Episode 454: Pulmonary Hypertension

Welcome back clinical problems. Yusuf here. At CPSolvers, our mission is to make clinical reasoning accessible to learners worldwide. reasoning together. Now over to you, Yusuf. Thanks Maddie. Just a quick reminder: this podcast is for educational purposes only and is not a substitute for medical advice. Details have been modified to protect their privacy, and the views expressed here are our own, not those of our employers. Now let's dive into the case.

Hello everyone. Welcome back to another episode on the schema series. We have some clinical problem solvers here. I'm Mark, hospitalist here at Stanford, and I have my great crew, my great scream schema crew. How are you doing, Matty? I'm doing great. Great to see you all. I'm super excited to present this case to you all. I have just about two to three weeks left of maternity leave, so kind of soaking in this this time at home before jumping back to the wards.

Um, what about you, Noah? How are you doing? Hey everyone, I'm doing pretty good. Um yesterday was my partner's first day at her new job, so I'm excited to kind of um I'm waiting for her to get home so she can tell me everything that happened and all that. So excited for that. What about you, Yusuf?

Yeah, hi everyone. I'm good. I uh was just telling Noah that I'm getting physical therapy done for ACL surgery that I had. And I love physical therapy. It's like a workout, it's like a positive relationship. You Check the weights, you get stronger, you get better, and uh I I now can confidently prescribe it to my patients and know that it's like a positive experience. So it's my PT journey.

Yeah, yes, yeah, I feel like I refer so many patients to PT, but I personally have not experienced it. So glad to hear that it's such a great thing. Yeah, bring PTOT to VMR.

Okay guys, well I am so excited to present this case to you all. Um so I'm just gonna jump right in. Uh so this is a case I saw um on my ICU rotation a few months ago. And um basically, you know, uh you get called to come evaluate a patient in the emergency department. And um the first pieces of information I hear is that this is a 79-year-old woman. And she was sent to the emergency department actually from an outpatient pulmonary hypertension.

So she presented to an outpate the outpatient pulmonary hypertension clinic for basically a new patient evaluation. She was there to establish care. But before she even had her appointment, she was using the restroom and a rapid response. was called when she was in the restroom for basically shortness of breath and um a syncable episode. So this rapid response was called and so before she could even have this appointment, she was transferred to the emergency department for further work.

Um, so Noah, maybe I'll pass the mic to you. Of course, you don't know too much information at this point, but you know, with these two things, like pulmonary hypertension clinic, syncope, how could those two things be related and what's crossing your mind? You know that's a that's a great uh introduction to the case and I um I have learned this.

In fact, always during my ICU rotation that patients with pulmonary hypertension they have to avoid doing valsalva. Um and the reasoning behind it is kind of the same reasoning why we are so hesitant in using positive pressure to ventilate those patients. which is to increase their anthroporacic pressure and then kind of reduce their preload and they're very preload state dependent with the pulmonary hypertension and the likely right sided um heart failure. Um so it's very good that she

Val salvad and syncopies, you know, in the clinic where there are people able to help her. And I'm very worried because to me that's a marker of pretty advanced disease. Um of course we have to do our due diligence and kind of exonerate other causes of syncope. Um but I think for me that would be a pretty convincing story for severe pulmonary hypertension um causing syncope with increased intrathoracic pressure. Um what do you think so far, Mark?

Yeah, I think no, you probably all of you guys have probably experienced this that I feel like, you know, when you're a resident and taking care of patients with polar hypertension, like that's kind of like the disease that everyone's the most scared of because these patients can go from Zero to a hundred really, really fast. And there's even that term like the RV death spiral, right? Um, and it's interesting, though, like we learned that, like, you know.

Pulmonary hypertension, these patients are preload dependent, like you know. Be careful when you're doing positive pressure ventilation, be careful diurasing them because you don't want to make that R V, you know, really small and deplete their preload. But Then you'll talk to pulmonary hypertension doctors. And essentially the the recommendation they give you every single time when this patient has severe pulmonary hypertension and is decompensated is diarrhees, diarrheas, diarrhee.

Um pulmonary hypertension doctors are much more aggressive with diuresis than we are. And really it is because while they are preload dependent, um, and while if you val salva and decrease your preload, And you syncopise, that usually means that your R V in is doing pretty bad and you're there's pretty high pulmonary pressures. If your RV is so dilated and so decompensated that RV starts to bow into the LV.

And then starts to cause, you know, decreased perfusion to the systemic circulation. So that's why really one of the main stages of treatment is diuresis because you want to prevent that bowing of the RV into the LV. So it's this really delicate balance.

That's why a lot of times these patients are such a low threshold for these patients to be in the cardiac ICU or the medical ICU when, you know, you're having RT um you know the arterial line in them and keeping a really close eye on their pressures. And um so yeah, they're really tough patients to manage. Um

But Yusuf, I'm I'm curious. What when you think of like a new ref a new patient with polar hypertension, really all we have now is the age. Um how do you think, how do you stratify the differential diagnosis based on the age? Does that help help you at all?

Yeah, I'll uh I would love to talk about that, Mark. And before I get there, I was hoping to talk about syncope as well, because we teach the schema of syncope as in reflex. Orthostatic and cardiac. And this is for all comers of syncope is a good framework. But one thing that we leave out of this framework is that any cause of shock And its early form can also cost syncope. And that is imp implied, and I would love to like just say that out loud.

And the causes of shock, you can spell out shock. So S is inseptic, H is hypovenemic or hemorrhagic, O is obstructive and C is cardiogenic. So in any patient with syncope, so in addition to the big buckets of free flex, orthostatic, and cardiac, you're thinking of any cause of shock. And uh there's a big overlap here between cardiac and obstructive. So we're thinking, is this like a right-sided pressure phenomenon?

And Mark, to answer your question, I think the age is really helpful. And the other thing that's really helpful is the center of attention. This, we didn't hear from Maddie that this patient presented to a heart failure clinic for lower extremity edema. We didn't hear from Maddie that this patient presented for

A COPD to a pulmonologist. We heard that they presented to a pulmonary hypertension clinic. And the vast majority of cases are going to be related to cardiac disease or obvious pulmonary disease, but the fact that they presented to a pulmonary hypertension clinic. uh has me worried about more esoteric causes and I'll leave it at that and would love to hear more from Maddie. Beautiful discussion. So let me tell you more.

Um, so when I get to go interview her in the emergency department um on history, she says that even before the syncopole episode in the bathroom, she's had basically progressive um fatigue. Shortness of breath and lower extremity edema really preceding the past month. And when asking a little bit more about this syncopol episode, she reports in the past one to two months, she's actually had several episodes that she described as uh blacking out.

And so that's that was kind of the main history that she described to me. Um The past medical history I was able to gather from her and from the chart is that she has Chronic hypoxemic respiratory failure on five liters at baseline. She also has AFib status post on ablation on a doa. She has hypertension and she her chart says OSA, but she's never had a sleep study and she's not on CPAP.

And then in terms of her, you know, I was looking like, why were you in the pulmonary hypertension clinic? So basically she had she was She was referred basically like one month before this current presentation, she was hospitalized at an outside hospital for basically an acute on chronic um hypoxemic respiratory failure and right-sided heart failure. During that previous hospitalization she was diuret and she was referred to this pulmonary hypertension clinic for further workup.

You know, I was digging through the chart and I see that basically she was diagnosed with pulmonary hypertension based on a right heart cath around four years ago or so. But the etiology of her pulmonary hypertension has been unclear. So and some of the notes are kind of contradictory. So some of the notes are documenting this concern for WHO group two or three, um whereas other notes document a concern for PAH. I'll get into kind of like her right heart cap maybe in a later subsequent aliquot.

But I see that from a chart from her chart that she was actually started on sildenophil uh two months prior to admission, uh, because uh most recent Brightheart cath um was kind of concerning for group one. And then medications, I mentioned the DOAC, and she's on WASIX, 40 milligrams daily, sildenophil, and those are really all of her pertinent medications.

And really no pertinent social history. She was a former nurse. She lives with her family. No relevant like exposures and no drug or alcohol use.

Um so maybe I'll pause there and Yusuf, I think at this point it might be helpful to just, you know, focus a little bit on the fundamentals, like how is pulmonary hypertension diagnosed, and maybe we can dive into how you all think about the causes. Absolutely. And uh great aliquat Maddie and thinking hearing things out loud, I'm still trying to label the problem. And we heard about a

Possible diagnosis of pulmonary hypertension. We heard about lower extremity edema. And then we heard about a lot about cardiometabolic risk factors. In general, when I heard about the lore extremely edema, the thing that came up to my mind is this is an evidence of right-sided disease, so right-sided heart disease.

And uh I would be hesitant to label this just heart failure. Instead I would label it specifically as right sided disease because we only heard about edema so far. We didn't hear about pulmonary edema, only w some in the lower extremity. So And then that makes the pulmonary artery potentially the center of attention of the case here. The patient is at risk for half path.

And what is half pef? So it's heart failure with preserved ejection fraction. And uh we used to think in the past that high blood pressure causes L V hypertrophy and that alone causes HFP, but now we think of it as a cardiometabolic disease that occurs in uh females who are older than seventy with risk factors such as aphib, uh higher BMI, uh diabetes and hypertension and etc.

But the fact that we don't hear about any sided any left sided symptoms is making me think is the pulmonary artery the center of attention of the case. And uh before I talk about the etiologies, uh, Noah, I would love to hear about how you think about the anatomy of uh pulmonary arterial disease and do you have an approach? And I know you love to take us through the journey of uh blood vessels, et cetera. I know you did it last time for uh our uh episode.

Actually, Yusuf, um I don't think about pulmonary hypertension in an anatomical um way. I have a much more pragmatic approach of pulmonary hypertension because I have found that We'll we'll talk about this in in federal quads. But the the way we classify pulmonary hypertension is in the WHO groups, so group one through five, and that's kind of based

Based on mechanisms and etiologies. And then on the Riharca, you classify it based if it's pre-capillary, if it's combined pre- and post, or if it's post-capillary. But all of them are kind of not very intuitive to me, because you can have group one having the same rye hard calf as group two and group three and so forth. So there's kind of like a lot of mixed um mixed data. So that's not the way I approach it. I have a pretty

management approach to pulmonary hypertension if that makes any sense. So once I see that the patient has pulmonary hypertension, I say, okay, do they have left heart disease?'Cause that's kind of the first big ideology. Do they have any pulmonary disease?'Cause that's the second one.

Do they have any risk factors for CTAF and then the VQ scan has great sensitive sensitivity for picking up that ideology? And if not, then I start diving into the serological workup of pulmonary hypertension. That's the way I think about it. What about you, Mark? Are you a fan of the anatomical approach or more like the management approach?

I think I I think I like both, honestly. I love thinking about physiology and anatomy, but then I think the five groups or more of the management approach helps me kind of get to those etiologies uh more quickly. Um so I don't r I I probably stick with the five groups more commonly than I do the anatomy um and physiology approach. Um, but I think both are great.

I think one of the things that's really tough about polymer hypertension and what can lead to a lot of diagnostic errors, it comes down to the law of proportionality, right? We talk about this a lot in CP solvers is that left heart disease is really common. Lung disease like COPD is really common. Pulmonary embolisms are really common, right? So I think it's really easy to say, oh, this patient has pulmonary hypertension from their hef pef. The patient has pulmonary hypertension from their COPD.

Oh, they had a prior PE, maybe they have CTEF, and kind of stop the work out uh work up there. And I've had I've seen patients get misdiagnosed with group, you know, group two or group three and wind up having group one PAH and really not be started on therapy. Um

or real or start on therapy much later in their course than they should have and kind of suffered some some consequences, unfortunately. So I think it's very important to be like, okay, if we're saying this patient is group two, let's say, is there a hef pep that severe to lead to this severe pulmonary hypertension? Is there C P D or you know hypoxemia like

in proportion to the degree of their pulmonary hypertension? Those questions aren't, you know, always easy to answer, but I think it's something you have to think about before you label someone as group two or group three. Again, because these diagnoses are just so, so common. I think the one thing that stuck out to me is I'm like, whoa, why is this patient on five liters at baseline? Like, what is going on there, right? Maddie put in our chat that this patient has a BMI of 26.

Um, but we don't have a really a past medical history of chronic lung disease. But you know, obviously chronic hypoxemia certainly can lead to pulmonary hypertension. Um and we need to explain why this patient is on five liters of oxygen. Like I need a high resolution CT chest um immediately to see if this patient has interstitial lung disease or just, you know, know what is going on um with their lungs that's being needed to be, you know, chronically hypoxemic at five liters.

I think the one other misnomer two is pulmonary hypertension does not or rarely leads to hypoxemia, right? Hypoxemia can result in pulmonary hypertension, but the reverse is not uh is not commonly seen. Right. Pulmonary hypertension, like PEs, is more of a hemodynamic disease. Right. When pulmonary hypertension gets severe, the RV starts failing, people get cardiogenic shock before they really get hypoxemia. I've seen patients like, oh.

Patient with pulmonary hypertension comes to the hospital with hypoxemia. Oh, it's probably just from the pulmonary hypertension. That is not true. It's a very late stage finding. And what I was taught by one of my um IC residents, my interne years that the mechanism really is a low mixed venous oxygen saturation.

So what that means is that when the pulmonary hypertension gets so, so severe, the lungs just try to extract, extract as much oxygen as they can because you're not getting a lot of blood throw through the capillaries. And that leads to a low mixed venous set on the on on the other side. And that can eventually lead to um hypoxemia. But again, that is a very, very late stage finding. So all my energy right now is like, what is going on with those lungs?

Um yeah. What el what else do you have for us, Manny?

All right. Um yeah, great discussion. So I'll share, I'll share on the next alacot here. So In the in the emergency department, when I go down to see her, um, her vitals, her blood pressure is 140s over a hundreds. Her pulse is in the 80s to 90s. Her respiratory rate was 16. And when I went to go see her, she was on her baseline of five liters.

And um I'll kind of comment on those five leaders. It was also kind of interesting to us because initially when looking through the chart, it was not clear what that was secondary to. So that was also kind of a question mark in our mind. So on physical exam. She what was most notable is she had um jugular venous distension to her earlobe. She had um lower extremity pity edema, even like past her knees, like up into her thighs. Her belly was generally soft, non-tender, non-distended.

Uh she was sitting in bed able to um answer questions there with her son and uh was not in like significant kind of respiratory distress when I went to go see her. And actually when listening to her lungs, there were no obvious abnormal breath sounds. Um, like no obvious crackles, um, no rails that I heard. Um and kind of no uh obvious rashes on extremity exam. So for her labs, her CBC was unremarkable. Her BMP, most notable for creatinine of 2.27 from a baseline of 1.4.

Her BNP was 5,000 and her lactate, the first one was 7.8. uh TSH was normal. I'll give you a little bit more work up here. So chest x-ray on admission commented on a small left poral effusion and an enlarged cardiomediastinal cardiomediastinal silhouette. Um and then looking kind of past in in her chart, she had a CTPE one month prior at that earlier admission that actually showed a normal appearing lung parenchyma and no pulmonary embolism.

And she had a transthoracic echocardiogram also during that last admission that had an EF of 55%. It commented on the right ventricle being enlarged, the RV systolic function was reduced, the right atrium was enlarged, and had ventricular septal flattening consistent with RV pressure or volume overload. It also commented on severe tricuspid regurgitation on that echo. On that TTE, there was an estimated PA systolic pressure of 71%.

Also kind of digging through her chart, I see that she had pulmonary function testing three months before this admission that had normal spirometry but an isolated low DLCO. So ultimately she was admitted she was started on IV diuresis, and we uh held her SIL denafil, given the concern that it may have been worsening her symptoms.

I can tell you a little bit more about, maybe I'll pause there and then I can comment a little bit on some of the like serologic testing that had previously been done into her plummetic. Mark, that was a lot of data, but um I'm gonna pass the mic to you just to hear your general thoughts and then maybe we can pass the mic to Youssef to give an overview of the WHO classes.

Awesome. Yeah, this is a really rich aliquot, uh, Maddie. But I took a deep breath and I'm there's definitely a sigh of relief when I see these vital signs. Anytime I'm like I was admitting a patient with pulmonary hypertension.

Um that seems a little tenuous. Like I get I get worried, oh they're gonna be hypotensive. You know, these patients can crash really quickly, like I said, with that RV death spiral. But luckily we have a decent, you know, a decent blood pressure, even on a little bit on the higher side. Um the patient isn't tachycardic.

They're, you know, they're saturating six percent on their baseline five meters that hopefully we're gonna find an answer to um at some point. But you know, not really overly surprised by the exam. Um, not surprised by the elevated G uh JVD.

Um, given the patient's pulmonary hypertension um and the echo that was given. Um, you know, the patient seems very overloaded from a pitting edema perspective. You know, they have edema even up to their bilateral thighs. But again, you know, their volume overloaded. And then we see the CBC, um, is normal, which is good. Um, the BMP, again, the creatinine, not overly surprising. They have an AKI.

A cratina 2.27 from their baseline of 1.4. Really, the most common reason that a patient would volume overload, this could be from left. Heart failure, this could be from right heart failure. Um the most common reason they would have an AKI on admission is cardiorenal syndrome, right? This patient's pulmonary pressures are presumably extremely high and are essentially just strangling the renal vein, right? Um

So that perfusion pressure to the kidney is severely reduced. So you're going to get an AKI. And usually with diuresis, they just get better, right? But In someone like this, I know the numbers look okay, but you know, you can have normo-tensive cardiogenic shock, right? And that's something you have to think about every time you have a patient with severe pulmonary hypertension is like, is this patient tipping into cardiogenic shock? Um, so you know, if that karatine doesn't get better.

um with diuresis. If this patient starts to have cool extremities and narrow pulse pressure, um we're gonna have to think about early ionotropic support for this patient too. And that really tr um you know, that kind of blends well with the lactate, right? So Maddie said this lactate was 7.8 and improved to 3.2 at diuresis. I'll say going back to the law of uh proportionality.

This lactase 7.8 is way out of proportion to this patient's hemodynamics. Even if they have normo-tensive cardiogenic shock. There is no way that is solely driving a lactate of 7.8. A lactate 7.8, if you guys just, you know, seeing a lot of lactates during residency, like that's like a lactate sometimes you get when a patient's like during a code, like, you know, it's a it's extremely high lactate.

But you know, it's important to remember not all uh lactic acidosis is from hyperperfusion, right? There's kind of type A and type B. Um type A is kind of perfusion related. It's the most common reason we see an elevated lactate. And it's any of your causes of shock can cause a type A lactic acidosis. One thing I s I can see missed sometimes is that, you know, you can have Systemic hyperperfusion, like I mentioned, from sepsis or carniogenic shock.

But then you want to think about local hyperperfusion can also lead to neulated lactate. And sometimes we see that with like mesoteric ischemia or like compartment syndrome. So it's not just global, it can be from localized, but we're not really getting a flavor of anything. Um, you know, global uh systemic hyperprofusion or local, that would lead to this degree of lactic elevation. Um, so I kind of have.

I kind of have my antennas up for type B lactic acidosis, which has a lot of mechanisms. The thing I'll bring up here is that Is something called the Warburg effect that you can see with cancers. And the reason I bring that up is that, you know, this patient had a widened uh cardiac silhouette. Now, that could just be because their pulmonary trunk is huge, right? But, you know, there's

you know, this patient could have some sort of mediastinal mass, right? Like some sort of like the terrible T's, right? Um like lymphoma or um all the other like uh causes of an anterior medocinal mass. And the I would say the forgotten category. of pulmonary hypertension is uh group four, which we think about CTEP, but it's really anything that causes pulmonary artery obstruction. And that could be external or internal.

So there's cases of, you know, lymphoma in the mediastinum that's just compressing on the pulmonary vasculature, uh, leading to pulmonary hypertension.

Now you might have thought, you know, you pr you probably would see that on the prior CTPE, but again, this is just like another hospital's imaging and there's probably not that much data. So I'd be very curious if this, you know, media style um Widening is just from the, you know, enlarged pulmonary trunk, or is there something actually compressing the pulmonary arteries leading to pulmonary hypertension?

And again, the r only reason I'm elaborating on that is just because I think this lactate is just like way too high and I don't want to miss a type B cause of lactic acidosis for cancers. Commonly liquid cancers can do that. But you know, again, Maddie said it improved with Diuresis. So that's a signal that maybe it was a more of a hemodynamic issue. But again, I just I don't love that lactea of 7.8. I don't want to blame it just solely on a hemodynamic issue.

But I rambled a lot. Um I think Yusuf's gonna talk about the the five groups of polar hypertension. So take it away, Yusuf.

Yeah, thank you Mark. I loved your note on normal tensive shock, really easy to miss. Uh one thing to note is uh if you want to like if you're listening you can Google pulmonary hypertension drawing and that's a quick way like a mnemonic to remember it. Uh so group one, uh if you put two ones next to each other, it looks like an artery.

Pulmonary arterial hypertension, group two, it's if you flip two twos next to each other, it looks like a heart, so it's left-sided heart disease. Group three is lung disease, group four is CTEF, and group five is the bucket. And to simplify it even further, uh you you can also think about it uh anatomically. So

Think about the R V, the pulmonary artery, and then going into the arterioles, the capillaries, and then all the way to the left ventricle. And one way you quickly want to think about this is is this the lung? So we hear that the CT of the chest has normal lung findings, so that's very reassuring. It could still be like OSAOHS, but we hear that the patient's game I twenty six, not extremely high, uh, so that's reassuring as well.

You wanna think about the heart. So whenever you do the uh right heart calf, you can see how high the left sided pressures are. And uh sometimes you can have a combination. You can have left-side heart disease and pulmonary arterial hypertension, that's also very common. Group four, so uh C T PE does not rule out chronic thromboembolic disease, so you would need

a VQ scan. And I think these three steps, uh, if you rule this out very quickly early on, like a CT, which we already have, a right heart cat to check the left sided disease. And a VQ scan, if you're you can get the vast majority of cases. And once you rule these out, you can then jump to group one and group five. And uh I'm not gonna go delve deeply into these until we get more information from Maddie uh the next adequat. So Maddie, can't wait to hear more.

All right. Well in this outclub, I will give you a right heart cath that was repeated during this hospitalization. She'd previously had some as well. But maybe first I'll say, so basically she was admitted, started on IV diuresis. Over the subsequent days, maybe the first day I admitted her, she was initially improving, but then her clinical trajectory worsened and she developed worsening urine output despite increasing diuretic requirements.

She was also required inotropic support. Her extremities, when I first saw her in the ED, I did not appreciate them being very cool, but over the subsequent days started having cooler extremities. Um, so basically we were managing her in the ICU for cardiogenic shock from this decompensated right heart failure. So she got a right heart calf and the uh right atrial pressure uh was 18.

Uh normal, you know, you guys can kind of talk about the normal values, but normal being generally less than um six to seven. Her uh pulmonary artery pressure, the mean pressure was 65. Systolic was 95, diastolic was fifty. The pulmonary capillary wedge pressure was five. That's normal. And then there was a low cardiac output and low cardiac index as well. Uh and the PVR was twenty-three.

So kind of the summary of that right heart calf is there was elevated right and normal left filling pressures. There were markedly elevated PA pressures and a reduced cardiac output. I'll maybe... Pause here and you all can talk about if you think this is what type of pattern. You know, Noah talked about pre-capillary, post-capillary patterns on right heart calf. Um so maybe Noah, I can pause here and um hear your thoughts on that right heart calf.

Yeah. This case gets more and more complex, so before I go into the pattern Just kind of want to brief recap. So we have a patient that now has kind of cardiogenic shock from braventricular failure with normal leaventricular function in the background of chronic, hypoxemic, respiratory failure of unknown ideology. And

with a normal spiro and technically normal gross lung imaging, right? D CTP is not the best at identifying subtle parent mode changes, but we do have a normal C D P E. Um going back to the spyro, it's pretty interesting that she has a isolated um Severe death. decrease the LCO. Um and that is a early clue of a vascular problem uh being present. Other causes of uh low DLCO would be kind of a restrictive uh ideology would also cause a restrictive pattern on the spiral like ILDs.

Um so I think the D L C O kind of points towards pulmonary hypertension in even in the spirometry. Um so with the calf now we have elevated mean pulmonary aterial pressure, which diagnoses this patient as broadly pulmonary hypertension. We have a normal wedge, which basically says that the left sided pressures are fine, and we have increased resistance. This would be compatible to me to a precapillary pulmonary hypertension. Um so that's how I'm labeling this patient in my mind.

What do you think, Youssef?

Uh I'm right there with you, Noah. So uh no left-sided heart disease. We're in the capillary. And now the big question: do we have chronic embolic disease or are we going to delve into the other etiologies? And uh so what are these other etiologies that we're talking about? So in in general you want to think about inflammatory causes and non-inflammatory causes. So uh inflammatory causes include the the

talk about the I made mnemonic infections such as like HIV, schistomasis of uh if the patients from the endemic region, malignancy, like Mark said. So either microthrombi or Macrothrombi, which and in this case I mean tumor tumor thrombus, and it can cause a TMA as well in the pulmonary vessels. Uh autoimmune disease, so uh lupus, scleroderma, mixed connective tissue disease, even sarcoids.

can cause it as well. And then uh drug w we don't hear about any drugs here, but thinking about amphetamines, for example, or some chemotherapeutic agent. I and then uh in terms of non inflammatory causes, uh

I think of uh shunt. So if you have like a big shunt physiology, that can be one cause, uh, thyroid disease is another, and then uh vitamin deficiencies such as Vitamin C deficiency, which is uh Mark's favorite disease, uh, and then there are rare etiologies like uh pulmonary veno obstructive disease and uh hereditary hemorrhagic telangectasia.

And then there's like genetic uh component as well. Usually it presents in a y younger patient who have the step one question, which is the bumper to gene mutation, and that causes like pulmonary arterial hypertension, but this patient is older and then Idiopathic, which basically means medicine has not reached a point where we know what causes it. Mark, uh, what would you add to this?

I don't think I would add anything, Youssef. I think we need to, you know, send those serologies, may maybe do a closer exam to see if we're missing any subtle rheumatological clues on the patient's skin or on the patient's joints and To be honest, you know, as I think Noah mentioned, like CTPs are good, but they're not perfect. Um, so I to complete the workup, I personally would do a high resolution CT to to

make sure we're not missing any s subtle parenchmal abnormalities. Now you might say if a CTP doesn't show any paranquimal abnormalities, it's probably highly unlikely that a high-res CT will show parenchmal abnormalities to the degree that the patient is on five liters, right? It a CTP, if it's um if the hypoxemia is from a pure parenchymal etiology, the CTP will show something, right? But you know a high-res CT might show some again subtle parenchymal abnormalities that can lead us

um down a certain diagnostic path, right? Because if this patient has any hint towards ILD, then we're really will be running towards the rheumatological bucket, right? But again, I would definitely want to do, you know, a good exam to make sure we're not missing any subtle features, which again, sometimes are hard to detect.

The one thing I just want to highlight, because I love physiology, are two numbers to keep in mind when you're looking at this cath and could kind of hint you early on that this. You know, in addition to the PBR and the wedge that you know the RV is doing really bad, and a lot of this is driven from solely like

uh our R V disease and precapillary disease as opposed to a mixed picture is the R V to wedge ratio, right? A normal R V to wedge ratio, like let's say like a normal RA pressure is about five. Our normal wedge is about 10. Right. So that that ratio is about 0.5, the RA to reg. Now that has completely reversed in this patient, right? This patient's RA pressure is 17. And his patient's wedge is five. So that reversal shows that the RV is doing really bad, right?

Another one to keep an eye on is what's called the pulmonary artery pulsatility index or the PAPI. It's essentially the stroke volume of the RV. And how you calculate that is you just take the um mean the systolic PA pressure of 95 minus the diastolic PA pressure of 50, and then divide that by the RA pressure.

And I won't get into the the nitty-gritties of the numbers, but this patient's PAPI is very bad, which essentially means the stroke file in the RB is doing really poorly. Um so that's just them some things I've learned at the CCU and some numbers that we that we would track daily on patients with uh suspected RBA failure. All right, Maddie, please teach us what your team did next. I love Poppy, by the way. Yeah, absolutely. And, um,

I loved your localization, Noah. You um nailed it that this was concerning to the team for a pre-capillary pattern. And so just to spell that out as you did, um, we had a you know a mean PA pressure greater than 20, which was kind of the Diagnostic right, that's how you diagnose pulmonary hypertension greater than 20. Um the pulmonary vascular resistance was elevated. I've generally learned the threshold of kind of greater than two woods unit.

And then the pulmonary capillary pressure was was normal and the threshold that I warned is less than 15. So all of those were consistent with um with a pre-capillary pattern.

So in terms of in terms of what happened next, um maybe I'll kind of answer some of the questions that Mark and Yusuf um were were asking about in terms of some of the um workup that you would send to investigate some of the causes. So kind of going by the WHO groups. So she had a TSH that was normal, her HIV hepatitis C serologies were non-reactive.

um had an ANA rheumatoid factor, CCP, that was normal. You had mentioned kind of on exam, were there any other signs concerning for autoimmune disease and kind of like a joint disease, skin disease, nothing then. um newtox was negative. So that's kind of goes into like the group one, and doego group one. For the group two, um kind of the uh left-sided heart disease, we I mentioned the right heart cache.

um and no other like new workup for that. Um for the group three, I mentioned the CTPE and the pulmonary function testing, but yeah, never got a high resolution CT scan. Um So that's for the group three. Group four for the chronic thromboembolic disease, you know, she did not have a PE on that CT scan, but did not get a VQ scan this. Um and no specific known risk for the group five category.

So um, you know, at this point, kind of the summary there was we were concerned about a pre-capillary pattern. There was reduced cardiac output for her, she was requiring increasing amounts of uh diuretics and inotropes. And based off of those right-heart cath findings, the concern was: are we in the WHO group one category pre-capillary disease? And so at this point the pulmonary hypertension team um brought up the idea of starting a pulmonary vasodilator, specifically epoprostenol.

And so um, you know, basically the patient's trajectory was was worsening at this point. And this was kind of seen as what what could possibly help her because even despite inotropes diuretics, she was she was not doing well. So she was started on epoprostenol after kind of discussion of the risks and benefits with the family. And basically after the administration of epoprostenol, her hemodynamic

worsened um even further. At this point I was off the team, but looking through the charts, she continued to decline and it was an even bigger decline after starting the evoprostenol, the pulmonary artery vasodilator. So I wanted to pause here and get your thoughts on kind of specifically what do you make of her declining hemodynamics with epoprostanol. Yusuf, maybe I can turn the mic to you.

Yeah, Maddie, uh thank you for presenting this adequat. One thing that comes to my mind, we we're thinking about group one etiologies and we're thinking of inflammatory versus non inflammatory symptoms. And here we don't hear about any inflammatory symptoms so far.

And under the non-inflammatory bucket, we talked about vitamin deficiencies. We didn't hear about any uh risk factors. And you can you can develop scurvy just from like avoiding citrus products and in this case we didn't even hear about that. One, uh telltale sign of uh pulp pulmonary veno occlusive disease, which is uh a disease that acts like heart failure.

But then once acts like left heart failure and then when you do the cat you see that the left sided pressures are normal and that is how a pulmonary veno occlusive disease presents. And one telltale sign is that these patients sometimes their hemodynamics worsen with epoprostenol or vasodilaris, because if you think about it they're

occluded at the venous side, so right after the capillary. So if you vasodilate them, they their uh hemodynamics worsen. So I'm adding that higher on my list. So that's one thing I'm considering Um and then we'd love to hear from Noah and Mark as well. As to could this just be worsening shock and is this just the uh right heart uh spiral that Mark was alluding to earlier? And both are on the differential. So Noah and Mark would love to hear from you both.

Yeah, I really like the PVID um hypothesis. Um I was thinking about it before with the diffuse the LCO and the cryptic hypoxia. It'd be The decreased DLCO in pulmonary hypertension can be from a problem in diffusion or from reduced blood flow in severe pH. In this case, it seems like the hypoxia predated the pH. And the etiology that causes severe hypoxia is PVOD because you have disruption of the gas exchange through proliferation of the alveolar membrane.

And the classic manifestation of the EPO, um it's kind of suggestive, I think it can cause either uh hemodynamic instability or pulmonary edema. And um I'm excited to see What else do you have in store for us, Matty? What about you, Mark? What do you think? I totally agree. I I think this would be a good case um for PBOD. And I love um your guys' explanation of the pathophysiology. That is the exact same reason why.

um patients with left heart failure and elevated wedge pressure, there that's kind of a relative contraindication to pulmonary vasodilators for the same pathophysiology that Yusuf highlighted. It's like if you have a stiff left heart,

um and you flood the left heart uh from pulmonary vasodilation um with blood, that's gonna get just thrown right back into the lungs. And unfortunately, I actually saw a case of that in the CCU, my intern year, when I think uh The the overnight team didn't realize how severe the patient's left heart disease was, even though they had pulmonary hypertension.

and they were started on eboprostenol overnight, the patient developed fast pulmonary edema and actually had a hypoxic arrest um overnight from that same mechanism. So it's real. And it's definitely something, especially pulmonary hypertension doctors worry about and especially with uh with PBOD. PVOD is really interesting. It's also called pulmonary capillary hemangiomatosis.

Um is another term that you'll see in the literature. And there is a heritable form that's, you know, more common in younger patients, but there also is acquired forms. They're definitely not that common, but there's certain like chemotherapies and even like systemic sclerosis while it can cause

um group one PAH from the arterial side, it also can cause PVOD as well. And there's also some implications of like HIV and which again is also associated with on the arterial side for pulmonary hypertension, but also has been associated with PVOD. So I think the age is interesting. But again, there is acquired forms that are non-heritable that definitely can occur in older patients. So I do think it's a a good case for PVOD.

That's why going back to the CT scan would be interesting. I know we didn't get a high IRES CT scan in this patient, but there are some very classic findings with PVOD on on CT scans. Classically they'll have interlobular septal thickening with centralobular nodules. It almost mimics actually pulmonary edema on a CT scan, but the patient won't have left-sided heart disease.

And the other interesting feature too, these patients have like a disruption in their lephatx and can have some mediastinal lymph adenopathy as well. So the classic triad essentially is mediastinal lymphadenopathy, interlobular septal thickening and centralobul nodule. So I would definitely Keep a close, I would take a closer look if that CTP is available to see if any of those features were at play. But yeah, Maddie, tell us what did you learn, what happened to the patient.

Yeah, first of all, just incredible teaching from from all three of you. So um I'll talk a little bit about kind of the what happened to the patient and then um I'll share a little bit about what I learned about in the final diagnosis. So um really she Her hemodynamics really worsened after the epoprostana and um despite, you know, kind of everything that um

Her clinical state was worsening. So ultimately she um her and her family kind of transitioned her to comfort care and she unfortunately passed away. And the suspicion for what the final diagnosis was was exactly as you all suspected, PVOD, pulmonary vasoeclusive disease. And really that it was that suspicion based off of the rapid deterioration with the pulmonary vasodilator and also kind of not having a clear alternative explanation for her pulmonary hypertension.

Um, you know, really you like make that diagnosis when if you kind of um uh basically like look at the lung after someone is is deceased, but uh basically on the path. Um but just based on kind of how her trajectory went with the pulmonary basodilators, that's why the suspicion was.

PVOD in this case. You all kind of commented, you all taught a lot about it, but I just want to tell you and summarize what I learned about it. So Yusuf mentioned this, but basically in PVOD, you get this fibrotic obstruction of the the post-capillary, pulmonary veins and venules. But exactly as Mark said, you often also get kind of obstruction of the pulmonary capillaries, and then you get this abnormal proliferation of pulmonary capillaries.

So there's you know a term PVOD, but then also what Mark said pulmonary capillary hemangiomatosis. And um I was reading about this and I encourage you all, there's a great NEJM um clinical case uh back in August of this year that is this case is very, very similar. As I was reading this case, I was like, oh my gosh, that's what the like very similar to the trajectory of the patient I saw.

And in this kind of clinical case discussion, they talk about how PVOD and PCH is kind of seen as like a single disease entity just on a spectrum. But the takeaway is it's it's a rare form of pulmonary hypertension, but it's um very deadly and um exactly based on the pathophysiology that Youssef mentioned.

uh pulmonary vasodilators cause this worsening because you get dilation of the pulmonary artery and then basically that enhances flow upstream to the site of obstruction and then get this life-threatening pulmonary edema. And what's um what's so tricky is that PVOD is so hard to distinguish from a PAH. And what's so what's so like I guess horrible about that is PAH, you use pulmonary vasodilators as part of that treatment.

And in PVOD, these pulmonary vasodilators cause this you know life-threatening um pulmonary edema, but it's they are almost indistinguishable on echo findings in terms of the RV dysfunction and the dilation and the elevated kind of tricuspid. What are you guys?

And then also the right heart calf findings are the same in PVOD and PAH. You basically get this, you know, elevated pulmonary artery pressure and a normal like normal uh pulmonary capillary ledge pressure. So they're very hard to distinguish, but the treatments are you know in one in pH the pulmonary visa dilators can be helpful and in pbld they are really not. Um so that um that's kind of like the summary of what I learned but it was

Um, it was a really sad case because of the the patient's outcome. Um but it really kind of uh prompted me to really do a deep dive into PVOD and learn about pulmonary hypertension and just loved all of your teaching and you all were suspicious of the final diagnosis. So curious to hear any thoughts or reflections you have. Thank you, Maddie, for sharing this patient's story and letting us learn from her case and

Uh yeah, I I don't think I've seen this diagnosis before. Uh but uh like you said, think if it's left heart failure but the numbers don't show left sided heart disease, then it's probably PVOD and that's how I remember it. I love this case and um thank you for bringing it to us.

I find P V O D to be one of the most interesting diseases and my favorite thing ever is go in the ICU to all like the pulmonary hypertension patients or the chronic hypoxia crushroid failures and say it's P V O D. Um, I think it part of it is kind of because it's kind of like a zebra diagnosis, but part of it is because it's like very It's not very suspected, right? You have to have a pretty high degree of like index of suspicion to even consider that diagnosis. Like you said, it mimics pH.

pretty well, mimics heart failure pretty well. Nose patients, they may have y you know, some FPF and you kind of get mislabeled and you're like, Oh, it's kind of what Mark said, it's not really That's if you're a FPF, but they're like really sick and then they get mislabeled and delays in treatment. happen and so forth. So I think just bringing it to a bigger audience, making more people aware of it, um you're doing many patients a good service, Maddie.

Yeah, sorry about the outcome of your patient, Maddie, but I think honestly P VOD is like the best diagnosis. uh to highlight um the workup for pulmonary hypertension because the our every single algorithm, PBOD evades it, right? It's like when you look at a right heart calf, like you can't diagnose PBOD on a right heart cath.

Um, the serology was a negative. Every single thing will be negative. So you have to go down the entire algorithm and then realize that like it's it completely sneaks away from the algorithm. So I think it's a perfect case to highlight uh this complex disease. So thanks for bringing it to us today. Yeah, thank you guys. It was a truly phenomenal discussion. Loved your teaching. And um yeah, we will end the session there, but thank you all and we'll That's a wrap everyone. Thanks for tuning in.

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