I’m Marc Simon. I am a cardiologist and a heart failure specialist at UCSF in San Francisco. I direct the pulmonary hypertension program there. I moved there about four years ago now in 2021 for this opportunity from the University of Pittsburgh where I was on faculty for about 15 years, taking care of pulmonary hypertension patients within our cardiology section. Very similar to UCSF, in a very multidisciplinary group with both pulmonologists and cardiologists. It’s really been a really wonderful experience over these past 20 or so years.
 
I’ve done a lot of research over the years in terms of right ventricular function and adaptation in pulmonary hypertension, really ranging from imaging with echocardiography as we’ll talk about today, MRI, some CT scans, as well as integrating with hemodynamics to understand cardiovascular physiology of the right ventricle, as well as some translational work to try to understand the biomechanics of the right ventricle, which is an exciting and ongoing story. Finally, some drug development over the last eight years or so. That’s been really exciting. As you know, with pulmonary hypertension, we’re very fortunate to have so many drugs available to treat patients, so it’s been a wonderful career so far. 
 
It’s a really interesting time in pulmonary hypertension. There’s continued to be a lot of drug development going on with a lot of focus now on ILD and related pulmonary hypertension, which is particularly exciting in a space where prior we had no therapies. In that context, I’ll be talking to you today about echocardiography and right heart catheterization for the pulmonologist. This is a talk I gave recently at the California Thoracic Society. I really look forward to presenting some of this information today as a cardiologist, I guess, talking to the pulmonary community and folks involved with pulmonary hypertension, and potentially patients as well, getting some insights as to some of the testing that we do to better understand disease and diagnose.
 
When I think about echocardiography for pulmonary hypertension, I’m kind of thinking really sort of broadly speaking in three different contexts that I find to be really helpful to think about this. One is echocardiography, of course, useful for estimating a pulmonary artery pressure. That’s what most people will think about and that can be really useful. That echocardiography is a great screening test for the pulmonary pressure.

Then, I really like to come at the echocardiogram in terms of trying to end up at a phenotype that is either right-sided or left-sided. I think that’s a really nice context to think about the echocardiogram as you’re going into this. By right-sided, I mean, sort of a RV failure type phenotype, and that’s really what we’re talking about for pulmonary hypertension, pre-capillary pulmonary hypertension. As opposed to left-sided, thinking about really ending up being group two pulmonary hypertension and all the causes thereof related to heart disease and things like this. You’ll hear me talking about right versus left-sided phenotyping as we go through some of these highlights of echocardiography for pulmonary hypertension.
 
Finally, it’s always important not to forget with the echocardiogram, that’s a great screening test for congenital heart disease. So, of course, that’s a very unique and specific cause of pulmonary hypertension. A lot of times, you’ll get your first inkling that this may be what’s going on, on the echocardiogram. 
 
I like to start off by highlighting a study that came out a few years ago, actually, out of Australia by a Strange and colleagues, it was published in Heart in 2012. They just looked at all echocardiograms that had an estimated pulmonary artery pressure greater than 40 millimeters of mercury. All of those coming through the echo lab, out of those, two-thirds ended up being left heart disease. So, the vast majority of what we’re seeing that’s referred to us as an echocardiogram that might be suggestive of pulmonary hypertension with an elevated estimated pulmonary artery systolic pressure really ends up being left heart disease. So, again, really important to keep this in mind. Only 2.7% of those patients ended up having pulmonary arterial hypertension. About 2% had chronic thromboembolic pulmonary hypertension and 9% had lung related disease.
 
The 2022 European Guidelines think about echo screening in terms of three contexts. This is the ventricles, the pulmonary artery and the inferior vena cava and the right atrium. Showing signs from at least two of these can alter your level of a probability of pulmonary hypertension. When we’re talking about the ventricles, there’s a couple of points. One is the right ventricle larger than the left ventricle. This can be as simple as a basal diameter in which the right side is greater than the left side. Along with this can be flattening of the interventricular septum.
 
Those two points right ventricular enlargement, RV size greater than LV size and flattening of the septum falls into that context of a right-sided phenotype that I was mentioning. Then, talking about the TAPSE, tricuspid annular plane systolic excursion or that ratio of that to the systolic pulmonary artery pressure being less than 0.55 millimeters per of millimeter of mercury. I’ll talk a little bit about what that particular measure is. Some people like it, some people don’t.
 
TAPSE is a measure of right ventricular function. Of course, systolic pulmonary artery pressure is the pressure afterload that the right ventricle sees. In terms of the pulmonary artery, a dilated pulmonary artery, like I’m sure a lot of pulmonologists are really keyed into. In fact, I usually receive several referrals a month based on an enlarged pulmonary artery seen on a CT scan and is this related to pulmonary hypertension.
 
So, the enlarged pulmonary artery can also be seen on echocardiography. That can be a real phenotype that keys you into precapillary pulmonary hypertension. Also, is the pulmonary artery acceleration time. This turns out to be my favorite, favorite term in echocardiography. I’m going to talk to you a bit more about that. But essentially, it’s the flow out of the right ventricle through the pulmonary valve into the pulmonary artery, and you can measure the onset of that flow to the peak velocity. If it’s less than 105 milliseconds, call it 100 milliseconds, it’s easier to remember. That is a good cut point to say, “Hey, maybe this patient has significant pulmonary hypertension.”
 
Again, I’m going to talk about that a lot more. Then, a dilated inferior vena cava, significant for right ventricular volume overload. Right ventricular failure, a high central venous pressure, for example, and a dilated right atrium. These are other signs of that right-sided phenotype again. Again, if you have signs from at least two out of these three categories, it can be highly significant for pulmonary hypertension.
 
A lot of people are familiar with this concept of the large dilated right ventricle and right atrium, the flat septum, the pericardial effusion that a lot of times can be seen in pulmonary arterial hypertension. We’ll have a link to some images of this if that’s helpful for folks.
 
Let’s talk a little bit more about my favorite echocardiographic measure, the pulmonary artery acceleration time or PA acceleration time or sometimes called PAAT. If you’re in the parasternal short axis view at the valvular plane, for those of you who have looked at echocardiograms, that view where you see the cross section of the aortic valve right in the center there and on the left side of the screen is the tricuspid valve with the right ventricular outflow tract arching over the center of the top of the screen over the aortic valve, and then the pulmonic valve on the right side of the screen leading out to the main pulmonary artery. That classic view of the basal cut of the parasternal short axis view.
 
When we look at the flow on that right side of the screen, so from the right ventricular outflow tract out through the pulmonary valve into the main pulmonary artery, we can look at the Doppler velocity of the blood flow in that direction. That flow is what we call the ejection from the right ventricle out into the pulmonary artery.
 
Again, we can measure the onset of that flow to peak velocity because in Doppler terms, we’re measuring velocity. So, the peak of that velocity, and this is really sort of a U-shaped type of velocity envelope as we call it. So, the onset to the peak of that U, the X axis is time, and we’re measuring that in milliseconds, so, that time is the pulmonary artery acceleration time. As it turns out, it’s highly sensitive to pulmonary pressure and it gets shorter as pulmonary pressure is elevated. So, it’s inversely related to pulmonary pressure. 
 
I quiz the trainees a lot on this. Why would that be? Why is it an inverse relationship? Well, it turns out this is related to cardiovascular physiology. So, if you think back to medical school, the idea of isovolumic contraction of the ventricle, because after the ventricles filled, you have to develop enough pressure to overcome the pressure that you’re pumping out against, in this case the pulmonary valve and the pulmonary artery. So, ventricular pressure during the initial contraction phase has to develop enough pressure to exceed pulmonary artery pressure. Then, the pulmonic valve opens once that pressure gradient is exceeded. Once the valve opens, then we have ejection. After ejection is complete in terms of enough volume has been ejected from the ventricle, that ventricular pressure then starts to fall. When right ventricular pressure falls below pulmonary artery pressure, the pulmonary valve will close again, and then you’ll have isovolumic relaxation until pressure falls below the right atrial pressure. Then, filling begins through the tricuspid valve. 
 
If you think about pulmonary hypertension, the higher the pressure in the pulmonary artery, the more that the right ventricle has to overcome in order to eject its volume. If you think about the cardiac cycle being fixed, then the higher the pressure, the more time the ventricle is going to spend in isovolumic contraction to develop more pressure to then overcome the pressure in the pulmonary artery and eject. So, there’s less relative time in ejection. So, that means, all of the blood flow out of the right ventricle into the pulmonary artery has to occur in less time. You can imagine that really squashes down, that narrows down the velocity window of ejection. So, the time from onset of flow to peak flow becomes much narrower. That’s that inverse relationship between pulmonary artery acceleration time and pulmonary pressure.
 
There was a nice paper published in 2011 actually, in the Journal of the American Society of Echocardiography, first author Yared that looked at the PA acceleration time and created an equation linking it to estimated pulmonary artery systolic pressure. I really like this because you can then relate directly the PA acceleration time in milliseconds to pressure. When I calculate that out, if you have a PA acceleration time of 150 milliseconds, that calculates out by this paper to 32 millimeters of mercury. So, not too bad. If the PA acceleration time, then decreases to 100 milliseconds, remember this is the cut point for the European Guidelines, 105 milliseconds, very close. That calculates out to an estimated PA systolic pressure of 50 millimeters of mercury.
 
You can see right there, you’re at a significant pressure in a range where we would really say, “Oh, that might be someone we should look at further.” PA acceleration time of 50 milliseconds, which I’ve seen quite frequently, calculates out to an estimated PA systolic pressure of 79 millimeters of mercury (mm Hg). Really, that’s significant pulmonary artery pressure. Beyond just being able to have another measure of estimated pulmonary artery systolic pressure, there’s a couple other things I like about this. 
 
One is that it’s not just numeric. I’ve told you a lot about the numerics and the physiology, but that can be a little bit complicated. There’s also a qualitative version of this, which is, if you’re looking at that velocity envelope, it’s is called mid-systolic notching. Along with a steepening of the velocity going out into the pulmonary artery, on the backside of that nice U-shaped (usually) curve, you’ll get a notching. This can look like a W or an M. It’s very obvious in many cases. That qualitative sign also goes along with significantly elevated pulmonary pressure.
 
A lot of times actually, when I’m reviewing an echo where I don’t have that measure already made for me and I don’t have the ability to measure it on my own on the fly, I’ll make a note to myself, “Oh, this patient has mid-systolic notching or this patient does not have mid-systolic notching.” Again, that to me is another one of those check boxes for is this a right-sided phenotype? There is mid-systolic notching. Or a left-sided phenotype, there is no mid-systolic notching? There’s a few examples of this that will be in the link.
 
The final reason, I really like pulmonary artery acceleration time is the incomplete tricuspid regurgitation jet. I’m sure everyone’s seen an echocardiogram report where it says there’s an incomplete TR jet. Therefore, we cannot estimate pulmonary artery systolic pressure. That occurs in really upwards of 25% of echoes. So, it’s quite substantial. When this occurs, almost always there’s a viable PA acceleration time or RV outflow Doppler signal that’s in the echocardiogram and can be pulled out. Even in these indeterminate echocardiogram reports, many times, we can actually come up with an actual estimated PA pressure using the PA acceleration time.
 
The other things I like to look at with the echocardiogram are right ventricular function. We’ve talked a little bit about right ventricular structure, is it dilated or not? We’ve talked about the estimated PA pressure and the related lauded pulmonary artery acceleration time. Finally, let’s talk about right ventricular function.
 
So, again, diminished right ventricular function will fall into that right ventricular phenotype echocardiogram versus normal right ventricular function, maybe, there’s not a significant pulmonary hypertension. There’s a number of metrics now out there to help evaluate right ventricular function. One of the main ones that I would say is reported on more echoes than not these days is TAPSE.
 
Probably, a lot of people are aware of this. It’s not a new measure at this point, but it is related to the longitudinal motion of the right ventricle. This is a large portion of right ventricular function, not all of it, but a large portion of right ventricular function. We can measure how much motion is in that tricuspid plane just by measuring in one dimension the motion in centimeters or millimeters. The more motion there is, the more normal the right ventricular function is. There are various cut points between 2.0 centimeters, that’s 20 millimeters and 1.6 centimeters or 16 millimeters. Why is this so important?

There are a number of papers that had come out thathave associated related diminished TAPSE with poor outcomes. 
 There’s a lot of prognostic value with this. It’s highly correlated with pulmonary pressure. So, it’s a really useful term to have in our reports. This is one of several that I’ll try to write down.
 
The next one is what’s called right ventricular S’. S stands for systole or systolic contraction. The prime (‘) indicates that this is a tissue Doppler measure. So, we’re actually measuring the velocity of the tissue in this case and not the blood. If we look kind of in a similar spot to where we look for TAPSE on the lateral wall at the basal level near the tricuspid valve, we can put a cursor there and we can measure the velocity of the myocardium of (the muscle of the right ventricle). A cut point for this is about 10 centimeters per second. If you’re above this, you have vigorous contraction. If you’re below this, you have right ventricular dysfunction. 
 
Again, another measure that is in many reports these days, I’ll add it along with TAPSE to sort of complete this story. I kind of find that with right ventricular function. Remember, the right ventricle is a very complex three-dimensional structure. Echocardiography is a one-dimensional or two-dimensional modality of imaging. You need to provide multiple views, multiple metrics to really best describe right ventricular function I find. I don’t think any one measure is good enough to really give you a full picture of right ventricular function. The more of these you can sort of put together the better.
 
So, we have TAPSE. We have right ventricular S’. Then, there’s also strain, right ventricular strain. In this case, we’re looking at image processing of the right ventricle, and we can look at the shortening of the myocardium from one frame to the next as the right ventricle contracts, and the percentage shortening is correlated with right ventricular function.
 
We can look at the free wall of the right ventricle. We can look at the septum. We can average all of those together. More often than not, I like to look at the mid right ventricular free wall, a shortening of minus 20% or so in absolute terms, more, if you want to talk about it or in negative terms, more negative is normal function, and less than that is abnormal.
 
Then, more recently, there have been some attempts to put together several of these metrics to help us guide is this more of a right ventricular phenotype, pulmonary hypertension, precapillary pulmonary hypertension phenotype, or more of a left-sided phenotype or Group 2 pulmonary hypertension phenotype. One of these is the VEST echo screening tool, which looks at three parameters. 
 
One is the mitral E/e’. I haven’t talked about this too much, but this is a measure of left ventricular diastolic function. I put left ventricular diastolic dysfunction into that left ventricular phenotype category. You can have a whole lecture just on that alone. But another probably good point to look at and keep an eye open for on our echocardiograms is simply has there been a mention of a grading of left ventricular diastolic function? If there is, that might be one of these warning signs that maybe we’re dealing with a left-sided phenotype.
 
But in any event, the VEST echo screening tool looks at the mitral E/e’, looks at left atrial size. We talked a little bit about right atrial size. A dilated right atrium, a significant for precapillary pulmonary hypertension, that right-sided phenotype. A dilated left atrium is a big marker of left-sided disease. Then, finally, septal flattening. We’ve talked about that before too. So, more to come on that measure (VEST echo screening tool), I think, as there’s more work being done on it. 
 
With that, I’ll switch gears to right heart catheterization and talk a little bit about that. So, with right heart catheterization, as many of you may know, access is through a vein and really can be done in a number of different spots at this point. We can, of course, access from the femoral vein in the groin area or the jugular vein in the neck area. But more and more, we’ve been accessing the brachial vein sort of in the elbow area. This can be a lot of times a little kinder and gentler on our patients, which is really nice. Every so often, as I’ll tell patients and prepare them for, the road from the elbow there to the heart isn’t complete. So, we may need to shift gears from trying to access the brachial vein to one of those other spots. In large part, it can be thought of as, “Oh, maybe it’s a little kinder and gentler to the patients unless it doesn’t quite work out.” Then, maybe it’s a little bit longer on that flat hard cath lab table. 
 
When I think about right heart catheterization, the thing to think about is what’s behind a number, right? We get these reports and it’s a whole bunch of numbers. If the numbers fit our definition of pulmonary hypertension, pre-capillary pulmonary hypertension, great. If they fit post-capillary pulmonary hypertension, great. But I think what’s really important to think about is what’s behind those numbers.
 
There’s a lot of areas where you can have sources of error in the right heart catheterization recordings. There’s a great paper that former colleague of mine, Navin Rajagopalan, was the first author on last year in Jack JACC: Heart Failure that went through all of these really lovely. I highly recommend this paper. That group put together about eight reasons, eight sources of error in the right heart catheterization.
 
This starts with improper zeroing and leveling. As you can imagine, you have to level the transducer. This is a fluid-filled catheter. It’s connected to a pressure transducer outside the body. Sometimes, in our cath lab, we connect it to a pole that’s connected to the cath lab table. But that transducer has to be leveled to the mid-thorax level, the level of the right atrium. If it’s a little bit off, it can affect all of your pressures. It can raise them up or lower them down. So, that’s number one, zeroing and leveling of the transducer.
 
Then, there’s damping. I think a lot of people have seen and thought about damping of a catheter and the measurements that we get. Again, this is a fluid-filled catheter. If there’s one tiny little bubble in the catheter or the transducer, that will dampen the signal that’s measured. So, our mean pressures may all be about the same, but it will definitely affect our systolic and diastolic pressures that we measure.
 
Another source of dampening, interestingly enough, I mentioned the brachial access, which sounds really great. We have to use a 6-French catheter for brachial access, which is a smaller, narrower catheter than the normal 7-French catheter that we use. That smaller tube creates a much damper signal. So, I see a lot of dampening with a brachial access.
 
The next source of error is catheter whip. Remember, this is a balloon-tipped catheter that’s in blood flow in the cardiovascular system, which is pulsatile. You can imagine the tip of that catheter in the pulmonary artery with each beat, it’s going back and forth, it’s going left and right. The more of that it’s doing on the tip, the more artifact that we’re seeing in the pressure reading. This can artificially elevate systolic pressure. It can artificially decrease diastolic pressure, if you’re looking absolutely at these tracings. You kind of have to in your mind’s eye, edit those out when we’re interpreting the waveforms.
 
Then, there’s over and under wedging. This is another thought I think a lot of people have had with the pulmonary wedge pressure. Again, this is a balloon-tipped catheter. The tip of the catheter could, when we wedge that balloon into a branch of the pulmonary artery, if the tip is a little bit twisted, then we can hit the side of the wall, and that’s called over-wedging, and we can falsely elevate our numbers.
 
Similarly, if we haven’t used that balloon to completely block all of forward flow in that little vessel we’re in, then we’re going to get artificially elevated pressures because we’re getting a leaking forward of the forward flow of the pulmonary artery. So, a couple ways in which the pulmonary wedge pressure can be artificially elevated.

There’s a respiratory variation, as I’m sure a lot of the pulmonologists out there are very keyed into. This can cause large swings in the pressures that we’re measuring. Particularly in the setting of COPD, we want to think about using the mean pressures in particular as opposed to the mean of the means throughout multiple respiratory cycles, as opposed to any one particular respiratory cycle.
 
There can also be errors from mitral regurgitation. This can lead to falsely elevated wedge pressures. Finally, there’s the cardiac output is another area where we can see a lot of error. Cardiac output, sort of the gold standard for this would be the direct Fick measurement. For that, we need to measure oxygen and carbon dioxide gas exchange, like a cardiopulmonary exercise test to get an accurate basal oxygen consumption for the Fick equation.
 
Most cath labs don’t have the ability to do this. So, they rely on the indirect Fick cardiac output calculation, which makes a really big assumption and that’s that basically everyone has the same basal oxygen consumption. Remember, our pulmonary hypertension patients are sick, and it’s not exactly a normal basal condition to be sitting on a cath lab table with an IV in you. So, all these things can alter the oxygen consumption at rest.
 
So, the indirect Fick, we sort of shy away from using that too much. So, that leaves us with thermodilution cardiac output. Thermodilution cardiac output is based on a specific equation with the temperature of the sterile saline that you inject and how different that is from body temperature. The amount of saline that you inject every time we try to make it exactly 10 cc’s. But maybe, it’s a little more, maybe it’s a little less. All of this will affect the cardiac output that you measure with thermodilution.
 
The final point of this can be tricuspid regurgitation, right? With severe pulmonary hypertension, we have a lot more tricuspid regurgitation. That creates a forward flow and backward flow with each cardiac cycle, which would create a lot of washing, right? So, that can artificially change how we’re affecting the temperature of blood when we’re injecting this one little bolus of sterile saline. For all of those reasons, it’s recommended to use an average of three to five injections to measure cardiac output. 
 
The final point I’ll mention is atrial fibrillation. So, atrial fibrillation, an irregular heartbeat, irregular amount of time between one beat and the next beat. This will greatly change the stroke volume that you measure with any given thermodilution. So, again, you have to use more measurements to get a nice average there. So, all sorts of ways in which we have to be really cognizant of the numbers that we’re getting from right heart catheterization, because there are a lot of pitfalls and sources of errors there. 
 
Now, I’m going to mention vasoreactivity testing. This is always a question that comes up whenever we’re talking about right heart catheterization. Vasoreactivity testing is really reserved for patients with idiopathic pulmonary hypertension, hereditary pulmonary arterial hypertension or drug induced, really not for any other forms of pulmonary arterial hypertension. The other point is that there is a very, very specific definition for positive response during a vasodilator challenge. That is that one, there’s a reduction in mean pulmonary artery pressure of at least 10 millimeters of mercury to reach an absolute value of 40 millimeters of mercury or less.
 
If you’re doing the vasodilator challenge and you go from a mean pulmonary artery pressure of 50 mmHg to 45 mmHg, that is negative. If you go from 55 mmHg to 45 mmHg in a mean pulmonary pressure, you’ve met one of the criteria, but not the other criteria. You haven’t gone below the absolute value of 40 mmHg, and that is also a negative vasoreactivity test. 
 
The final point is, you have to have an increased or unchanged cardiac output. I like to see pulmonary pressure, wedge pressure, and cardiac output on the vasoreactivity testing from the cath labs. I like to use nitric oxide. We just set it at 20 parts per million, 5 or 10 minutes is all you need. Many places have trouble getting nitric oxide, in which case epoprostenol could be used. It is recommended not to use IV adenosine anymore due to frequent side effects. 
 
At this point, when I’m talking about right heart catheterization, I like to take a step back and say that it’s real important to think about pre versus post-capillary hypertension. It’s real important to think about this before the right heart catheterization as you’re sending someone to the cath lab.
 
Why is that? Because that pretest probability for post-capillary pulmonary hypertension is highly, highly valuable, because there are some maneuvers that we can do in the cath lab that can actually bring this out really nicely. Yet, we need to know whether or not we should be doing those a lot of times ahead of time. I admit it’s a little bit like the chicken and the egg, but if you think about this a little bit ahead of time, you can perhaps order the right heart catheterization with one of these provocative maneuvers such as exercise or fluid challenge, or even a simple leg raise can be really helpful.
 
Well, how can you get a pre-test probability for Group 2 pulmonary hypertension? I really like the H2FPEF score. This is a score that Barry Borlaug published in circulation in 2018, and it’s a mnemonic. H two stands for the first H is heavy, so a BMI greater than 30. The second H is hypertension. So, two or more antihypertensive medications. As you can see, these variables that I’m listing for you are all risk factors for Group 2 pulmonary hypertension, really for HFpEF (heart failure with preserved ejection fraction), for diastolic dysfunctions. The older term for that is diastolic heart failure with preserved ejection fraction is our newer term with this. 
 
If we’re thinking about ILD, a lot of times this is a highly comorbid condition, as are some of these other conditions. So, H2FPEF, heavy, hypertension. The F stands for atrial fibrillation. That’s the highest risk factor for HFpEF. We get three points for atrial fibrillation. P stands for pulmonary hypertension. That’s the estimated PA systolic pressure on our echo of at least 35 millimeters of mercury. E stands for elder age over 60, and F stands for filling pressure. That’s the Doppler echo E/e’ greater than nine. So, it’s a rather low bar for that. 
 
Each of those has a point from one to three, and you add those all up and you get a score. Zero to one points is a low-risk of HFpEF. Two to five points is intermediate risk, and six points or greater is a very high risk for HFpEF. It only takes a few things to become really high risk for HFpEF, such as atrial fibrillation, hypertension, and a BMI over 30. Those three alone gives you six points, and that’s high risk for HFpEF.
 
Again, I think this is really worthwhile when I’m first meeting a patient and thinking about the right heart catheterization, because that really makes me think a lot more about post-capillary pulmonary hypertension than pre-capillary pulmonary hypertension. We know these patients can hide in plain sight, right? We’re all very good with diuretics. We can really hide an elevated wedge pressure very easily. We put our patients on Lasix or something similar, not too tough to hide a resting elevated wedge pressure. This is where these provocative maneuvers can come in handy. So, anyone with intermediate or higher risk of Group 2 pulmonary hypertension or HFpEF, I want to think about a provocative procedure in the cath lab. I won’t accept a normal resting wedge pressure in these patients.
 
Another way to think about this is what’s been more recently called this “zone of uncertainty.” This is a resting pulmonary wedge pressure of 12 to 15 or 12 to 18, but think of it as 12 to 15. No longer do we just say, “Oh, 15, yeah, that’s normal.” We don’t need to think about that anymore. That 12 to 15 range is really intermediate and we really should be thinking about provocative maneuvers, particularly in folks with some increased risk for Group 2 PH.
 
I mentioned the exercise testing can be really helpful to bring this out. An absolute increase in the pulmonary wedge pressure to 25 millimeters or greater is considered positive for HFpEF or Group 2 PH. But you can also do a passive leg raise that could be a lot easier in the cath lab. With a passive leg raise if the wedge pressure goes to 19 or greater, and this was published in 2022 by van de Bovenkamp and colleagues in Cirque Circ: Heart Failure. That can be diagnostic of occult HFpEF as well, which again would be Group 2 pulmonary hypertension.
 
The other way we can think about Group 2 pulmonary hypertension, or HFpEF, is how much does the wedge pressure increase per how much increase in cardiac output do we have? This was a paper published by Eisman in Greg Lewis’s lab in Cirque Circ: Heart Failure [MS1] [MS1]in 2018. If the wedge pressure increases by more than 2 millimeters of mercury for every liter per minute increase in cardiac output with exercise, that’s a very positive sign for HFpEF. There’s almost no overlap using that cut point between patients with HFpEF and those without.
 
To me, that’s a very physiologic measure. It may be a little bit more complex to calculate. I think Kovacs and colleagues have shown that this can be done by simply looking at the baseline numbers and the peak exercise numbers. So, that’s another way to sort of simplify this measurement.
 
I like to really think about this pre-test probability of Group 2 PH, really being able to pull those patients out. Even when I’m thinking about ILD, perhaps even more so sometimes when I’m thinking about ILD and related pulmonary hypertension, since I know that hypertension and heart disease are so comorbid in these patients.
 
 There’s a lot of examples that I and others could show you of normal resting hemodynamics and with two minutes of exercise, the wedge pressure has gone from about 10 mmHg up to about 25 mmHg or 30 mmHg. It’s just reiterating the usefulness of exercise in the cath lab if you can get it.
 
 So, in summary, echocardiography, think about this right-sided phenotype versus left-sided phenotype. Think about my favorite measure, the pulmonary artery acceleration time, PAAT. Don’t forget about HFpEF when you’re thinking about sending patients to the cath lab. Think about all of those caveats and pitfalls that can be behind the numbers that we see in right heart catheterization. 
 
 I’m Marc Simon, and I’m aware that my patients are rare.

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