We're going to get started today, and this is going to be a really fun session on debates in pulmonary embolism, and here are my co-speakers, and we're going to go in order as we try to debate different topics. We'd like to make this as interactive as possible, and after two of our talks, then we're going to have a show of hands for voting to see who agrees with who. So the first talk, it's going to be on surgical embolectomy is not obsolete in pulmonary embolism management. My name is Belinda Rivera-Lebron, I'm from the University of Pittsburgh. Here are my disclosures, none of which are relevant to this talk. So a little bit of a surgical history today, and probably the one thing that I should have said on my disclosure slide is that I'm not a surgeon. So I am debating pro-surgery, but I'm not a surgeon. But here's the history of surgical embolectomy. So you can see at the first report in 1908, can you believe that? That is, to me, kind of mind-blowing, by Frederick Trendelenburg, the famous Trendelenburg, and this is really 18 years before the introduction of unfractionated heparin. So just, again, think about, you know, put the framework in here. This surgery was not successful. He actually performed multiple surgeries after this, and it was not until the 1920s where he had the first patient that survived. And as you can see on the right, here is another case series of some patients reporting poor outcomes. And really, the reason why there were poor outcomes at the time were because there was, you know, no imaging, really. So CT, obviously, not available. So the diagnosis was just based on pre-test probability or just clinical scenario. And also because patients were taken to the OR when they're, like, end-stage really dying. So here are the common indications for a surgical embolectomy. You see here contraindications of fibromyalgias, the most common, failed systemic or catheter-directed thrombolysis, clot in transit, or having a shunt, a pulmonary, a PFO or an atrial shunt. Notice here that contraindication to unfractionated heparin or anticoagulation is not here because surgery needs to be done on full anticoagulation for cardiopulmonary bypass. So here are the factors affecting surgical embolectomy outcomes. So time period, and we're going to go through all of this in more detail. Time period, right, so if it was reported from the 1950s, 70s, 80s, et cetera. Surgical characteristics, so specifically volume center, so different outcomes if you do two surgeries, so a year versus 10, 20, 30 a year. Patient comorbidities, as we're going to go through in more extent, but, like, age or cardiopulmonary comorbidities will increase the risk of surgery or the risk of mortality. Clinical classification, so if you're operating on someone who's submassive or intermediate risk versus massive or high risk. Timing of surgery, this is very important, whether it is primary or salvage therapy. And if the patient has cardiopulmonary arrest during the surgery or pre-surgery. So here's the mortality trend over the years. As you can see here, what I've just mentioned that was initially reported by Trendelenburg in the 1910s, it was over 90%. The mortality did improve really after the 1960s, after cardiopulmonary bypass was introduced. And then up until recently, as you can see, the most recent series, 4 to 7% mortality rate reported, which is pretty remarkable. Here are the comorbidities that are associated with worse outcomes. This is taken out of the national inpatient sample that included almost 60,000 patients, of which 3,000 had surgery. But you can see here how atrial fibrillation, congestive heart failure, and age were most of the common increasing risk factors for having poor outcomes. However, here, very importantly, notice how non-saddle PE actually is a predictor of better outcomes. I'm sorry, saddle PE. So meaning the non-saddle PEs do worse. And I think that this is probably because when they do surgery, one, it's a shorter period of time if they're able to extract the surgery, and it's a much less complex procedure. So here's the mortality over if you divide it by the clinical classification. So low, intermediate, high, as you can see here. So we're going to be looking at specifically the ones that have submassive or intermediate, the ones that are massive without cardiac arrest, and the ones that are massives or high risk with cardiac arrest. So you can see here 30-day mortality and a year mortality. But they're much better when the patients have a more hemodynamically stable as they're going into the OR. Here's another question that we talked about all the time, right? So should we just take the patient to the OR from the get-go versus do we need to try something else and then go to surgery? So in this study, retrospectively reviewed, you can see here the longer you wait, especially after other failed therapies, is probably a worse outcome. So here's the time to the OR of over 24 hours versus less than 24 hours. And as you can see here, it's clearly remarkably different. How about CPR or cardiac arrest? So these are the three largest series that I selected, but they're modern, very recent and in the 2000s primarily, including a good amount of patients. But you can see there is a dramatic increase in their mortality when there is after cardiopulmonary arrest. Now, it's very important to kind of know that there are different kinds of CPR, right? So you know the preoperative, right, prehospital CPR versus the intraoperatively much more controlled CPR. The other thing that's important is the minutes, right? So can you arrest for 30 seconds versus the arrest for 20 minutes? So you can't really classify and all these studies are going to have different kinds of patients. But overall, the endpoint is that if you have cardiac arrest, then you're going to do poorly. But if you don't, mortality of surgical embolectomy without cardiac arrest can be very similar to the mortality of CABGIS. So that is really something to consider. Another advantage of surgery is that you normalize the RV pressures immediately after surgery. So here's a series where they showed that the RV dysfunction before and after a surgical embolectomy and it's essentially showing the same thing. But you can see on the right that essentially all patients but one had an improvement in their RV function by echocardiogram after surgery. And this is not an improvement by non-invasive methods but also invasively. So if you look at, this is a report by Goldberg where they saw that there was an improvement in central venous pressure and also in pulmonary artery systolic pressure. And this improvement is immediately post-op and it's different than what is reported in the catheter-directed trials, which is usually about a 48-hour period. So some of the complications that can occur after surgical embolectomy are usually sepsis, stroke, atrial fibrillation, pneumonia. But really they're not very different than what any other cardiac surgery may entail and they're not as common as you may think. So how does surgery compare to systemic thrombolysis? So you'll hear my opponent here try to convince you of different things. But here's the reality. So surgical embolectomy versus systemic thrombolysis, when you look at this is a very large series here that included patients that were treated with systemic thrombolysis versus surgical embolectomy as first line. So this is not rescue but first line. There's really no difference in 30-day mortality, I give you that. However, with systemic thrombolysis there is definitely increased risk of stroke re-intervention, meaning having to go back to doing something else as a rescue, and major bleeding. So again, just start considering things. Another report here comparing surgery versus systemic lysis in a non-randomized study from Iran did show that in these patients, despite them having worse RV function in the beginning when they're present, their actually recovery is much faster and much more profound when you have surgery as opposed to when you have systemic thrombolysis. So how about the comparisons of patients that do go systemic thrombolysis and then you need to rescue them with something else? So this was a study that included almost 500 patients in which they first were treated with systemic lysis. And as you can see here, about 40 of them, which is 8%, had not an improvement of their hemodynamics. So then they were further randomized into either surgery or systemic lysis. And as we can see here is that there really is a trend towards improvement in mortality, and also a decrease in the recurrent PE and uneventful evolution, which means there's less complications if you have surgery as opposed to systemic lysis. Well how about catheter therapies, right? So again, my opponent's going to try to convince you of that, but look at this. So you can see here how there is a very marked improvement in catheter-directed therapies over the years, especially since 2014 or so, which is where most of the catheter-directed therapies have come along. This is a large meta-analysis that included 11 randomized controlled trials and 42 observational studies that included catheter-directed therapy, systemic thrombolysis, and surgical embolectomy. The in-hospital mortality of catheter-directed thrombolysis, if you can see at the top, is slightly better. I'll give you that. However, the long-term mortality, when you look at this, so surgical embolectomy comes superior. And why is that? It's probably because you can get rid of most of that clot obstruction early on. Additional advantages of surgical embolectomy that you probably are not going to be able to get with any other therapy. So the ability to reach distal areas, right? So no catheter can reach very distally, as you know. The extraction of very large clots, especially the clots in transit that are irrespective of size. So some of the catheters can extract clots, but if they're very large, they may not be able to fit through that catheter. The other thing is our improvement of acute and chronic PE. So as we know, catheter techniques are not very good for clots that are there for more than seven days or so, because the clot has already sort of epithelialized, and you're not going to be able to extract it. And also fixing intracardiac shunting. So just things to consider. So my argument today is that surgical embolectomy is not obsolete in PE management. It's actually here to stay. And if I did not convince you, you can read it for yourself. So we could see that here is a very nice review that was published this year, and you can go through that yourself. And it will kind of get, it gives you a little bit of perspective of where things are coming and what should we do. Especially because I think that right now, surgical embolectomy is usually reserved as like last resource effort, when I think that we should be introduced early on, because that's going to really change how the patient's going to do. So thanks, everybody. Well, good morning. It's going to be my job to convince you otherwise, with the non-surgical therapies that are available for the treatment of patients with massive pulmonary embolism. I want to extend my great gratitude and appreciation to CHESS for allowing me to present and to talk today, also share the podium with some of my colleagues. My name is Brandon Hooks. I'm a pulmonary and critical care physician at University of Michigan Health West. These are going to be the objectives today that I hope to achieve with my talk. So let's talk about surgical embolectomy. As you heard from my colleague and friend, that surgical embolectomy allows for surgeons to get access to areas that catheters might not be able to get to. They might have a lower risk of recurrence, as reported in some of the studies, as well as mortality benefits compared to mechanical circulatory support. But what I will tell you about surgical embolectomy is most data that we have is based upon single study, and it's very operator dependent. In the perspective of patients, it is not available at most hospitals throughout the United States. It is sometimes inefficient, organizing a team, getting them into an operating room and having staff available. And it's also associated with increased length of stay for the non-surgical treatments. So let's review what we're talking about most as far as guidelines. So the ESC has identified high risk pulmonary embolisms, and these are patients that are incredibly sick and represent less than 5% of all the patients that present with pulmonary embolism. And just to give you some perspective as far as mortality data, 52% of those patients with high risk who present have mortality within 90 days. So these are very critical patients that need access to care fast, something that is readily available. So what do our society recommendations have in regards to treatment of high risk patients? And what you'll see is the treatment guidelines are really based on limited data. And I shared here the ESC and the ACCP, and it's an area that we have further opportunity to look into to answer the question about therapies that are non-surgical that may provide some benefit. And I think that's where the science and the research is evolving, and I hope to share some of the studies that are current with the progress. I forgot to mention within my slides I have QR codes at the bottom, and those are links to the references within my talking points. So we're going to talk about systemic thrombolysis, but I just wanted to share with you. The societal guidelines recommend for systemic thrombolysis mostly up front in these patients, but it does come with a cost. There is higher rates of bleeding risk, and the most alarming statistic with systemic thrombolysis is even those that present with high risk pulmonary embolism, it's a low usage. We have less than 30% of patients who actually do present with pulmonary embolism that are high risk actually receive it. And there is many risk associated with it that is also contraindicated and relative contraindications with use of that therapy. And most of our data that we have regarding systemic thrombolysis really started several years ago, and you could see within the thrombolysis group and the heparin groups as a comparator, the amount of patients that they had were very low numbered. The study that we hear most about from 1995 with Sanchez compared thrombolysis to heparin, and it was only a total of eight patients within that study. And what it showed is those that received thrombolysis did survive, but those that did not actually died. All four of the patients that did not get thrombolysis did die. Let's go back to the early days of catheter-based therapies, and if we look at probably the most earliest study when we were evaluating ultrasound-accelerated catheter-directed thrombolysis in 2015, it's hard to believe the study is almost 10 years ago, but it seems so new where we are with the progression of these catheter-based therapies. Well even in this study of 150 patients, there was 31 patients that were included that were massive pulmonary embolism, and what we do see within those is they did have a reduction in the RV-LV ratio, and we know historically those with high-risk massive pulmonary embolisms, those patients have signs of right ventricular dysfunction. So this is one study that did indicate some benefit of using catheter-based therapies in patients with high risk with reduction in both their RV-LV diameter as well as their pulmonary arterial pressures. Now let's talk about something that has been very recent, and hopefully will be coming out very soon. This is information from ACC presentation on the FLAME study. So this is actually a really interesting study that's looking at catheter-based therapies using mechanical devices. In particular, this is the ANARI device, and this study was actually specifically designed for patients with high-risk pulmonary embolism, and the inclusion criteria is shown there. But to my counterpart's point about those that needed CPR, they actually did include patients in the FLAME trial or FLAME study who actually did undergo cardiopulmonary resuscitation, which was less than 30 minutes, and some of those, in fact, were out of hospital that had presented into the hospital. So they were included as part of that. And they looked at the need for vasopressor support as part of their inclusion criteria. This study was actually stopped early because it met all of their criteria to meet power as well as to provide safety benefit. And that was within the first 50 patients that were enrolled. And what we see is the in-hospital mortality of those patients was rather low, 2% compared to other therapies which were used by either systemic thrombolysis or other non-catheter-based therapies. So pretty remarkable mortality benefit with this study. I wanted to point out, too, within this study, there was 41% of those that actually did have contraindications to thrombolysis. And they also did have some patients that did have underlying pulmonary hypertension more in the flow-triever arm than they did in the context arm. So can catheter-based therapies do, you know, things just as much as surgical-based therapies? And I think they can without having to do a surge, you know, have a surgeon available to do a surgical incision to open up the chest, put somebody on heart-lung bypass. I think it is very effective that we could actually rapidly decrease the thrombus volume as well as improve the right ventricular hemodynamics. And this is actually a picture of a case that we had three weeks ago in a patient that presented with high-risk pulmonary embolism. And the other interesting part, too, is this therapy has been FDA-cleared for not only non-surgical treatment of thrombus, but also for the treatment of clot in transit in the right atrium. So this allows another opportunity, another therapy, another device to treat patients with clot in transit. What we could do is minimize blood loss with a flow-saver device. So the actual blood volume that patients will actually lose based on that use is actually about 50 to 100 cc's of blood. As you can imagine, too, with surgery, probably the blood volume is more than that. So one of the things that we haven't really talked about as far as guidelines go in terms of high-risk patients is the use of mechanical circulatory support as a standalone therapy. I found a study that was based, it was a single-center study that was retrospective that were looking at their own data from Geneva. And they probably have the largest amount of data of patients that they followed over the course of almost 10 years. And what they found with just VA ECMO alone, they did have a survival rate of 64%. And none of those patients actually underwent surgical embolectomy. This is, however, encountered at some disadvantages. One of them would be increased length of stay. But in terms of the need and duration that they were on mechanical circulatory support, I think it was remarkable that most of them were on ECMO for three days. But if you look at the graph that's at the top right in the Kaplan-Meier curve, when ECMO, or mechanical circulatory support, was used with fibrinolysis or catheter-based therapies, it actually had a significant higher risk of mortality compared to the ones that were just used with mechanical circulatory support alone. So if you haven't really bought into my presentation or drank the Kool-Aid that I was talking about today, you don't need me to tell you. You just need CHATGTP to really answer the question. As you can see here, although it remains a valuable option for selected cases with very operator-dependent, accessible, in-reach surgeons willing to do the surgery, it's generally considered obsolete as first-line treatment. I didn't put that in there. That was CHATGTP. So to conclude from this, surgical embolectomy, I don't think it's obsolete. I just think it's not accessible. It's not readily available at centers where these patients that are high-risk need it the most. And what we can see is the mechanical thrombectomy can reverse obstructive shock, improve oxygenations, and it does not require a special skill set for the operators which perform this procedure. And I thank you for your attention. Good morning and thank you very much for coming and spending your precious morning with us. Instead of doing some fun things in Hawaii, it looks like we have quite a good audience. Before I say anything, I think the audience response system should work. I don't know how you guys vote on the phone or somewhere. Or no? Let's see. If not, then we will do the old traditional way. I think it does work. Looks like if you can scan this QR code. So before I say anything, please answer this question. From last September to this September, before you came here, how many of you guys have prescribed or ordered systemic thrombolysis for acute pulmonary embolism in the last one year? 0 to 5 times, 6 to 10 times, 11 to 15 times, or more than 16 times? Okay. So now you can vote. 0 to 5, 6 to 10, 11 to 15, more than 16 times. Okay, let's see the answers. Awesome. So, I don't think I need this talk. Because all of you guys are the experts who are treating the PE on a field every day, and the study we conducted here, which is the most latest study you can get in the world, because it's a time base, and all of you got the authorship of the study. And the TPA is a matter of the past, because none of you guys, or at least 90% of you did not even prescribe one time in last year. So, I mean, still I'm going to bore you with a few slides and data because I prepared it for the one and a half months, but I don't need to convince you anything. We don't need a vote after the two of our sessions. My name is Bhavin Dalal, and I'm a pulmonary critical care physician and a program director at the Corwell Health. It used to be known as Beaumont Health in Michigan. This is my disclosure, although it has nothing to do with this talk. So let's start with understanding the cases which you see almost on a daily basis. I don't think there is any exception. So the first case is a 40-year-old athletic woman came to the ER with a shortness of breath on the OCP and smoker found to have a right upper lobe pulmonary embolism, so segmental PE. The blood pressure, heart rate, oxygenation all were stable. CT did not show RVLV ratio of more than 0.9, and the echo was also okay. BNP is normal. So what is the next best step in a treatment? Again, you can vote, and I think it should be pretty easy now because you already have a QR code. ... Does this patient require reperfusion, IV heparin, or low molecular weight heparin followed by oral anticoagulation? Okay, let's see what you guys say. Yep, I think most of you guys agree that this patient will probably require either low molecular weight heparin or oral anticoagulation, and so many of these patients nowadays don't even require to be admitted in a hospital, which we have learned, which is not a talk for today. But if you go for the risk stratification of this patient, hemodynamically stable, no RV dysfunction, biomarkers are negative, and the ASPASI score is zero. Just to refresh our knowledge of the ASPASI, which is Simplified Pulmonary Embolism Severity Index, there are six different variables, which you can remember, if you want to, by this mnemonic ASPAPSI instead of ASPASI. But it's readily available on the MD-Cal, and you can give a one-point for each of those variables. If the ASPASI score is zero, no RV dysfunction, hemodynamically stable, these are considered to have a low-risk PE, and again, Brandon did go over with this one. So let's go on to the case number two. This is a 55-year-old guy, has a 20-pack year smoking history, and then recently diagnosed with COPD, came with an acute shortness of breath after taking a flight from London to Detroit, found to have a saddle pulmonary embolism. On admission, the blood pressure was good, the 120 or 76, but the heart rate was high, the pulse ox was low and required some oxygenation to improve it. RV-LV ratio is 1.2, BNP and troponins are elevated. So in summary, we have an ASPASI score of three, with a high intermediate risk pulmonary embolism, because he has RV dysfunction and biomarkers are positive. So again, the question for you, what will be the next best treatment? Would you give him systemic thrombolysis, IV unfractionated heparin, or low molecular weight heparin? Okay, the system looks working pretty good. Okay, wow. So, I have some work to do. The, I will actually say IV, I mean, sorry, the sub-q heparin, I mean, low molecular weight heparin, and I will tell you why in a minute. But the first question, I won't agree with the IV tPA up front. And this is what we have learned from the, our best, largest randomized control trial so far, known as a PYTHOR trial. They have randomized almost 500 patients for the intermediate high-risk pulmonary embolism patients to tPA and the heparin arm in the interventional group and only heparin in the conventional or the control arm. And this is, so far, the largest study, by the way, and did not find any difference in the mortality at seven days or a mortality at 30 days. Just have to remember that the mortality in the overall study was less than 2.5 or 3%. So, if the expected mortality is in this group, IV tPA or a systemic thrombosis up front for the high-intermediate risk therapy is not very, it's not gonna give you a meaningful benefit. On the other side, as expected, the major bleeding was significantly higher and the risk of the hemorrhagic stroke was almost 10 times more in the IV tPA or a systemic thrombosis arm compared to the control arm. Chatterjee from the Mount Sinai and his colleagues did a wonderful meta-analysis after the PYTHO study was published. They have collected almost 2,000 patients. So, remember, the PYTHO has almost 1,000 patients and another 1,000 patients from another seven randomized control trials. They did find, if you look at the p-value, a little bit significant towards the systemic thrombosis. I think that's why some of you guys probably have chosen that option. But number needed to treat was very high. For one saving life, you have almost 60 patients you need to thrombolize, which was nullified by the effect of the bleeding and the hemorrhagic stroke. On the other side, people always ask, is there something new in the pulmonary embolism or a systemic thrombosis? Unfortunately, there is nothing new in this last 10 years, but every year, there are one or two meta-analyses that are published. So, if you are looking for something new, yes, there is a new meta-analysis published last month and showed that there is no significant or statistically significant p-value for upfront thrombosis or upfront systemic thrombosis on those group of the patients. We do find this difference in the statistics. It's kind of a game. We have a lot of meta-analysis and one will find positive, one will find negative. Kind of confuses us in general because they do give a different weightage to the different studies in the meta-analysis and the things keep on changing. But our current ACCP guidelines, and Dr. Morris is the lead author sitting in the front table, mentioned that the upfront thrombosis is not indicated for the classic or a garden variety intermediate risk pulmonary embolism patient. Why low molecular weight heparin compared to unfractionated IV heparin? Again, kind of a controversial, but in this particular study, they found that the average time to reach to the therapeutic effect after the IV heparin drip is started is around 10 hours, while low molecular weight heparin just with one shot can achieve the therapeutic effect within 1.5 to two hours. Also, in another study they found when the people are on the IV heparin drip for three to five days while they are in hospital, only 22% of the time they are on a therapeutic range. Another 78% of the time they are either supra-therapeutic or infra-therapeutic. So the ESC guideline in 2019 actually mentioned that the low molecular weight heparin is preferable rather than the unfractionated heparin, but our ACCP 2021 guidelines did not comment on that and we are waiting for the next update. With that, let's move on to the last and the final case. Again, you have seen this 65-year-old female came to the hospital with shortness of breath of acute onset as a history of COPD and recently diagnosed to have a stage one lung cancer. On admission, the vitals are kind of scary, blood pressure is a little bit on a lower side, heart rate is high, pulse ox is low, respiratory rate is also high, chest X-ray was compatible with the COPD changes. So pulmonary embolism was suspected and the CTPA was ordered, which we do all the time, but before she actually get the CTP, she coded in the ER and the CPR was started. A quick ultrasound showed a significant right ventricular enlargement. I know what you guys are thinking. I'm going to ask you, will you give a thrombolysis or not? But when I know the answer, then I change the question. So my question is that systemic thrombolysis is likely to facilitate her discharge to home. Do you agree or you don't agree? So CPR is going on. You think this is a very high-risk pulmonary embolism, what two of my colleagues actually mentioned. Now, if you give a thrombolysis, is she likely to go home or not? Okay. Okay, that's a hard question. And then we have some split. But these are the data, I think they have shown the data, and these are the data from the PARTH. I think PARTH is here or not. I think I saw him earlier. Published last year in three large healthcare systems in the New York City and the Philadelphia area, they found out from a two years database how many times they had to give TPA. And they found 104 times they have to give a TPA. Out of those 104 times, 52 times, almost half of the time, it was for a presumed PE, like my patient. And you can see here that the one patient out of that cohort actually was discharged home out of those 52. So the risk, I mean, I don't know whether it's a luck or the treatment, but in general, it is not likely to be successful if you give a TPA when the patient is coding and we are anticipating, and this is due to the pulmonary embolism. So I kind of showed you these three different patients which you are seeing on a daily routine, and none of them actually qualify or benefit from the TPA or a systemic thrombolysis. So the million dollar question is who are the people will benefit, right? I think that's what you are eagerly waiting for. Before that, I need to show you the statistics of the acute pulmonary embolism. These are the database from the ER from the 2016 and published in 2021 by the Paul Steen and Group from the Michigan State University. 270,000 patients approximately in that year, in one year. 98% of them either had an intermediate risk PE or the low risk PE, and only 2% of the patients had high risk PE. If you divide them into our regular three compartment of the PE, almost 40% of them has a low risk PE, another 55 to 56% of the patient had an intermediate risk PE and three to 4% of the patient had a high risk PE. So if you think every 100 patients, you will have four patients who definitely require some kind of a reperfusion therapy. Now people always ask that this intermediate risk PE is the one bothering us because they are very heterogeneous group and the mortality can vary from 2% to 20%, agreed. How can we find out a better population or a sicker population who may benefit from the reperfusion therapy? That's a question always as a clinician we are asking. So to a subgroup of people, I will explain in the intermediate risk PE patients, one, over the next three to five days, some of those patients do deteriorate. So if you remember the Pytho trial, in a control arm, the 200, I mean 27 patients out of 500 actually deteriorate and require subsequent rescue thrombolytic therapy. That makes it 0.5 to maybe 0.7% of the patients may deteriorate and require secondary therapy. In one of the ad hoc analysis which I have put it here by the Barco and colleagues in 2018, analyze the patients from the Pytho trial, those who had a respiratory rate more than 20, like my patient, blood pressure below 110, like my patient, and the patients who have a history of a congestive heart failure. If you have two out of these three factors in a retrospective analysis of the Pytho data, they did find some benefit of thrombolysis. And currently the high Pytho trial is going on and they are enrolling the patients and they are enrolling these patients of this particular variety known as an orange zone patient, not red, not green, orange zone patient and they are enrolling this type of a patient also in their study. So we will know something in 2025 or 2026. So if I include those orange zone patient or the patients who deteriorate or likely to deteriorate from intermediate high risk PE, I think there will be another five or 6% of the patients because in a Pytho trial out of 1,000 patients, 8% of the patients were in those orange zone. So if you submit those two, the four from the high risk and six from the intermediate, you have 10 patients who have an opportunity to go for a reperfusion. The question is how many of them actually will qualify or benefit from thrombolysis. That's a talk I'm trying to do. Now again, Brandon and Belinda both actually showed you the data that when we think of systemic thrombolysis, the people have a contraindication to the systemic thrombolysis. So again, from the PATH group last year, they found in one study that almost 56% of the people who are requiring thrombolytic therapy have actually some form of a contraindication and 20% of them has an absolute contraindication, 80% of them relative contraindication. Part of the, Brandon showed you a data from the flame registry, again compatible with the same thing in a flash registry. Almost 40% of the people have some kind of contraindication. So if you go by a 50-50 rule, out of those 10 patients who require reperfusion, maybe five qualify or benefit from the systemic thrombolysis therapy. So for every 100 patients of PE, you are gonna see the five may qualify for TPA. This is a simple math, right? I guess the simple statistics. Now if you do a rough math on the napkin paper, these are the data from the 2021. None of these things I'm making up, right? It's a double AMC data. We have almost 22,000 cardiovascular physicians, 13,000 critical care physicians and 5,000 pulmonary physicians. So we are total 42,000 physicians in United States who are capable of providing a care for the patient of acute pulmonary embolism. Now we will say, yeah, all of them are not actually providing the care, but then on the other side, I'm excluding the ER physician, intermedicine physician, pediatric pulmonary and critical care physician. So hypothetically speaking, if you say there are 30,000 physicians who are capable of providing care to the acute pulmonary embolism patients, out of those 30,000 physicians, we have approximately 300,000 cases of the acute pulmonary embolism every year. So each of us in this room is gonna see 10 new cases of the PE every year. Some may see more, some may see less, but this is an average. And if you remember my slide from before, for every 100 patients, five patients may qualify. So for 10 patients, each physician is responsible for a 0.5 thrombolysis per year, meaning by every other year, one of you guys will have one opportunity, opportunity, I'm not saying you are gonna do, will opportunity for the thrombolysis or systemic thrombolysis, which was, I think, compatible with the study we earlier conducted. Right in the first slide, we conducted a study, and I think exactly the same data I am proving at the end of a talk. So in conclusion, I will say that the majority of the patients with acute pulmonary embolism do not require systemic TPA. Now, don't get a wrong message, by the way. They don't require anything other than the anticoagulation therapy. That's a very important part. Most of the people actually just are good on anticoagulation therapy. And then the second part, those few patients who may require systemic TPA, we have to be mindful about the contraindications, and they may require one of this treatment these guys are talking, either surgical or non-surgical embolectomy. With that, I will say thank you very much for patiently listening. We'll have a question at the end of the session. Thank you. Perfect. Good morning. Thank you all for being here. And this is very exciting. It's going to be fun. So I'm the most conservative person here. And how much you have minimized the role of systemic TPA, my job is to tell you that it is not going away. And we're still using it even for MI. So let me make my case. I'm Sophia Nadenov. I'm Associate Professor of Internal Medicine, Division of Pulmonary Care at St. Louis University Hospital. And no, disclose you're not relevant to this talk. So we know about the thrombolytic agent since the 1960s. The first study that came around, there were eight patients. Four of them got thrombolytic therapy and four did not. And those who got thrombolytic therapy, this is again for high-risk pulmonary embolism patients, they lived. The ones who got anticoagulation died. So we know how TPA works. The body has a normal mechanism to dissolve the clot. And this accentuates that process. And when it's needed, it does it very effectively. And it's a very powerful tool to cause thrombolysis. We don't use it for all pulmonary embolism patients. And as we know, most of PE patients are low-risk or intermediate risk. But we use them for that little orange zone that he mentioned here. It's the red zone. It's the high-risk PE patients. Mortality of these high-risk PE patients is high. One month mortality is 30%. 90-day mortality is more than 50% for the studies. So by definition, this is the patient whose systolic blood pressure is less than 90 or a 40-millimeter drop from their baseline, lasting about 15 minutes, or they're on vasopressors. So let's go on the patient's bedside. I have a case, which I will repeat a few times to make my point. This is a patient with high-risk PE. I'll give you a few seconds to review. But the point to mention or to highlight is the hemodynamics. And you have to go on the patient's bedside. The CTPE is given to you. So you see that there are significant burden of cloths. If you're on the bedside of this patient, the question is, what do you want to do right now? And it matters where you practice, and it matters what you have available to you. So I'd pause here for a second, let you think about it. I'm not taking any votes right now, but we'll come back to it. Same patient, exact same scenario, just the setting is different. Imagine you're practicing in a tertiary care hospital. You have all the capabilities. What about if it's 3 a.m.? And this is a high-risk permeabilism patient. Mortality is very, very high. No matter how insignificant the number is, but this is the patient that we are talking about for the consideration of systemic thrombolysis. And if you have a high-risk PE patient, a stroke patient, an MI patient, and you have one cath lab or an IR suite available, who do you think, at this present time, that suite will be given to? An MI patient, a stroke patient, or a high-risk PE patient? So this is just practical on the bedside. Third-case scenario, you're on the bedside, and you were maybe planning to consider other options that my esteemed colleagues here have mentioned, but what if patient develops cardiac arrest? Are you going to consider systemic TPA or not? Overall, their meta-analysis published when the systemic TPA made it to the guidelines, and there was clear benefit in patients who were dying of PE when it was given. It saved lives. As we all acknowledge, the studies are hard to do in this patient population, but it favored patient mortality, and if you look at the data collectively, and recurrent PE also. We already acknowledge that this is underused, 30% or less than 30%, even when it's indicated, but it does save lives. The strategy meta-analysis has been mentioned before, but please keep in mind, some of the data that has been shared is intermediate-risk PE, and I would not recommend using intermediate-risk PE and give them systemic thrombolysis or reperfusion therapy, unless they're deteriorating. Then you may consider it, but that's not the patient population that we are talking about. You're talking about the high-risk PE patients. From this strategy trial, there was benefit, but again, yes, it came back. It came at a cost of bleeding, but the bleeding was more in age more than 65. And yes, this is another dilemma of high-risk PE, when you have a clot floating in the heart, what are you gonna do, and if there's a threat. If you compare the study, the probability of survival was more when thrombolysis was given. There's also consideration of things being delayed when you're thinking of other options, which just haven't made it to the guidelines as of yet, because there is something you can do on the bedside, and if you're considering options, it does involve a lot of logistics, personnel, expertise to be taken into consideration. And yes, cardiac arrest has been mentioned, and anybody here push systemic TPA for cardiac arrest? A few, yeah. And I know mortality is high. I mean, how are you gonna discuss somebody's dead? And yes, it's important. You want them to make it to your, but you've seen maybe a few cases, or maybe just one, and I think that's all that you need to consider it when somebody's dead, because at that time, I think all contraindications are pretty much relevant. So yes, and there are recommendations to consider it, even when the PE is suspected, and I think I will emphasize the point that in the practical life, you have to be on the bedside to consider this. It's not an option where you're considering, like I said, where you practice and what you have is very important to take into consideration, and also how fast you can do it, because sometimes you just don't have a lot of time to understand these patient populations. There's recent Cochrane meta-analysis, and it compared TPE against many other options of impact on the RV, impact on mortality, and pretty much all, however you dissect it and slice it, it favors thrombolysis in high-risk PE patients. There's only one scenario where it does not, and we know that, and that's the big elephant in the room that it causes bleeding, and I'll come back to it in a second. But like I mentioned, there are a lot of devices that are popping out, really, like mushrooms everywhere, and I think it's much needed, maybe, to find that safer and effective option. Do we have it yet? I don't know, and I think we don't know, I should say. And there's another thing. Anything we do acutely for PE patients at this time, we don't know about if you're impacting the long-term mortality, long-term functional outcomes or not. We don't have that option available to us right now that we know of. So, but like I said, a lot of devices are coming, and yeah, I don't know where they've been all this time, 1960s and 2023, I think it's much needed. We just don't have the answer right now. Major bleeding is a problem with systemic TPA. Let's acknowledge that. Incidence is around 3%, and yes, it's a scale. You don't want this for your patient, but the other options on the right side in JVIR, you can see some of the trials mentioned reduce other options, endovascular options. They're not without complications, either. There are bleeding risks involved in that, procedures or devices as well. There's a lot of upcoming, I think the battle has just started, really. Endovascular options, which is the better their devices compared to other devices, and some of the thrombolysis trials are on the way. My colleague here mentioned the Pytho-3, which is the half-dose TPA compared to anticoagulation only. Worthwhile knowing, because we don't know, I think overall the question is how much of thrombolysis dose that you need, and for how long. So that's another argument, and I don't think we know exactly how much TPA do we need for a PE patient. And there's a recent trial, I don't know if you guys have seen, they used 25 milligrams for over six hours, and it worked. And you can critique the Optalyze study where they used the two milligrams, four milligrams, six milligrams, 12 milligrams, and all of them worked. So what does that mean? I mean, it's great that it worked, but I think the bigger dilemma is we don't know the exact, maybe it's just 10 milligrams that a PE patient needs. We don't have that answer yet. And they're also, the NALY trial is pretty interesting. They're looking at inactivation of alpha-20 plasmid that inactivates the plasmid, and it kind of generates and allows the plasmid to do what it does normally, and this does not have the bleeding effect that the systemic TPA does. So some things that are worthwhile, and hopefully we'll have some answers in the coming years. A lot of effort is being placed in this area. In the guidelines, I'm gonna review rescue reprofusion therapy, like I said. It's only to be considered in that hemodynamically unstable patient. It is not to be considered in somebody who has a normal blood pressure. Let's go to ACCP. Again, it's standard of care to give systemic thrombolysis to a patient with high risk, and I've already given you the definition. And also to be considered for those who are rapidly deteriorating in front of you. AC Forum, you can look at same guidelines, systemic thrombolysis preferred. ESC-1B recommendation to use systemic thrombolysis. You can look at ASH. ASH has similar wording. 20-20 knees, similar wording. High risk PE, the first choice for you is systemic TPA. However you slice this, however you dice it, as we stand today, systemic TPA for high risk PE against anticoagulation is lifesaving. Against CDT, I'd say CDT takes you need expertise, you need logistic, you need availability 24-7. Many places don't have. And those things are to be taken into consideration. It involves a lot of personnel. And even when you have it, I've had a case in my hospital, it's like, I think we could have done it. We were planning it, we didn't push TPA, and there was significant delay and patient deteriorated. So those things are to be taken into consideration until we know better and change and reverse that order of which therapy you're gonna opt for first. And it takes too long, as you all know. And then it's true when they do the trials, you know, eight hours, 12 hours, 16 hours, you know how hard it is to time those things in actual life. And all the meta-analysis published showing that it's better. There's so much heterogeneity. One, it's in the population that you're dealing with. Two, they're trying to assess the mortality of intermediate high and high risk collectively. It's difficult to do that. And you're basically studying two different populations. So the data is coming, it's just not there yet. And if you compare systemic TPA to mechanical thrombectomy, I do think it's a little unfair comparison to compare if you want a Drano or a plunger. Those are two different things that you do. But it depends on what you can do faster. Because really, time is very, very important. And they say 1% mortality is high mortality if it's your mortality, right? So even if you say that one patient, but I think it matters, even if it's that one patient. And no matter how much math my colleague did to bring it down to 0.5, but I'll tell you, being on the best side, it matters when you're going to do it and the patient will live. And that's why we do what we do until we know better. So you need expertise, you need personnel, you need resources. And these things are taking toll on people and your teams, whether it's your intervention radiologist, your vascular surgeons, or your cath lab teams. So because imagine, like I said, this is a practical scenario to have somebody with stroke and MI, and then you have PE. Guidelines are not there to tell you to, MI will go first, stroke will go first, PE will not be given that priority at this time, and we don't have the data for that. As of today, right now where we stand, systemic TP is indicated for high-risk PE, cardiac arrest to be strongly considered, even if it's suspected from PE, rapidly deteriorating intermediate-risk PE, intra-atrial clot, that's the thing that you can do faster, and this patient has high mortality. Pandemic, how about that? When people were in isolation, everybody was happy not to mobilize them and give them TPA on the bedside, how about that? So we've been there. And lack of resources, lack of expertise, lack of availability 24-7, even when you have it. And I think it's too narrow of a focus to just think about ourselves. What about other countries, other places? And they don't have the resources. So not only systemic TPA is not a matter of past, it is the standard of care for high-risk PE. And I arrest my case there. Thank you.

pulmonary embolism

surgical embolectomy

systemic thrombolysis

management

high-risk

patient comorbidities

hemodynamically unstable

cardiac arrest

treatment decisions