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CHEST 2023 On Demand Pass
Pulmonary Vascular Disease Clinical Case Puzzlers
Pulmonary Vascular Disease Clinical Case Puzzlers
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Video Transcription
Good afternoon, everyone, and thank you so much for being here. I know the conference is winding down, everybody's rushing to their flights, and so we appreciate everybody being here. First of all, I would like to thank Dr. Sela and the ACCP for inviting me to take part of this exciting session and talk about my favorite topic, which is pulmonary hypertension. And what I'm going to try is not just define the pulmonary hypertension, but because our cases are related to the pulmonary hypertension, I'll try to kind of give you my gestalt or my approach of how to see that patient or how I see that patient. It doesn't mean that it's the right way or wrong way. Sorry, this thing is going without me. Sorry about that. So first, we're going to define pulmonary hypertension, and I would like to bring to your attention the fact that recently, we once again changed the definition of pulmonary hypertension. So we define pulmonary hypertension hemodynamically by mean pulmonary arterial pressure over 20 millimeters mercury. And we further divided into precapillary pulmonary hypertension, which is the PAH, or the pulmonary hypertension that we're looking for, that we're trying to find and trying to treat, and that is mean pulmonary arterial pressure over 20, pulmonary artery wedge pressure less than 15, and pulmonary vascular resistance over 2 Woods units. The next category is isolated postcapillary PH, that is defined as mean PAP over 20, with pulmonary artery wedge pressure over 15, and pulmonary vascular resistance less than 2. We have a combined pre- and postcapillary pulmonary hypertension, and we see these patients a lot. I'll admit that. Defined as mean PAP over 20, wedge over 15, but pulmonary vascular resistance over 2 Woods units. And exercise pulmonary hypertension made its way back to the definition and the category, and it's defined as mean PAP over cardiac output slope between rest and exercise over 3 millimeters mercury per liter per minute. The main difference that I want to bring your attention to is the change from 3 years ago or 4 years ago, actually, where we were thinking the pulmonary, or putting pulmonary vascular resistance over 3 in the definition, and now it's over 2. And that gives us opportunity or chance to establish diagnosis earlier and think about treating these patients earlier if they are so inclined, or we are so inclined. So let's talk about clinical presentation. So how do we see these patients? So we do see most common symptom that is seen in pulmonologist's office, and I'm sure you guys will tell that same to me, is a dyspnea on exertion, or dyspnea. And that is the most common symptom that PH patients present with. Over 70% of patients will present with dyspnea on exertion. Fatigue and exhaustion, dyspnea when bending forward, palpitation, much rarer seen hemoptysis, abdominal distention. And that maybe is something that we take very, very seriously because that is a sign of a critical impairment of a flow in these patients, and that kind of tells us that these patients are in trouble. For those of us who are studying for the boards, maybe, or in general practice, the rare symptoms that we sometimes encounter is exertional chest pain due to compression of the coronary arteries, hoarseness due to compression of the left recurrent laryngeal nerve, shortness of breath, wheezing, cough, increased rates of respiratory infections due to compression of the bronchi. Signs of pulmonary hypertension when we encounter these patients in the office include edema, cyanosis, enhanced systolic marmor of tricuspid regurgitation, right ventricular heave. Some of those are kind of fine diagnostic criteria, but again, they're quite nonspecific. What we don't want to see at the presentation or when we first encounter these patients is the signs of right-sided heart failure that include distended, pulsating jugular veins, abdominal distention with ascites and hepatomegaly, and significant peripheral edema. So how do we classify pulmonary hypertension? And I'm including still the classification from the Six Worlds Symposium because I think it is still valid, and the one adjusted in 2022 doesn't have much of a change for us to be very, very worried about it. So we have idiopathic PEH that includes essentially pulmonary hypertension without any identified cause. Unfortunately, it affects younger people, predominantly female, in a 2-to-1 distribution in their prime, and often in females of reproductive age. Familial pulmonary hypertension, important to know, especially because a few of the genes are identified, and currently we are actually having a drug that being in target for one of these genes. Sorry. I'm very sorry about my technical incapability at all. So the bone morphogenetic protein receptor 2, or BMPR2, is the one that is currently being developed as a target for the medication use. There are other genes that are still testable, but I really would like to bring your attention to BMPR2 because it's seen in over three-quarters of the patients with pulmonary hypertension, familiar type, but it's also seen in about 50% of patients with different other problems of pulmonary hypertension. Drug and toxin-induced pulmonary hypertension. There was an incredible session during this conference talking about methamphetamine-induced pulmonary arterial hypertension. It's still prevalent, not in the Northeast where we practice, but from what I hear, quite a bit on the West Coast. But aminorax and venfluramine, dexfenfluramine, the so-called appetite suppressant drugs, as well as chrysal meth, as used as a recreational drug, are still seen as precipitants for pulmonary arterial hypertension. I would like to bring your attention to the most common group in the PEH that is associated with different conditions. Connective tissue disease being the largest group of all, and of those, systemic sclerosis being the most common condition associated with pulmonary hypertension development. HIV is a very important cause also for pulmonary hypertension-associated condition, and I think we will be seeing it more and more because pulmonary hypertension develops in these patients along the course of their disease. We often say that it has to be more than about 10 years or so of the infection to develop pulmonary arterial hypertension. And I think with the current therapies available for the HIV patients, we will be seeing them living longer and therefore seeing more of the pathology. The important part of that is also to remember that patients with PEH associated with HIV die more commonly from HIV than from opportunistic infection, and that's something to stay with us as well. The most abundant group of pulmonary hypertension is pulmonary hypertension associated with left-sided heart disease or post-capillary pulmonary hypertension. So when do we start thinking about it so we don't work up everybody for pulmonary arterial hypertension? So essentially what we're looking at is the older age of presentation, presence of vulval or heart disease, and often comorbidity supporting the LV disease, essentially metabolic syndrome, including diabetes, hypertension, coronary disease, and obesity. Pulmonary hypertension due to lung disease and hypoxemia, separate group. Importantly to remember that right now, again, we're having a target or targeted drug for this specific group, interstitial lung disease associated pulmonary arterial hypertension has a specific drug available for that treatment. And we are trying to identify patients who have more propensity to have pulmonary hypertension. Those are the ones that have a lower oxygen saturation with their walk, lower distance of walking, patients who have lower DLCOS compared to their MDC, patients who have signs of right-sided heart failure. Group four, also incredibly important group because theoretically this is the only group that potentially could be cured because chronic thromboembolic pulmonary hypertension, if comparable, could lead to a full cure of the illness. Other pulmonary arterial obstructions not to be missed, including benign and malignant tumors and infections such as parasites. Pulmonary hypertension with unclear or multifactorial mechanisms essentially includes different plethora of diagnoses that we just don't know how to classify or we don't know how to approach them. Some of these, such as chronic hemolytic anemia, and we have quite a bit of, in our practice, patients with sickle cell disease, used to be classified as group one or true, true pulmonary arterial hypertension, reclassified, I don't know, it moves by itself, guys, I swear I didn't touch it. I'll vouch for her. Was reclassified because the degree of pathology there does not fit in one criteria and we cannot approach it. The other important condition that we as pulmonologists encounter quite a bit is certainly sarcoidosis. And as intensivists, I'm sure a lot of you will agree that chronic renal failure will be there as well. So how do we work up these patients? And I, again, apologize. All right. So EKG findings, again, something that demonstrates us that there is increased pressure, and most importantly, right ventricular hypertrophy or right ventricular strain. Presence of pupil monolay, right axis deviation, RV hypertrophy. What signs I look on the echocardiogram when I get my report and before I go to our cardiologist and ask them, plead with them to look at the echoes with me to get better understanding of their report. Enlarged right-sided ventricle, flattened interventricular septum, very important sign. Distended inferior vena cava with diminished collapsibility with inspiratory effort. Enlarged right atrial area, increased systolic peak tricuspid regurgitant velocity. And I always want to bring up everyone's attention that the number that we get on that echocardiogram report is an estimation from the estimation. We're using Bernoulli equation to calculate pulmonary arterial pressure, assuming estimated right atrial pressure. So it's not all in this number. It's all these criteria together that will help us with diagnosis. Obviously, we cannot do anything without imaging. Chest x-ray certainly is in the diagnostic pathway, as well as ventilation perfusions can, as mentioned earlier, that could be the only type of pulmonary hypertension with cure. So what do we do when we suspect our pulmonary hypertension? I wish I could say differently, but still right heart catheterization, the invasive testing is the goal and is the gold standard for the diagnosis. And with those, we will try to weed out PAH, or pre-capillary pulmonary hypertension, from the PH, or pulmonary venous hypertension, or post-capillary pulmonary hypertension. And based on that, we will hopefully go for the further diagnostic parameters, looking for these associated conditions that we could potentially treat together with treating pulmonary hypertension with targeted therapy. How do we decide on the treatment? The treatment nowadays really relies mainly on the risk assessment and the functional class of the patient. And if, let's say, 10 years ago, maybe even 5 years ago, we could still say, OK, I stabilized the patient. I'm fine. I don't need to worry about the patient. We kind of stabilized. OK, good. Nowadays, we are trying to get best outcome for each particular patient, bringing them from wherever they started to a lower potential risk. And I hope to convince you guys with that as well. So our functional assessment starts with WHO, New York Heart Association, functional class. And it's very simple, used by a pulmonologist and cardiologist, something we agree upon. So class one, patients does not have symptoms with ordinary physical activity. Class two, patients with ordinary physical activity developing symptoms. Class three, patients with less than ordinary physical activity developing symptoms. And class four, patients who experience symptoms at rest or patients presenting with signs of right-sided heart failure. I would like to bring your attention to several risk calculators. And there are more. And I just couldn't fit them on this slide. And I apologize for that. So we are trying. And we don't need to remember it, thank God, because there are calculators embedded into applications that we can use. And I think they're extremely friendly. And I really try to use it every time I see my patients in clinic, because it does give us a perspective on what we need to do for these patients. Because again, by plugging in all these criteria and getting a number spit out at you, we can qualify these patients as low risk, intermediate risk, or high risk. And honestly, our treatment should not stop changing till we reach that low risk criteria for whoever we can reach it for. So how do we approach therapy? Again, I'm bringing you back to 2019. And I kind of on purpose didn't include the 2022 guidelines, because I think these still to me make more sense. And I apologize for that. But to be honest with you, I'm not short selling you, because they didn't change that much. The most important, again, we are assessing the risk of the patient. And patients who are at low risk, we can consider giving them single drug therapy. However, in most centers, most of the patients will still go ahead with upfront dual therapy. And we'll talk about it in a second. However, if we are dealing with intermediate risk patient, there is no question that this person is in this day and age should be on one agent. When we're dealing with high risk patient, then certainly initial combination, including and current recommendation is stressing it out even more, systemic prostacyclin is very important. What is even more important that we don't stop at that, and in a short term, after about three months to six months assessment, and it all depends on your patient's progression, we got to reassess. Patients who reach their maximum potential in terms of the medical therapy should be referred to the transplantation centers as early as possible. And on that last slide, I really just wanted to bring your attention to available therapies that have now and didn't include the timeline. But if you think about it, 1991 was the year when Flolan or IV epiprostanol first approved. So right now, we have all these plethora of medications and a couple more in the pipeline for being approved that are available to our patients. So certainly, the science or science and art of treating patients with pulmonary hypertension moves quite slowly. And we still don't have a cure, but at least we have more to offer to our patients. Thank you. Thank you very much, Dr. Saleh, and thank you, everyone, for being here. Good afternoon. So I have nothing to disclose, but the objective of this talk will be to go over pulmonary vascular anatomy. In radiology, I always say, you have to know what normal is. If you know what normal is, then abnormality is easy to recognize, but it's very important to know what normal is. I'm going to go through the different types of pulmonary vasculature. I think this is probably the hardest thing in radiology to master, is the different types of pulmonary vasculature. And I'm going to go through a lot of images and show you examples of pulmonary hypertension, some aneurysms, and malignancies. So this is a typical chest radiograph, and I always say that if you haven't reviewed hundreds or thousands, you probably really haven't learned the anatomy yet, right? Anatomy is to be learned by looking at many, many x-rays and normal and variations from technique in patients' body habitus. And if you become very comfortable, then it will be easier to recognize what normal vasculature looks like. Now, normal vasculature is normal, but there are four different types of abnormal vasculature in the lungs that we encounter. One is called diminished or under circulation. The other one is over circulation or high output. Pulmonary venous hypertension, everyone is very familiar with. Colloquially, we call that congestive heart failure. And then pulmonary arterial hypertension that Dr. Minkin just talked about, and I'll show you some examples. So these are the four different types of pulmonary vasculature that we have to kind of recognize from the normal. The extreme one on the left side is under circulation. Next to it is over circulation. Venous hypertension, and then pulmonary arterial. I'm going to go through each one quickly. So here's an example. The left image is normal pulmonary vasculature. The one on the right side shows a big heart, but when you look at the lungs, the lungs are kind of dark. But when you look at them more carefully, you can see that the blood vessels within them are very, very small. And we would call that diminished vasculature within the lung parenchyma. So the way to explain the pathophysiology is that the blood is coming through the vena cava into the right heart, but then it's not going into the lungs. And over a period of time, if things don't go into the lungs, then the vasculature is going to become small. So if you have a three-lane highway, but you only have one car going there in a day, then you don't need three lanes. You're just going to need maybe one lane. So the body recognizes and adjusts. So this is called under circulation. And this is a classic example of a patient with Epstein's anomaly. They have a big heart described as a box-shaped heart. The defect is a congenital heart defect where the tricuspid valve shifts lower into the right ventricle. And the right atrium is enlarged. It sort of moves there and causing an outflow obstruction. Here is a different patient on the right side. You can see the right lung, the hemithorax, the right hemithorax is very poor or diminished circulation. This is a pulmonary angiogram showing contrast in the main and the right-left pulmonary arteries. But there is a large filling defect on the right side. And you might have learned this in medical school. This is described as the Westermark sign. When you have a large filling defect in the pulmonary artery, the blood flow going distally into the lung diminishes, so you get oligemia and Westermark sign. So in summary, when you look at a chest radiograph, and if you encounter a small pulmonary vasculature then that's called diminished circulation or under-circulation. And there's a long list of differential diagnoses. Most of them are usually in infancy, congenital heart disease. Tetralogy of Fallot is a classic condition that gives you this. And I showed you an example of Epstein's here. In an adult life, probably the most common is a central mass or tumor. If you have a central tumor that obstructs the airway and the pulmonary artery over a long period of time, then you're going to get diminished vascularity or shunting of blood away from that site. So here's an example. You can see the right lung. There's normal vasculature. There's a large low attenuation mass in the subcoronal region. That's a bronchogenic cyst. And you can see there is paucity of blood vessels or diminished circulation on the right in the left lung. So that's under-circulation. The second circulation is high output or over-circulation. The left image shows normal vasculature. But on the right side, it's a little subtle, but the blood vessels are kind of big, kind of fat. I shouldn't use that word, but they're big. But they're very sharp, and that shouldn't be the case. And what that means is that there is over-circulation. Over-circulation means that the blood is coming from the right side, going to the right ventricle, going to the lungs, returns to the left, and then comes back to the right, and then again goes to the lung. So the lung is encountering a lot of circulation over a period of time. So now if you just have one lane highway, you're going to need three lane highway because the blood is going through that circuit over and over to accommodate that blood. And that's called over-circulation. And the classic conditions that do this are shut. So patients who have ASD or VSD will have over-circulation. They have bigger pulmonary arteries within the lung parenchyma than normal. So you can see this patient had ASD, left side, and after repair, you can see the blood circulation has returned to normal. And you certainly want to do this before the patient develops Eisenmenger's physiology or reversal of the shunt. So in over-circulation, the central pulmonary arteries are big. The pulmonary arteries are huge. And the classic conditions are shunt. But other conditions like metabolic diseases, AV fistulas, Osler-Weber-Randu disease can also have similar appearances. This everyone is very familiar with, so I won't spend too much time. Pulmonary venous hypertension, right, caused by chronic left heart dysfunction. Blood backs up into the pulmonary veins, so you get the classic cephalization. Fluid sips into the interlobular septa. You get curly B-lines. Along the peribronchovascular interstitium, so you get indistinct vasculature. Then fluid builds up into the alveolar spaces, and you get opacities and pleural effusions. So I know everyone is familiar, so I won't spend. But here are a couple of examples. The left side image shows very indistinct blood vessels after treatment. You can see how the vasculature has returned to normal. You can see the nice, crisp blood vessels. There's no more fluid in the lymphatics. And then finally, pulmonary arterial hypertension. You can see on the left is normal. The right side, the main pulmonary artery is huge. The right pulmonary artery is also enlarged. Similarly, when one looks at the chest radiograph, and can you see my pointer there somewhere? Here it is. Okay, so there is a trachea, and the aortic knob sits right above the carina on the left side in most patients. Below that, there should be nice convexity. If you ever see a convex border, that means that the main pulmonary artery is enlarged, right? The main pulmonary artery arises from the right ventricular outflow tract, where it's really hard to. I'm not drunk. My hands are not steady, but it should be concave underneath the aortic arch, and this is convex, so it's a big PA. And then the blood vessels, as they descend into the lungs, become sharply very small. So the central vessels are big, and then they become kind of prune. So again, just uniform decrease in the number of vessels, centrally they're engorged, and the causes that many, Dr. Minkin went through, the classification, the who. I like to approach it from the educational point of view. I break it down into pre-capillary, capillary, post, and then shunt as a separate, so it kind of helps me organize my thought process when I review cases of pulmonary vasculature in this manner. And of course, in the pre-capillary, thromboembolic disease is one of the more common things that we see. Primary is sort of diagnosis of exclusion. So I'm just going to go through some examples. So here is a patient. You can see the main pulmonary artery is huge, the right is huge, and the left pulmonary artery, which is best seen on the lateral radiograph, and here it is. So the main right ventricle is most anterior cardiac chamber, the output track comes out, and the left sort of continues above the left bronchus, and you can see how big it is. The main is huge, and the right is huge, and then the blood vessels sort of taper very rapidly into a small caliber. So big pulmonary artery. On CT, it's much easier to recognize. You can see the main PA is so much larger than the aorta, the right atrium, right ventricle are big. But the right ventricular myocardium has also begun to hypertrophy, which is not a good thing. And then sometimes in the lungs, you will see some areas that are loosened and opaque, what we call as mosaic attenuation. And that's more so seen in chronic thromboembolic disease, but sometimes in primary pulmonary hypertension, we may see that as well. A different patient, again, showing centrally the main PA is huge, right is huge, and then we're seeing this sort of patchy opacities peripherally, and CT makes it much more clear. The main PA is humongous, we see eccentric filling defects, and those opacities that are peripherally situated are infarct, so this is a patient with chronic thromboembolic disease. A different patient with similar findings. The lung images show sort of opaque and loosened lung, classic mosaic attenuation, and on the soft tissue windows, we can see the big PA. We can see some eccentric filling defects, some webs. And then you can see how the blood vessels in the left lower lobe are large, but there's more pruning of the vessels in the right lower lobe, all from chronic thromboembolic disease, and the resultant effect on the heart. The right A is big, right ventricle is big, and there is severe hypertrophy of the myocardium. A different patient who shows a big main pulmonary artery, right and left are big too, but then we're seeing this sort of thin lines, perpendicular lines in the costophrenic angle now. All of you kind of know to recognize this, right, learned in medical school, these are curly B lines. But patients with pulmonary hypertension really shouldn't have, you know, curly B lines, or the look of pulmonary venous hypertension, and CT here, we can see that too, right, these lines. Anyone with hypertension and appearance that looks like venous hypertension should think about venocollusive disease, so this is a patient with pulmonary venocollusive disease. Here's a different patient again, big pulmonary artery centrally, sudden pruning, CT shows same features again. But when we look closely, we can see that this patient, the blood was injected in the right side, always is. The contrast is now moving from the right atrium to the left atrium, so they have an ASD. But unfortunately now there is reversal of flow. So those are some examples of the pulmonary vasculature and pulmonary hypertension. More weight, pulmonary artery aneurysms, we see them every now and then. Catheter-related complications are rare. Most of the time they're catastrophic, but every now and then they'll come to us. Infections also are rare, but any infection can lead to a pulmonary artery aneurysm. The classic one that was described in the literature is a rasmussen's from TB, and they all appear as a nodule in imaging. So here's a patient who came to the ER on the left side with dyspnea. They put in a Swann-Ganz catheter that same day, and you can see that there is a large opacity in the right mid-lung that developed right after the Swann-Ganz was placed. And the patient had some hemoptysis, and they were okay after that. And on CT you can see that they have this big pulmonary artery pseudoaneurysm. It's about as big as the aorta. So this patient happened to survive. A lot of them don't do well at all. Here's a young patient who came in with pelvic inflammatory disease. She, as a result, developed multiple nodules, some with cavitation. This is her septic emboli. On the abdominal portion, we can see that there is a filling defect in the IVC, thrombophlebitis. Two weeks later, she developed some hemoptysis, so we repeated the CT scan, and you can see that she has developed a large aneurysm of the left lower low pulmonary artery. That's about as big as the aorta. And she went on to get angiogram and then embolization of it. So these are some rare conditions, but they do occur every now and then, so one should be familiar. And then, finally, tumors are rare of the pulmonary arteries. We always have the hardest time differentiating clots from tumors. But we found that when we do suspect, so here's the patient who has this sort of eccentric filling defect along both sides of the pulmonary artery, the main pulmonary artery, people often recommend cardiac MRs to help to see if there is. But I find that that is not very helpful. Cardiac MRs never work out well, no matter what. But PET scan is actually the best way to tell. And you can see that there is uptake in that lower attenuation area peripherally situated in the main pulmonary artery, suggesting that it is tumor as opposed to a bland thrombus, which should have no uptake at all. And here's another patient who also had a large sarcoma in the main pulmonary artery and has metastasized as well. So in a short period, I kind of went through probably one of the hardest topic in chest radiology, which is the pulmonary vasculature. It's not easy. Hopefully, I helped you a little bit with that. So with that, I'll end. Thank you very much. Thank you. We've made it to the last of the puzzlers this year. We'll see you in Boston next year, hopefully. So I'm going to cover some of the vascular disease pathology. But I want to emphasize that if you're suspecting vascular disease and you've done a surgical biopsy, please let your pathologist know that you are suspicious of vascular disease because it's often ignored. I call it one of the minimal change diseases. And an alternate thing that we'll go over in a second is the dual vascular supply of the lung. So years ago, Drs. Simons and Chaldress did a study that they titled gorillas in our midst. And it was a study of inattentional blindness, which said that if you're focusing on one topic or subject, in this case, passing the basketball, the subjects wearing white shirts, you were supposed to count how many times they passed the basketball. In the video, in the middle of it, a gorilla walks out and pounds its chest. It was their grad student, actually, in a gorilla outfit. Not a real gorilla. Do not be scared. And then they walk off the screen. And at the end, they say, how many times did they pass the basketball? And the observer goes, oh, 13 times. They go, did you see the gorilla? And the majority of the time, they say, what gorilla? Now, this has been done in radiology as well, where they say to the radiologist, can you please find any solid nodule greater than a centimeter? And then they show them the CAT scans. And they go through their 75, whatever, slices. And at the end of it, they said, well, did you see the gorilla? And you can see that the gorilla is here. And the majority of them, of course, missed the gorilla. So the same thing happens in lung, where most pathologists are looking at alveolar spaces for filling, alveolar septal thickening for fibrosis and masses of tumor. They forget things such as airways, vessels, and the pleura. So it's important to kind of point out that you need to be focusing on the vessels as well. Let's talk briefly about pulmonary infarction. If you block the pulmonary artery, it's going to make this classical wedge-shaped area of alveolar filling by hemorrhage, which is weird. Because in most organs, if you occlude the feeder artery, you get this blanched white appearance of ischemia. And the reason for that is when you block this, the lung becomes partially necrotic there. But the bronchial artery is still feeding the bronchi, draining from the bronchial vein back to the pulmonary vein. And then you get retrograde flow back into the capillaries. And that's what causes that hemorrhage. Now, strangely, though, if you occlude the pulmonary vein, you do get ischemic necrosis, usually as a nodular look just off of the pleural surface. So here's a classical example. I forgot to put in Dr. Rosen, but this is from his Flickr account, which I've been promoting all day today. So filling of the vascular spaces by red blood cells. And often, you lose the cellularity of the normal alveolar septa, as opposed to a pulmonary venous infarct, this from sclerosing mediastinitis, where you have this rounded area bound by granulation tissue, kind of a healing reaction. And then this just area, if you do an elastic stain on this, all the alveoli jump out at you. And you're like, whoa, this was actually lung tissue. It's not some big necrotic infection. So pulmonary arterial infarct, causing a wedge-shaped hemorrhagic nodule, pulmonary venous infarct, a rounded nodule of ischemic necrosis. Now pulmonary hypertension, and I put primary there, but pulmonary arterial hypertension is probably a better description here. We can divide it up into several categories pathologically. So there are some cases where you see the classical plexiform lesion, these glomeruloid bodies. There are some where you have what looks as though there's a thrombus in there. It could be that it arose from a thromboemboli or could be in situ thrombus. What you end up with is this intimal obliteration with little web-like areas of recanalization in those. And then you can just have bland thickening of the pulmonary arteries, what we just call medial and intimal thickening. You can separate these out often on just the H&E stain. But I always get EVG stains or some elastic stain to help me out to tease these out, just because like Dr. Shah was saying about radiology of vascular diseases, pathology of vascular diseases is really complex. And I want all the help I can get in terms of tools. We've already talked clinically about the various things that can cause secondary pulmonary hypertension. Here's what it looks like pathologically in the large arteries. So the large arteries, we're basically putting an increased pressure into a low pressure system in the thorax. And so we end up with accelerated atherosclerosis in the walls of these arteries. So this looks similar to what you'd see in someone with bad hypertension in their systemic arteries. We have thickening of the intima. And then you can see this pale area here. If we zoom in on that, we can see that there's accumulation of lipid-filled macrophages here. And that's from the cholesterol that's kind of been deposited here. This is an atherosclerotic plaque within the pulmonary artery. In the smaller vessels, as we go more distal, this is a classical plexiform lesion. It's as though the vessel blew out a sidewall and then tried to recanalize and repair it. And you end up with this tangle of endothelium. So here's one example. Another example here, where we can see the artery with the plexiform lesion next to it, these small, intertwining, I don't know what you'd say. Sometimes people say glomeruloid, because it looks like a glomerulus in a kidney. And then this is one of my favorite ones from an early case we transplanted in my career. And you can see the vessel. And it just blew out and then recanalized. This is a classical plexiform lesion. In pulmonary veno-occlusive disease, we see sclerosis of veins. And in some of the major textbooks of pathology, it'll be these large veins in the interlobular septa. But I'll tell you, in my experience, the majority of these cases are in smaller post-capillary venules, which are more subtle. But when you do an elastic stain, it's just this rounded thing of elastic. And the intima is just completely obliterating the lumen of these vessels. You often will see, as a side effect of this, upstream effects from the increased pressure within the alveolar septa. So you might see interstitial thickening from either edema or hypercellularity, sometimes from the capillaries proliferating, pulmonary capillary hemangiomatosis. And you can see leaking of blood into the alveolar spaces with macrophages coming in, siderophages in the alveolar spaces. Here's a patient that we transplanted. And we can see it's kind of, this isn't a great picture. We can see the alveolar hemorrhage fine. We can see this budding. But strangely, that's actually a collateral that's formed off of this pulmonary artery. And then here, we can see obliteration of what was a post-capillary venule. And when we do the elastic stain, it's just completely filled this intimal hyperplasia with a little recanalization. Now, Dr. Minkin mentioned that you can occlude vessels by things other than thromboemboli, for example. So we could have tumor going to the vessels causing occlusion. We could have so-called intravenous talcosis, where patients are injecting crushed pharmaceutical tablets. Here's a patient with renal cell carcinoma. And we can see these little, the lung looks completely normal. A lot of pathologists would just sign this out as normal. But then all of a sudden, we see these two things like a dragon's eyeballs looking at us. I don't know, that just popped in my head. We can see some tumor floating within there. And this stained up for renal cell carcinoma with various markers, such as RCC and PAX8. Another case, this was signed out as a necrotizing granuloma. And they did infectious stains. And they were negative. But the weird thing about this case is that it wasn't a granuloma with giant cells around the periphery. This is granulation tissue. This is a venous infarct. What's obstructing these veins? Well, if we do an elastic tissue stain, we can see the vein here, the inflammatory cells. And in that cell, that's squamous cell carcinoma, which was unfortunately just about a centimeter deeper from where they did the wedge. It was a dumbbell-shaped mass. And they took the wrong dumb instead of the bell, I guess. Another case, this guy was a bodybuilder. When I told the doctor that he was crushing pills and injecting them, he said, nonsense, he's a health nut. And I'm like, no, I'm not asking if he's injecting. I'm telling you that he's injecting. And it turned out he was getting human growth hormone from Mexico in the black market. And sometimes it came as a powder, sometimes as a liquid. And he normally injected it intramuscularly. But there were several times where he injected it into a vessel. And this is what ends up happening. We can see the vessel here next to the bronchus. So here's our bronchus next to the pulmonary artery. The pulmonary artery is filled with this crushed material. It's composed of microcrystalline cellulose, a common filler. And then crospovodone, which is the excipient that causes the drug to dissolve at a normal rate within the stomach. So there's the giant cell reaction to the microcrystalline cellulose, which is highly polarizable. And then the crospovodone, the filler. So vascular disease, commonly missed if subtle. And please alert your pathologist if you're concerned about vascular disease. And with that, I'll finish. Thank you for your attention. Thank you. OK. I could think of no better segue. You have the clinical, you have the radiologic, and you have the pathologic. So we have two great cases. And again, that's the barcode for questions when they come up. So the first case comes to us from Penn Presbyterian Medical Center. Unfortunately, the person who submitted the case could not be presented. So I'm happy to say it will be presented by one of our residents, Dr. Amanda Warren. Amanda, welcome. So for our history, we have a 60-year-old female with Eisenmanger syndrome, pulmonary hypertension, oncelexipag and macetetin, chronic RV systolic heart failure, hypothyroidism, BCC, status post radiation therapy complicated by radiation pneumonitis, and secondary malignancy of the right axillary lymph nodes, status post dissection, and restrictive lung disease. She presented with acute on chronic hypoxic respiratory failure. On physical examination, she had a moderate increase in her work of breathing. And her physical findings were notable for a loud diastolic murmur heard in the left upper and left lower sternal borders. She had notable right ventricular heave, and her lungs were clear on auscultation. She had a palpable large liver with tenderness present. Her extremities were warm, and she had no edema or clubbing. In the ED, her saturation was only 50% on four liters, which was her home oxygen. But it increased to 50% to 60% on 100% non-rebreather. Her VBG showed a pH of 7.33, 51-14. And she was placed on BiPAP at that time, 30 over 15, with FiO2 of 100%, with stats that improved to the high 70s to the low 80s. On labs, her creatinine was 1.05. Her BNP was elevated at 5,000, I mean, sorry, 7,583. Her hemoglobin was 17, and her RNR was 1.7. And again, we'll have Dr. Shah discuss the imaging. So we have a couple of plain films. And on the x-ray, you can see, one see my right? Here it is. Yep. So the right main pulmonary artery is very large. The heart is very, very large. The aortic knob, which we normally should be able to see, it's kind of hard to see. But we do see this extra bump. I presume it's the main pulmonary artery. That's big. The blood vessels are dilated centrally. And then they taper suddenly, and they become prune. We don't see anything else in the lung. Another just similar radiograph. The lateral is helpful. You can see the heart is big. And the lateral radiograph is really the best view, in my opinion, in telling cardiac chamber enlargement. And you can see the right ventricle is the most anterior chamber. It really has no place to grow behind or sideways. So when it does become large, it kind of grows in the retrosternal space and becomes really big here. And you can see that's the output track. And this is the main and then left pulmonary artery. They're really huge. And the right is big. So right ventricle is huge. Main right and left are huge. No pleural effusions. Lung parenchyma, the vessels are big, centrally pruned. And then we have a couple of CT images. This one in the right upper lung just shows minimal push radiation therapy changes, which a patient had for breast cancer. But the lung parenchyma itself looks OK. There may be some mosaic attenuation. Kind of hard to tell, but it's OK there. And then this is the next image. And this is, I can't say the phrase, but it will arrest me. Mother of all. I've never seen a pulmonary artery that huge. That's like humongous. That's not the stomach. It's humongous. And even the pulmonary arteries, which are paired with the airways, are just huge. So in summary, these big pulmonary arteries, pulmonary hypotension, hard to determine. Thank you, Dr. Shah. Some really interesting images. And just if I could go back one second. Many of our residents and fellows don't know what that is. That is a lateral chest X-ray. And I'm so glad you brought up the fact. I mean, there's so many things as a pulmonologist we don't have Dr. Shah's knowledge. But you could look at the retrosternal space. You could look at the paravertebral gutter. You could see the minor and major fissure. And it's so disconcerting to me that nobody, or just about nobody, looks at lateral chest X-ray. So thank you so much for bringing that up. OK. So let's get to our first interactive question. What do you want to do with this patient? A, you want to do a surgical biopsy. B, do you want to do a bronc with a BAL and a transbronchial? C, do you want to repeat a CT chest in three months? Or D, none of the above? This may be the first one I think everyone is in unity for the whole session. Not quite. Not quite? No. You're going to have to ship that scanner to the graveyard, I'm afraid. OK, let's see. Dr. Jones is cheating. He's looking at the responses before I can. All right, so we have a couple who wanted to repeat a CT in three months. We have the majority who wanted to do none of the above. And we'll see what Dr. Minkin thinks none of the above is. For me in this case, it might be call someone for end of life care. No, transplant. Yes. Although what isomingas, I don't know. And surgical biopsy. So Dr. Minkin, what do you think? Run us through this case. Super challenging. I honestly don't know where to start because, again, we're dealing with someone who has numerous medical conditions in addition to the severe pulmonary hypertension. So hard to say where to start, honestly. I do think I would have to agree with Dr. Sela that palliative care would be very important. And we should start this conversation, as painful as it is, on the presentation for that person. I think we have to think through here, again, going back to the presentation. She comes in. She already has chronic respiratory failure in addition to numerous medical issues, including issues outside the pulmonary system. But she does show us findings of right ventricular failure. We see the radiographic findings of ginormous right heart and gigantic right pulmonary artery. We're also seeing signs here that she has incredible degree of shunting because this lady is hypoxemic at presentation. We put her on non-rebreather. She's essentially not changing. And now we are using non-invasive endotoxic support with only marginal improvement in her oxygenation. So again, I would agree that none of the above is appropriate in our choices here. But I think we may need to kind of tease out what we can offer to that person, apart from saying we cannot offer anything. And to do that, we probably are forced to employ right heart cath because we don't have another way to measure what's going on exactly and try to see if we could reverse this condition or at least palliate this condition temporarily. So for the rest of her hospital course, we collected cultures. She was given 500 ml of LR and admitted to the MICU. At that time, she was still on BiPAP 25 over 10 with 100% FiO2 with saturations in the 80s. She was treated empirically with three days of azithromycin for possible community-acquired pneumonia versus post-obstructive pneumonia. She was supported with the BiPAP, inhaled a propresinol and was not a candidate for VV or VA ECMO. And she was considered for ultimately a transplant evaluation. She then had a right heart cath which revealed severe pulmonary hypertension. Her PVR was 8.7 Woods units. She had an RA pressure of 10. Her pulmonary capillary reg pressure was 11. Her PA pressure was 60 over 26 with a cardiac output of 3.11 and an index of 2.09 with evidence of bidirectional intra-arterial shunting with a mixed venous O2 sat of 59% and a PA O2 sat of 68%. Her pulmonary capillary O2 sat was 99.7 and her non-invasive arterial O2 sat was 85%. Her baseline non-invasive blood pressure at that time was 105 over 75 and her hemodynamics were obtained. She was continued on BiPAP and inhaled Epopresinol and discussions were held surrounding goals of care. The pulmonary hypertension team was consulted and recommended possible intubation and evaluation for transplant. She was later started on IV Epopresinol and was continued to be diuresed. Her course was unfortunately complicated by atrial fibrillation and she was treated with Dagoxin and Amiodarone for rate control. Unfortunately, her hypoxia worsened and she succumbed to her end stage disease and ultimately died in MICU after PA arrest from refractory hypoxemia. So ultimately her diagnosis was a severe pulmonary hypertension secondary to Eisenmanger's physiology. Eisenmanger's physiology, the patient had a longstanding pulmonary hypertension secondary to Eisenmanger's syndrome and ultimately it's the development of pulmonary hypertension due to untreated congenital heart defects. In this case, the patient had an atrial septal defect which occurs in one to 6% of adults that are born with heart defects. Thank you. So a very unfortunate case. Dr. Minkin, it seems like it was managed well. She was, we saw the cardiac cath data on two oral background therapy with added inhaled prostacyclin and the numbers were terrible and with shunt present in such an advanced disease in the setting of multi-organ dysfunction, seemed like not much else could be offered for that person. Okay, thank you. Next we have, is Dr. Valahabasuya here? No, Dr. Niu. Okay, Amanda, why don't you come up and present this case too. Amanda, you are our star. This case comes from Rochester, by the way. Another interesting case. Thank you, Amanda. I'm Amanda's star. All right. So this patient's history, she's a 25-year-old female with a history of obesity and end-stage renal disease on dialysis who presented with worsening dyspnea. The patient was admitted at an outside hospital a few days ago for left-sided pleuritic chest pain and dyspnea and a CT pulmonary embolism study showed a complete left main pulmonary artery embolism with markedly reduced downstream pulmonary blood flow and without evidence of right-sided PE or right heart strain. She was ultimately discharged on a pixaban and presented again a few days later to an outside hospital with worsening dyspnea. On physical exam, other than mild sinus tachycardia, she had stable vital signs, including normal oxygen saturation on room air. Her exam revealed a pleasant young female. She was in no acute respiratory distress. Cardiovascularly, her exam was unrevealing with a normal P2 and her lungs were clear without any additional sounds. She had no swelling of her lower extremities and the rest of her physical exam was unremarkable. For her labs, they were consistent with anemia of chronic disease and abnormal renal function from her ESRD. Her coagulation labs were therapeutic on heparin and her troponin and BMP levels were normal. An ultrasound of the bilateral lower extremities were obtained and negative for DBT. Again, for the imaging, we'll have Dr. Shaw. So we have a CT scan with contrast and you can see this is the main PA, the left PA, and there is a large filling defect in the distal left main pulmonary artery. Hard to tell what this is, I'd like to see more images, but certainly there is a large filling defect. And here is another image, again, showing nearly complete filling of the distal left main pulmonary artery. We can see there is, even though we're not showing lung windows, but there looks like paucity of vasculature on the left side compared to the right. So nothing is really going to the, oops, sorry. Thank you, Dr. Shaw. Okay, our final interactive question, what would you do next? Who wants to do a surgical biopsy? Who wants to do a bronc with a BAL and transbronchial? Who wants to repeat a CT chest in three months? Or D, none of the above? Maybe we'll be universal this time, Dr. Jones. No, we're not going to be, because of me. That wasn't very nice. You're delirious after so much time. Okay, so let's go back. Did it not? Here we go. Here we go. So 75% wanted none of the above. Dr. Minkin will tell you what she thinks that none of the above would be. A couple wanted to repeat a CT, and a couple wanted to do a biopsy. Dr. Minkin, what do you think? I think the one who wanted to do a biopsy likes Dr. Jones and wants to keep him busy. I wanted to send him to San Diego to pluck those thrombi out. That'll be a big pluck in this case, I think. I think it's very fascinating. We are seeing someone who, we should say relatively healthy, but the patient is in stage renal disease. So definitely prothrombotic state. And she comes in with this really madly occluded left main pulmonary artery. However, all the exam findings not pointing towards pulmonary hypertension or right ventricular strain. We're not given the cardiogram data or so, but she's not really presenting as such. And from what Dr. Shah was referring on the CT, there was no findings of the enlarged right ventricle or marked enlargement of the right pulmonary or main pulmonary artery. So if this is clot, we have to think it's an acute clot. And then concern is how would she compensate for this clot so well, so much? So then the second question that I have in mind, do we need to worry based on what we see if this is non-thrombotic occlusion of the pulmonary artery? And I don't know, Dr. Shah, if you think by imaging, it looks more like a tumor occlusion or pulmonary embolism, pulmonary sarcoma. Could look the same. So it's hard to say, but I would certainly ask that question to myself. I would still, I'm sorry, Dr. Jones, I'm not gonna not do a surgical biopsy up front. I'm okay with that. Thank you. Anticoagulate her certainly. I think we should evaluate her cardiac status and evaluate her right ventricular function because we may end up planning a biopsy for this patient. I think I would do a PET scan. And then we'll do a PET scan to differentiate further. Thank you. And that's probably the best thing we can do. Okay, so for the rest of her hospital course, she was given a typical unilateral, complete left main pulmonary artery occlusion, making the artery appear dilated. It brought up some worrisome and rare pulmonary artery angiosarcoma. Put that on our differential. For her, her chronic thrombus was also another possibility, but the patient's complaint of dyspnea was rather acute and her CT chest a couple of years ago showed no evidence of pulmonary embolism, making a chronic thrombus less likely. Her fibrin sheath embolism from her dialysis catheter was also another differential. Ultimately, she was started on IV heparin and interventional radiology was consulted. Due to the risk of massive hemorrhage with catheter-directed thrombolysis, in case it was a pulmonary artery angiosarcoma, the patient underwent pulmonary angiogram and biopsy of the left main pulmonary artery soft tissue and a mass was taken first, which turned out to be a thrombus on the frozen section. And again, a few more images for Dr. Shah. Yeah, so this is a pulmonary artery angiogram that shows the catheter in the left main pulmonary artery. We can see a filling defect. And you can see there is some contrast going up into the left upper lobe, but not much in the left lower lobe. A large filling defect, I think that's all we can see from here. Great. After it was confirmed to be a thrombus, she received mechanical and pharmacological thrombolysis with little effect. A final angiogram showed persistent lesion, but with slightly improved blood flow to the left upper lobe. It was decided to treat the patient with anticoagulation for left main PE and to consider repeat CTP study in a couple of months. So there are a few things that can cause a main pulmonary artery occlusion. One being a large pulmonary embolism, a pulmonary artery sarcoma, aneurysmal lesions, or different types of vasculitis. Thank you. Okay. I just...
Video Summary
It's a bit unclear from the transcript, but it seems that the first case involves a patient with pulmonary hypertension, likely due to Eisenmanger syndrome, who presented with acute on chronic hypoxic respiratory failure. Despite treatment with inhaled prostacyclin and non-invasive ventilatory support, the patient's hypoxia worsened and she ultimately died in the ICU. The second case involves a patient with end-stage renal disease and a history of obesity who presented with worsening dyspnea. Imaging revealed a complete left main pulmonary artery embolism, and the patient was started on anticoagulation therapy. A biopsy was performed to confirm the diagnosis of thrombus. The patient's treatment included mechanical and pharmacological thrombolysis, but with limited success. The cases highlight the challenges in managing patients with severe pulmonary hypertension and the need for individualized treatment plans.
Meta Tag
Category
Pulmonary Vascular Disease
Session ID
5005
Speaker
Kirk Jones
Speaker
Stephen Machnicki
Speaker
Ruth Minkin
Speaker
Anthony Saleh
Speaker
Rakesh Shah
Speaker
Henry Tazelaar
Speaker
Saarwaani Vallabhajosyula
Track
Pulmonary Vascular Disease
Keywords
pulmonary hypertension
Eisenmanger syndrome
hypoxic respiratory failure
inhaled prostacyclin
non-invasive ventilatory support
end-stage renal disease
left main pulmonary artery embolism
anticoagulation therapy
biopsy
thrombus
PH
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