Demosthenes Papamatheakis, MD, reviews a case of Pulmonary Hypertension with blood clots, and explains how they identified the problem and provided treatment.
Back to Symposium Page » we're going to continue on. I have a great pleasure of introducing Dr Papa Pathiakis from the from UCSD who works in their CTF program. A big part of pulmonary hypertension is chronic pulmonary emboli, and this has really been such a success story and pulmonary hypertension because you can literally take people that are class for and make them class one. And there are new technologies in this field as well. So, uh, he's on my cell phone, my speed dial. I guess we don't have speed dial anymore, but my contact list on my cell phone and it's great to have colleagues that you can collaborate with and that can help you help your patients. And he's somebody you should definitely get to know. So demos. Thanks for joining us today and take it away. Great. Wonderful. It's a great introduction. I have to definitely live up to that. Thank you, Dr Heywood. Thank you again for having me. So I'm going to start with a case. I think that's going to make it, uh, definitely a little bit more interesting. Regrets to the discussion and the topic is when to call the surgeon and former hypertension and blood clots. These are my disclosures here. Um, so first case, this is a young lady, Mrs. It's not asthma. 45 year old woman that presented her opponent vascular clinic. And this was a referral. After being seen in a couple of different clinics. Her main complaint was worsening this beyond exertion. That was quite long standing. She had a history of hypertension, a Hyperloop anemia that were treated with usual medications like ACE inhibitors in Staten. Before she had seen us approximately four years before this presentation to the poem Vascular Connection, we did have a single event of sync api. Um and at that time, she went to the emergency room where she was diagnosed with pulmonary embolism, or DVT. This was in the setting of oral contraceptive therapy, which she discontinued at the time. She was starting a job back on a direct oral anticoagulant for treatment for this. And then she did notice some improvement of her dystonia, but it did not completely go away. And she did not return to her based on nevertheless, the spending, despite having some symptoms and being functional class to she didn't manage to continue with all her activities and and get back to work. So she didn't really think much of it and did not really pursue any medical therapy or any further work up. About three years after that event, about one year before she came to our clinic, she did start noticing that the Disney was getting gradually worse. She was now advancing to functional Class three, and it was a lot more limited than what she was in the past and decided to go see her primary care primary care after an exam. And, uh, some interview discussion with her thought that this is most likely related to the conditioning kind of poor sleep, hygiene for diet and also throughout the possibility of asthma gave her an albuterol and the I and told her to go home and work on these things. Despite using her inhaler and some lifestyle changes, losing a little bit of weight and trying to be a little bit more active. She, unfortunately still had still had her symptoms, so she was referred to pulmonary and at which point, they got an echocardiogram that echocardiogram. Graham showed pulmonary hypertension evidence and she was starting on sildenafil. But again she had minimal improvement. So this is what her echocardiogram looked like the first time when she saw pulmonary pulmonary General pulmonary. So she had a normal LV size and function. She had severe right ventricular enlargement and right ventricular hypertrophy. Her RV function was reduced. Her RVs b was 64. She had severe right atrial dilation, So multi are intact at 1.6 when she saw pulmonary vascular about a month or so later, or actually should be about 2 to 3 months later. Again, her LV was normal in size and function at this time, her right ventricle. Uh, enlargement was mild. No significant revenue jiggle, hypertrophy, some mild, every free wall. His book Genesis and RSP of 76. What I should say is, actually that this was the echo that I just read you was the initial one. And the first one on top is the echo that she had vascular clinic and the point of asking Thank we did some blood work. Her pro bnp was elevated. Her total Billy was 1.3 and she did have a negative tox screen as well as negative and and HIV with a normal TSH Based on all these results and kind of the worsening echo. We did decide to do a write her catheter at that point. Her mean right? Atrial pressure was seven. Her peer pressure was 120 or 36. 32 with a mean of 60 her We couldn't get a wedge pressure. And because of her age, she ended up getting a left her Catherine as well. That showed no significant corn heart disease in the l G d. P F three, and her output was was quite depressed, especially on thick, giving us a quite elevated poofy PVR. Anything between 16 to 20 would units, which is quite impressive. Now. By the time she got to a point vascular clinic, she already had a CT scan and an X ray, and we got a VQ scan so I can show you here a little bit. Some of the defects, um, this is a VQ scan here at the bottom, on the bottom, right. What you notice here? This is only the profusion images, and you have a posterior profusion image right here. So you should have a left lung here and the right lung here, and you should see the contour of the lungs being filled out completely with the contrast. But in actuality, that's not happening. And this is what they should look like. I kind of did a crude Philip of the different angles. You have the poster angle here, the anterior angle here and then some of the poster obliques kind of diagonally. You see the left lower lobe right here? That should be the entire left lung from a diagonal view. And this is the entire right lower lobe here. So quite a few filling defects. Her x rays. She has big pulmonary arteries here. And interestingly, on her CT scan, you see this kind of large filling defects in her pulmonary arteries, both the right on the side and the left descending primary. They are a little bit eccentric, as you can see. Um, if this was an acute PE, you'd expect slightly different findings. And we'll talk about that in a second. And interestingly, as you go further down on on her long basis, you notice that her blood vessels basically disappeared. Look, how large is Pia is here. And look at how there's practically almost no vessels whatsoever. Um, she had a pony angiogram. We'll talk a little bit about that as well. But this is a great example of an abnormal pulmonary angiogram. You should see all the blood vessels feeling nicely with contrast. What you notice here, for example, in this descending right pulmonary artery, how there's this lumpy, bumpy appearance of the arterial wall and how it kind of gets small. There's some stenosis here, and then after that dilates again. So we have some post hypnotic dilatation when you look at the lateral view here. So this is the anterior view with your right lung. And this is the latter of you with the right lung again, with the front part of the patient being on this on the side, there's a big chunk of blood vessels missing here. That right middle lobe is completely gone. This blood vessel going at the right posterior apex of the right upper lobe is, um, kind of scraggly and not feeling well. And you see all this kind of differences and vessel wall and abnormalities Was the vessels kind of getting really small and disappearing? Yeah, On the left, she had similarly abnormal findings on her pulmonary angiogram. You notice here again. These abnormalities in the blood vessel walls should be nice and smooth. You see that? The inner part here, how it's nice and smooth versus the outer part here. It's not again this very large pulmonary area all of a sudden kind of tapers down to this relatively, uh, abnormal looking small vessel here and kind of goes away. It's not. I feel very well and just notice again. The difference in conscious feeling here at the base compared to how much conscious for examples here at the middle of the month. So those are quite abnormal pony angiograms. So what is the diagnosis? Says Dr Very Well alluded to this. This is C tech. This is chronic from bomb bolic, pulmonary hypertension. We'll talk a little bit about that and what to do. I think your best bet is to ideally call. Call your neighborhood friendly C test specialist and we'll try and give you a special. That's kind of how we work. So how do we define Sita for chronic from bombard pulmonary hypertension? Well, as you heard earlier from previous talks, we definitely want for my hypertension, and you heard about the definition of pH, which is mean ph greater than 20. In addition to that, we do want pH criteria, so you want your PVR to be higher than three and your wedge to be less than 15. But in addition to meeting all these criteria, we also want to have chronic from symbolic material that has been there for at least usually three months. That's kind of a cut off that we use three months of effective anti coagulation that has not resulted in the chronic from symbolic material to resolve. There are a couple of additional points that I think are interesting. So we do want to have this Palmer have tension, as I mentioned, persisting for at least two months after the anti coagulation. We also want to see the profusion defects, usually on VQ scan. I'll show you a few more examples and explain why this is a little bit better than CT pulmonary angiography. And then there's also an interesting phenomenon. Something called C T E p, D. Or chronic from symbolic pulmonary disease, which is the presence of chronic from symbolic material that's including the pulmonary arteries with symptoms but not necessarily causing pulmonary hypertension, so not necessarily causing elevation of the pressure. I'm not going to spend too much time in the pathogenesis and the path of physiology, but I thought it would be interesting to show you at least a couple of points. This is a great example of an acute thrombosis. How it looks like a string of jello here, and and this is what it turns into. So this is this very organized clot, this thrombosis, this scar for lack of a better term that's organized within the aluminum, the pulmonary artery to the point that is, you can see there's small new vessels forming within the within the organized clot, this new angiogenesis trying to open holes through it so that blood can flow through. And then when it comes out from surgery, so you show you more examples. But it looks like this this gnarly alien type of meat, the crux of the pathogenesis and path of his reality lies in the poor resolution of an acute pulmonary embolism. And this is either defective angiogenesis, uh, and or delayed fiber analysis. And a lot of this has to do with industry. Um, and how it works and or for that matter, works poorly. in general, the second phase of this is just misguided vascular remodeling. So those two components are what play a big role in all this. And unfortunately, we, um, even though there is a little bit more knowledge in this area, we still don't know enough to be understanding who and why they would move from this kind of a cute claw to this chronic from Lombok disease. From an epidemiology perspective, it's not very common. It's about 3 to 30 cases per million population that we see CTF, and we see about 500 to 2500 cases per year in the US In regards to its incidents, we we've estimated that it's between 0.6% to 9%. As you can see, it's a pretty wide range. Once you've had an acute PE, we suspect that this incident is closer to 3 to 4% based on more recent data that we have. But generally speaking, the thing to bear in mind is that this is only for patients that have documented a Q P E and we see our patients in clinic. There is definitely a good chunk of them anything between 25 to 60% that never had a P E and a good number of them as well, about half of them that never had a DVT before their CSF diagnosis. So it is possible to see that in someone that hasn't had Accu pe or DVT before. Therefore, even though we quote a relatively low incidence, I have a suspicion that that's probably closer to six or 7%. When it comes to initial assessments of CTF, One of the biggest components of it is index of suspicion. You have to be very suspicious that it's there. Of course, the fact that someone had a history of PE or DVT is super helpful, and hopefully that kind of raises a flag or a little light bulb goes off in your brain, saying, Hey, think of CTF. Um, one of the big problems like the case that I presented is oftentimes we don't think about it, and therefore the diagnosis is delayed for a long period of time. And that, of course, worsens both symptoms and human dynamics and for that matter, can increase the risk of surgery. The presentation is very subtle. Clinically, it's very similar to any form of Ph. with just this. Me, on exertion and early on can also be asymptomatic as well as with having this kind of honeymoon period after the acute PE, where people get anti coagulation feel a little bit better. Although usually, like our patient, they do not return to their baseline exercise and talents, and fatigue is one of the most common complaints we have. In addition to discipline. Of course, it's a disease significantly worsens. We'll have all the symptoms of right ventricular failure, as well as things like sync, api or hypothesis that sometimes will present. Remember, especially in cases with prior DVT and in cases where you find pH but don't have any other risk factors for Ph. And if you're thinking idiopathic Ph. Definitely consider this even in the lack, even in the absence of any prior history of Venus from public disease. So how do we do the work up echocardiogram? Electrocardiogram, as you heard from my colleagues earlier today, is kind of your best friend. It's a great screen tool. I mean, look how happy this guy is to get an echocardiogram. Happy the tech is to to provide it, um, you get very good information when it comes to, uh, elevation of right ventricular systolic pressure. And that's a great screening method to figure out whether this pulmonary hypertension, um, you can take a look at qualitatively What does the RV and the R a look like? Is it enlarges dilated? Do you have right ventricular hypertrophy? And, of course, you can see other things when it comes to, uh, into particular dependence, like the D shaped septum or what's happening to the L V. I have a couple of extreme pictures here to show you, and you've seen probably more impressive videos from the earlier talks. This is kind of a massive right ventricle that's completely squeezing on the left ventricle here. This is kind of a typical V shaped septum that we talk about. And of course, the echocardiogram helps you figure out, you know, is there any evidence of left heart disease to kind of rule out group to pulmonary hypertension? U V. Q. Scan is your best friend to rule out CF, and I know that, um, not everyone is familiar with this test. I'll show you a few more examples. It is kind of an older tests, and some of our radiologists are not excited about it. But we have good data from the early two. Thousands of sensitivity for CTF is almost twice as much The sea people my angiography 96 to 51%. So we still like this test a lot more. And part of the reason is C. T. P. A has a distinct difference when you're looking at chronic from symbolic disease versus in a QP, which is the most common reason why people get C T P s. Of course, there's newer data that you know you know what you're looking for. You have an experienced radiologist that's looking for Sita. A good quality CTP can also give you quite a good sensitivity. But part of the problem is that not everyone is familiar and experience with it. So this is a normal wiki on the top, right? You can see here you have the ventilation images here. This is a poster of you. So this is your left lung here. This is your right lung here. They're supposed to fill out nicely and you can see all the contours of the long and that die from here at the bottom. And you compare this little image here to this image right here, which is your poster of you of your profusion again, You need to see all the countries of the long term left here and on the right. We really like these two angled views that I showed you earlier. That's the left posterior oblique. So this is the left lung, and you can get a great view of your left lower lobe right here. And this is the mirror image of that, the right posterior bleak. And you can see the right long here and a very good view of your right lower. So this is what a normal vic you should look like. Everything should feel very nicely. And you see the Contras and all the angles. This, on the other hand, is an abnormal VQ scan. You notice, just by a quick glance of the ventilation here and the profusion here, these are definitely not symmetrical. You have the nice big arrow sign here showing you what's missing. And once again, I made an effort here to kind of fill this out for you, um, with my kind of poor artistic skills, but lots of different areas where profusion is absent. This is another example. Once again, the normal appear on the right for your reference. But just a quick glance between the posterior view of your ventilation profusion. You notice how there's big chunks missing here. So this is your right lower lobe right here. And this is your right. I'm sorry. Left lower lobe right here and right upper lobe right here. And this is another extreme example where you have a lot of kind of peripheral defect, and I started to try to fill in this, and I kind of gave up and I said, Hey, listen, this is what it's supposed to look like, but these are the most challenging ones. And I'll show you an example of what came out of this patient after surgery, because those are usually examples of very distal disease and distal perfusion defect. Yeah. So once your wiki is positive, what you want to do is the next step, the confirmatory gold standard test, which is digital subtraction, angiography. We like to do by plane both anterior posterior and lateral views. And I'll show you an example why we do that. Generally we do want to avoid doing the right heart catheter without a wiki, because if someone gets a writer, Catherine that have pH. But then you're suspecting CTF um, and you get a VQ after that, then you need to subject them to another invasive procedure to do the pulmonary angiogram. So it's probably a good idea during your work up to your I could do your V Q and then decided after the wiki if they need just a simple right heart. Cath read her Catholic digital subtraction angiography. As I mentioned, Chest Sita can be helpful, and there's different protocols for that. Yeah, so that can help a little bit with mapping, depending on the availability of pull me angiography and in some cases will avoid the angiography and just go straight into the chest. See to it that that's a requirement. This is one of my favorite examples of why, um, chest biplane. I'm sorry. Digital subtraction angiography is extremely helpful. If you look at this end to review here on the left side of your screen, this is the right lung, and you see the company already coming out and bifurcating nicely here. It almost looks like a normal pulmonary arterial tree. it goes to the right upper lobe because the right lower lobe. But in actuality, this branch that you see here looks a little bit small for a right lower lobe. And when you look at the lateral view so this is a lot of you of your right lung, you know, your spine is back here, your diaphragm right here in the front of the patients. Right here. You notice how there's a big defect here? This we call this a pouch defect basically just ends up in a dead end. Uh, in that branch that you were seeing on the anterior view is actually right middle lobe coming up here to the front. Whereas you're descending, right, pulmonary artery is completely gone. It's just described a little vessel that barely fills. So this is another helpful component of doing digital subtraction angiography where you can map out very nicely. Which vessels are disease. And that helps significantly the surgeon during the procedure that we'll talk about in a sec. So let's jump to case two. We'll talk about a gentleman that got Catherine directed lyrics. This is Mr Nada que clock. He's a 40 year old man that had no significant past medical history and presented to the emergency room with two weeks of dismissal. Exertion coffin hypothesis, a chest CT showed significant P was multiple areas of along being affected and a lower extremity ultrasound. Doppler confirmed that he had DVT as well. At the time, a presentation to the E. D. His anti pro bmp was almost 1700 and the echocardiogram showed some right ventricular enlargement. Depressed are the functions. Some are pH as well as elevated RVs p. Now based on this and based on an echocardiogram that that was done and these are some videos of his echocardiogram more you notice that he's got a significant increase in his RV size and his Ari size. It was decided that we should go ahead, um, to do ultrasound has Catherine directed from politics, and this was because of the diagnosis of some massive PE. So Hepburn was started. His Catholic director, Tom Politics, replaced You See, there that echoes Catherine is X ray, Um, but interestingly, despite spending 24 hours in the ICU and having to instead within the clock, his human dynamics didn't change. These are here's pre Catholic thermodynamics, and this is post Catholic thermodynamics. So this is not what we call a successful echoes Catherine use. This is after Thermal Isis. So they did a pulmonary angiogram angiogram at the end of those 24 hours, and you notice that he's got again this abnormal pool priority right here. And not a lot of contrast is filling his right lower lobe. So what did this happen? Well, this was not an acute clot. This was a chronic cloth, and this was CHF. And that's why we need to be very careful. We make decisions about Katherine directed from analysis. Were there any clues in the imaging before this That would have maybe helped. Well, first of all, on the city that he had that he was diagnosed with some Mississippi, There was some, uh, quite enlarged bronchial arteries that you can see here. This is definitely a finding that we see with chronic from Mombasa common hypertension. When he came to his right ventricle in his right atrium, you noticed that he had a significant Lehi petrified RV, and both RV and are they were quite large again. We kind of suspect this and longer lasting situations. And when it comes to P E when we see a QP, we want to see a string of Jell O clock kind of sitting in the middle of the Lumen. But this is not what we see here. We see kind of large, um, filling defects that are in some areas eccentric, and you can even see mild classification, so kind of wall lining type of organizing samba's. So there were definitely a few clues in the c. T. Also notice kind of the lack of blood vessels here in the periphery. Um, kind of suggesting kind of complete occlusion, no blood flow. So what should have been done instead of Vegas? Catherine will A PT surgery is the best way to approach chronic from above former hypertension. I'll explain to you why, um, this is the actual patient that had this P t surgery and after PT surgery, Is human dynamics normalized completely? As you can see, the arrow is pointing to some acute clot on top of chronic clot that this patient had on the right hand side. So how do we decide that someone is a good PT candidate? Well, so this is the CTF operability assessment. This is probably as complicated, um, as as the surgery in and of itself, since we need to figure out whether is he a good candidate from a past medical history, perspective and a risk perspective? How severe his human dynamics? What is this functional status and how that's going to be affected by the surgery, as well as the level and extent of symbolic disease? And how can we, based on our center experience, help or not help? If this is a complicated or high risk case when it comes to the surgery itself, it's a quite long. Surgery usually lasts about eight hours. We're talking about deep, hypothermic circulatory arrest with stern, Artemis and cardiopulmonary bypass. The reason for the circuit terrorist is because the surgeons need a bloodless field in order to see better throughout the primary care tree and be able to extend it and direct to me as distant as possible. We always do bilateral and dark directories with the incision in the PS within the pericardium, and this is what we call it true indirectly. So we not just take out the clock. We actually take out the intimacy, completely denuding the inner layer of the pulmonary artery all the way as far distant as we can. So this is kind of what the incision the pulmonary looks like. And as you can see, we find this plane between the intimate plus organized clot in the media, and we kind of take out this entire inner tube. The field, believe it or not, is quite small or not. They're not working a very big field. So we have extremely skilled surgeons that do this for us, uh, and are quite amazing at what they do. We level. We use this level type of, uh, stratification for the clock. Once we take it out. If it's extremely bulky and and the main pH. Level one as you go to low bar, it's level to, um, this is, uh, what came out from the first case, if you remember. So she had level one disease. And then if it's segmental, we called level three. And if it subsequently were called level four, if you remember the last week you that I showed you those looked almost like it was moth eaten. Well, you know what? This is what came out from this this week. You, with all the little peripheral, uh, filling defects, which is definitely kind of the hardest and technically most rigorous type of surgery when it comes to our institution of this kind of a bit of a shameless plug for UCSD here. We've been doing this for 30 years. These are the number of surgeries per year throughout the last 30 years or so. You notice that we're kind of between 1 82 100 even with the covid pandemic going on, and, uh, we're kind of ahead from from the competition, kind of throughout the world, who were very proud of that. Um, this is our pre operative mortality. Kind of. When we started out, we definitely had our challenges back in the nineties, and things continue to get better. As you notice here in 2011, we got 20% which is quite impressive. Then, you know, I joined the faculty. Um, things didn't go as well right after that, but I will neither confirm nor deny that had anything to do with me. Having said that are one peri operative mortality rate is around 2%. Uh, and we are keeping it like that now for a good amount of time when someone cannot get the PT surgery and he's considered a non operable CF patient. Things get a little bit trickier, but we do have options. At this point. We still want to do life long anti coagulation will do that for all our patients, even the ones that get surgery. But in addition to that and other supportive treatments like diuretics or oxygen of the hypoglycemic, we do have a couple things to offer, and one of them is BP A or balloon pony angioplasty, and I'll show you a couple of examples, and we do now have some form of therapy options for our CF. Unfortunately, this is limited. We do have only real ciguatera Tempus. That's FDA approved there a couple of other trials out there, um, but have not merited approval yet for mass attention, which is another drug that seem to be promising in this area. And the thing to remember is that we should not get to these especially pharma co therapy options. Unless someone has been appropriately evaluated for surgery, surgery is still the best option is still curative. As Dr Heywood mentioned earlier, these patients can go from functional class 4 to 1 after surgery. So only if patients are not operable. Candidates refuse the surgery or get the surgery and still have some form of hypertension. That's when we think about doing far Michael therapy, and now we're actually even approaching some of our post PT residual pH patients with this dual hybrid approach of offering balloon Puma angioplasty. So what is balloon permanent? Angioplasty were very simple, almost like any other angioplasty. What we do is we use grated balloons to go into the pulmonary arteries and stretch out this thematic areas. Um, this is a couple of examples before and after here. There's some organized plot here in the left lower lobe, and this is before, and this is after where the blood vessels starting to opening up and similar here. A nice before and after. This isn't the right right lower lobe, so this is definitely something that's been successful. We've been doing this for about five years. We've had about 100 patients come by, and the number is going up multiple sessions so each patient will get more than one session. That's why the procedure number is much higher. Um, the pressures can come down, the resistance can come down. It's relatively low risk procedure. We've had one major bleeding that had a significant hospital tape but stay but did not end up in death as well as having a couple of, uh, maybe about 3% bleeding risk, which is kind of what's been reported in the literature. I'm going to end their showing you this little graph. This is something that we published recently with the team on Journal of American College of Cardiology. And the main take home point here is think about CHF. And when you do think about CHF, make sure you go through your steps of an echocardiogram VQ scan and then depending on what your capabilities are, either send them to someone that can help you with it or take care of it yourself. I'll stop there. I think I have maybe a couple of minutes for questions. It looks like there's a question to chat. What does digital subtraction? Uh, check. Here we go. Um, question one. What does digital subtraction meaning the S B. A. That's a great question. So digital subtraction. The main thing is that we use software in order to take away some of the other characteristics. Um uh, findings of the rest of the chest. So I don't know if you notice some of the pulmonary angiography images they showed, you can see the bones of the ribs, whereas in some others, we managed to use this digital subtraction method to kind of take that away and have kind of a cleaner image of just the blood vessels. So that's the digital subtraction part. Another question is, why does c to not pick up chronic clot? Well, the short answer is kind of what I've alluded to earlier. Unless you look for chronic clot, you may not see it. It tends to be more distal than acute clot. It tends to be a little bit different. Instead of seeing this kind of string of jello um, lack of filling of conscious within the vessels, you may end up actually just seeing lack of vessels. So there is some nuance to to differentiate the two. And unless you're looking for it, and in time, the CT scan appropriately, you may not see it. Why do you do new the end of feeling in the operation that is the best way to be 100% sure that you relieve all the obstruction if you try to, um, the clot has organized to such an extent that it's basically become part of the industry, Liam. So if you try to only take out part the organized clot, you're gonna end up doing an incomplete job and leaving a bunch of stuff in there. And the question number three cannot be considered for lifelong integration, which ones prefer. So that's that's a great question, and I'll finish with that. We actually now have good retrospective data from our colleagues in Europe, where they did PT surgery. And then after that, um, let most of the patients go with no extra do X versus some going on warfarin. The patient's going home on dogs and No X had about twice as much likelihood of having a repeat clock. So after surgery were quite adamant that we want Coumadin or warfarin for at least a year after surgery. Also, patients that have anti fossil lipid syndrome, which is approached robotic state or puts you at very high risk for this specific disease, um, do not do as well with Dr Knox compared to Coumadin, so The short answer to this is definitely after surgery. Want Coumadin? Definitely. For anti fossil lipid patients. We want Coumadin. But in some cases we can do do X, and we will consider them as long as everyone's on the same page, understanding that there's a slightly higher possibility of clotting with those on board. Okay, Well, thank you so much. That was excellent as usual. And I can't emphasis how much how life saving this procedure can be in life changing for patients as well. Thank you, Doctor. Thank you, everyone.