Anjali Vaidya, MD, FACC, FASE, FACP, Co-Director of Pulmonary Hypertension, Right Heart Failure, and CTEPH Program at Temple Health shares advanced diagnosis and managment for chronic thromboembolic pulmonary hypertension.
Dr. Vaidya reviews:
Pathogenisis, epidemiology, and risk factors
Diagnostic criteria and evaluation
Pulmonary thromboendarterectomy (PTE)
Balloon pulmonary angioplasty (BPA)
Medical Therapy
Conditions CTEPH mimics
The Pulmonary Hypertension, Right Heart Failure, and CTEPH Program at Temple Health has conducted more than 350 PTEs, and has achieved a 100% survival rate in the last year (2021-2022).
welcome everybody to another of our series of pulmonary grand rounds tonight we have an incredible privilege to be joined by professor of medicine Dr Anjali Vaidya from Temple University Medical Center and Temple University School of Medicine in philadelphia. Um I have known Angelique now for I want to say almost 20 years or longer. Um Angela did her undergraduate and medical school at Boston University in a combined program and then she came to the University of pennsylvania for her internship residency in internal medicine. Chief residency, internal medicine, cardiology fellowship, Chief fellowship in cardiology and my multiple sub specialty training in cardiology all at the University of pennsylvania where she then stayed on as faculty member all the way up to I believe 2016 when Pen made the very bad decision to let her leave and go to Temple University Hospital, where now she's co director of the pulmonary hypertension, right heart failure and see tech programs at Temple University School of Medicine. Anjali is recognized nationwide and increasingly internationally for her expertise in all forms of hypertension and right heart failure with unique skills in the use of echocardiography. Since she came to temple six years ago, almost six years ago, Temple has grown to be a major CTF center and has one of the largest pulmonary thrombosis under artillery programs and bronchus bronchus, bronchus, coptic balloon, pulmonary angioplasty. I was thinking about bronchoscopy in this. Um in the United States, she's the associate program Director for the cardiology fellowship and a core faculty member for the Control Medicine residency program. Um She is going to serve as the founding director of a new pulmonary hypertension fellowship at Temple and for any of our fellows or maybe junior faculty who are interested and he's gonna send me information about the new fellowships if anyone's looking for for training. Um Temple is going to have a dedicated pulmonary hypertension fellowship, which will be open I assume, to both pulmonary critical care trained individuals and cardiologists and then they can duke it out at the end of the fellowship, we should be caring for location. Um She's a recipient of a number of awards, the Temple Health System Educational Excellence Award for Educational service, the Temple Health System Mentoring Award for women in medicine and science, recognized by her peers as a philadelphia top doctor for multiple years. Uh and at Penn uh she received the Donna Mccurdy Department of Medicine Teaching Award, which uh in in my memory as a faculty member of Pen for 26 years, is a huge, huge honor, which Anjali deserves. So we incredibly privileged to have dr video with us tonight to be talking about diagnosis and management in 2022. Uh and I'm sure that we have lots of questions at the end. So dr thank you so much for joining us. Well, thank you, that was the nicest introduction. Um dr Sturman, of course, I've been calling you since I was an intern. And so um dan, thank you very much. I'm so honored to be invited and really excited to talk with all of you today. Um this is a topic that I'm pretty passionate about. So I'm excited to to have a great discussion um before I jump in. These are some disclosures, disclosures and some objectives for today are listed. I think the most important objective that I would want to emphasize over and over is when it comes to palm hypertension, just do whatever dr says. I have found that to be a helpful rule of thumb since the beginning of my career and Roxana, if you're on, thank you for all of the wonderful examples you have lead in the field of pulmonary hypertension across the country. Um, since I was very new in this space, I've been so appreciative and have learned a lot from you also. Um so thank you again for that is so sweet. I really, really appreciate it. I'm so glad that you're here and I really need it for the world. I'm actually, you know, very excited to hear, you know, as we discussed yesterday, we have a lot happening in the city of program here. I saw actually Justin is signed in as well. So here's our surgeon. Uh, and then we are all literally looking forward to this. You know, this talk. I'm extremely excited and thank you so much for taking the time. Awesome. Thank you and this is what we're going to try to cover today in the, in this short hours. So pathogenesis at the interest back, I want to take a special focus of time to talk about something that I've um named mechanical venous thrombosis embolism risk. We'll of course talk through diagnostic criteria, evaluation. That's really a huge bulk of what it means to understand and take care of and be a part of CTF. Of course, we'll talk about PTE but I want to emphasize one of the most common questions that comes my way is what about if there's any pulmonary hypertension afterwards? What does that mean? So, we'll get into that in more detail, of course, in the current era. Now, balloon pulmonary angioplasty is a huge area of excitement. So we'll talk about that. There's medical therapy, you'll notice there's a lot less to talk about with medical therapy. Um, a quick emphasis on some mimics. So, without further overview, I can't talk about pulmonary hypertension without this sort of reminder of overview. Not gonna get into all of the different groups. You all are familiar with them, although I have to say I'm so pleased that our trainees in this era in medicine, pulmonary cardiology know this stuff, memorized it like the back of your hands, which is not the case when we were training. So it's it's heartwarming to see how this field and education has evolved. We're going to focus today on pulmonary hypertension uh due to chronic metabolic disease. So this is of course who group for this is one of my patients getting a pulmonary angiogram. Um and so you know, one of the things I always think of and say um when I'm talking about pulmonary hypertension in general, as you all know, there's huge excitement also in the field of pulmonary arterial hypertension. So if I may, here's the april 4th chamber of two hearts side by side. And the question is which of these patients has sita and which of them has ph and the point of this slide is that the answer is you can't tell actually. Um And so I always say a patient does not have Ph until CTF has been ruled out because the clinical presentation of dis mia and fatigue with exertion and right heart failure. And this Echo Doppler is showing this two D echo, showing RV enlargement and RV dysfunction. RV hypertrophy. These findings can be very identical. So if you if you're thinking ph don't go too far down that road until you fully evaluated for CTF first. So what is the incidence of CTF after a P. E. Many studies have looked at this. The range overall that you're here that you'll hear is somewhere between 3.5 to 8% or many different publications on this. The Pango paper is quoted over and over and over. So it's just worth mentioning this was a prospective study, a few 100 patients. Um I can't believe this study was also 20 years ago now. Um patients were followed for a period of years and you can see that they came up with 3.8% as the risk of an incident of CTF after a new p. Now, a theme that has come about and you'll hear over and over is the risk for developing CTF. If you've had an acute pe is higher. If it was thought to be idiopathic or sort of that unprovoked pe, we'll talk more about that. Also, if you're younger at the time of your first pe would make sense that you have a higher risk over time to develop. It was thought that if you have a large area of profusion defect, a relatively proximal clot burden or if there was high pulmonary pressures at the time, or if you've had prior p all of those things probably intuitive would would be a higher risk of subsequently being diagnosed with Sita. This is another study that was published about 10 years ago, looking at the same concept, but I want to emphasize that they broke it down. It's about 300 patients to begin with, but they broke it down to who had the first episode ever of PE versus those that had had a known prior pE and this is a really important point. It wouldn't surprise you to see while the incidence of CTF is notable in both groups and you can see if it was your first pe, the risk here was almost 5% a little higher than the Pango paper. But if someone has had a prior pe Multiple pes their risk of developing CTF goes up significantly and here it was a very small number of course, but 38% is what came from this and that really plays out. I think an important point from this is the concept. As pe doctors that if you see someone with a history of recurrent acute pe, I would have some significant skepticism that it's actually recurrent acute as opposed to an acute presentation. Clinically acute clinical worsening in someone that actually has chronic crumble anabolic disease that that kind of misconception or mix up happens quite frequently. So what's the pathology here? There's often a DVT, it symbolizes to pee and then there's this incomplete resolution of the clot. You get vascular occlusion of liberation high pressures. Then that causes shear stress in the open areas of the pulmonary vasculature and then a progressive increase in that pulmonary vascular resistance that leads to the diagnosis of C tap and of course leads to right heart failure which is a huge part of the mechanism of morbidity and mortality. So this is just looking at it in cross section on a histology slide. You can see organized rhombus, this fibrous intimate hyperplasia and the smooth muscle hypertrophy that occurs. These slight openings are these recapitalized lesions that are often called colander lesions, but also those partial recapitalized clot is also what's often referred to on ct angiography as a web. So I'll show some examples of that as well. But that's kind of what it looks like in cross section Now. These are the historically accepted tried and true sort of known risk factors for CTF. We've talked about the pe specific risk already that you can see here at the top of the slide. But then of course there's the hematology risk which is intuitive, particularly with an emphasis on those that have anti fossa lipid antibody syndrome or lupus anticoagulant that's really panned out in the seats of literature. Medical conditions that also increase the risk are noted history of cancer history of an indwelling pacemaker. I've seen that quite a bit that's been described. So, pacemaker I C. D. Any notice for chronic clot to form um patients that have indwelling ports. So cancer patients that have had chemotherapy so often the ports are not removed forever for many, many years and that can be an itis for clot. Um In fact it's just worth noting that those patients that often have very small clot because it's not something originating from the iliac femoral veins and that can lead to very distant rumble metabolic disease which can be even harder to diagnose and treat history of splenectomy also is a risk. Now this is kind of this new category that I've been named that I have named mechanical risk factors for CTF. Um And it might look a little strange. What am I talking about here, I'll explain. But I'm referring to the general concept of the veins in the pelvis, the the iliac and the, you know, the femoral iliac pelvic veins having a mechanical compression, literally that we have looked at and studied and published on and seen many cases of and heard others with anecdotes. Um as folks that ultimately also are diagnosed with C tough and I I would just highlight this category of patients in my mind as those that often fill in that uncertainty and fill in that blank of patients with the unprovoked recurrent pE. I would really think about this category of things that may not have been recognized. So listen, I'm a cardiologist, your pulmonologist. If I if you had told me 10 years ago that I was going to be talking about uterine fibroids and a grand rounds, I would have thought I took a wrong turn somewhere um in my career. But hear me out for a moment, this picture just kind of gives you the sense that um you're gonna see uh potentially quite large benign tumors in the uterus. And you can get the sense already about how that might put pressure on the pelvic veins. This is a paper now we published about three or four years ago looking at are the series of patients we have had thus far with CTF And 38 women in this in our overall population thus far had supposedly that unprovoked DVD or pe none of them had a hematologist risk or hipaa collectible state. And seven of them about 18% of these women had large fibroids large enough that we actually demonstrated directly on imaging pelvic vein compression. Five of them ultimately had a hysterectomy. No recurrent DVT or PE. And of course it's worth mentioning patients that have uterine fibroids of course are often presenting with maharaja which is often treated with estrogen based contraception or OCP use that can then kind of feed into that risk of clots. So this is a really significant sort of syndrome. These are just some pictures that show on the top left here. This is a patient you can see significant occlusion of the veins here. Pre hysterectomy the same patient on the right here after hysterectomy. This is invasive venogram that we did and it shows complete improvement and resolution of the caliber of those veins. These are two separate patients that also had a similar narrowing and compression. And we've shown this on venogram and the cath lab intravascular ultrasound demonstrating direct um compression as well as um C. T. Or M. R. Videography demonstrating direct compression of those veins. So not just the presence of fibroids but really shown the an atomic correlation with the with the veins there along the theme of mechanical risk um May 3rd owner anatomy which I remember learning first year of medical school and then happily had sort of put in the back of my mind for many years. And so just as a reminder, I'll show you kind of what that anatomy looks like in a moment. But this is something that we found also in our CF population. Um as a what seemed to be quite an important clinical association. This was published in jack interventions last year. And so just as a reminder made, turner syndrome is when that left iliac vein is compressed by the overriding artery and so it causes an extrinsic compression of that venus structure. We should, we looked at 100 and 48 patients with CTF that we did invasive biography on almost 30% actually have made Turner Anatomy. So that's a really high burden now in autopsy studies and normal population, the incidence of Nathan anatomy is not very well described but it's thought to be much lower less than 10%. So this was an interesting association and many of those patients not just had that anatomy, but actually the clinical syndrome, more than half of them meaning the peripheral venus, chronic venus changes or DVT in that left leg very common. When I first came to the program and we were building and growing it, we used to only look if someone had a really obvious venus syndrome in their lower extremity or that were current left lower extremity DVT for unclear reasons and we're finding it so commonly that we now do um screening on most of our patients. And so in our paper here those that had made Turner anatomy no surprise a significant increase of having that lower extremity DVT also. Um you can see that those that had made Turner anatomy were more likely to undergo pT. Which suggests that proximal venus source of the D. V. T. Leading to large caliber plots that end up having more of a proximal burden and being more surgically accessible. We're also starting to look at okay post PTE and resolution. What about the value of placing a stent to open those veins So please stay tuned. We're really learning this field as we go. And we're and we're going to be looking at kind of what that intervention may have long term. And then finally in this category is this concept of pelvic vein obstruction. And we presented this data at the seat of proceedings last year where it's similar concept but venus obstruction at any level. So we looked at 100 and 50 patients or so. 44% of them had some version of a pelvic venous obstruction. And of course a higher risk of a DVt in those patients. And that obstruction could be at the cave at the common iliac vein external iliac vein or even the common femoral vein. And these are just a couple of examples of of those patients on the left is again seeing more of that made Turner anatomy. And then here on the right side of the slide. This is a pelvic vein obstruction um here in the in the left external iliac vein and here in the right common iliac vein. Just another category of what to think about. So moving on to how does the patient present when they have see tough? It's unexplained dismay and fatigue as the most common symptom no surprise. But in pulmonary hypertension we're looking also for evidence of right ventricular dysfunction. So peripheral edema, profound exercise limitation on the basis of inability to recruit stroke volume. So on the basis of ventilatory and efficiency. My seat a patient in the office today we did a C. Pet in the office and showed ventilatory inefficiency, high V. V. C. O. To a reduced entitled C. 02. In addition to the cardiac limitation. Exertion, chest pain, angina pressure, exceptional pressing copy or sync api. So the presentation it can be some subtle initially but it can really progress over time and it can be severe advanced right heart failure. And it can, as I said before, be very similar to ph this is a review that I helped co author with some wonderful colleagues a few years ago. This was actually four years ago. Now that shows and the part that I wrote that I wanted to talk about a little more is sort of in that diagnostic evaluation. The testing that we that we focused on and look at. So I'll start with the V. Q. Scan. I know this audience knows this really well but just to emphasize it's a very sensitive test and we're looking for unmatched perfusion defects here of course is normal ventilation very homogeneous On the right side you have profusion defects. And it's obviously unmatched as you can see. But these can really vary that you can have perfusion defects that are unilateral versus bilateral very low bar um or entire lung that's out for example versus peripheral segmental distal disease. And so the appearance they're they're kind of like Phil flakes there. They can really vary from patient to patient. The ante and post the reviews are really helpful and the post your oblique views are also very helpful to get a more localized an atomic sense of the defects there. Now ct angiography is huge and there's so much to look at on the C. T. Of course. And I always remind folks that you know let's not forget to look at the cardiac structures. And so we're looking for enlargement of the right ventricle enlargement of the right atrium in the clinical common clinical question of is this acute or chronic pE which is not always so straightforward. Please just take a second to look at the wall of the RV. If it's if it's hypertrophy feed then that implies some degree of Cronus city most often and that can be a really helpful food that's not usually reported on on the C. T. Now we're also looking for abnormalities related to pulmonary ischemia or infarct. Um So I'll show you can see some of that power bankable abnormality. This curvilinear scarring, fibrous appearance can often go along with that. I'm sure you've seen this quite a bit. But so often patients with display on exertion. Recurrent are diagnosed with pneumonia refractory or recurrent pneumonia and given antibiotics without resolution. And when you look at the CT like that was actually a pulmonary infarct mosaic perfusion of the lung is also a classic finding seen in Panel B. Here. So this demarcated ground glass area of normal profusion in the dark area around it is a classic finding of CTF and then the variability of the vessel size. So chronic clot actually tends to bring the vessel walls in to the center of the loom in it. It causes tapering distantly and that can be very different than acute pe. So that can be a helpful clue. The C. T. A. Is also really a map, A roadmap for for surgical planning. So you're looking for organized the rhombus and then you might see these webs. These are these linear abnormalities within the vessel lumen. You might see true just pouch defects like total inclusions or it might just be lining the rhombus, the internal irregularities in the vessel wall bronchial collaterals are a really hot topic that people love to talk about to. I'm giving a talk specifically on systemic to pulmonary bronchial collaterals. At the P. V. R. I. Next month. So people are really into this apparently. But it can be a great clue and it implies it implies synchronicity also because oftentimes you'll see collaterals either coming off the aorta coming off the coronary arteries during the coronary angiogram and when you see them feeding the pulmonary vasculature, that also can be a clue for Cronus city and that is often the explanation for why patients might have hypothesis on presentation. There are so many advances in CT scan that's a whole separate talk I could give but I'm not gonna show all of the new technologies but it's worth just noting dual energy cT can acquire information for tissue characterization as well. There are two data sets that you acquire multiple energy level. This can give you a sense of parang camel densities, lung tissues, refused blood volumes as well. This is a publication last year from palm cirque evaluation of microvascular apathy using dual energy cT. And patients with CHF. And you can see in the photo here wedge shaped defect some sub plural infarct subdural defects that you can see. And it's really nice. Um This is of course the coronal matching up with the pulmonary angiogram and getting a sense of how that can correlate so as the technology is and has evolved there is really a nice kind of evolution of what's available on CT scan to get a little more refined. So I know we talk always about the V. Q. Scan is the screening test of choice with the high sensitivity. Believe me when I say that as the field is evolving. The C. T. Scan has more of a role front and center and early as well. By the way the reason it's not sensitive historically to find CTF is simply because those findings I described are not as well recognized and that you know the awareness has not always been there. But for all of the trainees that are watching this you're gonna see it on C. T. And when a patient has CHF and their C. T. A. Was read as normal but the VQ is abnormal. When you look at the images directly it's there it's not that it's just totally missing. It's just the recognition of some of those findings can be settled. Now, pulmonary angiography historically described as you know the gold standard for assessment. This is a patient of mine you can see some of the typical abnormalities. So some of these white arrows are looking at some pouch defects here. Another thing that's really notable are these post hypnotic dilatation is the classic finding of chronic disease on the left lung. These bands, those linear findings, those webs and bands again those are those partially recapitalized lesions, those are kind of ripe for intervention. So there's a lot of testing and diagnostic evaluations that go into this and we're all we always talk about guidelines. So guidelines in in CTF basically just say referred to as Ceta program and expert program and the outcomes similar to transplant. The outcomes in CTF correlate with the experience and the volume of the center, which absolutely makes sense. And there's a lot of emphasis on me medical therapy um which is important to know, but it's really important to keep in mind that if you're going to initiate someone on medical therapy for CTF, it should not delay referral to a large volume C test center for evaluation and it shouldn't delay the decision of operability at all. It's really a multidisciplinary effort um in our program here at Temple. It's run out of the cardiology program where all pulmonary hypertension doctors kind of career ph people. But we collaborate of course with our cardiac surgeons are chest radiology experts, interventional cardiology. Um they'll help us with the diagnostic um pulmonary angiography but also performing the balloon, pulmonary angioplasty will get into that more. It takes a whole army. I have the best nursing team program coordinators, administrative team in part because we have patients from all over the country that come and there's a lot that goes into that but just clinically it's really quite complex and and and I'm so grateful for my, my entire supportive team. Now, not all patients would seem to are operable. About two thirds are if you were to take kind of global averages from the major centers around the world medical therapy. Our options will get into that in more detail. Um and balloon pulmonary angioplasty. I italicized just because this is a really exciting area. We will definitely dive into that a little bit more. Um Oh yeah, our our chf meeting happens to happen every Tuesday, which is why I have that on this screen. It's just like a multidisciplinary transplant meeting or bad meeting and everyone's at the table. We review scans and images from around the country um and and move forward to taking care of these patients. So there's a lot that goes into the decision of surgical intervention for P. T. This is as simplified aversion um that you might see there's so much more to it than what's on here. But but these are some of the important concepts. So on the left, of course it's important that patients have to have surgically accessible disease, meaning not so distilled in the sub sub segmental branches. Now, I have evolved in this field from having no experience in C tech but being a ph person and being interested to now, I'm very fortunate to have more years under my belt of setups. So the reason I say that is because I've learned this is an important lesson that the concept of an accessible lesion is not uniform across experience and center and and this is a life and death distinction that's really important to know. Um and I take a lot of pride in safely building a program and so we have, we here and now kind of I'm proud about of our program to be a part of that. To say that virtually all through symbolic disease is surgically accessible. There's no patient that's not operable. This is something I used to hear when I wasn't to see tough person yet. Um and that's wonderful for those that do hundreds of these all the time but distilled diseases much higher risk and is much more surgically complex and medically complex. Post up in the I. C. For days and days and days. And so the the definition of what's accessible is variable based on program experience. It's not just about the surgeon, it's about the entire program. Um Patient consent and motivation sounds obvious but it's also really important because the the reserve the respiratory reserve after PT is very low and it takes it makes things more important um than you might see in other really complex cardiac surgery, cardiac plastic surgery. So for me I'm a heart failure transplant cardiologist. My reference point is, you know end stage cardiomyopathy with multiple valves in a cabbage or my VADs or my transplants, the PTE patients if they're not up and moving and using that incentives by rama tree and working with P. T. And doing all of those things that we need. Even a modest degree of ad electrolysis and de conditioning can make their hypoxic respiratory failure post op life threatening and so there does have to be some buy in and motivation and from the patient in advance. Um severe comorbidities. That's a huge category. That also varies in terms of contra indications for Pt based on program experience. Now the top says advanced secondary arterial apathy, this is important. There's this concept that is hard to quantify but it comes with clinical experience in your sense that does the degree of pulmonary hypertension, the human dynamic abnormality, the PVR elevation does it correlate with the amount of symbolic disease that you're seeing. Because patients with any background of comorbidities and medical history are well within the right to develop a P. And ultimately develop chronic P. But if their ph is more due to underlying lung disease or more due to an autoimmune connective tissue disease or any of them. Many other things that cause ph and they also have some degree of from bomb bolic disease. By definition they might have said. But that is not an appropriate patient for P. T. Because you will not achieve the post op human dynamic improvement that is absolutely necessary to have a successful outcome. The expertise of your team is of course key. It's I'm asked by a lot of folks, okay we have a surgeon and we need a surgeon that's all we need. You absolutely need talented surgical skills. There's no doubt about that. This is very complex. I'm clearly not a surgeon and I have so much respect for what goes into this but the medical team is equally important in the patient evaluation, the assessment in our program. We don't know patient comes out of the O. R. Without one of me or my faculty member partners are just a few of us at the bedside to greet every patient and really managing every I. C. Parameter. The other things that go into it is just demonstrating the the clinical effective CTF. So significant human dynamic burden. Maybe there's not ph but there's significant dis mia from ventilatory and efficiency that's important and and enough of a functional limitation for the patient overall to justify going into P. T. This is just a photo in the O. R. From one of my surgeons, Yoshi Toyota the pt itself. It's unique. It is the first line treatment around the world. First CTF even in the world and medical therapy and B. P. A. As I mentioned outcomes correlate with experience. There are some unique factors. It involves deep hypothermia. It involves circulatory arrest. So 20 minutes at a time for each episode of circulatory arrest. That's why there's deep hypothermia to protect the brain and distal organs. Um And then post operatively it can be very complex involving re perfusion lung injury with profound hypoxia. This is a common cause for requiring VV. ECMO. Um We manage that with diuretic and some some nuances with ventilator management and ICU care. We are our CTF program was born out of a heart, our heart failure expertise. So we're our heart failure, brains are very liberal and generous with diuretic therapy. And so we actually have a very rare need for VV ECMO but it is a well known need and complication around the world, all patients need to be on a coagulated bleeding risk is significant. The human dynamic management and um kind of linking that in with their lung perfusion and lung injury is is kind of nuanced neurologically. These patients are more complex because of that circulatory arrest and so managing that and their sedation is kind of a bit interesting. And any risk of arrhythmia post up in any patient with ph or right heart failure is really a significant risk. If you lose that baby synchrony you can lose a significant amount of right heart performance. And we've known that in the general ph world for for many years now. Post operatively this is some data from from around the world that has shown the outcomes that we would all want to see if we're going to undergo this for for our patients improvements and functional cross in six minute walk improvements in RV function, tr chemo dynamics quality of life. But patients do need to remain on lifelong anti coagulation. Now what if a patient is deemed inoperable believe it or not, the guidelines say, are you sure in other words and and this I think speaks to some of the youth of the field. Um but if there if a patient is deemed inoperable for some of the reasons we talked about before, then the answer is send them to a really big C. Tech program to be short because you might be surprised at the degree at the age and the B. M. I. And the renal function and the distal disease and the comorbidities that they might be able to take on. And I've certainly been uh lucky to learn a lot about that. And my program today will take on much higher risk patients than I did six years ago. For for good reason. I'm proud to say we have a 0% mortality over the last year in our P. R. P. T. Program and we take some of the highest risk patients from around the country. Um, and that comes with a lot of, a lot of teamwork and a lot of effort. Um, so this is just a cartoon showing what sort of proximal versus distance disease might look like, that kind of pink outline on the, on the images there. Um, and I mentioned already the distal disease comorbidities or ph being out of proportion to the thrombin bolic burden as reasons for patients to be deemed ultimately inoperable. Now, some semantics because these surgeries are really fun and really cool pictures come out of this. So this is a cute clot that comes from a pulmonary embolism to me. So a pulmonary embolism to me or thrombin ectomy, this is red, fresh acute clot. I'm sure you immediately recognize we've all seen that that worm going across the P. F. O. That gives us all small chest small amounts of chest pain When we're looking at the echo before these patients go to the O. R. So this is bilateral acute pE pE with embolism transit um and an emb elect to me now. PTE pulmonary thrombosis endarterectomy. It's different. It's an entirely different surgery and the material that's coming out is entirely different as well. These are just a few examples of patients that we've had and I just show show it to really demonstrate this is chronic disease. It's not really clot, it's scar material fiber and rubbery adherent to the vessel wall. And it varies so much in terms of unilateral, bilateral proximal distal. I would also encourage you don't just look at the amount of material from a distance. But what is the depth and the thickness of the material that's removed. That's how you know, it was a thrombosis endarterectomy and not just an endarterectomy, you will not have the same human dynamic and clinical result otherwise. So lots of variation that really fresh red looking stuff in the big clot sections. It's not acute clot, it's it stasis clot that happens when you have a large vessel low bar a proximal segmental complete occlusion. So hemo dynamic risk. Um the right heart cath of course is critical in the diagnostics. You can quantify right heart function that way. But also it's notable that if you have severe ph the outcomes are worse in terms of operative risk, the severe degree of PBR elevation. So now now post up. What about ph after Petey? How common is it? How do you even define it? What's significant? What do we do about this? This is one of the most common questions I get from referring doctors around the country. I wanted to share with you some of the data about this. So this is Coming from the folks out in San Diego who have really taught so many of us for decades on this. Um they're the biggest program in the country for CTF. We're the second biggest program in the country for C tough at temple. This is looking at 500 patients that they had and you can see their overall kind of human dynamic values in those patients. Now you'll also notice. I just I'm gonna give you just the highlights here. Most of the patients here as you can see had Proximal disease. So type one or type two disease. So that's the patients that they were looking at. And by definition these are the post PTE Human Dynamics I've highlighted by definition they're, on average their average values did have residual pulmonary hypertension. This is quite common. This is data coming from the U. K. Um Hundreds of patients. Pre op dynamics on the left three months post up by definition mean pulmonary pressure and PVR also, on average there is some degree of residual ph but you're noticing I hope the delta and the difference from pre op. So when we're defining ph post P. T. It's not just pure. What are the numbers in terms of maybe what that significance might be now in those patients from the same cohort. Those that had persistent ph on the right compared. And they defined it here with in this graph with a mean pressure greater than 30. Looking for really significant ph the functional class was on average, much much worse in those patients. So that's not a surprise. But you can see more patients had a functional class three relative to functional class too. And those that were that had a lower mean pulmonary pressure post up. So maybe there's some significance there in terms of what that means for the patient. They did look at survival over time. It was not statistically significant between the two groups. So that's interesting. Maybe we're just talking about maybe a morbidity rather than a mortality at five years or so. Maybe there was a separation of curves but not significant here. Just a suggestion. Now this is UK cohort a bigger group of patients. And again, looking post up mean pressures by definition and PBR by definition high compared to pre op P. T. But still quite a significant delta from the pre op. But what they did here, this was really nice. They they looked at these continuous variables and said, listen, maybe the threshold for what's significant clinically is not how we define ph in general, but post P. T. E. P. H maybe needs to be defined differently. So it's worth noting when you had really significant residual ph here, main pressure greater than 38. The PVR greater than five would units or 425 dimes. Now we're seeing these are survival differences, long term mortality differences. And it's really important to note that the mortality again, it's related to heart failure. And so no surprise that that cardiac index when it's really quite reduced, also made a difference in terms of mortality. So, a suggestion for the severity that that matters. I wanted to share some of our initial data from our program. This was a few years ago looking at our pre and post op human dynamics. So I'm happy to report all of these are statistically significant indifference from pre to post up a very similar delta in pulmonary pressures. By definition normal pulmonary pressures and normal pulmonary vascular resistance. Post out from P. T. E. And this is just a graph showing pretty much any kind of human dynamic parameter. That's not in the table. The pulmonary artery compliance cardiac index. Also with statistically significant improvements from pre to post op. We also looked at um functional class that things that matter to everyone. Average functional class reduced significantly six minute walk went up by 92 m. Um As you may know in most of the PPH data? The cut off of 30 to 35 m is thought to be clinically significant. That has led to most of our drug approval. And BNP dropped by 80%. And then you can see J. V. P. Also fell and oxygenation improved. And then this is our improvement in N. Y. H. A functional class thankfully much fewer patients functional class for a dramatic improvement in patients being functional class one after P. T. And we're echo based ph cardiologist. So um we follow echoes very close mostly and this also shows improvements. Any parameter that you look at regarding great heart size structure function. Doppler features also had a notable improvement including RV two Lv size RV function by fractional area change. And Doppler features that correlate with stroke volume and pulmonary vascular resistance. So these are just some picture examples of of our program this paper like I said came out earlier in our program's history. As of now we've done 335 pts. We average about 50 to 60 a year. Some weeks we have three in a row. Um We're continuing to try to serve as many as we can. Um So kind of summarizing residual ph after PTE it does seem to be quite common. Why is that the case. It makes sense that there is disk disease that might be limited to access to remove all of it chronic vascular remodeling. So how do we assess from that? What what predicts outcomes here? I won't read all of that too. But it summarize some of the features that we've looked at and think about in ph and what can we really predict? So I'll just jump forward to show you this is an example of a patient immediately post up in the ICU. The P. A. Catheter is in for a couple of days. This is a recent patient of mine. I've listed all of the clinical factors that we that you all know that can impact pulmonary human dynamics in the ICU. Immediately post up hypoxia, lung injury and elect assist the use of tropes and basil active agents inhaled ph therapy, arrhythmias, anemia. There's so much that can affect it. So what we do in all of our patients no matter where they come from is we reassess them 2-3 months clinically in the office. Post up we offer two or will guide their referring doctors and it's looking at so many features the history. Think many things post up even in a few months can affect functional capacity anemia. The iron deficiency and the and the other conditions. The six minute walk test is helpful in ph but we're looking not just for distance but what's the blood pressure response to exertion at the end of the walk to reflect stroke volume. What's their oxygenation? Physical exam features of right heart strain or dysfunction or failure labs be end P. R. N. T. Pro and then the echo features. I want to get into a little more detail here we do an echo on everyone post P. T. E. At three months and we're looking for features on the top is as a nice post PTE outcome on the bottom is someone that might have still significant residual ph what's that? RV two L. V. Ratio. How much tr is there? What's the base to apex relationship? You can see it's really abnormal here. That wide open RV. A. Pickle angle. Is there septal flattening insistently that correlates with that high PVR that notch in the R. V. Outflow track that also correlates with the high PBR and very importantly RV function. These are the things that we're focusing on post PTE to assess for residual ph you'll notice the most important factor is not to the R. V. S. P. Estimation because that alone doesn't give a sense of clinical significance that might warrant intervention. So let's shift gears a little into B. P. A. This is um balloon pulmonary angioplasty really reserved for smaller segmental and sub sub segmental vessels. This is our cartoon sort of showing how that balloon gets into those distal vessels. These are smaller than coronaries. They're tiny tiny tiny compared to coronaries. So most coronary docks want nothing to do with this understandably. Um But I really admire our team that does my two partners Dr Riyaz bashir doctor Vlad, laughter or increase. They've done hundreds of these now. Um And this is what we're going for. You're not removing clot but you're pushing it to the edge of the vessel walls to try to achieve greater perfusion. Now, this started in 1988. I'm going to give you a whirlwind story of the B. P. A global story to just give you some perspective, 1988 that started But it was not safe. The outcomes report too many patients needed intubation. They had re perfusion in Dema and mortality. So the practice really fell out of favor for many years. But it re emerged about 10 years ago. Thank you to our colleagues in Japan for really moving this forward that we've all learned from and my team has gone there to study and learn from them. But it was it was a safer technique they used IV's to help guide what was being done in the in the Cath lab to try to minimize the risk of vessel tear and injury. And I'll just highlight the significant points that thankfully in this experience now over the last 10 years, lower complications compared to the initial report in the eighties. This is just some examples of vessels that might be prime for BP A. These posts these ring lesions and post hypnotic salutations, tortuous lesions. This is just some examples showing how inter inter vascular imaging with optical coherence tomography or CT or FFR with the pressure wires. All of these different techniques are being used. We use FFR and angiography on every patient to help guide lesions that we should open up Now. B. P. A. Is done. If patients are inoperable, it can be done in conjunction with medical therapy and we have been doing it more and more in the last few years. If there's some degree of residual ph that's significant based on everything I described post P. T. It should be done serially. So multiple sessions and regions per patient using the guidance that I mentioned. But knowing that the risk can be quite significant of lung injury adama hypothesis. So I'll show you a couple of large centers from around the globe. Just some of the data and outcomes to hopefully make you a believer that there are really good potential here. And I'll go through this quickly because it's just some basic themes I want to show you. This is data that came from a japanese group 84 patients, 424 Bps, inoperable seats, all of them on medical therapy. You'll see really easily look at the trends in pulmonary pressures, pulmonary vascular resistance from initial to the end of the study, six minute walk distance going up significantly. Bmp falling dramatically. And I'll just highlight this theme that not just those outcomes but patients are requiring less ph therapy chronically after serial B. P. A. And less oxygen supplementation. These are things our patients like to hear it matters a lot to them, even a survival benefit over time over years complications, thankfully much less. So as experience has gone on in terms of hypothesis and the need for positive pressure ventilation. Although when I I read a lot of abstracts and kind of see data from around around the our world and um I will say that these complications are still quite high. Um I think in young centers as we learn to do this so we don't we don't take it lightly at all. Another group from Japan similar study looking at B. P. A. And just highlighted the similar improvements in functional Class walk BNP and human dynamics. Similar improvements in needing less therapy, medication and oxygen and a similar rate of complication post G. P. A. This is the french group thousands of B. P. A. Sessions. These are huge amounts of data looking at globally and even in the most recent kind of 21 months so like kind of their more contemporary experience and the human dynamic improvement is dramatic. The mean pulmonary pressure and PVR reduction just from BP alone in conjunction with the background therapy um complications also relatively small in the recent period. So a much safer experience. And this is some of our data from our temple program. We've done 210 Bps. Now we presented some of this at the CTF proceedings but also showing excuse me showing significant human dynamic improvements functional class six minute walk. Um, and we're hoping to continue to learn more and improve upon that even more. So that's B. P. A. In a nutshell, there's a lot to talk about. Their medical therapy is easily accessible to all of us. And this is ph medical therapy now in the CTF world we're talking about really what this is the soluble guana late cyclist stimulator that you're all familiar from the chest one study in the new England Journal Medicine for for CTF. This is what I've shown you here. It was also by the way in the same issue published in the Patent One study for pH so that was a big day for real. What about nine years ago in the new England Journal. But they took patients that had inoperable CTF and notably in this study, it was an adjudicated cohort, that expert CTF um centers and it looked at the data to deem a patient truly inoperable. And this made this study distinct from prior studies like the benefit trial and other historic medical therapy and Ceta. They showed a significant improvement in human dynamics six minute walk distance, six minute walk was the primary endpoint but also PBR Nt pro BNP and functional class. This is what led to the approval of in these patients now massive tent and I just wanted you to be familiar with. It's not approved for an indicated for CTF. So I want to be clear about that. But I just want you to know about the study that was done. This is the massive Tintin trial. It's called Merit One. It was small, 80 patients, 16 weeks phase two trial. Um Really small. There wasn't improvement in PVR um and as well as six minute walk distance but it was small and there are limitations here. So not ultimately approved for the use in in cita Now these are some mimics um that are in the literature that you should know about when you're seeing an abnormal VQ or C. T. A. And you're wondering CTF always have on your radar, could it be a sarcoma? Could it be tumor emboli? We've seen that from tumors all over the body. It can really mimic CTF fibrosis, media stein itis. You might see some calcifications. Could it be in sight to thrombosis? So congenital heart disease. This is a big one systemic to pulmonary shunts with enlarged pulmonary arteries. That's just normal congenital heart disease. But those enlarged P. A. S. Are at risk for abnormal kind of not laminar flow and those proximal big vessels and there's a risk for for insight to stasis clot that can form. They don't usually have perfusion defects. That's how you can tell the difference. Star coin mimics often in many ways and large vessel vasculitis, particularly Takayasu. So there you're you're feeling your pulses everywhere. You're checking your satellite, doing your M. R. Angiography. Your angiography sort of of the abdomen pelvis to get some clues at that. So I want to just share. This is a feel good story. Every single person on this team takes care of distinct patients for a living. So this is just a quick video. A patient sent 57 year old gentleman. He had a P. T. E. With us. He had some residual um pulmonary hypertension. We opted to offer B. P. A. He's had four sessions. I hope this will play. Can you hear this? I hope this is him dr before doctor too. I love this. See you Tuesday at your follow up appointment. So I hope you can hear that. Okay I've shown you so many echoes and pictures of human dynamics and scans that I think we all share in the joy of taking care of distinct patients who then can find some relief as a heart failure cardiologist. It's the most satisfying form of heart failure that I've taken care of. And it's really been a joy. This is a summary of what we've talked about today. I know it's a lot in an hour. Um We've had patients from all over the country about 22 states. Come to see us at temple. Um And thank you for mentioning this earlier. We are starting a ph fellowship and would be happy to chat with anyone. Please spread the word and tell your friends are only five in the country and this is a field that needs more dedicated training. So, if you're interested, please don't hesitate to to reach out. I'm gonna stop there. Thank you so much for your attention, all of you. Um and I'm happy to take any questions that you might have dr thank you so much for a tour de force presentation, so many things to talk about and uh and what a comprehensive overview that you've given us and uh tremendous growth for the program. And we hope for similar growth in our program. Let's open up to the floor for any questions. You can either something to the chat or you can amuse yourselves and and ask directly. Uh and if no one steps forward, I'm gonna call people myself using the Socratic method. Hello, this is Gabi. Um what a wonderful, wonderful talk. Thank you. I have one question when you think that, like with the uterine fibroids, that uh that it's mechanical issues that cause the city, the clots in the pulmonary vasculature, is it also possible that its molecular mechanisms because they're in the uterus, um the disease process maybe releases side kinds um that causes the clots than in the pulmonary vasculature? Thank you. I think that's a great question. It's it's really thought provoking and it's certainly very possible. I I don't have a direct answer based on my knowledge of that to tell you. But I think it's quite possible. I also think that there is a phenomenon in patients who bleed and then stop bleeding and bleed and then stop bleeding. I mean we see this in G. I bleeders all the time that have an acute coronary syndrome and you're like, come on dude, like that's not, that's the last thing you could have right now. Um I do believe that there is some mechanistic molecular effect from the intermittent bleeding of another cause that that makes the body a little more prone to forming clots. So that's my personal theory. But I don't have data to support that for you Angela. I'm gonna step forward with a question here and this is the ignorance of someone who is a lung cancer doctor. I'm trying to understand given the beautiful pictures that you showed us of the surgical outcomes in patients who have P. T. E. Uh and the large amounts of this organized material for those who are not candidates. How is RIA cigarette beneficial to these people? What is it actually doing in terms of mechanism of action when you have these these large central conglomerations of fibrous material. Yeah, I love that question. So thank you for asking that you know, if a patient is inoperable, I'll start by saying it depends on why. So if they're inoperable because they have very distal disease that's not surgically accessible but there is a rumble anabolic burden. Those are the patients that respond the best to reassess because that they have diffuse pulmonary arterial remodeling and mechanistic changes that resemble just like a arterial vascular, you know, smooth muscle hypertrophy. And and um internal wall thickening and fibrosis, there's an overlap probably a ph and the changes in those vessels. So really what serves to be a pretty profound Visa dilator that can help those patients. But your question alludes to a patient population that quite honestly does not benefit. So if a patient is inoperable because they're not interested but they have proximal surgical accessible disease or they're inoperable because they have such severe a patient. I saw today such severe anti fossa lipid syndrome that they've had massive head bleeds and thrown beside a pina and it's just not an option to go to the O. R. But they have proximal, otherwise accessible disease. So it's surgical disease. But they're not operable if you know what I mean. Those patients do not benefit from a cigarette and in fact when you use it, this is this is based on my experience. But we've seen this so often when you use it, you get more of the systemic Visa dilatory effect out of proportion to any actual pulmonary vascular effect. And so the patients will tell you what I heard today twice in clinic when it was used by other doctors. You know, I was just really dizzy and lightheaded and I had a headache and I felt terrible and it's like, well of course you did because it's not going to affect bulky proximal disease. Now, a lot of patients are kind of in between that spectrum and sometimes it's worth a try. But you have to kind of understand that potential limitation if they don't have a great response to it. Just a quick follow up to the new England Journal Medicine paper that you presented showing the benefits of do that differentiation between the different types proximal middle distal. They did, so to speak, because the patients that were deemed inoperable, it was based on the imaging clinical, you know, assessment. So and and uniquely they had real c tough experts making that assessment. And so these were patients that really were not surgically accessible and their incomes. The potential for benefit additional questions from the audience dr chan if you're still on dr silica. Yeah, I actually don't have really a comment. I want to thank Angela for the wonderful, wonderful, you know, presentation. We have learned a lot and since that we do have a couple of fellows that are, you know, on the call. I wanted them to look up the article that just got published in pulmonary circulation about something that Angela mentioned earlier and that's very important. Uh the post operative management on the of the CF patients. So uh it's I'm actually so grateful. I read it with great pleasure Angela. It's uh it's it's a great guideline because frankly we we don't know exactly how to deal with those patients. and I found it, you know, really important. And adding tremendously. Thank you. Thank you. That's been an area that has been an unknown really for so long. And one thing I'm sort of proud of with our program is that we invite every patient for follow up and you know, putting yourself at the bedside is how you learn and how you observe for all of us. And so, you know, we are unique in our country, in that we are the biggest program that follows patients, not just in the ICU and to discharge, but outpatient follow up in the subsequent months and years even. And that's how we've learned. You know, it took years of experience to put that paper together. Um but it's meant to be a guide to folks because it is a it's an unknown area. So, thank you for your comment. But when I see something in the chat um Justin chan thank you. So my question following up, Chf patients when they are referred from all over the country, what schedule a follow up? How do you ensure that they're seen by experts? So that's great. Um we see everyone immediately post discharge from the hospital within 1 to 2 weeks. That's just like good quality post surgical and medical care. Um There's also a risk of pericardial effusion. Post up about a 6 to 7% risk of a hemorrhagic pericardial effusion in CTF and you don't want to miss it because some of them are gonna need an intervention. So that's also why we do that. So every patient gets an echo a limited echo and follow up with within a couple of weeks and then again at three months we'll invite everyone to come back. But not everyone can we totally understand that. It's difficult and so we work really closely with their local, it's not usually a CTF expert but if it's a ph expert then then that's someone we can partner with um and continue to manage them and three months we will do an echo office visit and accuse can I say Q. Scan now because of covid a VQ scan. But the V. Scans as you all know are not accessible everywhere. Um And that gives us a little bit of a sense of where we are now. Other questions. Um I have a quick one about D. P. A. So I'm old enough to remember when coronary angioplasty was just a balloon angioplasty and that's all that we had available and that has evolved dramatically over the last 30 40 years. Um Do you anticipate that B. P. A. Will also evolve so that we're gonna be thinking about B. P. A. Plus stents are correct. To me, all sorts of things that we would be doing through catheters that might ultimately compete with some surgeries. Some pp. It's a good question, you know, Overall my instinct is not in the same way. But I wonder the same thing. But what the reason I say that is because we're talking often about like two millimeter balloons. I mean such small branches and such small uh you know, equipment that putting a stent in there, just the practical, you know, the feasibility of that seems less, but you know, maybe I'll be proven wrong in 20 years and I'll sound like that outdated person. They didn't know what was to come. Um But there are some differences that would be limiting in that way um correct amis sort of similarly because it's not that, you know, it's not that arterial sclerotic phenomenon um as much as it is more of a, you know, smooth muscle hypertrophy lining clot. So the removal of that um is very difficult. It's just adherent to the wall and to remove it from the small branches so distantly is quite, it's not really possible and and quite risky. Um Yeah and and john um I see your question what culture seen work for post? Absolutely it does. Sometimes um sometimes that's not enough. And so a very short course of a predniSONE taper, like not like four or five days. Sometimes that can help to um clinical observation. Sometimes it's enough to but we're balancing things like their infection risk and their glycemic control and their fluid retention and things like that. Any other questions if there are other questions. My heartfelt and sincere thanks to dr for taking the time. I know she has another talk to give tonight, so it's a very long day for her, but we're incredibly appreciative of uh this amazing presentation and answering our questions and congratulations on the promotion of medicine. Thank you so much. Thank you all. Thanks for having me. This was fun. Thank you. See you all soon, enjoy a. T. S. I'm sorry to miss it this year. Okay. Thanks a lot. Bye bye, love. Bye bye.
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