The average time from symptom onset to accurate diagnosis of pulmonary arterial hypertension (PAH) is 2.8 years, and more than half of patients have already progressed to functional class 3 or 4 by the time of diagnosis. Overlapping symptoms and clinical presentations can make it challenging to classify pulmonary hypertension patients correctly.
In this presentation, Anjali Vaidya, MD , co-director of the Pulmonary Hypertension, Right Heart Failure & CTEPH Program at Temple University Hospital, discusses using imaging to diagnose Pulmonary Arterial Hypertension and right ventricle failure and the management of these patients.
This content was featured at CVI Philadelphia’s Echocardiography Update on January 7, 2024. This recording is intended for educational purposes and is not eligible for CME credits.
Temple Health would like to Thank CVI Philadelphia for the content of this presentation and their partnership. For more information on CVI Philadelphia and their course offerings, please visit www.CVIphiladelphia.org.
Good morning. Hi, everyone. Thank you, Doctor Stenberg. Thanks for that wonderful case presentation. Um Any critiques of that case? I I would be happy to defend um she was presenting um my clinical decision making. So I really appreciate that and it's wonderful to be here. Thanks to all the organizers for having me this morning. Um I, I wanna just mention before I start just put this idea in your head that in the current era, the average time from symptom onset to an accurate diagnosis of pulmonary arterial hypertension is 2.8 years and more than half of the patients at the time of diagnosis are functional class three or four. So that for me is very motivating and sobering. We see it every day. That was what you saw in the case we just heard about. But it it's a big support of why using the echo cardiogram can help shorten that distance and time. So I thought today we would uh this is a huge topic, but we would go over the diagnosis of pulmonary hypertension specifically using the echo and the advanced sort of interpretation of echo Doppler to distinguish hemodynamic profiles and specifically that precapillary, pulmonary vascular disease, relative to the left heart disease, uh pulmonary venous hypertension and then shifting into an emphasis on how it's really all about the right heart um in the wrist stratification, in the guidance of medical therapy, in the perioperative and clinical care of these patients. And throughout, I'll share some of our most updated uh guidelines uh from the pulmonary hypertension statement that came out last year or actually the year before last. Um So here's just a reminder of the World Health Organization classification system for pulmonary hypertension. There's five who groups um as folks are likely familiar with but just a quick refresher who group one is that pulmonary arterial hypertension um group that we historically used to call pah uh we used to call primary pulmonary hypertension. Um who group two, that's pulmonary venous hypertension, that's left heart pulmonary hypertension with which all of us will see predominantly most frequently who group three is pulmonary hypertension associated with chronic lung diseases, who group four pulmonary hypertension related to thromboembolic disease or CTF. And then our miscellaneous causes in who group five. There's a long list of diagnoses here. This is in part why I love taking care of these patients because it's the final common pathway of internal medicine as I in my biased view think. Um but it can be a little bit confusing sometimes to phenotype these patients and to kind of go down the proper algorithm of diagnosis um to sort it out. So I wanna introduce this term, this concept of pulmonary vascular disease. This is really shifting into the hemodynamics and the physiology of the patients. So pulmonary vascular disease, referring to that precapillary phenotype that elevated pulmonary vascular resistance in the context of normal left heart filling pressures. But interestingly that phenotype really overlaps at least three of those who diagnostic groups. So this is the diagnostic criteria required to make a diagnosis of who group one pulmonary arterial hypertension. But it's also the same kind of hemodynamic profile that you'll see in patients with CTF chronic thromboembolic pulmonary hypertension. It's also the same hemodynamic profile you'll see in patients that have advanced lung disease and pulmonary hypertension. And of course, clinically, these patients have very important comorbidities and treatment algorithms and diagnostic workups that can be very different. As you can imagine just from some of the pictures I've shared. But the initial presentation, clinical history symptoms, physical exam echo Doppler can be very similar if not identical across these groups. So for today's discussion, I wanna think about echo Doppler to identify precapillary, pulmonary hypertension, the elevated PV R, the normal left heart filling pressures. Doctor Zinberg showed very nice examples and I just want to build on some of the, the pinna type uh pictures that we really pay attention to. The thing that worries everyone of course is that elevated pulmonary vascular resistance that high afterload on the right ventricle. So here are just some of those signature findings that are really quite specific for that on the left side of your screen is your parasternal short axis. Remember to uh acquire that image really at the mid cavity level, close to where your papillary muscles are. Simply because at the base of the LV, that mitral valve apparatus may give a false impression of septal flattening just from the normal valve. So we're looking for that d shaped septum. And we all understand the terminology, uh septal flattening and cystically cons consistent with RV, pressure overload. And I just want to reframe that in our minds to recognize that physiology is actually specific for a high resistance. And of course, pressure can be flow cardiac output resistance or pulmonary venous pressures. So when you see that D shaped septum in cysto, while it makes you think pulmonary hypertension, high pressure, it really is quite specific for a high resistance. And then the apical four is sort of the money shot. We always focus in on for pulmonary hypertension. And you'll notice here the right ventricle, it's apex forming the apex of the right ventricle is wide open. There's an open RV, apical angle, the right ventricle is quite hypertrophied when you see the trabeculations so prominent that tells you there is underlying hypertrophy of the myocardium. The seal shift is quite notable here. Of course, the R A is the size of Minnesota. You could see the tricuspid valve is not going to be able to co opt at all. And then there's that pulse wave Doppler in the right ventricular outflow tract, um which Doctor Sinnen beg showed very nicely that reduced acceleration time. And that notching profile very specific for that high afterload. If you're ejecting out of your right ventricular outflow tract in Sicily, and your blood flow is facing a high resistance and impedance, a poorly compliant arterial circuit, you will get that reflected wave back into the RV outflow tract before closure of that pulmonic valve. And that's what leads to the shortened time to peak velocity and that notched indentation. So some key features to recognize high pulmonary vascular resistance. Now we published years ago, um what we call the uh the echo score or a simple echocardiographic uh prediction rule for he dynamics. And the purpose here was to take routine echo images in patients that had an estimated elevated RVSP or PAS on the echo. And to look at routinely reported and and assessed imaging factors that were either most consistent with pulmonary venous hypertension who group two or most consistent with precapillary, hy hyper pulmonary hypertension, a high PV R. And so, in the context of an RVSP being elevated on the estimated pressure on echo, if you look at your echo and you have a Doppler estimation of high left heart filling pressures that elevated transom Miral evo velocity relative to the tissue Doppler and you have a enlarged left atrium, whether you're doing lava or a P diameter, any way you quantify it an enlarged L A and elevated E to E prime. You would get negative points in this score which were most consistent with pulmonary venous hypertension. On the flip side, if you had a patient with elevated RVSP estimation on echo, but the L A was normal in the context of a high RVSP. It's very challenging to have pulmonary venous hypertension, which is by definition, left atrial hypertension in the context of a normal left atrium. So I just wanna highlight the importance of the left atrial size assessment in the diagnostic evaluation of pulmonary hypertension. And then similarly just to emphasize when you look at those images, if you see that notching or that reduced acceleration time again, positive points. So let me show you side by side some examples of this on the left side of your screen is a patient who had an elevated RVSP estimated on echo. The L A was enlarged no matter how you quantified it. The trans mitral E velocity, very high tissue Doppler E prime, very low. So your E to E prime ratio was abnormally high at 18.6. And that pulse wave Doppler in the RVOT was beautifully normal round parabolic symmetric with no notching in that profile. On the right side of the screen, you have a patient who also has an elevated RVSP on their echo similarly elevated. But the left atrial size is normal, that E to e prime relationship and ratio is normal. So now you have suggestions that the left heart filling pressures are likely normal in this patient. And when you look in the RV outflow tract, there's a reduced acceleration and a notch. And when these patients had invasive hemodynamics assessed, both had very significant pulmonary pressure elevation. But on the left, that patient had a wedge pressure, severely elevated 29 with a normal pulmonary vascular resistance and on the right, the opposite normal wedge pressure, but severely elevated PV R. So I just wanna mention the concept that the echo doesn't lie. And we really do rely upon these echo Doppler features in the clinical assessment of these patients, whether it's cardiogenic shock showing up in my clinic or critical care in the IC U. And while the invasive human dynamics, right heart cath, of course, are the gold standard and that's what we're taught. And that's what we always say. That's only the case if they're done accurately and in the clinical context of the whole picture. And so that's a really important detail for this echo score. We compared using this score directly to the estimated RVSP or PASP on the echo itself to see the area under the curve for being able to predict that hemodynamic profile, the high PV R with normal left heart filling pressures. And this echo score was able to do so with an area under the curve greater than 0.9 relative to the estimated RVSP of 0.68. Now, we're slightly obsessed with echo and we look at echo on every patient in detail with pulmonary hypertension. And I've had colleagues for many years thereafter, say, you know, that's great. But I don't have access to the echo images or patients might come from an outside hospital and I only have a report or I don't have expertise or training in echo. And so kind of an evolution of this work was we created what we call vest the virtual echo cardiograph screening tool using very similar concepts. But truly looking at what is routinely reported in an echo. Uh on the report, you don't have to look at images directly for this and this is not advanced. This is meant to be clinically useful and simple and looking at just simple, routinely reported factors. So the vest consists of just those three parameters left atrial size, always commented on um basic standard of echo is to get a transmitral e velocity, either that alone or the E to E prime. Always we're always done by our wonderful stenographers even if we don't always report on it, but it's there in the in the echo data. And then the presence or absence of that septal flattening that D shaped septum will always be present. So if you're looking at an echo report, the RVSP is elevated on that echo, then you can apply this virtual score. And if you have a low E to E prime, you have a normal left atrium and ad shaped septum. Those would be positive points very concerning for preca precapillary ph as opposed to elevated RVSP estimated on echo. But you have an elevated E to E prime or an elevated E velocity and enlarged left atrium. And the pertinent absence of the description of septal flattening is very important in the interpretation of pulmonary hypertension on an echo. So just using echo reports, this is looking at on the left side of your screen, looking at patients who have pulmonary vascular disease versus those who don't. And on the bottom left, literally distinguishing between who group one and who group two pulmonary hypertension. And you can see if you have a fully negative score. All of those patients were who group two ph if you have a fully positive score quite the opposite, who group one pah. This is a paper that was done by some of my mentees and fellows um who really nicely putting together just summarizing some of those key factors. So, on the right side of your screen is what we're most commonly going to see pulmonary hypertension due to left heart disease. And those findings on the echo would be the systolic or the diastolic abnormalities. The ede prime abnormality, the valvular on the left side or the enlarged left atrium when you have an RVSP that's elevated with those echo findings, then the clinical uh suggestion would be to focus in on those clinical parameters, either directly the valvular disease or systemic hypertension, untreated, sleep disordered breathing, ongoing uh coronary ischemia and really a tweak of the diuretics very often just, you know, augmenting diuretic for, for example, furosemide to torsemide or something with a better bioavailability can be a world of a difference for these patients. As opposed to on the left side of your screen, you have a patient who has a concern for pulmonary hypertension. And when you look at that echo, there's that notch in the RV, outflow tract with a short acceleration time, an RV that's bigger than the LV. It's apex forming or apex sharing. Then your, your mind clinically is going down this algorithm of working this patient up quickly um efficiently for precapillary PH. And you're starting to order that HIV and the A N A and look for portal hypertension as causes for PAH. You're gonna look for lung disease, PFTs or chest imaging for that precapillary phenotype, the VQ scan to assess for chronic thromboembolic ph and these patients really should be triaged to write heart catheterization much sooner, quite urgently so that we can mobilize their Ph specific therapy. So that's how the echo can really help, try to distinguish between pulmonary venous versus pulmonary arterial. Now, our updated guidelines came out uh in the end of 2022. Um and I just want to show a lot of these concepts have been incorporated. So on the bottom, of course, there's the RVSP estimation, which you'll note is the least specific and least helpful part of sorting out these patients. But what they have included are a lot of the features from our work that have been reproduced elsewhere that are shown here using the echo to recognize findings that are specific for elevated PV. R that D shaped septum that RV, that's apex forming RV, greater than LV, the notch, et cetera. And then shifting gears forward. Once a patient is actually diagnosed with pulmonary arterial hypertension in the guidelines. Now, there's a large emphasis on echo Doppler parameters that reflect right heart performance. And I used to say right ventricular performance, but it's really an integration of the atria, the valve, the CAVA and the RV, and all of these things together are part of the guidelines. Now, in the assessment for PH now, he dynamics, I just wanna quickly remind folks that we are now using a mean pulmonary pressure of 20 millimeters of mercury as our cut off for defining pulmonary hypertension. Um This came from our last world symposium in 2018 and most recently, now there's a shift towards using a pulmonary vascular resistance of two wood units as opposed to three wood units as a re uh to recognize what is truly pathologic and abnormal isolated postcapillary, pulmonary hypertension would have a normal pulmonary vascular resistance. I mentioned right heart catheterization earlier. It's really important here for the technique to be done properly. I'm not gonna get into too much detail because we're focusing on echo here today. But this is a review we, we published in Jack a couple of years ago trying to really update and incorporate concepts of recognizing pulmonary hyper attention early moving towards right heart cath earlier, recognizing a lower threshold of abnormal uh human dynamics to to prompt further work up. And also for if anyone is interested, we go into more detail of how we will employ exercise during the calf hab also to further uh assess these patients. Now, shifting gears, let's say that now we've made a diagnosis of pulmonary arterial hypertension that who group one precapillary ph, how do we then manage these patients and use echo in the guide to predict their risk and to guide their management? The concept here is that the right heart performance is what guides everything. And I just want to show you some examples of data. This is actually human dynamic and and biomarker data um about a decade go from nickel that came out dividing patients with pah into quartile and the survival was markedly improved in the lowest quartile of anti pro BNP and the highest of cardiac index. So markers of right heart performance. This is our paper looking at TSI tricuspidata plane systolic excursion. If you achieved a taps, graded the two on one year of ph medical therapy, the survival curves are dramatically separated early as well. This is data that came from Mayo Clinic, integrating very nicely various features of right heart performance, both at the Rochester and the Florida site. Looking at right at the cava at the Tricuspid valve, the presence of that pericardial effusion in PAH, which is really a marker of impaired uh lymphatic and venous drainage into a severely constrained and pressurized right heart. And using all of these integrated features also was very predictive of survival in Pah. Even cardiac MRI data has been shown to correlate with survival in PAH. And so no matter how you want to assess the right side of the heart, these are the European guidelines um looking at the most recent version of risk assessment, the parameters here, I it's hard to memorize all of these numbers and all of these cut offs. But the concepts is that if your right heart is performing normally, you will be in a low risk status. So, clinical, right heart failure, the symptom of exertional pre syncope or syncope, which is a limitation of the right heart to augment stroke volume with exertion, the biomarkers, NT PRO B MP or BNP, right heart size structure function on echo cardiac MRI parameters of right heart function and hemodynamically. I just want to emphasize that the risk parameters for PAH are not pulmonary pressure or pulmonary vascular resistance. Although that is the underlying pathology. It's actually the markers of right heart performance. So, right atrial pressure, the goal is normal cardiac index, the goal is normal. Now, on the United States side, we have the reveal registry coming out of our American based registry. Just wanna show you very similar concepts. Um just to be aware of calculators that can be used to assess risk comorbidities and associated clinical conditions and how this reveal risks or is it just another way to predict survival over time Very well validated and combining some of the concepts of using the echo and risk assessing. So we mo most recently published this work using vest the virtual echo screening tool. Remember that 2.8 year delay in diagnosis from symptom onset, we took, we looked at our patients 100 and 32 with a diagnosis of PAH went back in time to find the very first echo report that the patient ever had that we had access to. Turns out the earliest echoes was 206 days. So over six months before the patients were referred. Oops, and interestingly, over 90% of them had a positive score as you saw in that last slide. And then when we did a formal risk assessment at the time of the referral to the accredited Ph Center of Excellence, when they saw us, it turned out that the majority of them had a high risk status already if not intermediate to high risk. So about 80 some percent. So really sobering in terms of how we can try to use, echoed to identify these patients earlier and we're working on that now at Temple to do so. Just to show you where we are in the field, the medical therapies for Pah are evolving rapidly. There's multiple treatment pathways that we target. I've just listed the names of the medications just to as a reassurance that yes, this is truly a subs subspecialty in and of itself as the field is growing rapidly. Um The in in the era that many of us were maybe students or trained, there wasn't a whole lot to offer these patients. But if you look over the last 1015 years, the field has completely exploded in such a positive way. This is just a on the surface example of of New England Journal of Medicine sort of landmark trials that have come out in the last decade, specifically related to novel indications, novel classes and therapies for pulmonary arterial hypertension really fresh and and we're very excited to anticipate this year. This is so Tatter Se this was published last year in the New England Journal of Medicine. A novel class, really remarkable outcomes likely to be FDA approved this year. So stay tuned more hope for our patients. All of us clinically manage patients whether they're in the IC U or in clinic. So a a common question I get about pulmonary hypertension and using the echo is how do you assess these patients per operatively and risk assess. All of us in cardiology have this role all the time. So I wanna share with you, we published this just last year, the first ever sort of a a scientific statement uh really addressing uh pulmonary hypertension risk assessment and noncardiac surgery. And a and a lot of the concepts here come down to the assessment of the right side of the heart and describing that kind of spiral of right heart failure. So the goals are really trying to optimize right heart function size performance in the perioperative state more so than targeting specific pressures as goals also just highlighting a couple of my other trainees. Um and some of the work they've done in the IC U for critical care management of pulmonary hypertension and right heart failure. Uh it's very helpful often in those very extreme clinical scenarios to rely on our noninvasive echo Doppler initially similar to the case that you heard earlier before patients may be suitable or safe or optimized even to have that right heart catheterization. So in the critical care setting, there's an absolute value to use that echo Doppler early, just like we did in that case, recognizing that even though the wedge was reported to be high, it was in the context of severe ventricular interdependence. I mean all of the features of the elevated PV R with normal left heart pressures were were clear on the echo Doppler to help guide us not to withhold ph medical therapy with the wedge of 29. But in fact, to give triple therapy and to save that young woman's life, some pitfalls to avoid is tapping the pericardial effusion. Um In PAH is a high risk of periprocedural death. Remember, the RV is not preload dependent in the context of a afterload mediated disease. So our goal is to decongest and diara these patients and mechanical support in the context of cardiogenic shock from PAH is is rarely successful in that the mechanism for disease is a high afterload, causing right heart failure and mechanical support will generally simply redirect flow into the diseased afterload circulation. So targeting the mechanism of right heart failure based on the underlying etiology. So I'll close here. I wanna thank you so much for your attention. This is sort of all of the things we reviewed today. The field really is moving along rapidly. It is a time of hope. This is some of my nursing team, one of our patients, we're at the Ph A walk. Um And I just wanna acknowledge all of my teammates. It really does take a huge army to take care of these patients and, and for all of the trainees, um We do have a dedicated one year PH fellowship if you're interested. So, thank you so much. Happy to take any questions. What is the gold standard for function? Yeah. The second. What is the risk for noncardiac, sir? How, how significant, great, so great questions. The first question was, what is the gold standard for assessing right heart function and echo? And what I would say is it doesn't have to be too complicated. I think there's a lot of excitement as there should be in strain in 3D imaging. But where the field is right now, I think any objective quantifiable measurement of right heart function is better than the current of what's happening. So whatever, if your echolab is measuring RV fractional area change consistently, then that would be wonderful if it's TSI and it's quantified it in that way, you're only representing the longitudinal motion, which is about 70% of, of RV contraction. But it is more uh reproducible between readers. Um S prime is very helpful. It's a similar concept in longitudinal velocity of the right ventricle. I don't know anyone that uses rim. Um But of course, it's on the echo boards. So, um and, and I'm seeing around the country more and more 3D RVEF being assessed on echo, which I think is wonderful. Um And so all of those things um in a quantifiable way are great. Um Your second question about perioperative. So the, that's a huge topic. And I would say in those scenarios, all the more reason to refer and transfer to a center that has PH available medically at, at the place where surgery may happen. Um But the, the goal is for that right heart function to be optimized for the jugular venous pressure to be normal for cardiac output index um to be as close to normal as possible, balanced with the urgency of that surgery. Um Our anesthesia colleagues really rely on us to do that per operative risk. It's not a population that generally makes it to the or routinely. So the there is a gap of comfort there in the operative setting. Yeah. Yes. Hi. Yes, that's a great question. Thank you. So, the question is about at what point do we use stress echo? And, and how do we uh what modalities? So I'll be honest and say routine stress echo protocols for what we normally use stress echo for coronary ischemia are not gonna be as informative for the PH patients. Um And so I do really believe in using exercise to understand the the severity of someone's disease or if it's left or right heart predominant. So uh the first answer I would say is mixed phys physiology combined, pre and post capillary ph is when exercise can be the most helpful. However, and you might not love this answer. It's most valuable to be done with invasive hemodynamics rather than echo Doppler images in that context. And most valuable to supplement with cardiopulmonary exercise testing. So for us, Supine Bike ergometer in the Cath lab with, with human dynamics and C PE and actually not using echo to assess at exercise for these patients. Yeah. All right. Thank you.
