see it in the bottom right of the screen, 8 to 10 milligrams in total dose over a period of 2 to 6 hours, you can see the general trend that's far different than in the middle Seattle-2 with its 20 to 24 milligram typical dosing. So clearly, a major push in the dose drop. And then when you look at Knockout PE, which was a real-world prospective look at how PE is being treated, a more current one, you can see the dose dropping over time in the community. So what was the significance of all that? Well, what was fascinating is in Optalyse PE, when you just think about physiologically, the profoundly lower dose, we still saw the mean change in RRV to LRV ratio for baseline persisting out of the year. So we still saw that despite the low dose. We still saw improvements in 6-minute walk. And so it seemed relatively safe. And then in Knockout PE, we saw, again, in the community, the dose was not as controlled as much, but 70% of the population or the patients enrolled had less than 20 milligrams of TPA, and 30% had less than 12. And probably more interestingly, the major bleed risk was 1.8% with no cerebral hemorrhage. So that's fascinating, right? We seem to be having our effect. It seems to be durable. The dose is dropping. The bleed risk is dropping. So it seems to create an opportunity. But yet, it's not that initially we miscalibrated the lytic dose. In fact, there is, from CoreLab data, clearly a difference, a dose-related response to lytics. More lytic, more clot gets busted up. Less lytic, you're going to have less clot. So it is kind of puzzling why it was still effective in the lower doses. Let's look at Seattle-2. 30% thrombus burden reduction by Miller score. And then look at something like the optilize-1 all the way in your bottom left, 5.5% reduction. So a huge range, yet effect was present. Seattle-3d was a really interesting, admittedly small, using CT, high-resolution CT pre- and post-procedure to potentially shed some light on what's driving the improvement in RV-to-LV ratio with catheter-directed license. And in fact, it turns out that the increase in blood volume through the small pulmonary arteries has a greater effect on RV volume or correlates more closely with RV volume reduction than does a reduction in proximal clot burden. So by knocking out the small clots in the distal vasculature, perhaps that's driving a lot of our effect. And maybe explains, at least one could reason, that is why smaller doses are still effective. Yet despite that, and despite the real excitement about small clots, there is a push to iterate. And that will then allow that and make our use of TPA much more efficient. If we are going to give it, we might as well break up as much clot as possible, hence the new ECOS device, which achieves 130% more clot lysis than standard CDT and its predecessors. So again, if we're going to give TPA, we might as well break up as much of the proximal clot as possible. And then what's also quite interesting, despite all the excitement about thrombectomy, look at the data that was presented very recently on the PERT consortium. Look how much CDT is actually going on in the community. Of the 1,233 patients, 56% are receiving CDT. So it's really unique. And then despite, again, the excitement, look at how it's performing. These are, again, we're just numerically looking at them, forgetting a statistical analysis, but if you can see in light blue, catheter thrombolysis is performing quite well in terms of in-hospital mortality, 30-day mortality, and major bleeding. That's all comers. And this on screen is intermediate risk PE, again, performing quite well. Look at the in-hospital major bleeding of catheter directed thrombolysis, 2.6%, comparing just to aspiration thrombectomy. And again, in high risk, performing quite well relative to the other approach. So stepping back, when you think about it, maybe the things are changing in the acute PE interventional thought process, and that is, while systemic TPA was clearly bad, or the risk was far too great for whatever return we got on that therapeutic intervention, when we looked at Seattle 2, it still seemed that that risk was a little excessive, that bleed risk was a little excessive for when we approached patients with acute PE. But perhaps lower dose therapy might allow us, might give us enough value to justify what's now seeming like a modicum amount of risk. That's it. Thank you. Firstly, the presence of trials, we all feel tremendous pressure to enroll in trials. But what has happened with the presence of trials, it has also driven practice, as many of us have seen. And so I've seen my hospital systems practice change with the introduction of new registries and randomized trials. So that being said, there are some patients we certainly do prefer CDT in. You can imagine somebody, a very obese patient, with a prohibitive body habits, that introducing a very large sheath in the groin is just going to create trouble. So therefore, especially now that everyone in the community has refined all their ultrasound guided access and does it pristinely, a CDT in that patient really might be better. Also, the ability to, in certain patients, go from the neck, which is not something we do for a thrombectomy, with any real ease. That ability to do that when needed or to go from some of the superficial veins in the upper extremities really gives us a lot of versatility. So that's probably the biggest group.

catheter-directed thrombolysis

acute pulmonary embolism

CDT

ECOS

Thrombolex