Okay, good morning or good afternoon if you're on the east time zone, east coast time zone. Well, we have a great session today talking about the novel insights and the diagnosis of pulmonary hypertension. I know some people are coming in in the back. If you have some room or an open chair, just scoot over to the side so that we could allow the people in the back to have a seat. My name is Brandon Hooks. I'm a pulmonary and critical care physician at the University of Michigan Health and it's my great honor to be one of the moderators of this session and hopefully try to keep us on time. For this session, what we will do is take one or two questions after each presentation and then we'll move on. If we have a lot of time for the end, we'll open that up for group discussion. Well, first I would like to introduce our first speaker, Laura Saldivar. I apologize about that. She's going to speak to us today about using factor magnitude counts as a modified home six-minute walk test. All right. Hi, guys. So, my name is Laura Saldivar. I'm a fourth-year MedPeds resident. I'm at the University of Rochester Medical Center. I'm here to talk to you guys today about our project using wrist-worn actigraphy and vector magnitude counts to perform home six-minute walk tests. I have no financial relationships to disclose. So, I wanted to start off by talking a little bit about the important role that a six-minute walk test plays in care of PAH patients. So, including serving as an important quality of life metric for our patients, it's also an endpoint that's used for many clinical trials, as well as many of our calculators pictured here that help predict transplant-free survival and help provide some risk stratification. So, with the onset of the pandemic, as you guys know, patients with PAH were at very high risk if they were to get exposed to COVID of having a bad outcome. And so, our team has been working on doing six-minute walk testing at home and trying to find a way to do this in an accurate and reliable manner that can be useful in the care of our patients. So, of the literature that's been done so far, some of which has been done by our team, we know that actigraphy has shown that patients with PAH have low physical activity time. Walking in a 90-foot walking space outside provides a comparable clinic distance. And a measure called cardiac effort, which looks at the number of heartbeats per walk distance, provides a comparable clinic and modified home walking space measurement. So, the objective of our study was to see can actigraph worn on the wrist be used to complete six-minute walk tests at home. And we aim to do this by looking at two measures. One is called vector magnitude, which we've used in some of our prior studies. And second was the number of steps. So, vector magnitude looks at the movement of a patient's wrist, x squared plus y squared plus z squared, square rooted, to measure where they're moving through space. And then we use the traditional step counter as well. Vector magnitude accounts for all movement. So, moving our patients and their wrist through space was what was being recorded. The accelerometer was used and trained using healthy control patients. And as we know, many of our patients with PH don't have, don't have, they're not healthy controls in terms of what they're moving, like along with them as they're walking. So, they may have a cane or oxygen when they're walking along as well. When we look at our study visits and what each one of our patients did, so we had each patient complete two walks in clinic wearing the actigraph device. And then another two walks at home in a modified walking space within 48 hours. And then they repeated both of those walks eight weeks later. So, for their walks at home, it had to be an unobstructed space of at least 30 feet. To give you some background on our patients, so we had a total of 47 patients, 29 of which had PAH or CTEF, 6 with HFPAF, and 12 healthy controls. They were a range of ages, though mostly middle-aged in the affected individuals group and mostly female in that group as well, but that also aligns with the demographic that's most affected by these conditions. So, in our healthy controls, we had more male participants to help provide some balance. And as you can see, in terms of the walk distance traveled, we had a wide range of distance traveled with the healthy controls, as expected, walking a further distance. So, when we look at vector magnitude and steps taken during six-minute walk tests, when we look at both the home and clinic environments and we look at vector magnitude and steps, the walks were not significantly different in either location. However, when you look at the distance traveled for each one of the patients, you'll see that for vector magnitude, there's a strong positive correlation between vector magnitude and distance traveled compared to no significant correlation when it comes to steps. All right. And then you'll see here also circled, some of our participants had some of the lower walks where they were having distance recorded, but not steps counted. And we think this may be related to use of a cane or pulling an oxygen tank, because as we talked about, the algorithm was trained using healthy controls. When you look at the difference between the two visits, the eight weeks apart, and you look at the clinic walks, average vector magnitude, again, and steps, you see, again, that the walks were not significantly different in the two locations. However, you will see across the bottom of the average steps graph, again, some zero recorded steps. So when we pull out some of these patients who are most severely ill and had the fewest steps, you can see that the variability in the step counter compared to the variability in the vector magnitude, there's a lot more variability in the step counter, suggesting that vector magnitude may be a more useful measurement to see how our severely ill patients are doing. When you look at the change in the six-minute walk distance over time and compare it to the vector magnitude and the steps, you'll see that there's a positive correlation in the change in distance traveled by these patients when you look from a vector magnitude standpoint compared to when you look from steps. In terms of in the home environment, so you'll see that it's nearly significant for the steps counted, but there was a difference when doing the home walk test. And we think this is likely related to that variability in the step counter that was tested with the healthy controls. As you can see, the box and whisker pot is very long and very tall in this diagram, again, counting for some of those zero recorded steps for patients who were moving. So some limitations. So these algorithms aren't perfect for severely impaled patients, and we weren't able to account for differences in effort. There are definitely some patients who benefit from having the external motivator of a study person or a provider on their care team. But we can look at this by doing continuous heart rate monitoring and cardiac effort to see a measure of how hard our patients are working in order to complete these steps and these tests at home. So in conclusion, risk-borne actigraphy provides a novel way for six-minute walk tests to be performed at home, but disease-specific algorithms are needed to provide more granularity, especially for our severely impaled patients. Incorporating a physiologic monitoring, so the measure of cardiac effort, heart beats over distance traveled, provides more stability by helping to account for the effort these patients are taking. So I'd like to take a minute to thank the members of the URMC PH team, including my mentor, Dr. LeChant, as well as the PH research team, without which none of this research would be possible. And thank you so very much for your time, and I'd be happy to take any questions you have. Hey, thank you so much. And next, we'd like to have Dr. LeChant, I guess your mentor, come up and give us a talk on cardiac effort, a tool to reduce variability and enrich enrollment for patients who will increase six-minute walk distance in PAH. So mentor to follow student. Perfect. You can tell Jim White helped with the title of this. I wanted to keep it simple and just have it be making the six-minute walk test great again, but he thought it was too controversial. So I do speak and consult with United Therapeutics and Bayer in the last two years. It's the only disclosure. It has nothing to do with this research. So I'm going to review the six-minute walk test quickly, describe cardiac effort for people who don't know what it is, and then kind of go over why it could be helpful in clinical trials going forward. So the good and the bad of the six-minute walk. So I was a former rower. I'm a big fan of six-minute walk tests and really exerting somebody. It really shows you functionally what somebody can do. It's a meaningful endpoint that we've had in multiple clinical trials to help get our drugs approved. And as Laura showed, it's incorporated into risk assessment, which, once again, it's a big component of the power of the risk assessment. And what people call ceiling effect, Jim White and I like to call variability, especially in longer walkers. As our drugs have gotten better, as people are on more therapies and walking further, the variability in six-minute walk tests is what makes it difficult to tell improvement. And then this was recently reported out of Steve Kawit's group. He noticed the minimally clinically important difference in six-minute walk was 33 meters, which falls into the variability of what you see in longer walkers. So because of that, it makes the signal to noise of the six-minute walk test difficult. So what is cardiac effort? Laura briefly talked on this. So this is the number of heartbeats used during the six-minute walk test divided by walk distance. So what we do is we integrate the heart rate curve, and we come up with a number, and we divide it by the walk distance. So you can see in this green line, this person has a cardiac effort of 1.4 beats per meter, and they walked almost 600 meters. And so they really were booking it. And so this person probably has a stroke volume impairment, but they also pushed themselves. And so if you were to put them in a clinical trial, their walk distance may not improve, but they have plenty of room for heart rate to go down to show physiologic improvement. The blue line shows a cardiac effort of 1.6, and they walked 515 meters. This is like the quintessential who would really be great for a clinical trial, because they have room to increase walk distance, and they have room for their heart rate to go down as well. And then you can see the black line. They have a cardiac effort of 1.25. And I'm not sure that they would improve with another drug. Their walk distance is 544. It's hard to improve on that. And their heart rate curve wasn't that high. So this person may be perfectly optimized in terms of their cardiac effort. So this also just highlights more the value of cardiac effort. So on the left is the clinically stable person. So they did two six-minute walk tests within 48 hours. This person's on triple therapy, and you can see there's over a 50-meter difference between his two walks, despite nothing else happening besides 48 hours occurring. But when you look at the two different heart rate tracings, you can see he wanted to beat a score on the second walk, and he paid for it with more heartbeat. So when you adjust for that, you get essentially the same number. And then on the right, you can see a treatment intensification person. This is a scleroderma person. She was on background therapy, and she walked 182 meters. And so the question always is, was this scleroderma, joint pain, something else influencing her walk distance? But when you see her heart rate almost at 140 beats per minute, that's stroke-buying limitation limiting her walk. So we added therapy. And when she repeated her walk again three months later, you can see not only did she almost double her walk distance, but the number of heartbeats used to do it shows impressive improvement in her physiology. So she was able to go farther with less stress on her heart. So this would make my life easier if we could just use risk-based devices. And we've gone down this road with three different ones. We've looked at high-end sports watches. We've looked at known and pulse oximeters. And we've looked at other hospital-grade pulse oximeters. And in every case, we found either significant data loss. So the top left shows what we got in about a third of our patients using a risk-based heart rate monitor. And due to low pulse-width pressure motion artifact, you just lose the signal. When you use ECG and compare it to continuous heart rate monitoring during the six-minute walk test with a known end, you can see that there's under-reporting by the known end. So ECG is about 14 beats per minute higher throughout the walk. And then when we've looked at six-minute heart rate with pulse oximeter versus ECG, once again, we found that ECG outperforms it. So in this study, we did six-minute walk tests with heart rate monitoring. We had two groups, a clinically stable who did the test twice within four weeks just to see what's the variability. And then we had a treatment intensification group 12 weeks later to see, at a time when they have benefit, what improvement could we see. So in our stable group, we had almost 60 patients, middle-aged, female, what we typically see in PAH. And then we had a treatment intensification group. We had 42. And this was a mix of treatment naive and treatment intensification, meaning they were on background therapy, but we were adding usually a prostacyclin at this point. And what's worth noting is that the six-minute walk distance was about 25% lower in the treatment intensification group, where the cardiac effort, 1.8 beats per meter, was almost 50% higher in the treatment intensification group. So it really starts to uncover some of the differences between the two. And when we say stable, we just mean there was no clinical changes, despite this doesn't mean every patient was at goal in terms of their therapy. And so what we found is that cardiac effort has less variability and more signal. So on the left, you can see the whisker box plot shows that 50% of the data was generally between 2% and 4% in the stable group, where when you look at percent change in six-minute walk distance, it's about negative 5% all the way up to 7%. So a bigger swing in six-minute walk distance in stable participants. And then when you look at the treatment intensification group, you get a bigger drop in the cardiac effort than six-minute walk distance. And really what's worth highlighting is that cardiac effort, 75% of the data drops below zero, which is what we want to see. You get a reduction in heart rate or improvement in walk distance. We're looking at six-minute walk, it crosses zero. So it just muddies some of the signal to noise that we have. And those top three values in the cardiac effort treatment intensification group is not failure of the measurement. It actually shows you the deranged physiology in patients who don't respond when you're trying to enhance therapy. So this is their walk distance in all three. One person went down, and you could argue maybe it's variability. One person was unchanged, and another person clearly got worse in the 12 weeks. But when you look at their heart rate and follow-up, despite not improving or going down, it goes up in all three participants. And so then when you calculate their cardiac effort, you get a clear signal that when somebody's not responding and getting worse, cardiac effort goes the way it should. When you use Steve K. Witt's 33-meter difference as a clinically meaningful change, and you look at cardiac effort versus six-minute walk, you can see that six-minute walk has a little more variability, so almost negative 10 to 10%, where cardiac effort is much tighter at negative 2 and 4%. And then when you look at treatment response, you can also see that the cardiac effort group in people who had a 33-meter change dropped significantly. So when you're trying to compare how somebody's doing in a trial, would you rather have the left two or the right two as your signal to noise in terms of evaluating drug efficacy? And what about people with more than 400 meters? So this is where there's a lot of concern that the ceiling effect is going to limit detection of improvement. And you can see that the difference between cardiac effort in the stable cohort versus the cardiac effort in the treatment intensification, there's a significant difference between the two, where statistically there is no difference between six-minute walk distance and treatment intensification in the stable group. So once again, it just increases the signal to noise in a group where it's extremely difficult to find improvement in a group that actually still benefits from therapy. And so limitations, this was single center. Our staff and research participants are trained extensively in doing six-minute walk properly and very motivated. And this was not a randomized clinical trial. It was just using different therapies for different patients. And so really, in conclusion, the bottom bullet point highlights cardiac effort, that incorporating cardiac effort into future clinical trials could help decrease variability in six-minute walk distance and rich for patients who are most likely to increase walk with additional effective therapy based on heart rate. And really what we're trying to find is stroke volume limitation during stress that would benefit. And so I just want to give a big shout out to Jim White, who's actually not here right now. But he has been tremendous in supporting this research as we've been going on. And with that, if there's any questions. Next, I would like to welcome Garrett Fiscus to talk to us a little bit more about optimal MAP targets in pre-capillary pulmonary hypertension. Thank you. Good morning, guys. So my name's Garrett. I'm one of the current second-year fellows up at SOI Connecticut. And I'm excited to share with you kind of the impact of our latest project as it may aid in just a little better inpatient outcomes involving these patients that have right heart failure with pre-capillary pH. I have no disclosures to speak on. And just before we get into the study, I just kind of want to have all of us have just this kind of brief overview of really the things that we were kind of trying to tease out here. I know pretty much all of us in the room are aware that pH itself is pretty bad. It has high... It's a progressive disease. It has high morbidity and mortality alone. And with some of the newer literature coming out, it's showing us that the right ventricle really is one of that single most determinants that are showing prognosis and the clinical capacity. And so as that right ventricle tends to fail, again, that mortality and that prognosis really starts to skyrocket. And so these patients will often come into the hospital with their shock a little bit complicated. And the reason that is, is because when you look at the relationship between the pulmonary artery and the right ventricle, it undergoes... The right ventricle undergoes remodeling really at all types on the scale, whether it's at the organic level in terms of the hemodynamics, the tissue stiffening, fiber reorientation, or really just at the cellular level. And so it fails really just like any organ in our body. It outgrows its blood supply. And when you look at the blood supply to the right ventricle, really you're talking about the systolic pressure minus the PA pressures. And so when you start to think of things like that, really it's just you're looking at what's going on in the left heart minus the right heart. So you just take that whole concept and you just now apply it to just the perfusion pressure against any organ. So now we're looking at really what's the MAP minus versus the CVP. And we've shown this time and time again when we're trying to find what the ideal MAP study is and what the ideal blood pressure goal is for all these patients. A lot of the literature coming out is really looking at all of the patients with septic shock in the critical care world. And they've actually tried to identify, is personalizing this MAP goal really what's appropriate? And so the question we always ask at the end of the day is, is there an appropriate MAP goal that we have for really anybody? And specifically we tried to say, was there a MAP goal that would have adequate perfusion really just to the right ventricle? And so our goal for the study was to really tease this out. So we tried to see what was the utility of really this dynamic or ever-changing MAP in patients that had specific pre-capillary pH that were admitted to our hospital with right ventricular failure. To start off with this, we had a retrospective analysis where we identified 60 patients at our single tertiary center in Hartford. And what we used was really just this conventional, the first 30 patients. We had identified were treated with the static goal, whether it was a set 65 or 70 as our MAP, whereas the next 30 that we identified were treated with this ever-changing MAP, which we'll get into. All definitions really for pH were just using the standard ERS guidelines that had previously been put out. Our primary outcomes, what we were looking for were renal failure, which again were just defined by the traditional KDGO guidelines, in addition to the in-hospital mortality. Our secondary outcomes were both length of stay in the hospital and in the ICU itself, need for ventilator or renal replacement therapy. The only definition we really had to tease out was really what we considered what right heart failure was. And historically, the right heart's really been kind of overshadowed by its left counterpart. So just using kind of the assumptions that we all made from the ERS guidelines in combination with really what's coming out with our cardiology colleagues, we defined our definition for right heart failure as both invasive and non-invasive techniques. So using echo to say that there was right heart dilation, low TAPSE score in combination with invasive hemodynamics. So a high CBP or right atrial pressure on a swan in combination with a low cardiac index and output. In terms of our management protocol, what we had done. So the first, like I had said, the first 30 patients we set as a standard static map goal. So either 65 or 70. Usually the clinicians would pick that traditional, the optimal 65. Whereas the next, what we did was we challenged them with a dynamic and ever-changing map goal. So based off of kind of assumptions and suggestions put out in the literature prior to this, what they were looking at was really just bolstering that map goal based off of whatever the right atrial pressure was. So whenever we had the initial assessments, if you just take somebody that has a CBP of 25, we now challenged them and made that new map goal 85. And so our protocol just listed off saying they need to be on diuretics or vasopressors to now bolster that up. And every 12 hours, they underwent reassessments with the team. That team being our pH team, advanced heart failure, nephrology, and then the intensivist in the unit itself. And every reassessment, once you found the new CBP, you readjusted your new map goal so you could come down on any of the therapies. And so every patient underwent this twice a day. When you look at our baseline demographics between the two groups, they were fairly identical. Their average age was around 65. There was a pretty male predominance between the two groups. And the most predominant class of pH was really that group one. When you look at the non-invasive studies, the two groups were nearly identical. And that's shown really, again, with both our invasive data as well. When it comes to our outcomes, so if I just direct you kind of really towards the secondary outcomes right now, our length of stay, we had a general trend towards the static group, not significant enough. But if I point you really to our primary outcomes, you see a pretty shocking difference between the two groups and really those favor that personalized dynamic map group. Our limitations, really, I think we're limited just by the fact that it was a retrospective study at a single center. Regardless of the weaknesses, though, this really presents a really novel study idea. To our knowledge, this outcomes are really the first time to ever look at a specific personalized map approach in patients really just dedicated to right heart failure secondary to the pH. So this kind of somewhat will challenge the universally accepted map goal for all that cookie cutter mold in all patients. With patients with pre-capillary disease that go on to develop right heart failure, should we start taking really a dynamic approach at things? So our hope is in the next several months to years that we'll kind of roll out a larger study, maybe multi-centered, just to kind of reconfirm the data that we're showing here with our single center. Thank you. catheterization practice. The study was conducted and designed by the pulmonary vascular disease section of the ACCP chest. These are our authors. I'm Francisco Soto with the University of Tennessee Graduate School of Medicine and UT Medical Center. I have nothing to disclose. The guidelines support this standardized hemodynamic evaluation of patients with pulmonary hypertension with very specific cutoffs. You would say there are only three numbers, your mean, more than 20, your wedge, 15 or less, your PVR, but depending on which waveforms you choose and what part of the respiratory cycle, which cardiac output you choose, the difference can be dramatic between patient A and patient B or center A and center B. We believe that there is a knowledge gap due to the variability among the PH specialists in the way we interpret and perform the right heart catheterizations. We were inspired by the study by Dr. Pugh and the Vanderbilt group back in 2014 when they looked at a very similar issue and they had 30 respondents at that time, so we decided to try to amplify this and see how much things have changed since then. We sought to identify this just looking only at PH physicians in the US. We surveyed the pulmonary hypertension physicians through the Pulmonary Hypertension Association. It was a REDCap semi-quantitative online survey and there were only two main inclusion criteria, that the providers identify as physicians caring for PH patients and that they provide, I'm sorry, prescribe pulmonary arterial hypertension medications. It was an anonymous survey that would go through a link. We did our best trying to make sure that we would keep this as anonymous as possible to get more transparent data. We look at general questions, demographics, description of the center, and then we look at right heart cath data specific to location, catheter of choice, and hemodynamics. A total of 145 PH physicians responded. 68, 2 3rds of these were male. Age range, 85% of them were within ages of 30 to 60. Almost 80% of them work in academic centers. However, about 50% of them currently practice not accredited pulmonary hypertension centers. So this is a very good sample of what happens in the community. 89% of them treat adults. The years in practice less than five, five to 10, 11 to 20, they were somewhat evenly distributed. With regards to the geographic regions, we had a very nice, somewhat even distribution which makes the answers and information that we got more reliable. 71% of the respondents were pulmonologists. It's very similar to the 2014. When we ask who performs the right heart cath in your institution, about 46% of respondents are performing it themselves. When we ask the pulmonologists, out of 103, so they said 45% of them perform it, and out of the 39 cardiologists, half of them perform the right heart cath. Most of the right heart catheterizations are being performed in the cardiac cath lab. And then we ask, if you have a new patient who already had a right heart catheterization, do you repeat the right heart cath? 23% said they usually repeat it, no matter what. The other 76%, they said depending on whether they are data missing or they have questions about the quality of the data. When we looked at the review of the hemodynamic tracings, if you didn't perform the right heart cath, do you look at this? So about 21% say they rely on the final report, 5% had no answer, so this might be a great area for work in the future compared to 2014, back then it was 50% looking at the hemodynamics. For the wedge determination, what part of the respiratory cycle do you check that wedge? 86% are using end of expiration, which is the recommendation. The other 14% use either a computer-provided wedge or they just average the respiratory cycle. If you got a wedge, a waveform, and you decided on that, how do you confirm that it was accurate? Do you use fluoroscopy? So 73% do this routinely, and on fluoroscopy, you might see if the catheter is anchored properly and not moving. How about a wedge SAT? You decided to use a specific wedge waveform, do you check a SAT to make sure that it's accurate? Only 42% are routinely checking this. And for LVDP, about 12% of them are routinely checking this number. How about cardiac output? Is there a routine cardiac output method that you use for every procedure? About half of them routinely check thermodilution and indirect FIC. An area that might be worrisome or for potential work is 12% are using indirect FIC. PVR cutoff, is there a number that you use to decide whether you're gonna treat your patient or not? 80% continue to use the more than three wood units. Interestingly, 16% are using the more than two wood units that was proposed in 2022 as the cutoff for that being abnormal. We don't know if treating those patients makes a difference or not. This was a great question. What if there is a discrepancy between a thermodilution and your indirect FIC? Meaning your PVR is more than three by thermodilution, but less than three by indirect FIC. Which one do you trust? Two thirds say that they would choose the thermodilution. Up to 30% said that they would choose the indirect FIC or that they don't know which one to trust. Another great area for future work. Is there a best cardiac output related variable? Meaning what gives you the best prognostic variable, cardiac output, cardiac index, stroke volume. 65% said cardiac index. And 17% chose stroke volume index. This is some French data that you might know suggest that this has some significant prognostic implications. How about analgesia and sedation? 48% of the providers use only local anesthetic. In my humble opinion, that allows you to get much more clean data, especially if you're using indirect FIC once you start sedating the patients. The most common vasodilator was nitric oxide. If your patient is already on PAH treatment, do you repeat a right heart cath? 80% said they would only do it when the patient is declining. About 20% said they do it at least annually. There are gonna be a few questions where the answers add up to more than 100% because the providers could choose more than one correct answer. And if we look at specific PAH therapies, is there a therapy that you say, okay, because you're on these, I'm gonna repeat a right heart cath? So 45% said no treatment therapy warrants a repeat right heart cath unless the patient declines. For prostacyclines, 53% they said they would do it for intravenous. The conclusions, this is the largest reported data on real world right heart catheterization practices by pulmonary hypertension physicians in the US. Close to half right now are performing the right heart cath themselves. Up to 21% of the physicians do not independently review the tracings. It doesn't mean that the tracings or the numbers are not accurate, but it could be an area for extra confirmation. We found significant variability in the wedge pressure confirmation and measurement. And the recent guidelines for PVR cutoffs and optimal cardiac output methods are not consistently followed. Clinical implications, since major diagnostic and therapeutic decisions are based on such strict cutoffs of more than 15, less than 15 for wedge, more than 20, obtaining this consistency is crucial. We believe that standardization of the performance and evaluation is crucial to ensure the appropriate pH management. Our thanks to my chairman and my division chief for their support. To the PHA, they were instrumental in allowing us to post the data. To the PHCR members, they generously donated their time to answer the survey. The pulmonary vascular disease section, the study would not have happened without this wonderful group. And then they highlighted a few of the members who were instrumental in making sure that we completed all of this data. Thank you. Thank you. These are fantastic talks, generating a lot of questions and interest while I'm loading up the next presentation. How many here in the room practices pulmonary hypertension, just by a show of hands? And then of those that are in the room, how many perform your own right heart catheterizations? Okay, a good amount. Because if there's any tests that I've ever encountered with more greater variability, it's the right heart cath. Not only with performing it, but also with the interpretation. So I really appreciate you highlighting the variability in practice. All right, so we have our last speaker, Didion Menon, is gonna talk to us about carbon monoxide testing with a diffusion capacity for pulmonary hypertension. All righty, good morning, everyone. Thanks for joining. I'm gonna be talking to you all about the diffusing capacity for carbon monoxide in pulmonary vascular disease, DLCO in pulmonary vascular disease. This is data from the pulmonary vascular disease phenomics or PVD-omics study. Presenting this on behalf of the PVD-omics study group, both at the Mayo Clinic, where I used to be a pulmonary hypertension fellow, as well as everyone else at all the other centers involved, my sincere thanks to the entire group. So just very briefly, the PVD-omics study is a deep phenotyping initiative that tries to combine clinical metrics with omics data with this overarching goal of trying to facilitate an updated pulmonary hypertension classification to aid management. And so the pivotal, the main manuscript that was published last year, one of the big findings was that low DLCO is common in groups one through three pulmonary hypertension. And so my aims were to describe the relationship of diffusing capacity and correlating that with patient characteristics and outcomes across groups one through five pulmonary hypertension within this cohort with a specific focus on group one patients. It's a busy slide, but just the methods in general. The study enrolled a little under 1,200 patients from 2016 through 2019 at seven centers within the United States into three major groups. So we have our pulmonary hypertension patient groups through one through five. And these patients were defined based on the 2013 WSBH hemodynamic guidelines. And we also had a comparator set for groups one through five. These were patients that had similar underlying disease processes, but mild or no pulmonary hypertension and about 92 controls. So moving on to our results. So this, the figure on the left just shows you the distribution of diffusing capacity in groups one through five amongst pH patients. And right off the bat, you see that it's in that high 40s to high 50s range and group three, as expected, has a much lower diffusing capacity with a mean of about 34.5% predicted. The table on the right goes through the DLCO in groups one through five, the respective comparator groups, as well as controls with the column on the far right showing you what proportion of these patients had a low DLCO, which we define as a DLCO of less than 40% predicted just based on prior data that's out there that shows that that has a discriminatory prognostic significance. And again, you see, as expected, within group three, you have the highest proportion of low DLCO patients at about 72% and a good number of the comparators as well had low DLCO at about 41%. Within group one patients and group two patients, it was about 23 to 24% and less than 20 in our other groups. And so moving on to just the characteristics of groups one through five patients stratified by high versus low DLCO. And we see here, you know, the column on the, the penultimate column on the right shows you the group with low DLCO. And these patients were older, male, lower VMI. Lower DLCO is associated with a smoking history, a shorted duration of pulmonary hypertension and less common with more prevalent disease. It also associated with pulmonary function test abnormalities including low FEV1, FEC, TLC, and a much lower six minute walk distance with a median six minute walk of almost 100 meters lower than those with high DLCO. Also correlated with a low pro BNP. Did not correlate with echocardiographic parameters that we looked at. Did with CT abnormalities including interstitial lung disease, emphysema, and some cardiac MR findings such as low LV ejection fraction. In terms of hemodynamics, we didn't see a correlation with several hemodynamic parameters, but there was an association with a higher pulmonary vascular resistance. And finally, in terms of P8 specific therapy, we did find that patients with low DLCO were less likely to be on any P8 specific therapy. And that included prostrate medications. Terms of our outcomes data, low DLCO, which is in blue over there, associated with worse transplant-free survival in all comers with pulmonary hypertension with an adjusted hazard ratio of 2.5. And a 10% decrease in DLCO increases the hazard of transplant and death by about 33%. This is our data within the group one cohort. I'm just focusing here on pertinent positives and differences from groups one through five. And again, we see that correlation with patients who had a smoking history, again, less common with prevalent pulmonary hypertension associated with a shorter duration of disease and correlated with established markers of disease severity including a higher probian P and a lower six-minute walk. And some echo parameters including RBSB and LVEF. In terms of the subgroups of group one, we did find that certain etiologies correlated more with lower DLCO. And this was seen with our PVOD subgroup as well as the connective tissue disease associated pulmonary hypertension. In terms of hemodynamics, we did not see a correlation between those parameters and low DLCO. But again, with pH specific therapy, we do see that these patients were less likely to be on pH medications. And again, this included prostanoids. Outcomes data. So low DLCO did associate again with worse transplant pre-survival in our group one patients with adjusted hazard ratio of 2.8. And so in conclusion, in groups one through five pH, low DLCO is associated with most established markers of disease severity such as probian P, six-minute walk, et cetera. And every 10% reduction DLCO correlated with a 33% increase in hazard of transplant in depth. In group one, we see that low DLCO is associated with older age, males, a smoking history, certain etiologies such as PVOD and CTD associated pulmonary hypertension, worse functional parameters, including six-minute walk and worse outcomes, including survival. And our group one patients with low DLCO were less likely to be on pH specific therapy, including prostanoids, despite a worse prognosis. Thank you.

DLCO

patient characteristics

outcomes

pulmonary vascular disease

disease severity

functional parameters

etiologies

prognosis