Welcome to CHESS 2023. My name is Dr. Benchikran Hassan, and I hail from San Diego, and you have a fantastic panel of physicians that are enthusiastic and passionate about pulmonary arterial hypertension, and I suspect the audience as well. We have a great set of lectures, and last year we were having a conversation at the Pulmonary Arterial Hypertension Network, or Pulmonary Vascular Network, after the lecture, and some of the Q&As from people like yourselves were centering around not just the guideline, not just the diagnostics, but what next if I'm in the community and I have a patient where I get a pulmonary arterial hypertension in one of the tests, then what? Can we chart for the community physician as well as for the faculty in a university setting, but mostly for the community physician, a path that would tell us what's the next step? So it is my distinct pleasure to start with someone I consider a friend and actually a mentor, and we were just joking wherever he is, I follow suit, but he leaves that leadership seat whenever I come in, so I'm starting to take it personal. Victor, Dr. Test, is a pioneer that I've called many times on patients that I had pulmonary arterial hypertension, tough cases. He is professor of medicine at Texas Tech and chief of the division of pulmonary, and he's my good friend, and I am very excited to see what he has to share with us this morning. Victor? Well, thank you again, Hassan, for that overly generous introduction. And howdy to y'all. Welcome to Hawaii. I guess I should have said aloha. It's good to see some familiar faces. I think it's an honor when someone calls you a mentor, although the white hair I guess suggests why that is. But I think the greater thing is to be called a friend, and so I'm grateful for that. And one thing about this meeting that's so awesome is it's a convocation of friends, and if you're in Texas, we have this saying, there's no strangers, only friends you haven't met yet. Hopefully, if I haven't met you yet, I'll get to see you, and then we can be friendly. Now, I'm going to talk today about pulmonary hypertension, timing criteria, and the start treatment and the follow-up schedule. And, as I said, I have nothing to disclose other than a strong bias and love for pulmonary vascular disorders. You know, these are the objectives of the overall of the session. At the end of my talk, I really want you to understand, you know, the importance of a thorough evaluation and the thought process that goes through the diagnosis of pulmonary arterial hypertension, and ultimately, you know, how do we determine what therapy to start and how quick, you know, how do we follow up people, how do we determine who needs urgent or emergent aggressive therapy. So, just as a poll, you know, those of us who practice PAH or pulmonary hypertension know that the referrals of the cause of PAH is often quite diverse, so we have this poll asking you, you know, what the, let's see here, oh, goodness gracious, that was a really good audience response. I gave you the answer. So, what is the most common cause of referral to a PAH center, and actually, according to this study, it's quite old, but reflects general practice, and there's a similar study from Australia, left heart disease actually is the most common thing, about 85% of patients referred to a PAH center don't have PAH. Now, everybody that comes to my PAH center, the assumption is that they have PAH. That's why they're being referred to me. There's a little bit of resurgence of group three and group four as awareness of those disorders become more familiar to practitioners, but ultimately, the main thing we do as practicing pulmonary hypertension people is to sort out the etiology of the pulmonary hypertension, because the treatment, of course, goes directly from that. So, I'm not going to, many of you probably are very familiar with the evaluation of pulmonary hypertension. What I would just tell you is that the overwhelming majority that come to my center, whether they come from cardiology, pulmonology, or family practitioners, general practitioners, have had only a fraction of the evaluation that they need. And that's okay, because that's why they're sending them to me, but there's a growing movement and tendency to start therapy prior to referral to a pulmonary hypertension specialist, and if you don't have a complete workup, it makes it a lot easier to miss the underlying disorder. And so, I think basically, you start with simple testing, right? You have your EKG, your echocardiogram, chest radiograph, which is neither sensitive nor specific, but gives us real clues to the diagnosis, as indicated, polysomnography, we'll come back to the right heart catheterization in a minute, ventilation, perfusion, lung scanning, exercise testing, and PFT, and of course, lab work. There was a study that I participated in several years ago called the QUERI study, which is Quality Enhancement Research Initiative, in PAH, and it was a really enlightening study of centers in the U.S. and Canada. I don't remember how many there were, but there were quite a large number of patients, and even after a three-year period in that study, only about 50% of people had been screened for chronic thromboembolic pulmonary hypertension, which is, as you know, a tragedy, because I mean, if I said to you, you have a potentially progressive and lethal disorder, and there's a simple test I could do to look for a curable form of that disorder, how many of us would not leap at the opportunity to take that test to look for the possibility, and the answer is most of us would say, please, give me the curable disorder, okay? And unfortunately, even now, in referral centers across the country, that is ignored, okay? Now CT scanning and CT angiography is often, is done probably with more frequency than VQ scanning, and while that, I do believe that CT scanning is evolving more, much more rapidly than VQ scanning, and in capable hands with good quality scanning, you know, it may be almost equivalent to VQ scanning in terms of sensitivity, and certainly in terms of specificity, it's better. I don't think, you know, that, you know, we still shouldn't deviate from the effort to look for that disorder, and actually, if you look at that query registry, the most common test that was left undone in the evaluation of patients with PAH was HIV, which only five or ten percent of patients in that study had been screened for HIV, and while that is a very small percentage of the patients I have in my clinic, it's a very, very important one to recognize because of the severity of the disease and the implications of the other comorbidity. So in this poll, what is the gold standard to diagnose pulmonary hypertension, and, you know, we're going to see if it comes up with the answers here, let's see, no, it did not, so, you know, the options here were echocardiography, VQ scanning, cardiac MRI, pulmonary function testing, which that one was a give me if you didn't know it, and I think if you ask most people, and actually in the fellows course yesterday with almost a hundred some odd fellows, oh, there it is right there, see, I'm looking at the wrong screen, no wonder, see, this is what happens when you have the white hair, you become the technologically impaired guy in this, so there you go. So we have two participants in the thought right heart catheterization, so this is a great, this is a trap, right, you know, don't you love that when the white haired guy throws out a trap, the most important confirmatory test is a right heart catheter, of course, and an echocardiogram is the most important screening test, all that other stuff is important, but actually, and, you know, I'm going to quote someone here, and Paul Forfia is a really interesting guy, and he said this at a meeting one time, and I think this is the most important thing, and this is why, if you want to take something away from this, the gold standard diagnosed PH is not the heart catheterization or the echo, but it's the clinician who takes all of the clinical data, and including the cath and the echo, and puts it together to determine the appropriate diagnosis. So often, we see people that clearly, when they present, say, to the hospital with pulmonary edema, pleural effusions, orthopnea, uncontrolled hypertension, get diuresis, and they get a heart, they have an echo that shows pulmonary hypertension, and normal left ventricular ejection fraction, they get a cath, you know, six days into their hospital stay after they've been diuresed, and they come up with a diagnosis of PAH, and you have to take all of the data that you get, and including EKGs, and chest x-rays, and CT scanning, and synthesize it to come up with the correct diagnosis, and if you don't do anything else as a community practitioner, that is the most important thing, okay, and it is also really hard to do in some patients. All right, so when do I start therapy? Now this is, I'm not going to go through this really lovely and excessively complicated slide. The first thing is, you take care of basic, you know, medical problems, you take care of symptoms, hypoxemia, and so forth, and my point is not specific therapy and how you determine it. The early study, which was a study looking at both Santan and functional class two patients done almost 20 years ago, answered the question of when do you start therapy on people, okay. In that study, they had patients in functional class two, because at that time, all of our medications were approved only for functional class three and functional class four, and intrinsically, those of us in PAH said, well, that doesn't make any sense. Why would, if we diagnose someone and they have really minimal symptoms, why in the world would we wait until they were more symptomatic and had a worse prognosis? And so, the basic answer to when do you start therapy is, as soon as you make the diagnosis, okay. It's not complicated. It's a really easy answer, you know, because, and I'm going to show you data why coming up here in a minute, and, you know, we know historically from the NIH registry that life expectancy is very clearly linked to functional status, right. So patients with functional class one and two disease, untreated in the original NIH trial, had a life expectancy of six years. If you had functional class three symptoms, your life expectancy was on average 2.3 to three years, and then if you had functional class four disease, you had a life expectancy in the order of six months to a year if you were untreated. So why in the world would we want someone to be, wait until we get to functional class three to treat them? The answer is, and it was confirmed in the early trial, which didn't show a functional improvement, but showed hemodynamic, prevention of hemodynamic progression in just six months that we should treat people earlier, hence the title early. So what can we use to help us figure out what's a high risk feature? And this is, again, a highly complicated slide, but the historical factors that you can get from patients that are important in helping you figure out what to start are age, older patients with PAH do worse. No great mystery there, okay? And if you look on the slide, the data to the right, you can see in grades 80 and 65, the relative risk is higher for death than it is if you start off younger. What gender? Men with pulmonary hypertension do worse. It's one of the rare cardiovascular disorders where men do worse than women, but it is generally true, and particularly men above the age of 55, that their risk for progressive disease and death is much higher. Etiology. Well, if you look at the bottom of that slide, it compares idiopathic versus familial PAH and versus connective tissue, and the risk of death is higher in patients with connective tissue disorders, particularly scleroderma. And I would also throw in there that the HIV and liver associated, cirrhosis associated pulmonary hypertension carry the highest risk that we have, and so we need to treat those people earlier. But the other things you can get are just when they're talking to the patient, or do they have syncope? Well, that puts them in functional class four, which we've already established has a high risk for poor outcome, and then ultimately hemoptysis, which carries also a very high risk of progressive disease and death. So again, why do we want to start treating these people early? And that comes based on functional status, and functional status is one of those things that in research is sort of like a punching bag. Everybody hates it, right, because it's so subjective. What can you do? But the reality is that you get a lot of information from asking a patient, can you walk across the room? If you can't walk across the room, that's generally considered a bad sign, okay? If you're fainting, that's a bad sign. If you can run wind sprints up the hill in the middle of August in Austin, Texas, you're probably going to do better than the guy who can't walk to the bathroom and back. And you can see in this study from the reveal data that, again, over time, functional class strongly predicts your outcome. Well, you know, one of the things that happens in our hospital and most hospitals around is the patient comes in and they're short of breath, they get a pantheon of tests, including a D-dimer, which is, of course, the bane of many of our existences at times. They get a pro-BNP and a troponin, which I think may be the bane of the cardiologist's existence, okay? But the pro-BNP, when it was first, well, actually the BNP, when it first came out and was presented in a paper by a fellow from San Diego named Alan Mizell, was very good at predicting, you know, pulmonary disease versus cardiovascular disease. But unfortunately, it's not nearly as good at predicting cardiovascular disease versus pulmonary vascular disease, right? So if you have left heart failure, you know, the BNP doesn't differentiate between PAH necessarily. However, the higher your BNP, and the cutoff used in this Kaplan-Meier curve was greater than 1,200 on the pro-BNP, is closely linked to outcome. What about the six-minute walk? Now, how the six-minute walk came to be part of our testing is a really good story, but we don't have time for that today. But if you want to hear that story, I'll be happy to tell you about it when you come up after the, if you have questions afterwards. But the six-minute walk, again, in the endpoint history of PAH, it originally started with the Iproprostanol trial in 1996. And people hate the six-minute walk. It's a terrible marker, they say, for exercise capacity. But the minute we had trials looking at morbidity and mortality, everybody just complained about the fact that the six-minute walk data wasn't as good. So I don't know what to make of that. But I do know that the six-minute walk and the distance walked is very clearly linked to exercise. And in the Kaplan-Meier curve there on your left, that's from the Japanese data, looked at 332. And on the right is the revealed data using a cutoff, using different six-minute walk cutoffs and looking at their outcomes over time. And again, in the United States, we typically use a cutoff of 380 to 400 meters to divide people who are higher risk versus lower risk. And so even though it is not a perfect test, and it is a cheat test, it's a test you can do every time you see the patient. And anybody can do it if they have a hallway, an oximeter, and a blood pressure cuff, and a brain. Okay? Well, the other thing came up, and we get to thank Dr. Paul Porphy again for the TAP-C because he was one of the people, drivers behind that. And we look at the echocardiogram in a low TAP-C, a massive enlargement of the right ventricle, pericardial fusion, Bowenian septum, changes in the tie index or RV strain, which can be calculated on using echocardiographic techniques that I'm not really expert in, are all related to this. But I chose the TAP-C because it's the easiest one to measure. It's the easiest one to quantify. And if you have a TAP-C greater than 1.8 centimeters, which means the tricuspid annulus is moving more with right ventricular contraction, that then you are going to have lower risk the more it moves. And if it moves less, then you are at higher risk. Well, what about prognostic scoring systems? Because those are all the rage in the pulmonary vascular world, but most people don't use them, right? We know this very clearly. And there's a zillion of them, and you get to pick which one you like best, but they're non-invasive criteria looking. And you can see that looking at functional class, the six-minute walk distance, which they use a threshold of 440 meters, a BNP with relatively modest numbers, you know, if you take those three criteria, they are actually very predictive of outcome. If you achieve functional class 1 or 2 symptoms, or you are functional class 1 or 2, you walk greater than 450 meters and you have a normal BNP, your long-term outcome and your predictive outcome is going to be better. You're in the low-risk category. If you add in right atrial pressure and cardiac index into that mix, then it becomes a more accurate but more invasive measurement. Just to take a little spiel here, the right atrial pressure, the CVP, in the world of sepsis and volume resuscitation has a bad name. People say, well, it's not very good. And maybe it's not. It's probably not very good to reflect overall volume stats. However, in the world of pulmonary hypertension, it is crucially important, and several different studies have confirmed this. If you have a right atrial pressure greater than 20, call in backup, okay, because those patients are at high risk with an 80% mortality at six months unless you treat them. And I see that particular value on right heart casts, and people refer to me, ignored over and over and over again. And when it should get your attention and say, stand up, we need to treat this patient. And this is, again, looking at the non-invasive criteria. And then, please don't by any means look at this, but I can tell you, you can go to Google, and type in reveal risk calculator, and it pops right up there for you to use. And I use this in all my patients when I start them on therapy. Every time I do a heart cath, I recalculate their reveal risk, and it is very good at predicting progression of disease. And it separates out low, intermediate, and high very well based on the score. I'm not going to make you go through that data, because I'm going to run out of time here in a moment. So, which one to use? There's the Compara. There's the French PAH registry. And if you compare them, I think on average, the reveal data is probably better at separating out low, intermediate, and high risk, but they are all good. It doesn't matter which one you use. If you use the four-point non-invasive criteria, the five-point combined invasive and non-invasive criteria, it doesn't matter, as long as you have a strategy to determine who is high risk and who is low risk. Now, what about a negotiating follow-up? I live in West Texas, so I have patients that drive five to six hours to see me. I obviously can't see them every week, and even if I could, I don't think I have the bandwidth to do that. So you have to figure out how often to see people. Well, frequency is the biggest thing when people have to drive and come see you. What kind of testing do you do, and when do you refer to a PAH center? Well, I'm a PAH center, so that one's out of the mix for me. I think frequency in general with PAH patients more often is better. I typically, when I start people on therapy, I see them within a month. Every time I change their therapy, I see them on every patient every three months, and every time I see them, I do pro BNP, chemistry panel, because I look at serum sodium, serum creatinine. I sometimes do uric acid, depending on the patient, and I do a six-minute walk every time I see them. I typically do echo once or twice a year, depending on how often their insurance will allow me to do it and how the patient is doing, and when do I determine to do a repeat right heart cath. I always do that when the patient is obviously getting worse or when there is a big discordance between what the patient tells me, because a lot of these patients have been really, really sick, and they'll come in and tell you, you know, oh, I'm doing great, when their six-minute walk is 210 meters, and you say, well, if there's that discrepancy and I can't sort it out from using non-invasive methods, then I'll do a right heart cath. But I don't routinely do one every time I, you know, see somebody in clinic, thank goodness, that would be a lot of work. Now when do you refer to a specialized PH center or lung transplant? Again, functional class for patients need to be treated very aggressively, and if you're not comfortable with that, you need to refer them immediately, all right? If they have disease progression on oral therapies, they need to be referred, because these patients are on a downward track, and they will continue on a downward track unless you change something. So in conclusion, you know, I think the most important thing for a community physician taking care of PH is doing a complete and thorough evaluation, taking that data, synthesizing it into the patient's diagnosis, using risk stratification tools, because there's a lot of nuance in determining how patients are doing. And because of that nuance, using risk stratification tools can make it easier for you to sort out who the patient is. And the follow-up needs to be very individualized and is quite variable. So thank you very much. Are we taking questions afterwards or right now? We'll take questions afterwards. Okay. Next, we have Dr. Jory, and Dr. Jory and I spoke last week, and she has been quite encouraging since last year to put this together. So we owe it partially to her that she wanted to have something for the community physicians. Dr. Jory is sharing my passion for pulmonary arterial hypertension and the challenges faced in the community. She's a graduate of the Cornell campus of New York Presbyterian, and she's one of the authors of an open-label study for inhaled triprostanil in patients living with PH. I look forward to what she has to share with us. Thank you for the kind introduction. I'm Shilpa Jory from Richmond, Virginia. I am a part of a large single specialty pulmonary critical care group where I see my PH patients. My disclosures are on the slide, they're non-pertaining to this talk. The objectives of today's session would be to, sorry, recognize the changing demographics as well as the different phenotypes in patients being diagnosed with idiopathic pulmonary arterial hypertension, to learn about designating the probability of having pulmonary hypertension based on echocardiographic findings, discuss the role of risk assessment in patients with PH and cardiopulmonary comorbidities, as well as review the concept of initial monotherapy for pulmonary arterial hypertension with comorbidities that was introduced in the most recent ERS ESC guidelines. So we shall start with a case example. This is a 70-year-old female patient who presented with progressive dyspnea on exertion for about four to five months duration with echocardiographic evidence of elevated right ventricular systolic pressure of 58 millimeters of mercury. Her past medical history included a history of severe pneumonia, and she had post-inflammatory pulmonary fibrosis, was requiring home oxygen at three liters per minute. Her other comorbidities included heart failure with preserved ejection fraction, systemic hypertension, diabetes, hyperlipidemia, sleep apnea. She was a nonsmoker, and she had no prior history of venous thromboembolic disease or rheumatologic disease. Her home medications were almisartan, glypsite, atorvastatin, furosemide, as well as pantoprazole, and she took some multivitamins. Her exam, she had normal vital signs with peripheral oxygen saturation of 95% in three liters. She had a VMI of 36. She did not have JVD, and lung exam showed bi-basilar crepitations with two-by-six holosystolic murmur at the left lower sternal border, and she had traspedial edema. So her chest imaging showed that she had some basilar pulmonary scarring with traction bronchiectasis. Her upper lung fields were relatively preserved. She had moderate restrictive ventilatory defect on PFDs with FVC of 65% and severely reduced diffusing capacity. Her BQ scan was read as low probability. She did have sleep apnea that was well managed with CPAP of eight. And she had an echo that showed left ventricular ejection fraction of 55% with a TAPC of 16, tricuspid jet regurgitant velocity of 3.3, moderate right atrial and right ventricular dilatation, estimated right ventricular systolic pressure of 58. Her IVC was dilated and collapsed less than 50% with respiration. And this is a short clip of her echo. So patients like her are presenting more and more in our real world practices. And it's important to recognize that the demographics of patients being diagnosed with pulmonary arterial hypertension is changing. And the average age at which the diagnosis is made is closer to 60 years based on contemporary registry data. In fact, a cluster analysis of about 841 newly diagnosed patients with idiopathic pulmonary arterial hypertension, only 12.6 had the classic phenotype of mostly young female patients without cardiopulmonary comorbidities. And when elderly patients present with pulmonary hypertension, they often have cardiac and pulmonary comorbidities that make differentiation from WHO Group 2 and 3PH somewhat difficult. So two phenotypes have emerged in elderly patients with PAH. The left heart phenotype consists of mostly female patients with risk factors for HFBIF, but with pre-capillary pulmonary hypertension, and approximately 30% of these patients have atrial fibrillation. The cardiopulmonary phenotype mainly consists of male patients who have lower diffusing capacity, have smoked in the past, are often hypoxemic, and have risk factors for left heart disease. So when we see patients with dyspnea or for a workup of pulmonary hypertension noted on echocardiogram, the patients often undergo extensive testing, sometimes for lung disease, sometimes for heart disease, but more often for both. An echocardiogram is probably one of the most common tests that is ordered for a dyspneic patient in whom pulmonary hypertension is suspected. We have become better at asking, even in the community, as PH practitioners, asking for the tracings for a right heart catheterization for looking at the wedge pressure just to make the accurate diagnosis of PAH, but I think we are lagging behind with the familiarity of looking at the pulmonary hypertension signs on echocardiogram when the patient presents to us for consultation. The probability of pulmonary hypertension, there's several signs on the echocardiogram that can determine it, and when a patient has high probability of having pulmonary hypertension, they should undergo, for the workup, that includes a right heart catheterization, which remains the confirmatory test to diagnose PAH. So take a moment, it's a busy slide, but to take a moment to review some of the findings of pulmonary hypertension on the echocardiogram so that these patients can be detected early as well as interventions can be started early, and we don't have patients presenting with this kind of, this echo, which shows massive RV enlargement, this patient is in trouble. So the recent ERS-ESC guidelines have a beautiful illustration of different findings on the echocardiogram that suggest pulmonary hypertension. It ranges from the morphology of the right side of the heart and the fractional area assessments, the position of the interventricular septum, the left ventricular eccentricity index, of course, measuring the TAP-C, measuring other parameters of RV strain like a tie, and then there is the tricuspid regurgitant velocity, which has received more attention given that estimation of systolic pulmonary arterial, pulmonary artery pressure on the echo is sometimes difficult and challenging and maybe erroneous. So the most recent guidelines put forth a suggestion and recommendation of how to use the peak tricuspid regurgitant velocity. There are three ranges they identified. In patients who have tricuspid regurgitant velocity of less than or equal to 2.8, you look for other pH signs on the echocardiogram, and if there are no pH signs and there are no risk factors for presence of pulmonary arterial hypertension or CTEF, alternate diagnosis should be considered in these patients and they should undergo further workup. For patients who have a tricuspid regurgitant velocity between 2.9 and 3.4 and have no pH signs, they are considered to be having intermediate probability of pulmonary hypertension. These patients can be followed with an echocardiogram and closely monitored. Now if the tricuspid regurgitant velocity is more than 3.4 or if they fall in the range between 2.9 and 3.4 but have other pH signs and have risk factors for PAH or CTEF, then they should undergo further workup that includes a right heart catheterization, and that's a class one indication by the expert panel in the ESC, ERS guidelines. So let's see how many signs our patient had. She had a normal EF, we know that, and then she had a TAPSY of 16. She had a tricuspid regurgitant velocity of 3.3, right ventricular systolic pressure of 58. Her IVC was dilated with less than 50% variation during inspiration. Her basal RVLV diameter as identified on the echo there had a ratio of more than one. And the echo also gives us an opportunity to derive some other parameters like the TAPSY S-PAP ratio which is a good reflection of the RVPA coupling and correlates well with outcome. So putting our patient's echo finding in the chart here, we can see that her TR velocity fell in that 3.3 range there. And then she had findings that were from two out of the three columns in the chart that's mentioned. And her echocardiographic probability of pulmonary hypertension was high. So she did undergo further workup. Her right heart catheterization showed that she had pre-capillary pulmonary arterial hypertension with a PBR of five ward units. She had elevated antipropane P. She was at functional class three and her six minute walk distance was 200 meters. She was diagnosed with WHO group one PAH with comorbidities. We've come a long way in treatment and therapeutics of pulmonary arterial. This is not uncommon by the way. We get these patients in the office all the time. Every patient with pulmonary hypertension regardless of the cause should have the general measures for treatment instituted as Dr. Test mentioned about the oxygen supplementation, about diuretics to prevent volume overload, supervised exercise, psychosocial support and all that stuff. And the risk assessment although validated in patients with pulmonary arterial hypertension with comorbidities has somewhat of a limited use in patients with comorbidities because most of these elderly patients who had risk factors for left heart disease were excluded from therapeutic trials for PAH. So this formed the basis of a change in recommendations in the most recent guidelines for treatment of patients with PAH and it was differentiated into those that had comorbidities and those that didn't. The pathway that is followed for patients with PAH without comorbidities will be discussed in more detail by Dr. Irving in the next talk. But for patients with comorbidities, the expert panel was a little cautious in their recommendation and recommended starting with monotherapy with either PDE5 or ERA and that was a class II-A recommendation. These patients still have to be closely followed and further escalation in treatment may be needed based on how they're doing. The recommendation came from some of the subset analyses from the clinical trials. The ambition trial analysis of data showed that the subset analysis of 105 patients who had risk factors for left heart disease had lower improvement in their six minute walk distance, lower improvement in their antiprobian P-levels but a higher rate of discontinuation and higher rate of adverse events when they were on either combination or monotherapy. So the recommendations, as I mentioned, for patients with PAH and comorbidities at this time has been proposed to be starting with monotherapy. So our patient was started on sildenafil 20 milligrams TID and that was escalated to 40 milligrams TID in about three weeks after she demonstrated adequate tolerability. And she was reassessed in the office in about three months and she remained at intermediate low risk and inhaled troprostenil was added. Just a word of caution, not all comorbidities are equal. So a 45-year-old patient with scleroderma who has well-controlled systemic hypertension and diabetes and single vessel coronary artery disease that has been treated with a stent and has a mean pulmonary artery pressure of 60 and a PVR of 10 word units, please treat her as the classic PAH. She should not be treated with monotherapy, especially with an echo looking like that. So in conclusion, overall, as practitioners in the community and generally overall as PAH practitioners, we probably should become more familiar with evaluating the echocardiograms personally and clicking that show images button under the echo report to see if patients have all those PAH signs. It's important to confirm the diagnosis that it's indeed PAH and continued risk assessment is essential for prognosis in patients with comorbidities as well as to form the basis of shared decision-making in case escalation in treatment is needed. Close follow-up, like I said, is important and selective advancement in monotherapy would be indicated. Thank you for listening. Thank you. I hope that you enjoyed the smiles as I did. My last colleague whom I welcome to the podium is Dr. Elwing and she's a current professor of medicine and the director of pulmonary hypertension program in the division of pulmonary critical care and sleep medicine at the University of Cincinnati. But we were also congratulating her today because she will be presenting the distinguished scientist honor lecture in cardiopulmonary physiology and that's on Wednesday. It's a very high honor and we congratulate her for that. I personally learned a lot. Thank you. Thank you guys. And thanks for all my friends being here. Appreciate it. So I'm gonna take what these two fine people talked about and try to put it together for us in a way people can use it on a day-to-day basis. We know that pulmonary hypertension is complicated and the more we talk about it, the more we know that we need to learn. Every time we do a guideline, we change something to make it even more confusing. And that's just to keep everybody on their toes. So if you wanna check that QR code because I have a few questions for you. Worked? All right. And I'm gonna be talking about initiating therapy on a case-to-case basis and how to work with your center that you might be referring to and how we work with you. All right, so I'm gonna talk about Jonathan. Jonathan, he's 42. He has mixed connective tissue disease, hypertension. And you see him in your clinic, your community-based clinic. And this guy is rapidly worsening. He's got exertional chest tightness, lightheadedness, and he's feeling it when he's going up the stairs. He hasn't yet passed out, but almost. And he's getting dyspneic with routine activities. He's got his normal mixed connective tissue disease medications, a PPI, something for Ray nodes, and hydroxychloroquine. I want you to pay attention to his vitals. 102 over 68. He is not usually that low. He's got a heart rate of 99. He's a 42-year-old man. And you walk him in clinic, and he can only walk 130 meters. So this should start triggering you to have some acid reflux yourself. So, and he desats. So you're like, oh, and maybe it's the Ray nodes talking, but you're worried. On exam, he has JVDs, pulse fatality JVD. He has a little bit of a heave. He has an accentuated P2 and a two out of six murmur. So now you're thinking, he's actually gotten, he's developed some pulmonary vascular disease. His lungs are clear, because they should be clear, because this gentleman, you're worried about right heart disease. Abdomen's a little bit full, and he's got two plus edema. All right, so what's your next step? You're gonna start his work up as fast as you can, and you're gonna start thinking about where you're gonna be able to send him once you get a little bit more data. So you get his labs. Creatinine of 1.5, sodium of 134, BNP of 940. That's already putting you at a high risk status. So just be aware of that. All of those things are high risk. Get your BQ, it's negative. You already did your walk-in clinic. You had PFTs recently, and he has an isolated low DLCO. DLCO predicts the development of pulmonary vascular disease in our connective tissue disease patients that have those scleroderma features, even before you see it on echo. You can see it trending down for almost a decade. HRCT, he's gonna have a little bit of fibrosis. Almost every scleroderma, mixed connective tissue disease patients will have a little. It's not the driver of this. The echo shows you everything. All right? You've got a very diseased echo there. So you have RA dilation, RV is dilated. The septum is showing diastolic and systolic flattening, and the LV's working fine. Your TAPSY, as Dr. Tess talked about, it's low at 1.5. Your pressures are estimated at a very high level, and you've got a pericardial effusion. So confounding that feeling of anxiety for you and the patient. When you do a peristernal short, you look at it, you're confirming that this is not really new. There's a lot of trabeculation, that right ventricle's thick, but you see your nice pericardial effusion and that flattened septum. And you look at your TR jet velocity, you're like, do I believe it? Yes, I believe it. It's a nice envelope. And you look at that TR jet, and you say, ooh, that's much higher than what Dr. Jory talked about, 2.8, it's 4.14. So again, confirming what you're worried about. So you have an opportunity at this point to send to a center or to do the right heart cath. It really depends on what kind of support you have in your community. If you are going to have to wait three months to get a right heart cath, do not. You wanna get on the phone and talk to the referring center you work with, or figure out who they are and find their phone number, and make sure this patient can be seen quickly. But in this case, you actually have good colleagues that help you out on this, and you get your right heart catheterization, and it confirms that you have, indeed, pulmonary arterial hypertension. Your mean is 55, and you have that pre-capillary pattern with an elevated PBR, 8.8. Okay, so you confirmed it. You're worried because of many factors, your labs, your rapid progression, that pericardial effusion, the right heart dysfunction, and you clearly have right heart failure symptoms. Okay, you're sending to the center. So you got on the phone, you talk about it, and you get this person referred right away. So this is a progressive disease. It starts in the pulmonary vascular bed, and it is relentless. We can knock it down a little bit with drugs, but we know the sooner we find it, the faster we treat it, the harder we hit it, the better we do. So this patient is pretty far into their disease course. He's having functional class three symptoms, and his RV is really taking a hit. So what do we want to do? We want to risk assess him because we want to know on paper how we're doing it so we can track it. We already know this guy's high risk. If you know all of those factors we looked at already, you've pegged him as a high risk patient because of all of those things we talked about. He's rapidly progressive. His RV is diseased. He's got functional class three symptoms, and his BNP is elevated. His right atrium is enlarged, and his SVO2 is low. He has a couple things that are tending on the more intermediate risk. You're gonna go with the symptoms and signs that are more commonly seen. So you're gonna go with high risk in him. So you're like, I really like Reveal. As Dr. Test talked about, that's what he prefers. So you're gonna plug him in, and what do you get? You get a high risk status because of those same factors. So Reveal 2.0 is a nice way to start. It's a more robust, has more parameters than the light version, so you should get that when you meet a new patient. You have those non-modifiable and modifiable risk factors, and you can put that in and get a score. And that's really helpful because it gives you a number, and we all like numbers to track. So again, confirms he's high risk, and he's on the high risk of the high risk spectrum. Okay, I'm gonna ask you a question. What's your next step with this gentleman? Do you wanna start the PDE-5 and follow up closely in three months? Do you wanna start an ERA and follow up in three months? Think of what Dr. Jory told you about the second patient. Initiation of the PDE-5 and the ERA therapy, and then revisit in three months? Or do you want to initiate aggressive PAH therapy with a parental prostacycline? Okay, and we go. So the vast majority of you are gonna say we're gonna hit this guy as hard as we can and see how much better we can get. Okay, so in the algorithm, in the 2022 ERS ESC guidelines, he needs as much therapy as he will tolerate with our currently FDA-approved drugs. More is to come in terms of new drugs, but this is what we've got, and they're oftentimes very effective. So we've gotta go through all of these things and figure out which therapy, which combinations, and what do we want out of it? Well, I want this guy to be low-risk. And how am I gonna get there? I'm gonna get there with infusion therapy. There's nothing that we have right now that can match the impact of infusion therapy. We have multiple choices of infusion therapy, but this, the ibuprostanol study, our oldest study, took patients and looked at them for 12 weeks and saw we could reduce mortality by 20%. Think about any other drug that does that. Why do we make people do these arduous tasks of being on infusion therapy? Because of this. And why do we add other things to it? Isn't it strong enough? Well, we've shown that other medications added still have benefit. This is the PACES trial. It sometimes gets a little bit neglected, but it looked at adding PDE5 to prostacyclin with added benefit in terms of exercise tolerance, hemodynamics, and quality of life. And we know combination therapy is the way to go from other studies. So another question. All right, your patient was initiated on the combination therapy. He asks you, what's next? He's coming back to you. What should you respond? Monthly follow-up and walk test each appointment and watching for improvement. Monthly follow-up with echocardiograms every three to six months and a right heart catheterization if he doesn't improve. Close clinical follow-up. Looking at that four-strata model. Close clinical follow-up looking at the three-strata model. Which one? Which one of these choices do we want? This is just to help you know that the guidelines are a little tricky. All right. So I'll cross the board because I haven't told you this yet. All right, so what is recommended is you use the three-strata model when you see someone. So you can see this guy every week if you want to. But you're gonna re-risk assess in about three months. You've gotta let that medication take effect. You've gotta titrate it. You're not gonna change in five minutes. This is not a left heart failure patient that you're gonna diaries 50 pounds off and they're gonna feel dramatically better. This takes time. So then you come back and this guy at your three-month follow-up is much better. Walking 450 meters, BNP 25, functional class two. You say it's too good to be true. I'm gonna tell you, you can achieve this. This happens in your patients that you treat really aggressively. So he reached low-risk status. You wanna say, okay, I wanna prove it. I wanna use my reveal calculator. He meets low-risk status by reveal also. Reveal light, the shorter calculator. All right. So in the French registry, they looked at more than 1,000 patients. And if at that first follow-up you got to low-risk status, you had this exceptional life expectancy. Look at five years, almost all of them are alive. But then you're like, oh, those are the mild patients. Actually not. In the most recent look at the French registry, the sickest patients on triple therapy are the people who are getting there. So this is triple therapy outcome. These are these kind of patients. This is 10-year survival. Think about this compared to where we were. If you allow transplant, it's like 90%. If you don't allow transplant or you're not a transplant candidate or you weren't one of those people, about 70%. So this gives us hope. All right, but what's reality? Why do we want you to refer? Because in the reveal registry, there were 908 deaths. 56% of the patients were not on prostacyclin therapy at all-cause death time. And that's a huge number. So we are not treating our patients as aggressively as we show it in the guidelines. So we're still missing a lot of people. So about half of people didn't get prostacyclin therapy that were in need of it. Okay, so you started him on his therapy, he met his low-risk criteria, and he wants to think about clinical trials because he knows there's some good medications down the pike. All right, one last question for you guys. Where does he go from here? He lives three hours away. And this is the whole point of this conversation. You want him to follow up as a local pulmonary provider, no further need for the advanced center? You want to recommend him going forward with the PH center and he doesn't need to follow up his local docs? Or do you want to use both resources and maximize how much you can help this gentleman? And of course, you guys are gonna get it all right. Yes, all right. So what is this? This is all about the patient. This is not about me, and it's not about you, and it's not about your staff and your office. This is about getting this person the best chance that he will have a reasonable life expectancy, better quality of life, less burden of disease. He may need you to manage his diuretics. He may need me to manage his ibuprofenol. And all of those things can be morphed based on the patients. You know, every one of the people we care for is different. We have to be willing and able to work together and be accepting of the fact that one day I might change a diuretic and the next day you might, but it's because we're trying to get this person on the right track. So, and we have different resources. You know, have the cardiopulmonary rehab locally, and we might have more support in terms of nursing and things of that nature. So putting those resources together in a resource-limited situation is the best way to help these individuals. So with that, I'm gonna turn it over to discussion. Thank you.

PAH

diagnosis

treatment

risk assessment

therapy

combination therapy

follow-up

monitoring

collaboration