Thank you so much, Dr. Sethi, that was really great. And like you said, it's always a picture's worth a thousand words, and we love seeing those valvuloplasty images, so thank you so much. So we'll move into our next speaker. Dr. Sanjam Sethi is an interventional cardiologist specializing in advanced coronary and endovascular interventions at Columbia University Urban Medical Center. He's the director of the pulmonary embolism response team. His research interests focus on investigating catheter-based therapies for venous thromboembolic disease. Thank you very much. Thank you, Dr. Park, for that introduction, and thank you all for tuning in and for allowing me to present today. I'll try to be mindful of your time at this late hour, so we're gonna go through some things quickly, then obviously we can talk more offline or in the discussion panel. I'm gonna talk about venous thromboembolism broadly, not just pulmonary embolism, because I do think that they are related. And the learning objective is to discuss the risk factors for venous thromboembolism in obstetric patients, discuss medical therapy considerations for VT in the peripartum period, and then understand some of the options for advanced invasive therapies and the potential complications and things that you must consider. So PE overall, there's an increasing incidence. It's the third most common CV disease after MI and stroke. And the reality is that the mortality rate of acute PE in an unselected population remains, in my opinion, at least, unacceptably high. We're talking about 17% at three months. And then obviously, depending on the severity of the PE, it's upwards of 50% in those highest risk patients, but even those that are intermediate risk can have mortality rates up to 25%. When we think about the pregnant patient, the obstetric patient, thrombotic pulmonary embolism is the fourth leading cause in terms of mortality. And actually, look at those bar graphs carefully. In some of the years, it eclipsed some of those ones that are higher. So similar to infection or hypertensive disorders, thrombotic pulmonary embolism is an important issue, as we had learned earlier when we talked about cardiogenic shock as well. And the timeline of when the patient is most at risk tends to be towards the end of their pregnancy, actually into that early peripartum period. So if you look, this is a case control study from 600,000 patients in the Netherlands. And if you look and see that the risk, there is a risk throughout pregnancy, but that risk really increases into the third trimester and then peaks right at delivery and that first six weeks postpartum. And so if you are treating a patient who has a PE or who you think is high risk for PE, it's important not just to anticoagulate or prophylactically anticoagulate, depending on what strategy you're gonna use during pregnancy, but also in that immediate postpartum period. It's very important to make sure that the anticoagulation, if you're choosing to go in that direction, is appropriate during that time period. And so one of the reasons that this is when the degree of risk peaks is due to some of the physiologic changes in pregnancy. This is a review from Circulation last year, which was a great article looking at cardio obstetrics. And one of the things that was discussed was some of these changes in physiology, one of which is that systemic vascular resistance goes down. So there is decreased in SVR and then there's increased preload back to the right ventricle. And that is one of the reasons that we have increased in lower extremity edema. But when you think about some of the signs and symptoms of PE versus that of pregnancy, dyspnea, tachycardia, elevated respiratory rate, lower extremity edema, elevated D-dimer, those may all be normal components of a healthy pregnancy. So sometimes it can be difficult to distinguish from what our classic PE signs and symptoms are in a pregnant patient, because they may have some of these signs and symptoms due to the normal physiologic changes that occur. And additionally, the pregnant state does have all components of what we classically remember as Burkow's triad. So you have vascular damage from either compression at delivery or maybe assisted or operative delivery. You have a hypercoagulable state with increase in procoagulant factors, decrease in anticoagulant activity. And then there's potentially stasis occurring because there may be compression of the iliac veins from a gravid uterus. We're actually looking at this in our institution and looking at those patients who are either pregnant or have fibro uteruses. And what are the uterus due to the iliac veins where they cross over the artery there in the pelvis? And there is a thought or a question that maybe a part of the reason that pregnancy is associated with DVT at least, and then as well PE, is that there may be a predilection for the left leg because of compression of the left iliac vein by the right iliac artery and the gravid uterus. And because the spine is behind, you're compressing the vein behind it. I don't think this has been proven yet, but it is one of the questions that's out there, especially as pregnancy associated DVTs are left-sided in the majority of cases. When you suspect that a patient may have a PE and who is pregnant, there are some algorithms out there. This is one algorithm called the YEARS algorithm that's published in the New England Journal in 2019. And really this relies on signs and symptoms of PE and if there's clinical signs of DVT and ruling on a DVT. But if you look at this criteria carefully, it's still very difficult to discern which of the patients actually have a PE because it's really relying on D-dimer and a D-dimer cutoff to then further investigate if the patient has a PE. And as we all know, D-dimer can vary depending on different disease states. And it's not certainly, while it is sensitive, it is by no means specific for an underlying thrombotic process. This is another algorithm that was from that same circulation article published in 2020 which again, you think about signs, symptoms and risk factors, think about venous ultrasound of the leg as well as a chest x-ray ruling out alternative causes. And there's still a high suspicion going through with a CTA or a VQ scan. However, I would challenge the fact that echo I think can actually be very helpful in these patients if you're on the fence about what to do and if you want to spare the patient radiation. If the right heart is not strained, that gives you a lot of comfort versus if there's severe RV enlargement which can be done non-invasively that may lead you down the route towards a CTA and or treatment. On the right side, they have some of the emerging data. And as you can see here, catheter directed lysis is down there in the emerging data category. And we're gonna talk a little bit about beyond anticoagulation. If you do have a patient with PE, what are the things that we need to think about and what treatment options do we have for them? The reason that I make a point about echo is that the RV is really the important part of a PE diagnosis, at least in the acute phase. This is a often shared slide from one of the guideline documents, which shows that when the arm starts to dilate, the patients have a decrease in the, decrease in RV contractility ischemia, decrease in RV output, the LV goes down, low cardiac output, decreased of the preload back to the right ventricle and then that cycle continues. So really, as we all recall, the RV is a volume chamber, it's not a pressure chamber. It's used to pressures of about 25 in a normal patient in terms of the pulmonary RV circulation. So if that pressure goes up because of obstructive physiology acutely, it goes above about 50 or 60, the RV will rapidly fail. And so the RV really compensates until it can't compensate anymore. And then you go down into the spiral and the patient can become critically or very, very quickly. This is what the RV looks like on CT. The reason I'm showing this picture is that one of the ways in which we determine whether an RV is at risk is the first piece of information we often get if we don't have an echo is from the CT and that is determined by looking at the RV to LV ratio. So a normal RV should be smaller than the LV. An RV to LV ratio greater than 0.9 is considered abnormal. And this is the same thing on echocardiogram. And the reason is that in patients, and this is non-pregnant PE patients, an RV to LV ratio greater than or equal to 0.9 is associated with a fivefold increase and an independent predictor of mortality. And that's why when we think about patients and how they're evaluated for procedure, we look at what the RV to LV ratio is, or if you have an echo, RV enlargement McConnell sign as a marker or a guide towards those patients who may benefit from a procedure. So when we look at the patient evaluation, we want to think about their clinical vital signs. You may restratify them with a PESI score and S-PESI score, but we did talk about how some of those signs and symptoms may be masked in a pregnant patient. We want to think about imaging, particularly looking at the RV function and size and echo can be very helpful, a CT scan if you're going to be obtained. And then the biomarkers, the D-dimer, troponin, NT-proBNP, lactate. And all of those things are going to help us restratify a patient. So this is from the ESC guidelines. This is, I think, the most contemporary way to think about acute PE management. Europeans are always a little ahead of us Americans. And when you think about this, that if somebody has hemodynamic instability, severe clinical parameters, and then RV dysfunction, they're in the high-risk category. That person needs urgent intervention. So in a pregnant patient, that might be somebody we would think about ECMO, think about urgent thrombectomy, think about surgery. The low-risk patients who are negative across the board are easily treated medically. Now, as those intermediate-risk patients where there really is a question, that's why this has replaced low-risk, submassive, and massive, has divided out that previously known as submassive category into intermediate-low and intermediate-high. Because the intermediate-low patient may have one of these parameters, other may be negative. Those can usually be treated medically. And those intermediate-high are the ones that have at-risk RVs that we should really think about treating aggressively with an interventional therapy. Before we get to intervention, we'll talk a little bit about anticoagulation options. These are the normal options for anticoagulation for PE. Warfarin, direct thrombin inhibitors, anti-factor Xa inhibitors, unfractionated heparin, low molecular weight heparin. The reality is that warfarin is teratogenic, crosses the placenta, really is not an optimal therapy. Direct thrombin inhibitors, anti-factor Xa inhibitors do cross the placenta. There's insufficient data, and they're really not recommended in pregnant patients. And therefore, unfractionated heparin is the treatment of choice in the IV form, in the acute phase, and then low molecular weight heparin really is the standard for patients who are pregnant in terms of anticoagulation. Minimally secreted in the breast milk, not substantially orally available. You can use it with a nursing mother. You can use it in the pregnant patient. And then the additional benefit is that should there be a bleeding complication, it is reversible as a relatively short half-life compared to the oral agents. We do wanna think about the fetal and maternal risk with imaging. I'm not gonna go into this slide in depth, and Dr. Sintag did allude to the fact that we want to think about the mom before the baby, but we do wanna be mindful of what the radiation implications could be for the fetus. When you think about if you are gonna treat a patient who is intermediate or high-risk with a catheter-based strategy for PE, there are four current FDA-approved devices. The Inariflotriber device is a large-bore thrombectomy device, goes up to 24 French, so that's really good for your central, clod, saddled, PE, hemodynamic, unstable patient. Now, the Penumbra device is smaller-bore, may get enough out to accomplish the job. There's continuous suction there. ECOS is the FDA-approved catheter that is catheter-directed thrombolysis that is much smaller French, and if you're comfortable with TPA in that situation, that may be an option. And then Alphavac was just approved earlier this week, also used in the PE. The first inhuman, or I should say, the first studies are being, or first cases are being done this week. So when you think about intervention for PE, catheter-directed thrombolysis, this is a standard catheter, but the ECOS catheter is very similar. It also has an ultrasound component to it. You drape a catheter across the thrombus, allow the TPA to penetrate in, soften the clot, and then it allows for there to be fibrinolysis. This is very good for acute PE, but you have to be mindful of the bleeding cost or bleeding hazard. These are the devices for aspiration or mechanical thrombectomy, which I went over. And then, as these devices have proliferated, we think about what factors may favor CDT or catheter-directed thrombolysis, what factors may favor thrombectomy. So factors favoring catheter-directed thrombolysis, if the patient's more distal thrombus, if they're more hypoxia predominant, suggesting they're microvascular obstruction and that they have impaired gas exchange. Those who do not have a trauma or surgery, or in this case, pregnancy, it may not be a favorable situation. And then the logistics of your lab, right? If you're using the STEMI call team to do a PE case, you may want to shorten the time that you're in the lab or if you have competing priorities. Similarly, factors favoring thrombectomy, more hemodynamic predominance. If you can get the clot out faster, you're going to have better hemodynamic effects. If it's more proximal, if there's a bleeding contraindication, or if logistically, if you don't have ICU space or nurses trained in a drip, then thrombectomy may be a favorite strategy. A little bit about adjunctive procedures in the PE patient. You want to think strongly about ECMO in the high-risk patient, particularly in the pregnant patient. ECMO may be used to stabilize the situation if they're hypotensive. You may not want to give systemic TPA. And the fear is really moving away from systemic TPA as a frontline therapy, although that's still in the guidelines. It's on your boards, it's still the answer. But in centers who can do it, ECMO often allows you to stabilize the situation then stratify the patient to whether they need to go to surgery, a heparin alone, or maybe a catheter-based strategy. You want to think about IVC filters in those who have a contraindication to anticoagulation, again, in the pregnant patient that may or may not be applicable. And then RV support devices is an often question. And while people have used it, so I shouldn't say no data, there's some case reports out there in situations like this, the mechanism of dumping blood from the RA into an obstructive PA circuit, ECMO really is a more attractive way to bypass the RV in that situation. But if that's what you have, it has been used successfully in PE patients. I don't want to go too much over time here. I do want to make a quick point that PE is not the only hazard to our patients. DVT can have both short-term and long-term consequences. This is a patient with DVT who was treated with anticoagulation alone who developed post-thrombotic syndrome. And that's because thrombus may lead to obstruction, valve damage, leaky valves, reflux, venous hypertension, and ulceration. There was a case of a thrombectomy patient that I'm not going to go through in the interest of time, but this was a woman who had lower extremity edema, three plus after premature delivery, even though they were on DVT prophylaxis, had a strong family history of DVT, had an echo with only a mildly abnormal RV, had a complete occlusion of their left external iliac vein on CT venogram, had complete occlusion up into the IDC. We decided to go with a catheter-based therapy here. And this is the venogram. You can see here as it's playing, and I promised you that it's playing, but the dye is taking that long to get up because of the obstruction. It's really pretty significantly occluded which masks a CT scan. And then even after thrombectomy on the left side, that's about all we were able to get. So while we were able to restore some blood flow, there was still significant issues. We left a catheter behind. We did an ultrasound, found that she had iliac vein compression. She probably had it the whole time and it was exacerbated by her pregnancy. She eventually had no thrombus remaining after treatment. And we came back and stented her later. And she's actually doing very well in follow-up and her baby is also doing very well. In my last couple of minutes, I want to take a quick mention of the fact that a team-based approach to medicine in these high-risk multidisciplinary patients is I think the wave of the future or even the wave of the present, I should say. And with your cardio-obstetrics team, you can pair a PERT team. And the idea is that we're using a rapid response concept. You can have collaborative multidisciplinary team-based urgent consults to treat these patients. And this is a slide from Chris Cabral, one of the initial PERT documents. We show that this is really the way that PE management was being done and is being done in a lot of places, where it's haphazard depending upon who you talk to. Whereas when you have a multidisciplinary team and immediate conference, you can have a rapid disposition and rapid treatment strategy for that patient. And in our institution, we've seen that length of stay at least has dramatically decreased once we instituted this concept. The idea is that it's a multidisciplinary collaboration with all of those involved, including OB, although it's not on this particular slide. And I'll leave you with the guidelines that we had discussed earlier. And the idea is that high-risk patients should get medical therapy, catheter-based or surgical intervention with or without hemodynamic support, really do need that multidisciplinary team to come to a consensus in those situations. But those people need urgent intervention. I would argue that those are the STEMIs. Intermediate high-risk, consider catheter-surgical-based treatment in those patients. In the pregnant patient, you wanna weigh that against a risk of radiation and the risk to the fetus. But those, and that's really your NSTEMI group. If those patients need urgent but not emergent therapy, then your low-risk patients can get medical therapy, which in this case is usually low-molecular heparin. This is an algorithm, similar kind of a thing. Think about PERT consultation, circulatory support in your high-risk patients. PERT consultation may be a catheter therapy in your intermediate risk and low-risk, actually with heparin balancing against the imaging issues. Take-home points. Pregnancy is a risk factor for VT due to physiologic alterations. Multiple therapies exist if anticoagulation alone is not enough, but there's a paucity of data in peripartum patients. And then PE teams may enhance care for patients with PE and other manifestations of VT. I thank you for your time. I'm happy to take questions.

venous thromboembolism

obstetric patients

risk factors

diagnosis

treatment options

pregnant women