 So I'm going to talk about management of pulmonary embolism and one of the things that I'm going to include here is our data from Baltimore from Maryland. So, and I think that's why this is very important. So I start as a director of the pulmonary embolism response team in 2017. So there's a lot of changes that you can see that occur during that time. And I'm going to show you what we have already. So I have no disclosures. So we know that the venous thromboy embolism affects about three to 600,000 patients a year in the United States. We've been talking about pulmonary embolism. 10% of the pulmonary embolism are rapidly fatal. So they kill you right away. About 5% they kill you during the hospitalization, you know, and is the third leading cause of mortality of cardiovascular mortality in the United States. And about 3 to 5% of the patients develop chronic thrombombolic pulmonary hypertension. That is a late complications of pulmonary embolism. So what happened here in Baltimore in the University of Maryland? So when I start here, I start doing basically a chart review of what kind of patients we have. So we saw that we diagnosed with about 769 patients at the University of Maryland during two years. So this is a large volume of patients, but a lot of those patients were admitted with a different diagnosis and then they were found to have a pulmonary embolism. Not all of them where that was the cause of the admission. And if we see there was a lot of people that had like a recent trauma, 16%, that had some recent surgery, 32%, 25%, 26% of them have cancer. But what is very unique about our area is that we have almost 50-40, you know, between Caucasian and African American. So that makes our area unique. If you read any other cohorts in the United States, usually Caucasians about 80, 90% of the cohort in our area is almost 50-50. So what is how the part work, you know, we receive a consult from in the hospital, from inside the hospital, but also we receive referrals from other hospitals. So from 2019 to 2020, we received 97 requests for transfers, but we only accept about 60% of the transfers. And those are the hospitals that usually request for transfers. Most of these hospitals are within the University of Maryland Medical System, but we also receive even, you know, from other hospitals too. So whenever we talk about pulmonary embolism, we have to talk about what are the risk factors and why pulmonary embolism happened. So I always say this is a balance between pro-quagoland and anti-quagoland factors. So usually you can have some inherited risk factors and acquired risk factors. In the inherited risk factors, you have factor 5 lightning that is the most common one among Caucasian patients. That affects about 5% of the Caucasian population. Also, pro-thrombin G mutation affects about 3 to 5% of the Caucasian population. Factor 5 lightning, this is a common mistake that I always read in the notes, is a resistance to one of the anti-quagoland system that is a protein C and protein A, protein C basically. So the factor 5 itself has a mutation that does not accept protein C as an anti-quagoland. So also you can have patients who have a deficit protein C and protein S. Deficits of anti-trombin, those are the anti-quagoland system. In African American, that is what we see in this area, you know, that in this cohort, we have also elevated factor 8. Sometimes we have patients that you do all these work-ups, it's negative, and then you check for factor 8 and the activity factor 8 is about 400, you know. You have patients with sickle cell trait, sickle cell disease, they also have an increased risk of having venous thrombosis, and you have elevated homocysteine. You have several mutations of MTHFR, and this is not a strong risk factor for thrombosis, you know, just recently discovered, but we still consider it as a risk factor. And then we have, on the other hand, acquired risk factors for venous thromboembolism. As I show in the previous slides, you know, you have cancer, hospitalization, surgery itself can increase up to 20% your risk. I'm sorry, 20% falls your risk of venous thromboembolism. You have trauma, you have air travel, now we have COVID-19 infection, antifulfolipid antibodies, and malignancies, et cetera. So we have multiple things that we have to think about venous thromboembolism, and as I say, this is a balance between proquagolants and anti-quagolant factors. So then, how much these inherited thrombophilias can increase your risk of thrombosis? If we see, you know, factor five, heterozygos, that is what most of the people has increased between three to four times, you know, the risk of thrombosis. If you have a homozygos, it's way more. But if you have a combined factor five lighting plus pro-thrombin mutation, it goes up to 20 times. But this is really rare. You don't see that very often. And also you can have anti-trombin deficiency that is very, very, very rare also that increase up to 16 times. You know, antifulfolipid antibodies we see quite often, but it is between two to 11 times, you know, the risk of thrombosis. So what happened when somebody has a pulmonary embolism? You have the pulmonary embolism, you increase the pressure in the right ventricle because you increase your pressure, there is an increase in wall tension. Then because there is an increase in myocardial oxygen demand in the right ventricle, then you can develop ischemia of the right ventricle plus minus infarction. You develop hypokinesia and dilated right ventricle. And also you develop hypoperfusion of the coronary arteries. You have a decreased preload of the left ventricle and then you develop systemic hypotension and patients start getting dizzy, shortness of breath, etc. But the mortality is directly linked to this. And when we have a patient that comes, shows up to you with a normal blood pressure, you know, the mortality is quite low. But if you have a patient that comes to the hospital and is in hypotensive or even you're required to give CPR in those patients, the mortality can go up to 65%. So the clinical presentation is very important for this. Diagnosis, how you make the diagnosis. So then we have a multiple test. I'm sorry for the busy slide, but you have multiple scores that is telling you what is your pre-test probability to have a pulmonary embolism. But basically, all those scores includes history, clinical presentation and symptoms of the patient. You know, and depending on the score that you use, they tell you you have to do some biomarkers like in the year's score, they also go for the de dimer. And then you say, okay, you ordered a CTA. So in our area, I think if anybody has a suspicion of a patient can have a pulmonary embolism, they just ordered a CTA. And CTA basically is the gold standard. It's the gold standard for the diagnosis of pulmonary embolism. Now with the new CT scans that we have, you can even diagnose subsegmental pulmonary embolism. What is the problem with CTA that sometimes we have is in patients that has any allergy to iodine, or if the patient has some acute kidney injury or chronic renal failure, you cannot expose the patients to iodine contrast. So then you can use a ventilation or perfusion scan or VQ scan, and you can see the areas of mismatch. How is the ventilation perfusion scan done? You ask the patient to inhale synone gas, and also you inject radiolabel albumin. So and then you put the patient in the camera camera, and then you get pictures of the perfusion and the ventilation phases, and then you compare both and see if there's a mismatch effect. Then let's say you cannot do neither one. You don't have a nuclear medicine or you cannot do a CT scan. You can also do an echocardiogram. And if in the echocardiogram you find that the patient has signs of rib and tricolor strain or the dilatation or dysfunction, you can think about pulmonary embolism. Also, you have to do a venous duplex ultrasound of the lower extremities. If the patient has an acute blood clot, give you or increase your suspicion of pulmonary embolism. And regardless of if the patient has a DVT, you have to treat the patient. You can do an EKG. In the EKG, you can have the most common sign is sinus tachycardia. But you can have a new rib under branch block or some STT changes that can you can think about a pulmonary embolism. You can have a chest X-ray, you know, the most common chest X-rays and normal chest X-ray, but that could be an exclusion criteria that other pathologists like a pleural effusion or pneumonia is occurring in this patient. There's few signs like a oligoemia sign or the, you know, but those are really rare and rarely seen in the chest X-rays. An elevated de dimer is a good test that indicates that you have some kind of blood clot in your body. So it could be arterial venous, etc. It's not specific for pulmonary embolism. The problem that the dimer is also elevated in other pathologies. Let's say if you have cancer, if you have a recent surgery, if you have fever, you know, everything can elevate the dimer. So it's not specific. You can check for biomarkers of myocardial injury, you know, the troponin, the probium P can give you some idea. And also we use that for a stratification that I'm going to tell you later. And whenever you have a, I'm going to call severe P, later I'm going to call massive P or submassive P. You can check biomarkers or hyperperfusion lactate. That helps a lot in the stratification of the patient as well. So, but we have to think that every time that we talk about pulmonary embolism is not only the size of the club, you know, it's also the cardiovascular reserve. So I put as an example, Serena Williams, she had, I think like two or three episodes of pulmonary embolism, and she still is completely functional. She's still able to play. I think she just retired, you know, but she was able to do a top sport lady. So because she has a great cardiovascular reserve, and that's why, you know, whenever we're talking about classification, we're going to talk about the American Heart Association clinical classification of pulmonary embolism. In any of these categories that we talk here, we talk about size of the club burden. So we always talk about clinical presentation. And we have a patient that comes with a massive pulmonary embolism, and patient has a sustained hypertension for more than 15 minutes is not responding to IV fluid, you know, you give one to leaders of patients do not respond. Patients usually require vasopressure, and you cannot find any other causes of this. And also a patient can present with pulses electrical activity, and bradycardia and signs of shock that is a patient that has a massive pulmonary embolism. Then on the other side, you have the patient that has a low risk pulmonary embolism is a patient basic that comes sometimes have shortness of breath sometimes is just an incidental finding the V. And you have a normal patients, no hypertension, no evidence of right heart strain and no evidence of myocardial injury. And in the middle, you have a huge amount of patients, you know, from all flavors that you can have patient that are hemodynamically stable but has some signs of right ventricular dilatation some dysfunction. Maybe some enlarge right ventricle in the CTA, or in the echocardiogram, maybe some changes in the EKG. But you know the presentations are completely different in those patients. So that is a little bit of a problem. These two, you know, the massive and low risk. I think the treatments is straightforward in this one is what we have a lot of controversy. So there's other scores that we can use. We can use the PESI score that basically the PESI score divides into five categories, you know, you have multiple risk factors that you assign some points. Let's say if you are a male, you have 10 more points. If you have cancer, heart failure, chronic lung disease. Then you have clinical signs of presentations, you know, a tachycardia if your blood pressure is low, et cetera, you know, after mental status and then you can calculate what is your PESI score and this is the mortality risk at 30 days. That goes from 1.6 to up to 25%. There is another score that, you know, this score is great, but the thing is takes a little bit of time to calculate and when you are in the emergency room on the ICU, that you have to go fast, you have something that is easier to do it. So then you have the BOVA score that basically has four elements. If the patient is hypotensive, you know, with a systolic blood pressure less than 100, you know, or I'm sorry, more than 100, between 90 to 100, you give one point or zero points or two points. If you have a elevated troponin, if you have ribenticular dilatation or dysfunction or if you have an increased heart rate. So depending on the point of score, you can have a BOVA 1, BOVA 2 or BOVA 3 and this is the 30 day mortality. However, we found that if you have a patient that is a BOVA 3 and you add an elevated lactate, you know, this is an important predictor of mortality in pulmonary embolism patients. So normally you classify BOVA 1, 2 and 3. In our hospital, we use a lot of the lactate plus the BOVA 3 to stratify those patients. So whenever we're talking about ribenticular strain, we can see the ribenticular strain in the CT scan and like in this CT scan, you can see that ribenticular is huge. But what is the sensitivity of the CT scan compared to the echocardiogram? Because sometimes the patient has, do not have or has ribenticular strain in the CT and they say why I have to ask for an echocardiogram. The sensitivity of the CT scan for ribenticular strain is about 40% and the specificity is about 80%. The other problem is that gives you only ribenticular dilatation but you don't have any idea about the function of the ribenticular. So that's why we always recommend to do an echocardiogram to confirm this. In the echocardiogram, you can have multiple signs like a ribenticular dilatation, ribenticular dysfunction and there's multiple parameters to evaluate for that. And usually what we do, you know, if you go to the studies, they say, okay, what is the RVLD ratio or TAPC and they based the outcomes is just one measurement. What we do here is we try to listen to the cardiologist and say, you know, I think patient has mild, moderate or severe dysfunction, mild, moderate or severe dilatation. One of the signs that we can see when a patient has a pulmonary embolism is a McConnell sign. And basically McConnell sign is global hypokinesia of the ribentrical and with hyperkinetic apex of the ribentrical and that gives you an idea that this patient has a lot of overload of the ribentrical. The other measurement that we check in the ribentrical is the TAPC or tricuspid annular plane systolic extrusion. So basically what we do is we measure the distance between the apex and the base and how they shorten in the ribentrical. So this distance and that is to give you an idea of how much the ribentrical contracts and normal values are above 15 millimeters, 15 millimeters and above. If it's less than 15 millimeters, you can say that patient has a ribenticular dysfunction. So in our hospital, you know, we found, we did a chat review and we say, okay, what is the difference between African-American and Caucasian? If you see that in the literature, you know, African-American has an increased mortality compared with Caucasians, but all those cohorts I'm telling you is 90% Caucasian, 10% African-American. So we decide to see what happened in our area when we have almost 50-50. So we found about 53% Caucasian and 46% African-American. If you see they are not similar, you know, the Caucasians are a little bit older, have more males. There is more diabetes in the African-American population, more chronic kidney disease. There are more smokers and they have more trauma in the Caucasian and more surgeries also in the Caucasians. So when we saw the presentation of the ribentrical, it was quite interesting because, you know, African-American have more underfilled left ventricle that you remember when I was talking about the path of physiology. You say that you decrease the pre-love of the left ventricle. So that occur more often in African-American that Caucasian, but also the ribentrical, you know, Caucasian has more normal ribentrical than African-American. But African-American has a more dilated ribentrical and more severe dilated ribentrical are more severe dysfunction when we compare with Caucasian. We think this might be related because of comorbidities. But when we compare about the mortality, there was no difference in the whole mortality between Caucasian and African-American. However, in those patients that require advanced therapies, I'm talking about systemic thrombolytics, catheter-based intervention surgery, there was higher mortality among African-Americans was 18.5 versus 3.8. So this is something that we need to look into a little bit more, but it's an interesting finding that I'd like to share. So now we're going to talk about treatment, you know, what kind of treatments we can offer to patients with pulmonary embolism. We have a lot of options right now. And it's not only that we have one or two anticoagulants, we have like a six, seven different anticoagulants. And we have a lot of advanced therapies that, you know, are in the market. So we have to talk about that. So I'm talking about anticoagulation, we have unfractionated heparin. If we, you know, it still is a great drug, we use it a lot, especially when we have a patient in the hospital that we don't know if we're really going to do an advanced therapy or not. We have low molecular weight heparin, we use it a lot. And if you have a patient that has any, we call allergy to the heparin or heparin induced thrombocytopenia, we have other options like argatroband, bivalidudin, and even we can use fundaparinox in those patients. For long term treatment, we have like a vitamin K antagonist like warfarin, you know, is still a really, really good drug, you know. But we have the new drugs also like apixaban, rivaroxaban, edoxaban that are anti-tenet inhibitors, or we have direct thrombin inhibitor like a dabigatran. So if you think, and this is a business slide, I'm sorry for this, this is a coagulation cascade, the anti-coagulation system and the thrombolytic system. And we know that like in the case of warfarin, we know that warfarin works in several steps of the coagulation cascade and apixaban, edoxaban, you know, they work in one specific factor. So just keep that in mind, you know, the new drugs are really good. I use it a lot, but there is still room for the old medicines like warfarin. Tips about anti-coagulation, if you suspect that patient has antiphoffalipid antibodies, or if you suspect that your patient has a not reliable APTT, just switch the patient for anti-tenet activity. You know, it's not reliable to follow this patient with APTT. When is heparin resistant? We do require a lot of heparin. Let's say you have a patient that is requiring 60,000 units a day, 80,000 units a day, and you still don't have any changes in the APTT. Okay, maybe you have to check the patient, you have to switch the patient to anti-tenet, and if the anti-tenet is still not therapeutic, you have a true resistance to heparin. So maybe you have to switch to a different anti-coagulant. And also, as I said before, if you suspect heparin induced thrombocytopenia, maybe you have to switch the patient to a different anti-coagulant. Also for low molecular weight heparin, if you suspect that patient has HIT, you have to switch to a different anti-coagulant. And also you have to check anti-tenet once in a while in patients with that you are using low molecular weight heparin, especially if you have a patient that has a borderline kidney function, a patient that have like a borderline obesity, you have to think that for a low molecular weight heparin, the cutoff weight is about 150 kilos. If you have somebody in that weight, maybe it's a good idea to check anti-tenet as well. Also, in the underweight patients, you know, if you have a patient that is really thin, maybe it's a good idea also to check anti-tenet. Fundaparinux is mainly used for heparin induced thrombocytopenia. And argotrobin and bivalid are almost the same. Vitamin K antagonists, just remember now maybe the new physicians, they have all these new medicines. And I have these questions on and off about bridging of warfarin, you know, you still have to bridge warfarin. And usually you have to bridge warfarin for at least five days. Just remember that the factor 10 and factor 2 are the factors with the longest health life. So they check up to three, four days to suppress. And the first thing that you suppress when you give a vitamin K antagonist is protein C and protein S that is your anticoagulant system. So the first two, three days that you give vitamin K antagonist, you cause hyper-coagulant states. So that's why you have to bridge these patients with a different anticoagulant. DOAX, DOAX are really good. But avoid using DOAX when you have a patient with a confirmed antifulfolipid antibody syndrome, especially if you have antifulfolipid antibody syndrome for lupus anticoagulant. Where it's two or three antifulfolipid cardiolipin and beta-2 glycoprotein, you know. There is a study that is a trapstrile that they found that the patients that were treated with river oxaban, they bleed much more and they thrombose much more than those patients treated with warfarin. So be careful with antifulfolipid antibodies and DOAX. Those patients that has poor absorption, these drugs, the DOAX absorb in the stomach and the proximal duodenum. So those patients with gastric bypass, especially ROX and Y, you know, they probably have a decreased absorption of DOAX. Patients with Crohn's disease, patients with large bowel resections, just think about that kind of patients. And in hemodialysis patients, interesting, there's a bunch of information outside about anticoagulation for atrial fibrillation in patients using DOAX. And the results are really good, but there's no information about hemodialysis patients and venous thromboembolism. So we can extrapolate the information from the studies from AFIP, but there's no studies dedicated for hemodialysis patients and venous thromboembolism. I think there are a couple studies, you know, running right now, but that is something that we have to be careful. And morbid obesity, there is still some controversy about morbid obesity. There is some in the early ages of DOAX, you know, there was a statement that was not safe to use DOAX in morbid obese patients. Later, another study shows that, you know, there was no events when they use DOAX in patients with BMI is more than 40. So I personally, I use DOAX in morbid obese patients, but there's no good data about that neither. Advanced therapies. Anybody has any questions so far? No? Okay. So we go to advanced therapies. What is advanced therapies? We're going to talk about systemic thrombolytics. We're going to talk about catheter-based interventions that now is not only thrombolysis, we have a thrombectomy. We're going to talk about surgical pulmonary embolectomy, and we're going to talk about advanced cardiovascular support. Here at the University of Maryland, we have the ECMO program that we have a lot of patients. So let me start with this. This is one, you know, from the analysis that we did at the University of Maryland. We use about, you know, 75%, 76% of patients that require with pulmonary embolism that require only anticoagulation. About 11% of patients, we couldn't offer any treatment for multiple reasons. And about 14, 15% of patients require some kind of advanced therapies. And if you see most of the advanced therapies that we use was surgical pulmonary embolectomy and catheter-based interventions, we use some ECMO and very few systemic thrombolysis alone. But also we have a lot of combinations like systemic thrombolysis plus surgical pulmonary embolectomy, systemic thrombolysis plus catheter-based interventions, plus VA ECMO, etc. So I'm going to talk about those. Systemic thrombolysis, we know that they work these multiple trials that they have done in the past. I'm going to quote these meta-analysis that was done in 2015. And in these meta-analysis, they see, you know, they put all the patients together and they found that overall mortality improved when you use thrombolysis in those patients. You know, it favors the use of thrombolysis versus anticoagulation alone. Whenever they divide these in those patients that were stable, you know, they divide the unstable P versus the stable P, they found, you know, they just lost statistical significance with a P0.08. You know, but still, you know, it's not a bad idea. But when they found about bleeding, you know, all the studies they show that thrombolysis increased your risk of bleeding. So what the guidelines say, you know, if you have a patient who has an acute pulmonary embolism that is unstable, we're talking about hypertension, you know, and they do not have a high risk of bleeding, you can use thrombolysis. You know, if you have a patient that is stable, you know, the guidelines do not recommend thrombolysis because the patient is completely stable. However, if you have a patient that is stable now, but you start seeing signs and symptoms that patients deteriorating, you might give systemic thrombolysis to those patients. And when I, you know, this is one of the talks that I have with the people here. Here at the University of Maryland, we have ECMO, we have many other resources, but if we have a patient that they are requesting for transfer and the patient is far away. They say, you know, if the patient is unstable or is becoming unstable, just give thrombolysis, don't wait for that. Give one shot of TPA and then send the patient because this can save lives. So now we're going to talk about catheter direct therapies. And this is a really hot topic right now. There is multiple products outside. However, even believe it or not, there is only a few good level of data. And I summarize this data in this table and believe it or not, this is the only randomized control trial that we have. That was the ultimate trial that was published in 2014. It includes 59 patients only, you know, that's the only randomized trial and the outcomes, you know, was the RVLV ratio improvement at 24 hours. If you see, you know, there was a statistically significant improvement of the RVLV ratio with the ultrasound, catheter ultrasound guided therapy. And, you know, with an acceptable bleeding and acceptable mortality was no different difference than that. All the other studies, the Seattle perfect flare and exact trials, those are single arm. This is a registered single arm. They did not include any control patients. The optimized PE trial, it was randomized to different doses of thrombolytics, but there was no control patients. There were no patients that were given just anticoagulation, you know, the flare is with a different catheter. This is a flow trigger from Inari is a single arm trial and also they extract PE with subnumbra catheter that is also a single arm trial. So we cannot say that we have a strong evidence in favor or against these catheters because there is not enough information. So what, you know, the AHA, they released a scientific statement in 2019 that says that current data shows that catheter based therapies improve surrogate outcomes such as ribentricular dysfunction improvement in acute pulmonary embolism, but currently they cannot support the use as a, you know, one A indication for patients with pulmonary embolism. They say they might benefit long term complications like chronic thromboembolic pulmonary hypertension, but there's no good data yet. So I know that if you go to any hospital and many people are going to think, okay, let's take the patient to a catheter based intervention. Let's say, let's use ECOS catheter or Inari thrombectomy. But what are the real consequences of using that if you increase your risk of mortality when you are in the hospital or what is the real benefit, the long term benefit of those interventions? So that is one thing. Now I'm going to talk about surgical pulmonary embolectomy. A surgical pulmonary embolectomy is used when you have a massive pulmonary embolism that is refractory to other treatments. Let's say if you try pulmonary embolectomy, you, I'm sorry, you try a catheter based interventions, the patient is not doing well, maybe you can call the surgeons, hey, you know, we need to do pulmonary embolectomy in this patient. When you have a patient that has a clot in transit, that is an indication to do a pulmonary embolectomy. When you have a clot in transit and a patent for Amino Valley, that is another indication. Patients with acute and chronic pulmonary embolism, but this is more an indication for a pulmonary thromboendarterectomy. That is a more complicated surgery. When you have a patient with the thrombus in the right ventricle or right atrium, and this is a very soft, but maybe I have seen this like a once or twice that you have a patient who have a pulmonary embolism, but also they are scheduled to have a cabbage or valve replacement. They take the patient to the ER and they do the two surgeries at the same time. So in our hospital, you know, what is our data from our hospital? So there is two big case series. One is from Brigham and Woman, the other one's from University of Maryland. And from Brigham and Woman, they show about 115 surgical embolectomies during 14 years. They had about 55 during four years. And the 30-day mortality was, I can say, very similar. Also one-year mortality was a little bit different, but I think the patients were not exactly the same. And the 30-day mortality was very, very similar. The difference here is that in our series was a lot of patients who require the surgery for acute on chronic. So we're a little more stable patients. But now, what is the best treatment? What will you use for your patients? So cataract-based interventions, we did this analysis. And what happened is we compare all the patients that received cataract-based interventions that were about 30 patients in our center. And we did a propensity score match. And we matched with patients who received medical therapy, just anticoagulation versus surgical pulmonary embolectomy. So what we found is that this patient was not, and we compare over time. We went up to two years, you know, of follow-ups. It was crisp to try to get all the data from other hospitals. And we found there was no difference in thrombus resolution in those patients. The patients who received cataract-based interventions versus surgical and medicine approaches. There was no difference in improvement of the right ventricular dysfunction recovery. All patients recovered that. The length of the stay was a little bit longer in the surgical arm. The first patients that received surgical pulmonary embolectomy stay a little bit longer than the other patients. And there was an increased risk of bleeding in patients who received cataract-based intervention group. So when we draw a Kaplan-Meier for mortality, we can see in the top, those are the patients who received surgical pulmonary embolectomy. And we can see everybody else, I'm sorry, we can see the patients with cataract-based interventions in blue. We can see that there's a difference here. But when we compare the cataract-based interventions with the patients who received medical group that is the yellow line, there was almost no difference in mortality between cataract-based interventions versus the medical group. One of the critiques of this study is most of the patients who received cataract-based interventions, they receive is a cataract-based thrombolysis with an ECOS catheter. There was only one patient who received a cataract thrombectomy. Now in the market, we have the inatic catheter that they use cataract-based thrombectomies, but we need to check the data in the future. But that's why it's important to do a comparison between medical therapy and cataract-based interventions. How about extracorporeal membrane oxygenation or ECMO? This is a patient that we have on ECMO. We have an arterial and a venous cannula, and we have the patient's cataract may walk while they are on ECMO. And now, during this pandemic, ECMO has been used a lot, especially in those COVID patients. So we use ECMO in our PE patients. And a couple years ago, Dr. Kahn published this case series of about 20 patients who received ECMO for treatment of massive pulmonary embolism. And there is another group from Europe that they also use ECMO in massive pulmonary embolism. And what we found is the outcomes for them, they report about 61% mortality and in our patients was about 5% mortality. And this difference is explained not because of the technique, not because of the equipment, it's basically the selection of patients. We found that if we have a patient that is more than 65 or 70 years old is not a good candidate for ECMO because almost everybody dies if you put them on ECMO. We found that if you have a patient who has a bad disease, let's say it's a cancer patient, or a cancer in a late stage. They usually, we don't use the ECMO in those patients because we know that mortality will not be good. So we have to be careful on which patients we select to put them on ECMO. So we did a couple of things while patient is on ECMO. One of the things that we saw is in few patients that we had before that we tried the catheter-based interventions. Whenever they come from the other hospital, we try to put the patient in the OR, we put the catheter in, the patient decompensates. And the patients sometimes end up in ECMO. So we say, okay, maybe those patients that are high-risk, it's not a good idea to use catheter-based interventions because they can go worse. But that's why if we stabilize the patient on ECMO, and then we tried the catheter-based interventions. So we did couple of patients before, and we did, I think, with six patients only. But we found that all those patients with massive pulmonary embolism that they were on ECMO, we found 100% survival in those patients. None of the patients require a tracheostomy. None of the patients require dialysis after the therapy. None of the patients develop an stroke, but they all require much more blood transfusion. So again, this was with ECOS catheter with direct thrombolysis was not with catheter-based thrombectomy. So there is a room for research in that area. If you have a patient with massive pulmonary embolism, maybe we can use ECMO plus catheter-based interventions. There is another question. Why if I gave systemic thrombolytics to my patients and then I put them on ECMO? Are the patients doing well or not? So we found in about 80-something patients that were on ECMO during, I think, was from 2017 to 2019, those patients were on ECMO for PE. And about 18 of those patients had received previous systemic thrombolytics. And we want to see what is the outcomes, you know, if the patients die more or not. Because usually we put them on ECMO because there was a failure of systemic thrombolytics. So we found that the interesting, the survival to discharge in that in those patients was a little bit better in the patients who received systemic thrombolytics and then require ECMO was 88.9 versus 84.6. But there was no statistical difference. However, you know, they require way more blood transfusions. You know, the mayor bleeding was 61.1% in patients who received previous systemic thrombolytics versus 26% in those that did not receive systemic thrombolytics. But, you know, mortality outcomes was okay. Then which therapy is better? And that is a million question, million dollar question. And when I came here to the University of Maryland, there was a lot of controversy between services because we don't have a good data. And still, I think we don't have a good data for that. So let me tell you a little bit of history. Let me see. Okay, a long time ago in 2018, PERT was created in the middle of the battle between medical rebels and the surgical empire to treat PE. As a result, an algorithm was created to keep the peace between services. So this is the algorithm that we use at the University of Maryland. And after I present all the data that I show it to you, we decide to work better with an algorithm. So after we diagnose the pulmonary embolism, you know, we see if the patient is stable or unstable. So we have the express PERT activation that we activate only if we have a moderate-risk patient that has a submassive, high-risk submassive, a Boba-3, or if you have a massive patient. If you have a patient with a massive pulmonary embolism or a high-risk Boba, I was telling you, you know, here, most of the time we use Boba plus lactate. We usually put an access for ECMO in those patients. In Massive PE, we connect the ECMO. In the high-risk Boba-3, we use micro puncture only and we just leave the access, but we don't put the cannulas. If we have a massive patient, we can use systemic thrombolytics plus minus ECMO, or we can use ECMO plus minus catheter-based interventions. Then we put the patient on ICU for cardiovascular support. Whenever you have a patient that is a high-risk or moderate-risk, we usually don't do any intervention at this time. We repeat the echocardiogram at 48 hours. We see if the patient has a clinical improvement or not. Why 48 hours? Usually, if you see other guidelines, they take this patient right away to catheter-based interventions. But what we found is what is really the benefit to rush a patient for the catheter-based intervention? Most of these patients that we repeat the echocardiogram at 48 hours, we start seeing an improvement of the right ventricle function. The function is what really recovers faster than the dilatation. The patients remain dilated for a couple of days, but at 48 hours, we see that the patients start getting better. Most of the time, the patients do not require an intervention. However, if the patient doesn't improve, then we have to see if the patient is a surgical candidate or not. And if the patient, in fact, is a surgical candidate, we evaluate the patient for either catheter-based interventions or surgical pulmonary embolism. When we talk about catheter-based interventions, everybody thinks about myocardial infarction. In myocardial infarction, you have some goals in time between when the patient comes to the hospital, you have a door to balloon time, et cetera. And pulmonary embolism is not right equal to that. Whenever you see, you have up to 14 days to do a thrombolysis in those patients and it's successful. So as long as the patient is not unstable, you have some time to plan your interventions. You don't have to rush the patient to the OR. Also, you know, for surgical pulmonary embolism, if the patient is in this area that is on ECMO, you can also plan the pulmonary embolism. Because you have time, that means given by ECMO. Then if a patient has a clinical improvement, you just start a patient on anticoagulation and then you discharge the patient, and we have the pulmonary embolism clinic in the outpatient clinic. On the other hand, if you have a patient that is completely stable, that is low risk, you can either observe the patient or you can even send the patient home from the emergency room if they have a low risk of bleeding and low social profile. You know, the patient is reliable, basically. Now I'm going to talk about what consequences you have after having a pulmonary embolism. Not everybody goes well. You know, you have a PE, about 50% of patients after a pulmonary embolism have some kind of dysfunction. And this is based on the trial from Dr. Susan Tan, that is the ELOP trial. They found that 48.5% of patients after a pulmonary embolism, they develop shortness of breath. You know, they don't have a good quality of life. And when you check the echocardiogram, they don't have a normal right ventricle. You know, they have maybe mild RV dilatation, mild dysfunction. They can have also an abnormal VQ scan or they have still significant residual thrombosis in the CT scan. If you do a pulmonary function test, you see the gas exchange is not the best. You ask the patient to walk and you don't have a normal walking test, like a six minute walking test. You say, hmm, this patient might drop into the post pulmonary embolism syndrome. And this is basically like a new term. We don't know exactly why this occurs, why some patients develop post-PE syndrome, why patients do not develop post-PE syndrome. When they try to check if the residual thrombosis has something to do with this, this was not related to the residual thrombosis. So we are still looking in this area to see what's going on. We don't have a pathophysiology for this post-PE syndrome, but that occurs in our patients. But if we see what is the worst case of post pulmonary embolism syndrome, we talk about chronic thromboembolic pulmonary hypertension. In chronic thromboembolic pulmonary hypertension, we see significant residual clot in the pulmonary artery that could be proximal, like in type I or type II, or could be distal in type III and type IV. And those patients not only have residual thrombosis, they also have increased pulmonary pressure. And this patient comes with a pulmonary pressure of 50, 60, and they have signs of ribosecular dysfunction or failure. You need to have at least one pulmonary embolism, but up to 60% of the people do not remember having a pulmonary embolism. The mortality, if you don't treat this, is about 70% if your pulmonary artery pressure is more than 40, and 90% if your pulmonary artery pressure is more than 50, and you don't treat those patients. Those patients are usually treated with surgical pulmonary thromboendarcterectomy. You have to go and remove those clots, and you can use medicines to decrease the pulmonary pressure as well. When we did, we tried to check why these patients do not have a complete resolution of the clot. So we did an analysis of our population, and we found about 350 patients that has some kind of images after pulmonary embolism. They have either a CT scan or a VQ scan after APE, and we found that almost one-third of the patients do not resolve the clot. And the risk factors for an incomplete thromboids resolution were a history of cancer. If they have a concomitant lower extremity in DVT, and also if they were a non-calcation by race. The patients who resolved the clot really fast were those patients that had a provoked event such as after surgery or trauma. So those patients resolved really fast. So this is another interesting area that we are working on right now. So post-PE care, what we do when the patient has a pulmonary embolism, we need to check for thromboids resolution images. We usually do is a VQ scan. We don't repeat CT scans all the time. Also, we do an echocardiogram to see if they normalize the ribentricular function. You know, I usually see patients after a month, but I send all these tests between one month and three months. So as I told you, the ribentricular systolic function normalizing almost all the patients. The problem is some of the patients remain with a ribentricular dilatation. Also, we do a six-minute walking test to see what is the exercise tolerance on those patients. If a doctor can in her trial, they show that an abnormal pig VO2 measure, they use six-minute walking test. And they use also cardiopulmonary exercise testing. An abnormal pig VO2 that is less than 80% of predicted is a good predictor that the patient can develop post-PE syndrome. Also, if you think that the patient still have the shortness of breath and you don't know what's going on, you can also send a pulmonary function test. Maybe the patient has any other like a COPD or any other lung disease that the patient hasn't been diagnosed before. So those are the usually post-PE care that we see. Sometimes we have to change anticoagulants. Let's say you have a patient that you do the VQ scan at three months and the patient is not only that hasn't resolved the clot. The patient having new clots. Maybe the anticoagulant that you are using is not appropriate for the patient. You have to switch to a different anticoagulant. Sometimes we have to think about a filter. But those are the things that you will see in your patient after a PE. So in summary, the correct risk stratification is key to apply the most appropriate treatment. You have to be very familiar with what you have in your hospital. You have ECMO, you have a cath lab, you have cardiac surgeons on call. Or if you don't have that, you have to be familiar to use a systemic thrombolysis or you can refer the patient to another hospital. If you have a patient with massive PE, you don't have time. You have to treat the patient right away. And if you have a patient that is stable, you know, you can use other therapies. Caterbase interventions are a great tool, but we don't have enough information yet. So we use it, but not as much as we used before. We are very cautious with Caterbase intervention. And I recommend to have a post-PE care in every single PE patient, because what you don't want is that the patient comes at six months and they have severe shortness of breath. And then you find that the patient has chronic thrombolypumillary hypertension and something that you might intervene earlier in the disease.